Full text of "Report of program activities : National Institute of Mental Health. Division of Intramural Research Programs"

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AWJAI. REPORT

NADONAI, INSIITUIES OF HEALTH

NATIONAL INSTITUTE OF MEOTAl HEALtI

mm.

Library, Ac^u.. Unit

National Institutes of Health

Building 10

Be&esda, Maryland 20014

U-^ NATIONAL INSTITUTE OF MENTAL IffiALTH ^
Annual Report for the Calendar Year 1957
TABLE OF CONTMTS

SUMMARIES:

Basic Research

Biometrics

Clinical Investigations

Community Seiyices

Professional -Services
PQblications and Reports
Research Grants and Fellowships
Training and Standards

PROJECTS s £asa

C^^rtiraX Invastigations.

Office of the Dire^ctor of Clinical Investigations

Budget Fheet
M-D(C) 1 The Analysis of the Psychotherapeutic iVocess,

Particularly the Psychoanalytic Process 1

M-D(C) 2 Development of an Ego Integration Conceptual System

for Studying PsychotheraRjr ^

M.D(C) 3 Establishment of a Near Zero Level of Fhjrsical

Stimulation and of Action Possibilities and its

Effects on Mind and Brain ■'Activity 7

Adult Psychiatry Branch

Budget Sheet
M.AP(C) 1 The Study and Treatment of Schizophrenia as a Family

Problem "^1

M-AP(C) 2 Investigation of the Character Structure in the

Alcoholic Patient 15

M-AP(C) 3 A Study of Clinical and Experimental Depersonalization:
The Effects of Psychotomimetic Drugs on Psycho-
logical Processes 17
-M-AP(C) 4 A Study of Tranquilizing Drugs: The Effects of a
Tranquili«ing Drug on Fsychodynamic and Social
Process 20
M-AP(C) 5 FVoblems of Psychoanalytic Research with Schisophrenics 24
M-AP(C) 6 Family Relations in Schizophrenia 2?
M-aP(C) 7 Perceptual Impairment in Psychogenic l^iental Disorder 32
K-AP(C) 8 Linguistic Study of Emotionsl Expression 35
M-AP(C) 9 Social Mobility and the I^aiieu of the Psychiatric

Hospital 36

M-AP(C) 10 Psychiatric Research in a Clinical Setting: Integrating
Research and Treatment in the Role of the Clinical
Investigator 39

- 1 -

Adult Psychiatry Branch, Continued Page

iyl-AP(C) 11 Selected Aspects of the Social Structure of a Clinical

Research Program in the Mental Health Fields Problems
Posed by the Variety of Roles Built into the Social
Structure ^

M-AP(C ) 12 The Nat^l^al History of a Hospital Case Presentation hZ

M.CR(C)
M-CR(C)

1
2

M-.CR(C)

M-CR(C)

i^CR(C)
M^CR(C)

8
9

M-CR(C)

Child Research Branch

Budget Sheet

Milieu Therapy ^5

Studies in Psychopathology of the Hyperaggressive

Child ^

Technical Problems in Individual Psychotherapy

with HTperaggressive Children 53

Studies in Learning Disabilities in Hyperaggressive

Children 51

Studies in Life Space Interview Strategy and

Techniques 61

Studies of Change in Hyperaggressive Children

During the Course of Residential Treatment 65

Interaction Patterns of Nprraal and Hyperaggressive

Children 68

Research on Anger in Interpersonal Situations 70

Staff Values Concerning Therapeutic Inteirventions

with Hyperaggressive Children 73

A Study of Behavior Reporting by Child Care

Workers 15

Laboratory of Psychology— Section of the Chief

Budget Sheet
M-P-C(C) 1 Administration of Laboratory of Psychology ( A Joint

Operation of the Clinical Investigations and

Basic Research Programs) 77

M-P-C(C) 2 The Analysis of the Psychotherapeutic Process: The

Cumulative Information Derived Prom Repeated

Viewing of Complex Material 80

M-.P-.C(C) 3 Psychology of Schizophrenia 82

M-P-C(C) h Linguistic Study of Emotional Expression 84

M-P-C(C) 5 Judgment of Facial Expression from Short Sequences

of Motion Picture Film 86

M-P-C(C) 6 Interaction Patterns of Normal and Hyperaggressive

Children 88

M-P-C(C) 7 Studies of Dimensionality of Psychological Variables 90
M-P-C(C) 8 The Self-Concept and Body Image as Related to Disease

Susceptibility and Organ Choice 92

M-P-C(C) 9 Precocious Puberty and Pseudohermaphroditism 9^

]y^P-C(C) 10 Study of Intractable Pain 96

M-P-C(C) 11 Drug Study 98

M-P-C(C) 12 Schizophrenic Illness In a Set of Idential

Quadruplets 99

M-P-C(C) 13 Responsivity Patterns in Schizophrenics 101

Laboratory of Psychology — Child Development Section SSJSS.

Budget Sheet

iy[-F-D(C) 1 The Preparation of Procedures for Observing and
Recording Infant Behaviors and Mother- Child
Interactions in Testing Situations for Use in a
Study of Infant Development 103

M-P-D(C) 2 Standardization of the California Infant Scale of

Mental Development 105

M-P-D(C) 3 Long-Term Sxperisacf-s With Methyltestosterone as

a GrOTrbh Stimulanx. in Short Iramatux-e Ecys IC?

M-P-D(C) k Relationship of Jfeternal Behavior to the Subsequent
Social, Emotional, and Intellectual Development
of Children 109

M-F-D(C) 5 Develcpraent of a Theory of the Role of Parental

Behaviors in the Utiology of Personality Structure

and Psych ops thology 112

M-P-D(C) 6 Organization of Maternal Behavior and .'.ttitudes

Witliin ; 'wo' Di^uensioilal Space llij-

M-P-D(C) 7 Dsvelopnient of a Maternal Behavior Ivesesrch Instrument 116

M-P-D(C) 8 Origins of Zmotional Dependency in 3arly Childhood:

An Experimental Frograra 118

M-P-D(C) 9 The Effects of Depr!.vation and Satiation on Social

Reinforcers 120

M-P-D(C) 10 .A Screening Test for Selecting Parents on the Basis
of Their Attitudes Tof/rard Children: Fteletions
Between Attitudes Expressed During the Lying-in
Period and I^ater Behavior With the One-month Old
Infant 123

M-F-D(C) 11 Early Infant Personality Characteristics: Studiss

of Crality, -activity, and Sensitivity in Neonates 125

M-P-D(C) 12 Further Studies of the Conditioning of Vocal Behavior

in the Huifian Infant 12?

M-P-D(C) 13 The Chick's Preference for Some Visual Properties

of Water 129

M-P-D(C) 1^1- Increasing Social Vocalizations in the Infant by
Means cf an ."dult's Social Response (foriTierly:
The Pf.fect of Social "{einforcetnent Upon Social
Behavior in the Human Infant; The Effects Upon
Vocal Behavior.) 132

t!t-P-D(C) 15 A Follow-Up Studji- of Social Responsiveness in a

Group of Institutional Babies 13^

M-P-D(C) 16 The Differential Responsiveness of Infants to

FarAHiar and Unfamiliar Fersjons 136

H.P-D(C) 1? The Effect of a Strange Environment Upon the

Behavior of Infants 138

- 3

Laboratoiy of Psychology— Section on Personality

Page

Budget Sheet

M-P-P(C) 1 Coininunication of Value Systems Between Therapist and

Schizophrenic Patients 1^0

M-P-P(C) 2 Natxire and Stability of Psychiatric Nurses Concepts

of Their Roles 1^2

M.P-P(C) 3 Evaluation of the NIH Research Associates Training

Program 1^4

M.P-P(C) 4 Attitude Changes in Nurse Trainees Subsequent to

Psychiatric Training 1^6

M-P-P(C) 5 The Process of Change and the Communication of Value

Systems in Psychoanalytic Therapy^'- 148

M-P-P(C) 6 Development of an %o=.Integration Conceptual System

for Studying Psychotherapy 150

M-P~P(C) 7 Patterns of Responses on Psychodia gnostic Tests Yielded
by Patients Suffering from Various Psychosomatic
Diseases 153

M-P.P(C) 8 Development of Objective Measures of "Mental Health" 155

M-P=P(C) 9 An Analysis of Interpersonal Communication Patterns
Within Families of 'Schizophrenics and Non-Schizo-
phrenics in Quasi- Experimental Group Situations 157

M-P"P(C) 10 Value ^hanges in Psychiatric Nursing Trainees 159

M-P-P(C) 11 Validation of Specificity Theory of Psychosomatic

Disease l6l

M-P-P(C) 12 Processes of Acceptance of Social Influence 163

Laboratorj"- of Clinical Science-=Office of the Chief

Budget Sheet
M=CS.OC(C) 1 Biological Studies in Schizophrenia 166

M-.CS=OC(C) 2 Comparison of the Excretion Patterns of Metabolites

of Aromatic Amino Acids by Normal Subjects and

ScM.zophrenic Patients 169

M-CS-OC(C) 3 Study of the Metabolites of Epinephrine and

Norepinephrine in Human Body Fluids 171

]yt=CS=OC(C) k Studies of the Interrelationships of the Nei^rous and

Circulatory Systems 173

Laboratory of Clinical Science^^Section on Medicine

Budget Sheet

M=.CS-xM(C) 1 Behavioral and Biochemical Correlates of the Electro-
encephalogram (EEG) in Schizophrenic Patients 176

M>CS-M(C) 2 Qualitative Intraspecies Variations in Human Serum

Cholinesterase 180

M=CS=M(C) 3 Effect of i^ferphine and Nalorphine on Plasma

%dr-o= cortisone Levels 182

M-CS-M(C) h An Evaluation of Certain Reported Biochemical Differ-
ences Between Schizophrenia and Non- psychotic
Subjects 184

Laboratoi'y of Clinical Science— Section on Medicine, Continued. Pa^e

M-CS-M(C) 5 The Relationship Between Endogenous Antidiuretic

Hormone Activity and ACTH Release in Man 186

M-CS-M(C) 6 Morphine Suppression of Pitressin-induced ACTH

Release in Man 1S9

Laboratorj'- of Clinical Science — Section on Phj-siolog;^

Budget Sheet

]4.CS-P(C) 1 An Attempt to Differentiate Between the Thinking
Disorder Found in Schizophrenics and That Found
in Patients with the Diagnosis of Chronic Brain
Sjmdrome 191

M-CS-P(C) 2 The Effects of a Vari«?ty of Centrally Acting -rugs
on Intellectual Mot or ^ and Perceptual Behavior
in Normal Subjects 192

M-CS-P(C) 3 Studies on the Effects of Various Centrally

Acting Drugs in the Rat 195

M-CS-P(C) h A Comparison of the Effects of Chlorpromazine and
Secobarbital on Intellectual, Motor and
Perceptual Behavior in Schizoplirenic Patients 197

M-CS=P(C) 5 Behavior-ally and Pharmacologically Induced Effects

on the Electrical -^ctivity of the Brain 199

Laboratory of Clinical Science— Section on Psychiatry

Budget Sheet

M-CS-Ps(C) 1 Correlation of Psychiatric Evaluation in-th

Neiirophjrsicological, Psychological and Socio-
logical Evaluation in the '"'ged 203

M-CS-Ps(C) 2 Psychiatric Evaluation of Normal Control

Volunteers 20?

M-CS-Ps(C) 3 Psychological Variables and Cerebral Physiology 210

M-CS-.Ps(C) iJ- Correlation of Psychiatric Evaluations and Their
Physiological Correlates of the Effects of
1- Epinephrine in a Normal Control and a
Schizophrenic Population 213

M-CS-Ps(C) 5 Psychiatric Investigations in the Biological Study

of Schizophrenic Subjects 215

Socio- environmental Studies, Social Studies in Therapeutic Settings

Budget Sheet

M-S-T(C) 1 Social Life of the Mental Hospital Patient 21?

M-S-T(C) 2 The Relationship Between the Value System of the
Mental Patient and His -Mjiistment to Hospital
Life 220

M-S-T(C) 3 Development of Objective Measures of "^^^ental Health" 222

M-S-T(C) 4 Construction of Measures of Affectional and

Authority Relationships of Parents and Children

in the Families of Schizophrenics and Normals 223

= 5 ^

Socio- environmental Studies=~Social Studies in

Therapeutic Settings, Continued Page

M-S-T(C) 5 Evaluation of the NIH Research Associates'

Training Program 224

M-S-T(C) 6 Sbcploratory Study of the Mental Hospital as a

Social System 225

M-S-T(C) 7 Psychiatric Research in a Clinical Settings

Integrating Research and Treatment in the Role

of the Clinical Investigator 22?

M-S-T(C) 8 Changes in the Social Behavior of Child Patients

Associated with •'-'ifferences in Treatment Setting 229

M-S-T(C) 9 Selected Aspects of the Social Structure of a

Clinical Research Program in the Mental Health
Field; Problems Posed by the Variety of Roles
Built into the Social Structure 231

M-S-T(C) 10 A Fhenomenological Study of Child-Patient Behavior 232

M-S-T(C) 11 A Study of the Structure of a Therapeutic Milieu in
a Psychiatric Ward — Its Impact on the Patients and
the Patients* Response to it 23^

Baeic Research

Laboratory of Neurophysiology— C-eneral Neurophysiology

^ ioy

Budget Sheet
M-NP-GW 1 Measurement of Local Circulation in the Brain 236

M-NP-GN 2 Effects of Drugs on Specific Ionic Conductance 23?
M-NP-GN 3 Measurement of Soma-Dendritic Membrane Current 238
M-NP-GN ^■ Studies on Role of Superficial Neurons "Dendritic

Reactions" in Spreading Cortical Depression 2^1

M-NP-GN 5 Effect of Curare on the "Dendritic" ^Reaction 2^3

M-NP-GN 6 Tests of Certain Drugs on Specific Electrical

Reactions in the Brains of Animals 2^6

M-NP-GN 7 Activity Cycles and Interaction Between Callosal

and Direct Cortical Reactions, and to Determine

Regions of Chief Activity of Each 2^7

M-NP-GN 8 Measurement of pH Changes in the Cortex During

Spreading Cortical Depression 2^8

Laboratory of Netorophysiology— Section on Cortical Integration

Budget Sheet
M-1^]P-CI 1 Analysis of the Electrical Activity of the Brain of

Unanesthetized Monkeys 250

M-NP-CI 2 Mapping the Behavior Elicitable by Electrical

Stimulation of the Brain 252

Laboratory of Neurophysiology— Limbic Integration and Behavior

£ag£

Budget Sheet
M-NP-LI 1 Studies on Localization of Function in Limbic System
M-MP-LI 2 Studies on the Limbic System

Laboratory of Neurochemistry

M-NC-PC 1

M-NC-PC 2

M-NC-PC 3

M-NC~PC k

M»MC-PC 5

M-NCPC 6

M-NC-PC 7

M-NC-PC 8

M-NC-PC 9

Budget Sheet

Structure of Transition-Metal Complexes

Physical Chemical Studies on Synthetic Poljrribonucleo-

tides
The Formation of a New Helical Complex Between

Polyinosinic Acid and Polyadenylic Acid
Computation of Helical Transforms for Synthetic

Polypeptides
Physical Properties of Ribonucleic Acids
Frictional Properties of Cesoxjrribonucleic Acid in

Solution
Structiire of a Complex Formed Between Polyadenylic

Acid and Polyinosinic Acid
DeterTiiination of the Structure of Collagen

Investigation of the
Acid Complexes

tructure of teroid Amino

Laboratory of Cellular Pharmacology

Budget Sheet

Methionine Activating Enzyme in Rabbit Liver
Studies on Methionine Activating Enz3me of Yeast
Study of Methionine Synthesis by Enzym&tlc Transmethyla-
tion from Betaine o:- Diraethylthetin
Metabolism of S-Adenosyl"L.hom.ocysteine (ASR)
Amino Acid Analogue Studies of Protein Synthesis
The Conversion of Phenylalanine to Tyrosine
Hormonal Regulation and Protein Synthesis
Studies on the Cofactor Required for the EnZvTuatic

Conversion of Phenylalanine to Tyrosine
Clinical Studies on Phenylketonuria
Biossmthesis of Noradrenalin
Sulfate Metabolism in Chlorella

The Enzymatic Mechanism of Generation of the MetVQrl
Group of Methionirje From One Carbon Compounds Such
as Forma.ldehyde
Amino Acid Uptake ay Escherichia coll

Amino Acid Incorporation and Protein Synthesis in Liver
Metabolism of ' .-ictive Methionine" in Yeast

M-CF

M-CP

M=CP

M-CP

M-CP 10

M-CP

M-CP Ik

M-CP

260
262

266

268

271

27^
277

280

282
285

288

290
292

29ii.
296
298
300

302

30^^
306
308
310

312
31^
315
317

Addiction Research Center Page

Budget Sheet

ti-AR 1(C) Addictive Liabilities of New Analgesics 318
M-AR. 2 (C) Acute and Chronic Intoxication i-n.th Drugs Other

than Analgesics, Barbiturates or Alcohol 323

;4-AR . 3 Chronic Intoxication T-iith Barbitiorates and Alcohol 326

M-AR 4 Biochemistry of Addiction 329

M-AR 5 Neuroplis'siology and Neuropharmacology of Addiction 331

M-AR 6 Psychological Studies of Addiction 335

Laboratory of Clinical Science — Section on '-'erebral Metabolism

Budget Shee-5-

.I-CS-CM 1 Studies on :.e Circulation and Metabolism of the
Human Brain, I. .-.ge Changes in Cerebral Blood
Flaw and Metabolism. II. Effects of Anxiety and
Emotional States on Cerebral Circulation and
Metabolism 3^0

M-CS-CM 2 Rapid Continuous Measurement of Leg Blood Flow and

Metabolism ty^ Means of Radioactive Sodium 3^

li-Co-CH 3 Measurement of ^-ocal Circulation in the Brain 3^

M-CS-CH k The >?echanism of Action of ThjToxine and Its

Relation to Cerebral Metabolism 350

J^CS-C I 5 Chromatographic Studies in Intermediatry I%tabolism

Related to Diseases of the Nervous System 353

M-CS-CK 6 Determination of the Spinal Fluid Levels of

T -Aminobutyric Acid and the Lnzyme Responsible
for Its Formation, Glutamic Decarboxylase, in
Normal Subjects and in Patients vlth Mental and
Neurological Disease 357

!^CS-CM 7 Copper Dynamics in NoriKal and Schisophi-enic Serum 359

Laborator-y of Clinical Science — Section on Drug Evaluation

Budget Sheet
M-CS-DE 1 Detertoination of Cerebral Blooi Tlcn-r and rfetabolism
in Brain Disease by Means of the Inert Gas
Technique Utilizing Krypton 35 361

Laboratory rT Clinical Science— Section on Biochemistry

Budget Sheet
M-CS-3 1 ractionation of Brain Constituents. Isolation and

Identification of Antigen Responsible for Praiuc-

tion of Allergic Sncephaloticrelitis 364

M-CS-B 2 Iir; lunological Studies on .Allergic Encephalomyelitis 363
M-CS-B 3 Biochemical Studies on Brain, Blood, and Spinal Fluid

c' Encephalotnyelitic /uiimals 371

iy^CS-B 4 Antl'iuretic Effects of LSD in Normal and

Sc' Izophrenic Subjects 37'^

M-CS-B 5 xMeta'tolisra of Radioactive Histidine in Schizophrenics

and formal Humans 377

- fi -

Laboratory of Clinical science — Section on Fharraacology Page

Budget Sheet

M-CS-Fh 1 Biochemical Factors Involved in the Action of
Drugs. I. Studies on the Development of
Tolerance to Narcotic Drugs and the Action of
Narcotic Drug Antagonists 379

M-CS-Ph 2 The 'Tiyslological Disposition and Metabolic Fats of

Drugs Affecting the Nervous System 3S2

M-CS-Ph 3 Cellular Kschanisms in the Metabolism of Drugs 385

I-aboratory of Psychology — Section on Aging

Budget Sheet
M-P-A 1 A.ge Differences in the Behavior of the Hats learning

and Transfer, and "sychomotor Behavior 388

M-P-A 2 Age Changes in Time and Intensity "'elations in Hmaan

Sensation, Perception, and Response 390

M-F-A 3 '"^ge Changes in Mental and Ferceotual Abilities and

Personality Structure 392

M-F-A. k Cj'tological and Cytochemical Changes in the Nervous

System as a Function of iVgei .in Investigation of

Submicroscopic Morphology Employing the Light and

Electron Microscopes 395

M-P-A 5 Age Changes in Brain Electrolytes in the Rat 393

M-P-A 6 Metabolis-n of Nei'vc-us Tissue ~s s Function of Age 402
M-P-A 7 The Kctabolism of Neuropharniacological Agents as a

Function of Age ^05

M-P-A 8 The Effects of Hypoglycemia, Anoxi?-, and Drugs on the

Phosphocreatine Content of ^-ist Brain in ini".als of

Different Ages ^07

M-P-A 9 The Effect of Age on the Distribution of Glucose

Between Blood and Bi'ain ^08

M-P-A 10 Components of Cellular "tructure as s Function of Age ii-lO
M-P-A 11 Preparation of a Handbook of the Beha\n.or3l Aspects

of Agj.ng iil2

M-P-A 12 Electrophysiologic Correlates of ""ensatlon and

Perception 414

Laboratory of Psychology— Section on Animal Behavior

Budget Sheet

ItP-B 1 The /analysis of the Relationship Beta.'een ^.motional
Behavior and Certain Cortical and Subcortical
Structures in the Subhutnan Primate Brain '(•15

M-P-B 2 The Analysis of the Relationships Between Problem-
solving Behavior as Demonstrated in the Delayed
Response and Discrimination Tasks and Certain
Cctical and Subcortical Structures in the Subhuman
Primate Brain 41?

M-P-B 3 The Effects of Brain Lesions and Immediate Post-
operative Experience on Dominance Behavior in
Primates 420

- 9 -

M-P-B
M-P-B

5
6

M-P-B
M-P-B

7
8

Laboratory of Psychology--Section on Animal Behavior, Continued Page

M-F-3 k- Further Analysis of the Continuous- Performance

Technique as a Research Tool and Diagnostic Device

in Assessing the Effects of Drugs and Brain Pathology 423

Defining an Extrageniculostriate System, in Vision 42?

A Comparative Study in Friiiates on the Effects of

Temporal Lobe Damage on Visually Guided Behavior kjO

Histological Ajialysis of Brain Lesions in Primates ^32

Electroencephalographic Correlates of Sustained

Attentive Behavior in Man ^3^

M-P-B 9 Electrical Activity in Temporal Cortex During

Visual-discrimination Learning and Performance ^36

Laboratory of Psychology— Section on Perception and Learning

Budget Sheet
M-P-L 1 Effects of Lysergic Acid Diethylamide (L3D-25) on

Visual Functions 438

M-P-L 2 Test of the Satiation Theory of Perception 441

M-P-L 3 Electrical Recording of SJyemoveraents 443

M-P-L 4 Visual Discriminative Processes in the Pigeon 445

M-P-L 5 Individual Differences in Normal Perceptual Processes 449
M-P-L 6 Environmental and Genetic Modification of Biological

Systems 452

Laboratory of Socio-environmental Studies— Office of the Chief

Budget Sheet
M-S-C 1 Analysis of Theoretical and Methodologicsl Issues in the

Sociology of Mental Health and Illness 458

M-S-C 2 The Impact of Mental Illness Upon the Family 461

M-S-C 3 The Adaptation of the Mental Patient to His Family Upon

Return from Hospitalization 464

Laboratory of Socio-environmental Studies — Social Developmental and
Family Studies

Budget Sheet
M-S-D 1 The Formation of Children's Peer Relationships 466

M-S-D 2 Adult Leadership in Children's Groups: A Study of
Leader's Sensitivity and Functioning in Relation
to the Social-cultural Composition of the Group 470
M-S-D 3 The Validity of Retrospective Data on Parent-Child

Relationships 47^3

M-S-D 4 Life-styles in Aging 475

M-S-D 5 The Identification of Self in Identical Quadruplets:
A Special Case of the Problems of Sibling Rivalry
and of Multiple Status 478

- 10 -

Laboratory of Socio-environmental Studies — Social Developmental Pag'e
and Family Studies, Continued

M-S-D 6 The "X" Family as Seen by the Community kSO

M-S-D 7 Exploratory Study of I'fethodol ogy for /.ssessing Inter-
personal Relationships Within the Family ^+82

Laboratory of Socio-environmental Studies — Community and Population
Studies

Budget Sheet
M-S-P 1 A Comparison of the Social Relationships of Children

in the Middle ^snd Lovrer Socio-economic -'trata ^85

M-S-P 2 Exploratory Study of the 'Ir-e of Local Community

Resources for Handling Mental Health Problems 487

M-S-P 3 Pre-hospital Social Factors, Treatment i>T.th the

Tranquilizing Drugs, and Behavior as Prognosticators

of Successful Release from a Mental Hospital ii-89

M-S-P k A Twin Family Study of Mental Deficiency 491

M-S-P 5 Social Mobility and the Milieu of the Psychiatric

Hospital 494

- 11 -

Annual Report of the Basic Research Program, NIMH-NINDB

January 1 to December 31., 1957

IlSrTRODUCTION

There are relatively few resources around the world for basic
research in the mental and neurological field. Problems that need
solution are staggering,. The present overdemand for medical ser-
vices cannot be diminished except through fundamental advancement
of concepts., With few resources and lamense problems we need to
make especially effective use of what is available » How to do
this? Simply stated, it is by giving encouragement and stimulation
to the most creative scientists interested in fundamental problems
in this field and by providing that support by which they can be
most effective.

Unfortunately, there is no simple recipe for achieving this
goal. Something' worthwhile may be accomplished, nevertheless, by
setting forth new and compelling reasons why it is desirable to
pursue research basic to neurology and psychiatry. And it may
also be helpful to make even a preliminary enquiry into what is
the nature of scientific creativity.

All of the old reasons for exaiainiag the functions of the
nervous system still exist. Among the laost important of these
has traditionally been the desire to know on the part of those
involved in research— pure intellectual curiosity. The nervous
system is concerned with those things that Keaini the most in
hvfflfian life. Man's o>s/n cariosity absut himself as a perceivings
thinking being cam only be satisfied by pursuing the aaatomy,
physiology, biocheirdstry, pharmacology, psychology, sociology
and allied disciplines relating to the brain. Always there has
been a pressing need to know in order to solve clinical problems .
This reason has generally been uppermost in the minds of those
who have provided support for research.

THE IIRGEICY OF BRAIN RESEARCH

It needs to be emphasized that the braiia is aa instrument
for social as well as physiological integration. The peoples
of all nations are in need, rather suddenly, of the means to
understand and cope with a myriad of problems relating to

For this Annual Report the Laboratory Chiefs have provided
cqmprehensive statements of research progress during the year.
In the following paragraphs I have attempted the exploration of
some longramge issues that may be important to our ultimate
best achievement.

perception p memory and emotion and to learn how to become more
constructively adaptive as interdependent individuals. Social
and technological revolutions are hurtling us, as one of the
authors of the recent Gaither Report succinctly remarked,
"right into the mouth of Hell." It remains to be seen whether
we can find ways to maintain freedom where it exists and to
establish it where it is lacking. In the meantime , some kind
of world government under law is called for to forestall a
global catastrophe that now seems so probable. The shield of
our republic will depend more and more upon the creativity of
human social thinking and less and less upon direct inst|"umentali-
ties of war. The latter can only provide a gap of time within
which certain crucial social adaptations must take place.

At the root of the matter are as yet unsolved problems relat-
ing to the perception of actions and of shibboleths, the trans-
lation of ideas, the momentum of traditional concepts 3 the
adhesive behavior of groups j the communication of ideals and goals.
Many scientists have confidence that these problems can be solved,
given time and effort. Our country is presently buying time; we
can undoubtedly improve our effort . Ignorance of basic mechanisms
acts as a handicap to current attempts to meet these problems.
There may be short cuts, but few are evident. We have to learn
how signals enter the nervous system, how they are distorted by
concurrent and antecedent events, how they relate to mechanisms
of reward and punishment and emotional expression, how learning
occurs, and what are the limitations of our ■mnemonic and
behavioral response systems. These mechanisms have their
anatomical, physiological, chemical, psychological and socio-
logical manifestations. What more interesting or important
labor than to be involved in the unravelling of these mysteries?

There are bases for optimism in relation to finding solutions
to these difficult problems;

lo Creative thinking will undoubtedly be more and more
deliberately cultivated within the government , In the past,
creativity has not been favored in relation to social or
political action; instead, the emphasis has been on stability
and continuity of the familiar » Creative talent for several
hundred years has had to find individual, usually unsupported,
expression through music, literature, art and science. Recently,
and with spectacular results, creativity in scientific endeavors
has been supported by governments and industry to the enormous
material advantage of mankind. The object of this lesson
appears too clear to be missed in relation to man's psychological
and sociological needs. A more creative approach to governmental
issues will invite answers to these problems; one can already
discern the trends. Leadership in government will hopefully
become less like steering the car of a Juggernaut and more like
deliberating the most advantageous moves in chess.

- 3 -

2. Progress in fields basic to sociology, psychiatry
and neurology is rapid. There is a natural tendency, at any
given moment , to imagine that science is in a pretty comfortable
state; the directions are obvious for a great deal of work to be
done just to clear up "loose ends." Nevertheless, a glance over
one's shoulder just a few years back elicits a rather giddy sense
of speed of events in any branch of science. Physicists have
in the last year had to throw away three of the most fundamental
principles of the universe. Although less spectacular, revolu-
tionary changes are also taking place within the psychological,
neurological and sociological sciences. Twice in the past year
the Basic Research Program has been asked to prepare reviews
concerning recent advances in areas of our interest ; it has been
genuinely surprising to take notice of the speed of overall
conceptual growth. Furthermore, discoveries among complementary
disciplines now appear to dovetail in ways that could not have
been anticipated even three or four years ago. Resources of the
National Institutes of Health and of a number of other governmental
and private agencies have played an important part in the achieve-
ment of these advances .

3„ Progress in these fields will be even more rapid if
we deliberately cultivate the best oppoi'tunities for creative
contributions . The most favorable utilization of creative talent
is not a trivial issue. It needs to be thoroughly and thought-
fully examined. Albert Einstein wrote: "It is, in fact^ nothing
short of a miracle that the modern methods of instruction have
not yet entirely strangled the holy curiosity of inquiry; for
this delicate little plants aside from stimulations stands mainly
in need of freedom; without this it goes to wreck and ruin without
fail. It is a very grave mistake to think that the enjoyment of
seeing and searching can be promoted by means of coercion and a
sense of duty." The most fruitful achievements by creative persons
apparently require three things: personal mastery of a province of
science, personal discipline and personal freedom. All three
factors need to be of a high order.

4. The brain is a very incompletely exploited instrument
for survival"! The nervous system is an evolutionary product that
has played its role in human development and survival just as have
teeth and claws. But we can expect from it much more constructive
and creative possibilities. An adequate utilization of present
knowledge in areas of our greatest national need has not been
attempted in any systematic way. As further insight emerges, v/e
can expect to better understand human capabilities and limitations
in perception, memory and communication and to learn ways of
engaging reward-punishment and emotional mechanisms along rela-
tively more constructive channels.

As Professor Percy W. Bridgman, the eminent physicist at
Harvard, has been careful to point out, all knowledge of the
universe is dependent upon the level of understanding of

4 -

neurophysiology and psychology; this is essential for the inter-
pretation of sense data and for certain logical, mathematical
and verbal operations that are involved, many times in a limiting
way, in the formation of concepts of physics. It was in an
analysis of comparable instrumental operations involved in the
measurement of length and time that Einstein discovered certain
non-common-sense aspects of the universe which form the basis of
special relativity. As we learn more about human perceptual and
conceptual processes, we will gain insight not only into ourselves
but into more general features of the physical world as well.

We consider that the public need for basic knowledge in all
fields relating to the nervous system is one of the most urgent
and worthwhile as well as fascinating areas of scientific
endeavor. Warren Weaver, Vice-President of the Rockefeller
Foundation, recently said "in the realm of human behavior
including all those social, economic, and political aspects of
individual, group and mass actions which constitute the social
sciences , . . progress in understanding, and eventually in
controlling, these phenomena is just as sure to occur as is
progress in understanding the cell. We must not be impatient
or critical — surely not contemptuous — of the tentative and
fragmentary nature of the successes to date . . . the first
exciting invasions into the world of the mind and behavior."

We would welcome an objective disinterested examination of
the dimensions of these issues; the urgency of our national
need for new basic knowledge relating to the brain and its
activities; the potential value of current research; the ultimate
promise of basic research in this field to public problems; and
a consideration of all of these evaluated findings in relation to
the total research endeavor being supported by the Federal
Government .

CREATIVITY

Problems that resist solution may be insoluble, yet, if you
will believe the history of science, it is more likely that the
means of solution being attempted are inadequate. Certainly, in
the absence of fresh insight, sheer devotion is powerless to do
more than refine what is already known. It takes a creative
person to turn aside from established schemes of consciousness and
to seek out that which can lead to something more fundamental.
Occasionally the entire framework in which a problem is presented
needs to be creatively reformulated, A theory can be tested by
experience, but there is no direct path from experience to the
setting up of a theory.

A more adequate understanding of nature cannot be achieved in
the abstract; it must be brought about through the consideration
of materials with which the scientist is already familiar. Even
the most gifted and energetic person must have achieved a certain
mastery in the field of his pretended accomplishm.ents , He must
have a keen sense of what needs to be done to solve a given
problem and a sufficient skill to do that. He needs not only
carry out a program of thought and action at the limits of con-
ception , but he must follow through by communicating in a clear
way his new level of understaniding. His scientific achievements
in the end represent only a better approximation— the end can
never be a statement of finality.

Highly creative ability in any field of endeavor is so
relatively rare and little understood that it is usually suspect.
Every new step in the development of an. idea is likely to seem
alien and eccentric. One who would be creative must deliberately
encourage the imaginative manipulation of ideas that have only
tenuous credentials. Yet the mechanism of creative scientific
accomplishment are not under any satisfactory degree of voluntary
control. It requires from the scientist a thorough understanding
of the problem, discipline and hard work, but also something more
than that: creativity cannot be squeezed out as paste is extruded
from a tube. It needs the exercise or "release" of some nimble
elements of com.binatory play of imagery in a form that usually
precedes logical construction into words or symbols. Moreover,
and this is a feature of the greatest importance, the process is
easily disturbed or put off. Even too urgent a desire to arrive
quickly at logically connected ideas may foreshorten a conceptual
advancement in the making. Because of this, discipline of the
creative process should largely arise within the individual, or
be provided by example.

There is another feature of creativity which is less clearly
appreciated, that of nonconformity. As Ben Shahn has recently
written: "Without nonconformity we would have had no Bill of
Rights nor Magna Carta, no public education system, no nation
upon this continent, no continent, no science at all, no
philosophy, and considerably fewer religions. All this is
pretty obvious. But it seems to be less obvious. But it seems
to be less obvious that to create anything at all in any field,
and especially anything of outstanding worth, requires non-
conformity, or a want of satisfaction with things as they are.
The creative person-=the nonconf ormist==may be in profound
disagreement with the present way of things, or he may simply
wish to add his views, to render a personal account of matters...

"Yet, when it comes to the matter of just what kind of non-
conf oiinity shall be encouraged, liberality of view recedes.
There seems to be no exact place where nonconformity can be

fitted in: it must not be admitted into the university curriculum—
that would produce chaos « In politics it is certainly inadvisable—
at least for the time being. It cannot be practiced in journalism..,
In scieace -- least of all, alas I" Shahn goes on to conclude that
"The degree of nonconformity present— and tolerated--in a society
might be looked upon as a symptom of its state of health."

Important scientific achievements thus seem to depend upon
the fruitful combination of a group of essentially positive
factors; some of these relate to the competence, self-discipline
and nimble imaginativeness of the scientist himself and others
concern his surroundings. Research in laboratories of the Federal
Government will surely progress in the sense of advancing the
frontier. And the rate of advancement inay be speeded up somewhat
by administrative hustling or by providing additional money or
personnel in a given field. But saltatory advancement of concepts—
the kinds of change in point-of-view that may alter the entire
character and direction of scientific pursuit, the kinds of advance-
ment that may cut short years of striving--these are not likely to
occur except where circumstances are especially favorable for
creativity. In the long run, the reputation and credit of any
laboratory will depend upon a few advances of this sort far more
than upon the extension of studies that now seem entirely familiar.

AN INHERITANCE

A year ago when invited to participate in the Basic Research
Program of NIMH-NII'fDB, I already had a high regard for the
individual scientists in the Program and for their overall endeavor.
The group, recruited and led by Dr. Seymour S. Kety, was widely
recognized throughout the United States and abroad as performing
outstanding research across most of the frontier of complementary
disciplines relating to the nervous system. All this had been
accomplished within five years. Despite Dr. Kety's heavy commit-
ments to purely administrative efforts, he continued to pursue
research; he perfected his theoretical treatment of blood-tissue
exchange, e:?Jtended his pioneering studies on human cerebral cir-
culation and metabolism, and demonstrated a new method for
determining local cerebral blood flow simultaneously in
individual regions of the brain.

It is understandable that after such achievements, simply
maintaining the Program xn being could pall for Dr. Kety. Moreover,
he needed to be relatively more free to accelerate his own labora-
tory research. He would also then be able to provide immediate
leadership for a group that would undertake a broad-scale investiga=
tion of the "biology of schizophrenia." For these several reasons,
Dr. Kety asked for replacement in his job and thereby established
a precedent for rotation of this administrative office.

7 -

Before accepting so large a responsibility, it was natural
to take a deliberate and hard look at the Basic Research Program.
Close examination satisfied me and associates to whom I appealed
for advice that the excellent reputation of the Program was
entirely deserved. In addition to a feeling of satisfaction as
regards the purposes and character of the Program, I also felt
a strong conviction that the United States Government should be
supported by its citizen-scientists in every way they are able.
Dr. Kety's invitation to join the Basic Research Program was not
only flattering in one sense, it was also an opportunity for
dedication to an important cause. Having completed a "Freshman
Year" in this job, I can say without qualification that my regard
for the Program and for Dr. Kety's contributions has risen still
higher. I can scarcely measure the agreeableness that stems
from respecting and liking every scientist in the Program: this
is a continuing reflection of Dr. Kety's wise recruitment.

GENERAL COMMENTARY

During the last year we continued trying to recruit a
Laboratory Chief for Neurochemistry . In succession, two very
excellent men were invited. Each was keenly interested in joining
the Basic Research Program, even though it would mean no increase
in salary. When it came down to particulars, however, we did not
have enough space. Each was willing to come at a sacrifice of
their present considerable space, believing that some of this
deficiency could be made up by the central and collaborative
facilities of the National Institutes of Health. But neither
could establish even skeletal programs within the number of modules
we had available. Space discussions occupied us for months, but
no adequate adjustment or construction possibilities appeared.
The same contingency proved critical in relation to recruiting a
Chief for the Section on Perception and Learning in the Laboratory
of Psychology. Finally, we had an opportunity to develop the
important area of auditory physiology and psychology, but again,
space limitations were critical. It is gratifying to know that
we could build with strength and that our Program is competitive
on equal or even disadvantageous terms, but it is also obvious
that space is our most precious commodity.

Limbic Integration. By taking advantage of Dr. Kety's fore-
si ^jht^d^pTanMrn^TorTa Section on Brainstem Mechanisms which had
never been activated, we werg fortunate to be able to invite
Professor Paul D. MacLean of Yale University to join the Program.
Dr. MacLean 's interests in psychosomatic mechanisms and his
brilliant studies concerning the anatomy, physiology, chemistry
and behavioral aspects of the phylogenetically older parts of the
brain have attracted world-wide respect. At the time of our

invitation Dr. MacLean was on leave of absence from his
university, spending a year of study in ZUrich. He brings
with him not only his own exceptional talents and the tradi-
tions of Professor Fulton's laboratory at Yale, but also the
rewarding influence of recent visits to many of Europe's
finest laboratories. The new section headed by Dr. MacLean
is called the Section on Limbic Integration and Behavior. It
is jointly identified with the Laboratory of Psychology and
the Laboratory of Neurophysiology.

Graduate Students. The Laboratory Chiefs agreed that we
should restrict the acceptance of graduate students to the
best possible candidates throughout the nation instead of
favoring scholars of the Potomac Basic. We now encourage
suitable graduate students from any part of the country who
wish to do thesis work in our laboratories. They may find
this advantageous by reason of the opportunities to work
with particular scientists, have access to special facilities
and the interdisciplinary setting of the Basic Research Program
and at the same time discharge their military obligation. The
local preceptor would undertake the special responsibility of
supervising the candidate's thesis and may if mutually agreeable
become a member of the Doctoral Committee at the candidate's
home university. The university faculty advisor would at the
same time become a Consultant to the Basic Research Program
and would participate in planning and supervising the thesis
work here. The first graduate candidate participating in this
plan is Dr, Stanley Glauser, a medical doctor now completing
his thesis for a Ph.D. in Chemistry from the University of
Pennsylvania. His local preceptor is Dr. Alexander Rich, Chief
of the Section on Physical Chemistry. His faculty advisor is
Professor Philip George, Research Professor in Biophysical
Chemistry, University of Pennsylvania.

Research Associates. A Research Associates Program designed
nearly two years ago was launched last July. The purpose is to
provide two years of combined preceptor and didactic training
in basic research to outstanding men .vho have completed an
internship and who wish to continue in academic medicine. The
didactic training is intended to supplement and extend in a
more penetrating way the exposure to basic biomedical science
provided in medical school. Four of the National Institutes of
Health are participating in this Program. Seven out of the
first class of fourteen Research Associates are being supported
by the Basic Research Program j NIMH-=NINDB. Scientists in the
Institute of Mental Health are making a study of the aspirations
and creativity of the Research Associates and of the impact of
this training program on their career development .

- 9

Visiting Scientists. The primary objective of the Visiting
Scientist program is to provide a mechanism for cross-
fertilization of ideas and for collaboration between our
Institutes and Universities elsewhere in this country and
abroad. During the calendar year, we have enjoyed the associ-
ation and profited from the scientific skill of some eighteen
individuals participating in the Visiting Scientist program.
Six came to the Basic Research Program from England, three from
the United States (one of these was from Puerto Rico) , two from
Japan, and one each from Australia, Canada, Denmark, Germany,
Hungary, India, Korea, and Switzerland. Six of the eighteen
are senior scientists. We are fortunate that by mutual agreement
four of the eighteen are imjnigrating to fill Civil Service posi-
tions in the Basic Research Program. One of the four received
his papers during the year and has already transferred to
permanent status v/ith us.

We are very pleased that Professor H. W. Magoun of the
University of California at Los Angeles chose to join the
Intramural Research Program of NIMH as a Visiting Scientist during
his sabbatical leave. He pursued research v^ith Dr. John Lilly,
Chief of the Section on Cortical Integration, and with
Dr. Edward Evarts, Chief of the Section on Physiology , in the
Clinical Program of Dr. Kety's Laboratory of Clinical Science.
With Dr. Evarts, Dr. Magoun demonstrated that the recruiting
response in cortex is modified by alerting reactions on the
part of the animal. With Dr. Lilly, Dr. Magoun examined
behavioral stop-start mechanisms in subcortical structures,
mechanisms apparently related to pleasure, fear and sexual
excitement. Dr. Magoun also attended courses in the History of
Medicine at The Johns Hopkins University and Hospital and gave
a few seminars and lectures at various universities on the
Atlantic Seaboard. He was responsible for initiating the
Anglo-American Symposium on the History and Philosophy of
Knowledge of the Brain and its Fianctions which was held in
London, July 15-17 under the sponsorship of the Wellcome
Historical Medical Library with the cooperation of the
National Hospital, Queen Square, and the Maudsley Hospital.
This was reported as being the most successful and interesting
international meeting of last summ.er. We would like to
encourage the practice of other notable scientists as well
taking sabbatical leave here at the National Institutes of
Health .

ROBERT B. LIVINGSTON, M.I>.

The Basic Research Prograni, NIMH-NIUDB, includes
the following laboratories which are combined with Clinical
Investigations;

Laboratory of Psychology
Laboratory of Clinical Sciences
Laboratory of Socio-environmental Studies
The c^ummaries for these laboratories on the following
pages include only those Sections in the Basic Research
Program.

The overall summary for these laboratories is
included under Clinical Investigations, pp., 33-56

- 10 -

Laboratory of Psychologr
David Shakow, Chief

SectioB on Aging

This has been an active year for members of the Section on Aging and
the specific research findings of the present year will assist considerably in
outlining long-range research programs in aging* As in the past, research
effort has been divided among projects employing animals and studies of the
normal human subject* The work of Dr* Jack Botwinick and his associates
indicates that there is evidence for a chjinge in inhibitory processes and
control functions that are involved in motor, perceptual, and mental abilities.
This is an extension of previous experimental and conceptual work of the la,bora-
tory. Analysis of the data on over 59 human subjects with a broad range of
psychological de asurements is now in process of statistical analysis = It is
expected that these results will be available for publication in the spring of
19^8, Dr. Alfred Weiss who also participated in the studies of human aging
is concerned, xfith three areas: click perception, dual chjinnel auditory per-
ception, and delayed auditory speech feedback. Only the click perception
data has been analyzed thus far. The data on click perception indicates
something of the nature of the perceptual deficit which can occur in some older
individuals * Older individi.i3.1s have increasing difficulty as the number of
clicks increases, However, response time does not differ for two age groups,
suggesting that the relationship between response time and perceptual ability,
or accuj.-"acy, is more complex than previously realized. As an outgrowth of a
study on age changes in retina,l potentials, a licro-electrode study of retinal
and optic tract potentials of the cat's eye in response to light was carried
out in collaboration with Dr. Robert Gohn of the ^-aval Kedical Center by
Dr. Weiss » The results of this studjr are now being anal /zed. In another
collaborative study wi'th Dr. Gonan Kornetsky of the Clinical Sciences
Laboratory, it was found that chlorpromazine was irjithout effect on delayed
speech feedback while secobarbital markedly increased susceptibility of the
subject to speech disruption with this method.

Dr. Edward Jerome has been studying age changes in rat activity, rate
of learning, and ability to transfer in a series of ten, escape choice problems
employing light aversion as the drive. Preliminary analyses of the yet incom-
plete results indicate that, although the older animals were somewhat slower
than the young ones, the txro age groups did not differ with respect to reaction
to obstruction, type of errors, learning rate, nor ability to transfer. These
results can be interpreted as impugning the hypothesis that impairment of
learning ability and flexibility of behavior are necessary concomitants of
a decay of biological organization with increased longevity of the organism.
They are, on the other hand, consistent V7ith the hypothesis that when apparent
impairment of these functions is observed in human beings, or does occur in
animals, it is due to experiential factors, e.g., absence of recent relevant
practice, low motivation, accumulation or strengthening of sources of inter-
ference, or lack of familiarity i-jith the test situation in general or in
particular. These preliminary investigations are being extended.

- 11 -

Section on Aging (Cont'd)

Dr^ iiugene Streicher has continued his studies of age differences in
calcium of the brain. In all age groups ^ from one month to two and a half
years, the calcium content of the rat brain is varj variable. The two halves
of tha saiiie brain often differ by 100 percent or more in calcium content.
However, the values for the txjo halves of the same brain are more closely
related to each other in the tissues of old rats than in young animals regard-
less of the level observed^ On the basis of relatively few observations, it
appears that the magnesium content of the brain is somewhat diminished in
animals over two and a half years of age. i'rom measurements on the magnesium
content of brain from rats of different ages, it appears likely that, in
contrast to the reports of other investigators, the magnesium content of the
myelin sheath is relatively low.

Dr. rtilliain Bondareff has continued his studies of age changes in
nervous tissues of rats. His electron microscope studies of spinal ganglia
from aged rats conventionally fixed vjith osmiiom tetroxide, have resulted in
the demonstration that the genesis of the lipofuchsin (the so-called senility
pigment) is not directly related to possible age changes in mitochondria.
This work which has been published in the Journal of Gerontology emphasizes
that pigment originates in the c:,,i:oplasm of old nerve cells in association with
vacuoles of su':Tdcroscopic siae and it is suggested that this process is
associated with age changes in the golgi complex. In an attempt to further
investigate the process of pigment particulates, tissues fixed by freezing and
drying have been investigated. These investigations are currently being
continued and some progress has already been made in the application of these
methods to the study of submicroscopic cellular changes of aging nerve cells.

Hr, Joel G-arbus has extended his studies reported last year on the
oxidative phosphoiylation of fortified brain homogenates to include studies
using other brain particulate fractions . A preparative procedure was developed
for the isolation of cellular particulates of high metabolic activity and
stability. Oxidative phosphorylation, measured in mitochondrial fractions
prepared by these methods show no decline '.fith age in central nervous system
preparations from aged rats. These activities are measured under ideal in
vitro conditions, xxhich may not pertain in vivo . It is therefore proposed to
make similar measurements using less than optiraum conditions, such as anoxia,
limited substrate, etc., reproducing a. less favorable cell environment which
may be a factor in senescence. Collaborative studies undertaken last year with
Dr. Eugene u'einbach of the rational Institute of Allergy and. Infectious
Diseases vri.ll be continued to study other aspects of cellular metabolism and
aging.

The Section on Aging has continued to act as a coordination center of
the research pro ;:ram on human aging in the KIMIL At present this pro.loct is in
the stage of analysis of data. Kr. Samuel Greenhouse and i-Ir. Donald Ilorrison
are now actively developing high speed computer metliods to intercorrelate the
many variables from the different laboratories concerning changes in personality,
cognitive and perceptual abilities, and physiological factors, in normally aging
individuals «

= 12 -

Section on Perception and Learning

During the year Dr. Carlson's studies of the effects of LSD on the absolute
visual threshold have been completed » The findings in man indicate a central
effect of this drug in that the photopic threshold was raised significantly more
than the scotopic threshold o Brightness vision in man undoubtedly depends to
a great extent upon the cortex^ and presently available evidence suggests that
cone vision depends more on the complete integrity of cortical functioning than
does rod vision. The presiuned hallucinogenic effects of LSD were not found with
the normal subjects used here. Psychotic and nexxrotic patients have shown evi-
dence of an elevated visual threshold^ however j, so that this effect of LSD may
constitute another point of similarity between the effects of the drug in normal
htmians and the manifestations of more naturally occurring psychological impair-
ment.. The absolute visual threshold was found to be raised more strikingly in
the pigeon, although the effect is probably mediated subcortically in this animal.
Another very interesting finding with LSD in the pigeon is an improvement in
performance in a conditional visual discrimination task. The reason for this
effect is not clear at the present time^ but it may have a possible parallel in
himian perf ormaixce . Under certain conditions normal subjects with LSD, anxious
or tense subjects^ and some schizophrenic patients seem to be better able to
maintain directed attention aoad interest in what usually is a simple and tedious
task for a normal subject. One effect of LSD may be to render the subject less
susceptible to outside distractions and at the same time less able to integrate
accessory cues into a xmitary perception. Partly for this reason, the effects
of LSD are being investigated on more complex perceptual tasks such as size-
const^ajacy and visual illusions.

Dro Carlson has also continued his study of the Kohler theory of
satiation in relation to neural processes associated with perception with a
view towards using the methods developed for the st\3dy of basic processes of
attention and short-term memory. He has also continued on the difficult technical
problem of recording eye-movements electrically. The problem at present breaks
down into three stages s (l) To work out the technical problems^, which is the
stage in which the work is concentrated. (2) To work out the methodology measur-
ing psychological variables by means of eye -movement recording. (3) To apply
the methodology to specific problems in the percepttial-attentional realm. It
is in relation to the last that this technique may offer us a method of attain-
ing an objective indication of what the subject perceives and where and how he
directs his attention. With increasing interest in studies involving attention,
such a technique would be most useful.

Dr. Carlson has finally made arrangements for obtaining students as
a normal control population. Some of these subjects are being tested intensively
both as a comparison group for results obtained with patients and as an experi-
mental group for investigating normal relationships among basic psychological
processes. An example of the latter is an investigation of the extent to which
personality J, emotional, and motivational variables are related to the perfor-
mance aspects of behavior rather than to the perceptual process itself. Another

= 13 =

:aon and liiearning (Cont'd)

avenue of inquiry concerns behavioral experimental distinctions between those
perceptual processes which may depend more directly upon neural structure in-
dependent of experience and those which depend to a greater extent upon develop-
ment through experience and upon the general psychological state of the individual.
These and other researches with this normal pop\;ilation have just recently been
initiated^ but experience thus fax indicates that this program shoiild prove to
be a workable and successfvil operation »

Dro Blough's studies of techniques for the experimental analysis of
instrtmiental behavior in the pigeon have been further developed and refined.
These techniques are proving especially valuable and efficient in the study
of the basic processes involved in the stimulus control of behavior and in the
stiid^ of certain responses which would be difficvilt to explore with more traditional
methods. For example^ the pigeon has been successfully trained to stand still
for food reward, a response which promises to be particTolarly useful in assess-
ing effects of the treinquilizing drugs o Chlorpromazine was fotmd to increase
the ability of the pigeon to staxid stiH, whereas pentobarbital reduced this
ability o In nany respects pentobarbital, though not a tranquilizer, has effects
which are difficult to distinguish behaviorly from those of the tranq.uilizing
drugs. This emphasis on exploratory work with drugs^ however, is now being
shifted more toward elucidation of the behavioral principles themselves which
imderlie stiaxulus discrimination and stimulus generalization.

Most of the physical construction and equipment procurement for Dr.
Calhoun's Rockville Faorm Project has been achieved, and initiation of the
first pilot studies should be possible by the end of this year. This project
will enable more comprehensive controlled study of the environmental and genetic
modification of biological systems o Some provocative findings are emerging from
present studies in this area. Analysis of two field studies of mice and shrews
living in woodJ.ands revealed that the several species forming the community
express a social hierarchy in their utilization of space. The more dominant
species enjoy greater home ranges, but within each range the individual members
of each species maximize distance from other individuals. Behavior of the rat
in aa activity alley shows a negative escponential relationship between frequency
and duration of the 'behavior j, and the frequency with which trips are terminated
from a starting point is inversely proportional to distance. It is not known
yet to what extent principles describing the utilization of space through time
by small mammals wiU be generalizable to man, but the movsnent of an animal
within its own home range have been fotmd to describe the distribution of church
members about a church, and the emotional past history of a rat appears to alter
its utilization of space and time. Initial studies have suggested the possibility
that emotional conditioning processes may affect space-time utilization through
function of the retictilar activating system of the brain stem. This and other
physiological hypotheses will be further explored in rglation to variables of
environmental structure and social organization.

» lij. „

SECTIOW ON MTMAL BEMVIOR

In general^ this yeax's activities have concentrated on specifjring more
precisely the behavioral deficits following brain damage, delineating
more exactly the anatomical systems related to cognitive behavior, and
developing automatic-testing devices for use in these problems o We
have been unable to pursue that part of our program concerning the emo-
tional and motivational aspects of behavior as actively as intended be-
cause of lack of funds and personnel o

The study involving the effects of frontal-lobe damage on delayed-
response type tests in chimpanzees has been completed except for the
last stages of anatomical analysis. The results of this study indi-
cate that chimpanzee performance like that of monkeys is impaired fol-
lowing frontal-lobe damage. Unlike monkeys, however, they are able to
recover from these effects and after several months of training regain
their preoperative performance level. Thus, at the end-point of their
training the effects of frontal-lobe damage in chimpanzees resembles
that in man where no consistent effects of frontal-lobe damage on prob-
lem-solving behavior have been demonstrated. This study has served a
valuable purpose in clearing up some discrepancies in the literatiore,
and in demonstrating the important point that in the highly developed
brain, the effect of damage in a particular area may be less than in
the more primitive brain.

The work on the effects of brain lesions on social behavior in primates
m8.y be summarized as follows s Unlike the findings in monkeys, social
dominance in chimpanzees appears to be unaffected by temporal- lobe le-
sions. Further, frontal, lobe lesions in chimpanzees produce a tempor-
ary decrease in dominance. This finding is compatible with the sub-
duing effects in the famous ehimpanzeesj, Becky and Lucy^ but is in the
opposite direction to the effects of such lesions on social behavior
in monkeys (i.e., increased dominance) described by Rosvold and Erody.
In monkeys our studies show that hippocampal lesions do not affect
social dominaneej this is an unexpected finding, since lesions in the
amygdala^, wMeh is anatcsmically and fmietionally closely related to
the hippocampus, produce striking decreases in dominance. The studies
on the interrelation between postoperative escperience and brain lesions
in determining postoperative change suggest that postoperative experi-
ence can determine this effect to some extent; this research area, which
is of considerable theoretical ijmportance, unfortunately cannot be pur-
sued at present.

A numb.er of cent rally ■= acting drugs have been investigated with the con-
tinuous performance technique; ehlorpromazine, L.S.Do;, meperidine,
several barbitui-ates, meprobamate, benzactyzine and d- amphetamine . The
results siiggest that agents which appear to depress activity in the
brain- stem reticular system will impair performance on the C.P.T. Tlaese

- 15 -

Section on Aalinal Beliavlor (Continued)

data a,ppear to mesh nicely with the results of our epilepsy studies:
those patients in whom the focus of abnormality is presxmably in the
brain-stem region perform more poorly on this test than other patients
in whom the pathology, althoiigh equally great, is confined to cortical
structures. Other tests of "brain- damage" that have been used have
failed to differentiate the cortical from the non-cortical subgroups.

The new, improved version of the C.P.T. has recently been delivered
to us and should provide great flexibility in investigating the para-
meters of the task. In addition, it will make possible precise study
of clinical ictal and subclinical ictal phenomena (recorded electro-
graphically as hypersynchrony) in relation to the mainteneuice of vigil-
ant or attentive behavior. The instrument hs,s aroused interest among
other investigators by virtue of its versatility and capacity to elicit
and measure behavior that covild not be handled so efficiently previous-
ly.

The study of the role of inferotemporal neocortex in visually guided
behavior is being approached in a variety of ways. Attempts to de-
lineate the anatomical connections betvreen the inferotemporal region
and the primary visu^ system have finally met with at least tentative
success. After removing the temporal lobe in one hemisphere eind the
occipital lobe in the other, monkeys were trained to discriminate
visual stimvili. The corpus callosum was then cut in these animals and
they were re-trained on the same visual discrimination. Marked impair-
ment in re-learning was found, siiggesting callossal transection had in-
terrupted long association tracts, running presumably from the intact
occipital lobe through the corpus callosum to the opposite intact tem-
poral lobe. The lack of impairment following various control opera-
tions demonstrates that the deficit in the escperimental animals was
specific to their particular combination of lesions. Final evaluation
of these results must await replication of the experiment axid histo-
logical examination of the lesions. This positive finding is of par-
ticular interest in view of the consistently negative findings that
have been obtained in animals with subcortical damage. Thus, neither
the pulvinar nucleus in the thalamus, nor the superior colliculus ap-
pear to serve as an essential relay station between the inferotemporal
region and the primary visual system. How it appears, on the basis of
preliminary resixlts from monkeys with combined ptilvinar and collicular
lesions, that the two structvires in combination are not the essential
relay stations. At the moment then, cortical- cortical connections ap-
pear to be implicated.

The finding that teiaporal-lobe damage produces visual impaiirment in
monkeys would be of greater theoretical interest if similar resuJLts
could be obtained in man. Unfortunately, there is little evidence to

Section on Anipjal Behavior (Continued)

support 2h an extension of the animal data. A reasonable
explanation for this discrepancy has been gleaned from recent
work on chimpanzees. It wa.s foiand that bilaterally symmetri-
cal inferotemporal lesions produced impairment of visual dis-
crimination in chimpanzees which had shown no impairment after
only a unilateral removal. The negative evidence in human pa-
tients may be due simply to the fact that temporal -lobe path-
ology in man is rarely, if ever, bilateral and symmetrical.
Recent work with monkeys, however, has demonstrated that even
imilateral damage may produce impairment if vision is limited
to the field opposite the lesion. On the basis of these re-
stilts an experiment has been planned to test for possible
differences between tachistoscopic recognition in the left
and right visual fields in patients with left or right tem-
poral-lobe pathology =

The evidence which has been accumulated so far supports the
notion that the inferotemporal region constitutes -s^ link
in the chain of cerebral structures serving vision . The
study of the neural activity of this region should provide
important information on the sequence of cerebral events in-
tervening between stimulus reception at the cortex and the
motor response. Experiments are therefore being planned in
which the inferotemporal cortex will be electrically stimu-
lated or recorded from during the learning and performance
of visiial discriminations. Evidence for disruption in per-
formance following stimulation or changes in electrical
activity during learning would bring us one step closer to
an understanding of the neural processes underlying vision
and perhaps other modalities as well.

An important discovery has been that subcortical structures,
such as the head of the caudate nucleus and the splenium of
the cojrpus callosvim, are involved in performance on delayed-
resp-yife- -type problems = Several points have been raised by
these findings, (l) What anatomical relationships exist
to account for these findings? Anatomical studies are \mder
way to answer this question. (2) Are these effects in fact
similar to those apparent in animaJ-s with frontal lesions?
Studies are under way comparing anmals with caudate lesions
and frontal lesions on a variety of t .'rsc (3) What other
subcortical structiires may be involved? Studies are under
way in which animals are being tested after lesions in other
subcortical structures, (h) What functional relationship
could exist between the frontal cortex and the head of the
caudate nucleus to account for their similar effects?
Evoked potential studies are planned to answer this question.

SuiTimary Report of Laboratory of Biophysics
Calendar Year 19?7

Kenneth S . Cole 3, Chief

The Laboratory has continued its efforts to understand the nature and
the implications of the ion movements fundamental to the initiation and propa-
gation of a nerve impulse and it has made substantial progress ^

The squid giant axon, which first allowed the direct measurement of the
ionic currents through a nerve membrane^ remains the most useful source of
experimental information. The continuing improvements of techniques and
equipment have resulted in data on this a:con that more closel;:/ approach the
ideals of accuracy^ reproducibility and significance than heretofore « The
transient and steady state ion current flows after an abrupt change of the
potential difference across the membrane are determined much more by the values
of the initial and final potentials than by the difference between them^ For
an initial h3rnerpolari2ation depending upon the axon and its condition, these
currents approach maxima which are determined only hy the final potential
and correspond to the rather surprisingly high peak conductances of 200 m mho/cm
for both sodium and potassium:

Further investigation of the effects of external calcium and magnesium
ions added further et/idence of the qualitative similarity of the actions of
these ions. A decrease of either ion concentration tends to increase the
membrane excitability by allowing sodium current flow at a reduced depolari-
zation^ and in spite of the opposing increase of potassium conductance and
more easily evoked sodiom inactivation» In procaine the potassium conductance
and sodium inactivation changed slightly in the directions instability^ but
the decrease of sodiura conductance and the increase of depolarization required
to achieve it accounted for the net stabilizing effect and suggest that
procaine not only reduces the number of available paths for sodium ions but
also increases the difficulty of opening each path^

Not only do the speeds of the sodium and potassium processes increase by
a factor of three for a ten degree centigrade temperature rise as previously
reported, but the peak conductances of both of these ions also increase bj
about sixty percent,. In addition to confirming a preliminary report that the
squid axon action potential is almost identical in artificial sea waters
containing either the normal sodiura ion concentration or the same concentration
of lithiiim ion, it was found that none of the ion conductance characteristics
are probably changed bj more tlian twenty percent by this substitution^ Both
the temperature and the lithium effects Iwrite explanation in terms of non-
specific physical processes rather than chemical reactions, A complete analysis
of the many records of the ion currejits has been delayed by the need for a
critical examination of several methods, including those originally used hy
Hodgkin and Htixley, for the separation and empirical representation of the
sodiiira and potassium components ct

An investigation of some characteristics of a lobster giant axon has
been completed. The changes of the resting and action potentials produced
by alterations of the normally occurring external cations, and by some
organic solvents, are compared and contrasted with those found in the squid
and other axons in forthcoming reports. The disparities between the activi-
ties of synthetic anti-cholinesterases on the enzyme and on frog nerve were

- 18 -
Summary Report of Laboratory of Biophysics (cont'd.)

found to include the optical isomers of one compound before the work turned
to the more critical experiments on a single node. Some progress was made
towards the determination of ionic conductances of a single node before the
project was suspended.

Recalculations of the Hodgkin-Huxley equations for the squid axon on an
IBM 70U have shown that mistakes in earlier computations were not of physio-
logical importance although they had been the source of some theoretical
difficulties. The new analog computation program has begun with a systematic
examination of sin^jlified Hodgkin-Huxley equations in which one or more
variables are held constant. One result is that either a constant potassium
conductance or a constant sodium inactivation produces a plateau in the
recovery of the action potential rather similar to that of heart muscle cells..
An investigation of passive iron wire models of nerve activity resulted in
the first quantitative theory of one such system.

2 -

- 19 -
LABORATORY OF NEUROANATOMICAL SCIENCES

"William F. Windle, Chief

The Laboratory of Neuroanatomical Sciences occupies space in
D Wing of the Clinical Center and the East Wing of Building 9. In
addition, certain research projects have facilities m Puerto Rico. There
have been no changes in the regular professional staff during 1957.

Section on Development and Regeneration

This report of the activities of the Section on Development and
Regeneration will be divided for convenience into work in the Bethesda and
the Puerto Rican laboratories. Professional personnel at Bethesda are:
Lloyd Guth^ Richard L. Sidman, Irene Miale, Kenneth M. Wolf and
William F. Windle, Chief. Harry H. Wilcox^, of the University of
Tennessee, is a consultant. Those working in San Juan, P. R. , are:
C. J. Bailey, J. A. Ranck, S. A. Altmann. Marisa I. R. Ramirez de
Arellano and Max Ramirez de Arellano are consultants. C. A, Pfeiffer,
J. G. Frontera and W, Stiehl of the University of Puerto Rico Medical
School, are collaborators.

Projects at Bethesda: Histological studies of the spinal cords
of cats, paraplegic for 1-2 years, have been continued. Regenerative
activities of central nerve fibers which succeeded in traversing the site
of the transection under the influence of such agents as piromen were
blocked by encroachment of massive scars which apparently were formed
from the pia mater, dura mater and surrounding tissues. Vascularity of
the site of transection increased with time and the adventitial sheaths of
the vessels provided routes for regeneration into both the rostral and
caudal portions of the spinal cord by nerve fibers, principally from the
spinal nerve roots. Anatomical confirmation of successful regeneration
of central fibers of the mammalian spinal cord has been published by
scientists m another laboratory and plans are being formulated for
collaborative experiments with monkeys in our laboratories late m 1957
or early in 1958.

Dr. Guth has continued investigations of neuron specificities.
He has succeeded in restoring motor function to the rat's diaphragm by
anastomosing the central end of the cut vagus with the distal end of the
cut phrenic nerves, demonstrating that visceral motor fibers can take over
the function of somatic motor neurons. Dr. Sidman has carried out
experiments by other techniques to explore trophic properties of nerve
fibers. In the adult newt, the epidermis plays a special role in limb
regeneration but this is not under nervous control. Motor nerve fibers
regenerating into the limb do not enter the epidermis.

Z0--

Studies of development of intrinsic brain structure in the human
embryo have been confined principally to assembling and correlating
information from the literature. Dr. Guth has translated Ramon y Cajal' s
classic^ but now almost inaccessible monograph^ entitled: "Etudes Sur la
Neurogenese de Quelques Vertebres". It is expected that his translation
will be published next year.

Studies of the process of aging in the nervous system, have been
continued, mainly by Dr. Wilcox, working on contract with the University
of Tennessee School of Medicine, In well-controlled material from the
brains of guinea pigs between birth and extreme old age, he has found
that the process of aging involves a decrease in interneuronal substance
(neuropil). During the year a conference on the Process of Aging m the
Nervous System was held at Bethesda, the proceedings of which are being
edited for publication.

A tissue culture laboratory in Building 9 for Dr. Sidman' s use
has been under construction for the past year and now is nearly ready for
operation. In the meantime, Dr. Sidman has devoted his energies to
other types of work, notably, stiidy of the structure and chemiistry of
photoreceptor cells in several species but especially the squid. Dr. Feder
of NIAID, Laboratory of Clinical Investigations has collaborated. Details
of their study of fine structure and histochemistry of visual elements are
presented m their annual report.

Studies of effects of reserpine and other drugs on monkeys and
chimpanzees which produce states resembling parkinsonism in man are
being terminated. Results of an attempt to abolish the hypokinesia,
rigidity and tremor in monkeys by alcohol injection of the globus pallidus
were reported at the First International Neurological Congress in
Brussels in July by Drs. Feringa and Windle. The tremor and rigidity
was abolished transiently on the contralateral side but returned within
24 hours in chronically reserpinized monkeys. Perhaps the most
significant observation resulting from research in this area is that
obtained from histological study of the brains of African green monkeys
kept on minimal daily doses of reserpine (0. 2-0, 6 mg/kg) for over 18
months. In contrast with control of material^ neurons of various brain
stem nuclear groups and cerebral cortex (but not cerebellum) show a high
incidence of vacuolation in nucleus as well as cytoplasm. The contents
of the vacuoles have not been identified. The significance of the observation
IS unproved, but it would appear that continuous administration of the drug
reserpine, in doses comparable to those in common use in human
subjects, may not be without adverse effects on the cytological structure of the
primate nervous system.

Other activities of the scientists in the Bethesda component of this
section pertain to interpretation of function of neural elements by techniques
of histochemistry and fluorescent microscopy. An investigation of the
development of the blood-bram barrier has begun (see annual report by Wolf).

--21

Projects at San Juan: During 1957 two groups of laboratories were
established at San Juan^, Puerto Rico, one adjacent to the Medical School
of the University of Puerto Rico and one on the grounds of the U. S.
Public Health Service Clinic, Facilities on the small island, known as
Cayo Santiago, where a free-ranging colony of about 250 Macaca mulatta
monkeys is located, were renovated, A caged colony of 3 5 breeding
females in the San Juan laboratories, and one of about the sanae size in
Bethesda have been established. These several facilities provide for
studies of adverse factors in the perinatal period of monkeys which may
lead to neurological and psychological deficits in the offspring. Pilot
studies have been carried out in guinea pigs and cats.

The principle topic of research at present is asphyxia neonatorum
in relation to neurological and psychological deficits in the offspring of
monkeys. Before summarizing this work, a number of other topics,
touched upon during the year, are noteworthy, (a) Dr. Ranck and others
have been standardizing procedures for a neurological examination of the
monkey from birth to maturity. This became necessary when it was
found that no standard procedure existed, (b) Certain adverse effects of
hormonal imbalance during gestation have been investigated m the cat by
Dr. Windle. Dr. Pfeiffer is studying endocrine organs of monkeys
subjected to various degrees of anoxia or asphyxia, (c) Anthropometric
studies are being carried out in the free-ranging monkeys on Cayo Santiago
as well as on specimens in caged colonies. This part of the work will
soon be taken over by Dr. James A. Gavan of the Medical College of the
State of South Carolina on a collaborative basis, (d) An opportunity
presented itself to study hemolytic anemia during pregnancy of one monkey
in the caged colony. The fetus of this animal was dead at delivery and
the mother went into eclampsia with convulsions and urinary shutdown.
This appears to be the only reported example of this condition m a primate
other than man.

One of the main objectives of the project m Puerto Rico is to
relate episodes of asphyxiation at birth to possible deficits in learning
ability and behavior patterns after birth. Dr. Bailey has completed a
study of learning in guinea pigs 1-2 years old, half of which were asphyxiated
and resuscitated at birth. He succeeded in demonstrating that ability to
perform m certain mazes was impaired even after the animals had attained
adu].t st3,ges. In this same group of animals Dr. Marisa Ramirez de
Arellano carried out studies of the electrical activity of the brain. She
established the characteristics of EEC's in the normal animal at different
ages and found that abnormalities manifested themselves in some of the
asphyxiated guinea pigs. All the guinea pigs of this group have been killed
by the perfusion fixation technique and the brains are being prepared for
histological study.

-2;

A two-year study of behavior and social organization was begun
on Cayo Santiago in June 1956 by Stuart A, Altmann (see his annual
report)o The free ranging colony of monkeys provides a unique
opportunity in the new world to make controlled observations^ not only
of adults but also of newborn and infant monkeys. These observations
will help interpret the behavior of controls as well as asphyxiated
infant and young monkeys of the caged colonies.

The feasibility of breeding monkeys in caged colonies has been
thoroughly established^ To date 24 timed pregnancies have been obtained
in the caged colonies , which numbered only 24 females at the end of
January and has gradually increased to 70,

The main endeavor since establishment of caged colonies of
monkeys^ beginning the end of January 1957, has been to study acute
effects of asphyxia neonatorum induced near the end of gestation in
cesarean section delivered animals or within a few days after birth in
vaginally delivered animals. This^ in a sense, has been an exploratory
investigation. To date^ the principle results have been as follows.
Survival time after asphyxiation appears to vary inversely with age of the
subject. At the end of gestation (164-168 days) monkeys were readily
resuscitated after 13 or 14 minutes of asphyxiation By 7 weeks of age
the maximum tinne of survival in an atmosphere of nitrogen was less than
4 minutes All infant monkeys subjected to experimental asphyxia
neonatorum exhibited marked neurological deficits after resuscitation. The
acute effects were impairment or cessation of respiratory activities, impair-
ment of the establishment of consciousness, blocking of sensory functions,
blocking of reflexes _, depression of the rate of the heart beat with
abnormalities in the EKG , blocking of visceral functions. Recovery of
many of these functions occurred gradually with time However^ all
animals remained unnaturally guiet and presented acute nursing and care
problems^ inasmuch as they lost the ability to suck. By 24 hours after
resuscitation^ most of them improved to such a degree that the investigators
expressed optimism for eventual recovery However, by 36 to 48 hours ;,
the condition of those which were most severely asphyxiated deteriorated
markedly; muscle fasciculation_, nasal regurgitation ^ impaired motor and
sensory functions . somnolence^ visceral disturbances ^ status epilepticus^
and respiratory arrest were encountered-

Most of these young animals were killed at different ages for
histological studies. Some of them are still living and being used for
psychological studies together with randomly chosen babies delivered by
similar techniques. Sections of the brains of 6 monkeys have been
examined. These were animals killed between 2 hours and 6 days after
resuscitation. They have been compared with similar sections from control

- 23-

brains. Extensive cell changes are evident in the brains of all the
experimental animals. The only animal which showed petechial cerebral
hemorrhages was the one which exhibited status epilepticus. In 5 others
the principal abnormality appeared to be neuronal lysis. This was found
throughout, but the changes were more marked in the cerebellum^ dentate
nucleus and certain centers of the brain stem than m the cerebral cortex
or basal ganglia. The damage was diffuse rather than focal. It was of
such a nature that, had the animals lived for 6 months or more, it might
have been difficult to ascertain with certainty that structural abnormalities
existed. Such changes after asphyxiation at birth have not been reported
in any primate.

Section on Experimental Neuropathology

The professional personnel of the Section on Experimental
Neuropathology consists of Helen J. Ramsey and Jan Cammermeyer, Chief.

The main objective of the section has been to reveal factors
concerned with development of the myelopathies. Research activities
have been directed towards three aims:

(1) To develop a procedure which permits an estimation of volume
of the spinal cord on the basis of the animal's size and then to conclude
whether the spinal cord is affected m a given experimental situation.
Another procedure attempts to predict the size which the spinal cord will
attain after several nnonths of growth of the animal. Such information is
needed for an evaluation of long term experiments. In the course of these
studies sex, age and species have been found to be the factors influencing
the size of the spinal cord.

(2) To study the distribution of extradural fat. This study has
been almost completed by Dr. Ramsey in several species of animals of
different age. Although certain specific patterns have been established
in the distribution of fat, the amount of fat is quite variable. This would
seem to be another factor of importance for the proper functioning of
the spinal cord,

(3) To perfect histological techniques for the purpose of
establishing standard conditions of microscopical investigations of
experimental myelopathy. After having critically surveyed the technical
procedure, the investigators are now in position to evaluate properly
subtle changes of neurons, myelin and glia and to dismiss as not
significant certain other changes usually encountered in microscopical
material, such as variability in the staining of neurons, the size of

glia and appearance of myelin. The emphasis has been placed on
formulation of standard procedures for examination Ui >be spinal cord in
animals because only when such formulation is completed ib '^ne able to
correlate moderate functional neurological dysfunctions with subtit, ^^norpho-
logical changes. This will be necessary before an attack can be directed
against the problems concerned with the development of myelopathies,

Section on Functional Neuroanatomy

Professional personnel of the Section on Functional Neuroanatomy
are; Leo C. Massopust, Richard Gacek and Grant L Rasmussen, Chief,
This section concerns itself primarily with nervous pathways and
connections of the brain and spinal cord,

The origin and termination of the medial longitudinal fasciculus in
the brain stem and spinal cord by means of axonal and terminal
degeneration methods have been studied by Drs, Massopust and Rasmussen.
The termination of spinal components of this tract, consisting chiefly of
vestibulospinal fibers, has been more definitely localized to cell groups of
the spinal gray matter, m the brain stem the medial longitudinal
fasciculus has been found to send some of its fibers beyond the midbrain
to the subthalamic region

Studies on the auditory afferent and efferent systems have been
continued by Dr Rasmussen, with the cochlear nucleus receiving
particular attention during the past year. The experimental anatomical
findings indicate that the dorsal cochlear nucleus plays an important role
in control over cochlear nerve afferents received by the ventral cochlear
nucleus. The vast majority of cochlear nerve fibers ter^ninate m the
ventral nucleus while the dorsal cochlear nucleus receives predominantly
short and long efferent or feed back connections from different parts of
the central nervous system.

Mr, Robert Boord, a graduate student of the University of
Maryland, worked during the summer on a problem dealing with the
innervation of the chinchilla inner ear: This study will be completed at
the University of Maryland and NIH during the coming year.

The efficaciousness of the synaptic stain developed by Dr
Rasmussen has been further explored and tested on various synapses m
different regions of the central nervous system. It has proven to be
specific for demonstration of a "granular synaptic substance" in
practically all endings in the young as well as the adult animal. The
clarity and completeness of staining is a virtue taken advantage of in
present studies of interneuronal relationships by the experimental method
of Wallerian degeneration. Disappearance of synapses related to neurons

-25 -

damaged can be noted and the relative number of synaptic connections
playing upon a single nerve cell that originates from different anatomical
and functional sources may be determined. In studies of normal material
dealing with the maturing terminals of young kittens ^ this technique shows
that synapses make their appearance much earlier than previously noted ,
a finding which correlates more nearly with behavior studies of the young.

Dr. Chaco of India, guest of this section during one month of
the summer, employed the synaptic stain successfully to a problem
dealing with synaptic endings of the spinal cord of lower vertebrates.

Section on Neurocytology

The professional personnel of the Section on Neurocytology are:
Milton Wo Brightman, R, Wayne Albers and Sanford L, Palay, Chief.
Dr, Samuel McGee-Russell , Birkbeck College, University of London,
spent the year with this section as a Visiting Scientist. Dr. Jean Gruner,
University of Strasbourg, was a guest m the laboratory for a two-month
period, January to March, The principle objective is to conduct research
into the fine structure of the nervous system, histochemistry and neuro-
secretion.

A laboratory for studying fine structure by means of electron
microscopy has been activated during the past year with the installation
of an electron microscope and associated equipment. Investigation of the
structure of synapses and neuron-glia interrelations m the brains of fish
and mammals is m progress. Dr. Palay attended an international
symposium on the structure and function of the neuron held in Caracas,
Venezuela, at which he presented a paper on the ultrastructure of the
synaptic junction.

DrSo Brightman and Albers have studied the distribution of true
and pseudocholmesterase activity in the central nervous systems of cats
and rats. The perikarya of neurosecretory neurons contain true
cholinesterase activity whereas their endings in the neurohypophysis do
not. Pseudocholinesterase activity occurs in the glial cells of the cat's
spinal cord whereas in spinal cord and brain of the rat, activity is
confined to the vascular endothelium. This observation may be related
to the locus of the blood-brain barrier and may be helpful in an
analysis of myelogenesis.

Drs. Albers and Brightman have also completed an interesting
study of dilute alcohol extracts obtained from frozen sections of the
neurohypophysis of the rat. These extracts contain a proteina.ceous
material which is present in large amounts in the neurohypophysis of

.26 -

hydrated rats but is absent from the glands of animals given restricted
amounts of water for several days. When this material was assayed, the
investigators found that practically all of the antidiuretic hormonal
activity of the neurohypophysis was in this fraction. Since it has been
known for several years that the neurohypophysial hormonal activities
can be isolated in small molecules (octapeptides) , this work demonstrates
that the active natural hormones are not secreted as small molecules but
are m fact associated with a protein.

Dr. Albers, in association with Dr, Brady of the Laboratory of
Neurochemistry, has been studying the localization of glutamic
decarboxylase m the nervous system. This enzyme is absent from white
matter^ the neurohypophysis and the pineal gland, but is high in certain
areas of the gray matter. The reaction which this enzyme catalyzes results iiji|
the production of y -amino butyric acid, which is an inhibitor of synaptic
transmission. The localization of this enzyme is therefore of undoubted
importance in an analysis of cerebral metabolism and function.

- 27 -
Laboratory of Neurochemistry
Robert B, Livingstorij Acting Chief

During the past year^ efforts to recruit a chief
for this laboratory were continued. We identified success-
ively two distinguished investigators each of whom could
mount a most impressive and fruitful program of research in
this field. Each was greatly attracted to the Basic Research
Program. The only handicap v/as lack of sufficient space.
Each was willing to give up much of the luxury of space
where they were in favor of the values of interdisciplinary
transaction available hereo But if they came here they
would have to amputate too much of what they want to do
and are prepared to dOj in order to be accommodated within
the space we have available. We considered a number of
alternate plans for re-arrangement of space available to
the Basic Research Program as a whole, in order to make
this key recruitment possible. We tried to win back space
which historically had been "loaned" outside the Basic
Research Program. In every case^ we failed. Each of the
scientists concerned would have been content to join the
Progranij, do as much as possible with the space presently
available and await the construction of new space,, provided
only that we could indicate that such construction would
probably take place witLiin a few years. There are clearly
many uncertainties in such contingency. Therefore j the
matter was dropped for the time being. Until more space
becomes available^ it will not be possible to establish
the one or two additional Sections and bring to the Labora-
tory the overall leadership needed to fulfill our research
objectives in Neurochemistry.

Meanwhile 5, the two already established Sections
have continued to deiaonstrate that they are capable of
pursuing important issues profitably. The Section on
Physical Chemistry under the leadership of Dr. Alexander
Rich, has made significant advances in the determination
of the shape and dimensions of several families of large
molecules. These are variously concerned with cell re-
plication and grovi/thj the "coding" of amino acids along
protein strands, the control of protein conjugating
systems by metallic ions, the binding of key metallic
ions to protein complexes, and the structure al role of
certain protein-steroid complexes relating to myelin.
The Section has already received wide recognition for its
investigations concerning the structure of collagen, DNA
and RNA and for its comparative studies of natural and
synthetic polynucleotides. The key to many problems

of importance to an uuderstartdirig of the nervous system

will be found by exaiiilaing the shape and activity-configuation

of these molecules o

The Section on Lipid Cheir^istryj led by Dr., Roscoe Brady,

has completed a year of accOiaplishiEent in relation to our
understanding of lipid formation and structure, and of the
mechanisms of action of certain niirible eleraents concerned
with the initiation and inhi'bition of the nerve action
potential. Sphingosine synthesis has now been accounted
for, the mechanisn of incorporation of glucose and galactose
into cerebrosides has been shown and a further advance
has been made toward defining the nature, origin and dis-
position of myelin. Gai;;;i.ia-amno butyric acid has recently'
caused quite a stir among neurophysioiogists and neurochemists
as an example of a synaptic inhibitor coiTiparable to the
synaptic excitants such as epinephrine asid nor~epinepyrine.
The Section has contributed toward knowledge of both the
source and fate of this compound within the brain. By
combining talents with the Section on Special Senses in
the Laboratory of Neurophysiology , Dr. Brady has found that
compounds releasing free radicals, and cozipcunds interfering
with certain redox potential nechanisas within the squid
axoii may provide an avenue of approach for the ultimate
chemical analjrsis of the ZLechscrlsms governing the nerve
action potential.

Summarjr reports prepared by the Section Chiefs
follow:

Section on Physical Chemistry

A. Rich, Chief 29.

One of the main activities of the Physical Chemistry
Section consists of studying the properties and physical structure
of ribonucleic acid. This substance, an elongated polymeric mole-
cule composed of a sequence of nucleotide units, has been shown to
be of fundamental importance in the economy of the cell. It is
found in the microsomal particles which are the site of protein
synthesis. It is believed that the RNA in these particles somehow
determines the sequence of amino acids in the protein to be syn-
thesized. Thus, the RNA has an important function in transmitting
information, i.e., concerning amino acid sequences, from one poly-
meric species (nucleic acids) to another (proteins). In addition
to this, another function of prime importance is the transmission
of genetic information. Thus, it has been shown that RNA can act
as a carrier of genetic material in several RNA-containing viruses.
In this role, the RNA acts as a carrier of information from one
nucleic acid molecule to a large number of nucleic acid molecules
in the daughter viruses. In this respect, RNA shares this ability
with deoxyribosenucleic acid (DNA) which is the main carrier of
genetic information.

In view of the participation of RNA in these two fundamental
cellular processes, the Section on Physical Chemistry is studying
the molecular architecture of the RNA molecule in the hope of
elucidating its molecular structure in order to obtain an under-
standing of the molecular mechanisms behind these activities. In
this regard, it is quite possible that the role of this molecule
is even more significant in nervous tissue than in other tissues
since an essential activity associated with nervous tissue is
information transfer. How this is accomplished on the molecular
level in nervous tissue is of course unknown at the present time.
However, fragmentary information is available which suggests that
the nucleic acids play an essential role in this activity.

The Section on Physical Chemistry has been studying the
synthetic polyribonucleotides. These are molecules composed of
the same linear array of nucleotide subunits as is found in the
naturally occurring nucleic acids. However, they can be prepared
enzymatically and, what is most significant, the sequence of
nucleotide bases can be controlled during the polymerization.
Thus, it is possible to prepare not only a nucleic acid-like mole-
cule which has all four of the constituent nucleotides found in
naturally occurring RNA, but it is also possible to prepare nucleo-
tide pol5rmers which contain only one nucleotide. This is of funda-
mental importance in terms of elucidating the structure of the
molecule since it superimposes a degree of simplicity on the mole-
cule which is not found in nature. This simplicity permits us to
study the conf igurational details of the molecule in a form which
is simplified to a point where we can solve the problem.

-30 -

About a year and a half ago, we discovered that two of the
synthetic polyribonucleotides, polyadenylic acid and polyuridylic
acid, would combine together to form a two-stranded helix in
which the uracil and adenine residues are hydrogen bonded to each
other with a specific set of hydrogen bonds. These are, in fact,
the same type of hydrogen bonds which hold together the two-
stranded helical DNA molecule. This discovery attracted a great
deal of interest because it showed how intimate was the relation-
ship between DNA and RNA. As was noted above, both of these
molecules have the ability to transmit genetic information, and
this discovery has led to the tentative conclusion that both
molecules carry out this function, using the same molecular
mechanism, i.e. separation into two single strands with the
formation of a complementary strand to yield two identical mole-
cules.

During the last year, we made a series of additional dis-
coveries. Among the first of these was the discovery that it is
possible to make a three-stranded nucleic acid. Thus, when the
two-stranded polyadenylic acid plus polyuridylic acid is put into
a solution with an additional molecule of polyuridylic acid and
small amounts of magnesium ions, it will combine to form a three-
stranded molecule. This three-stranded molecule was discovered
by a spectrophotometric and ultracentrifuge investigation. More
recently, a detailed X-ray diffraction pattern has been obtained
from which we will be able to work out the details of the molecu-
lar arrangement of the three chains. This is the first time that
a three-stranded nucleic acid molecule was discovered, and it may
be significant in pointing out the manner in which nucleic acid
molecules function. One of the probable reactions of the DNA
molecule is that it aids in the specific synthesis of an RNA
molecule. By doing this, it transfers information, i.e., nucleo-
tide sequence from one polymeric species to another. It is
possible that this is accomplished by forming a single-stranded
RNA molecule which is wrapped around a two-stranded DNA molecule.
Accordingly, the discovery of three-stranded nucleic acids seems
of potential importance.

Further investigations concerning other polynucleotide
interactions have been carried out, and several have been dis-
covered. Among the first of these was a combination involving
polyadenylic acid with polyinosinic acid. Polyinosinic acid is
closely rela1;ed to polyguanylic acid and as such is of importance
in our understanding of the naturally occurring nucleic acids.
It was found that polyadenylic acid and polyinosinic acid would
combine together to form a two-stranded helical molecule. It
was also found that an additional strand of polyinosinic acid
could join the two-stranded complex to form a three-stranded
complex, polyadenylic acid plus 2 polyinosinic acid. This is,
of course, similar to the system polyadenylic acid plus 2 poly-
uridylic acido

-31 -

Another discovery was made concerning the interaction of
polyinosinic acid and polycytidylic acid. These two molecules
will combine to form a two-stranded helical arrangement. It is
interesting to note that this two-stranded molecule will not
form a three-stranded one in contrast to the two systems men-
tioned above. The most interesting feature of this combination
is that it has an X-ray diffraction pattern which is very simi-
lar to that which is found in naturally occurring RNA. Accord-
ingly, by working out its structure, we should learn something
about the configuration of RNA when it is extracted from cells.

Another discovery was made concerning the structure of
polyinosinic acid itself. It has been found that this molecule
exists as a three-stranded helical structure with a cyclic
system of hydrogen bonds holding together the three strands.
Although this structure is quite interesting, it is difficult
to relate it to the configuration of the naturally occurring
nucleic acids .

If we assess the total amount of information known about
the configuration of the synthetic polyribonucleotides, we find
that we have deduced a total of eight different structures which
will form from these polynucleotides. These provide an adequate
basic set of information from which we hope to go on to deduce
the configuration of RNA in cellular systems.

While studying the synthetic polyribonucleotides, we have
not neglected to study naturally occurring RNA itself. Thus, a
study was carried out of methods of extracting RNA from muscle
tissue in order to obtain it in an undegraded form. In addition,
studies were made of the effects of metal ions on the stability
and sedimentation properties of naturally occurring RNA. These
have shown that metal ions in small quantities are able to
stabilize naturally occurring RNA probably by serving as sites
which bind together the negatively charged phosphate groups and
thereby decrease the amount of internal electrostatic repulsion
energy in these molecules.

Another aspect of the program of the physical chemistry
section has been the study of the structure of protein mole-
cules. As in previous years, we have continued to work on the
structure of collagen, the major fibrous protein in the animal
kingdom. Refinements have been carried out on the molecular
structure proposal made two years ago. This proposal has now
been accepted quite generally by the scientific community as
providing a basis for the structure of collagen. Studies have
been made concerning the interaction of different collagen
chains with each other and the effect of various amino acids
side chains on the stability of the molecule. A recent addi-
tion has been the study of elastin, a closely related protein

-32 -

which provides the elastin components of blood vessels and con-
nective tissues. Preliminary studies of this molecule indicate
that it has a structure similar to a somewhat degraded collagen
molecule.

An investigation has been carried out on the coordination
of the porphyrin group to the protein part of cytochrome C.
This has been done by making a thermodynamic study of the bind-
ing of various small molecules such as azide or cyanide to the
iron atom in cytochrome C. From this, information may be obtained
concerning the amino acid side chains which are of importance
in holding the heme group to the protein.

Further work has been carried out on the interesting inter-
action between steroid molecules and amino acids or peptides.
These interact to form a helical structure with a diameter of
40 A. Studies have been carried out on the number of amino acids
which will interact with the steroid (sodium desoxycholate) . It
has been found that a large variety of amino acids and peptides
will interact. All of these form the same helical structure
although there is some modification of the helix as a function of
different amino acids. Further studies are being carried out on
this complex to ascertain the molecular configuration of the
steroid molecule. Steroids play an important part in the struc-
ture of the myelin and fatty components of nervous tissues and
it is hoped that these studies will provide some understanding
of the modes of packing steroid molecules together. This may
lead to an understanding of the unique role which steroids play
in the nervous system.

Section on Lipid Chemistry

R. 0. Brady, Chief 33.

The primary goal of this section is to elucidate the path-
way of synthesis and metabolic fate of the complex lipids of the
nervous system. This problem has been approached by investigating
the formation of several of these components using enzyme systems
obtained from brain tissue. The distinguishing characteristic of
the major portion of neural lipids is the presence of the long
chain dihydroxyamine, sphingosine, which forms the basic structural
unit of these complex lipids. Accordingly, an elaboration of the
enzymatic mechanism of sphingosine synthesis is of paramount
importance for understanding the formation of these lipids. We
have succeeded in demonstrating for the first time the enzymatic
synthesis of sphingosine (NINDB-NCl) and have characterized the
enzjrrae system and identified the cofactors required for this
process. That the reaction is exceedingly complicated is indi-
cated by the observation that at least eleven non-enzymatic
components are required for the final step in this process. These
findings are of considerable interest since a relative insuffi-
ciency of any one of these materials could potentially interfere
with the formation of myelin. Furthermore, in the course of these
investigations J the pathway of formation of long chain fatty
aldehydes has been discovered. These latter materials constitute
the characteristic moieties of another group of cerebral lipids
called plasmalogens.

Perhaps the most representative of the complex cerebral
lipids are cerebrosides . These compounds are composed of an
extra-ordinarily long chain fatty acid in an amide linkage with
the amino group of sphingosine. A third portion of these compounds
is a molecule of either glucose or galactose joined with the
primary alcoholic group of sphingosine by a glycosidic bond. We
have succeeded in demonstrating for the first time the enzymatic
incorporation of glucose or galactose into cerebrosides (NINDB-
NC4) . The enzyme system obtained from brain tissue has been
characterized and the specific uridine nucleotide cofactors
required for this synthesis have been identified. Of particular
interest was the identification of the pathway of incorporation of
galactose into cerebrosides. The experiments performed in this
series of investigations indicated that in contrast with the
mechanism of formation of uridine diphosphate glucose from glucose-
1-phosphate and uridine triphosphate, an analogous enzyme for the
formation of uridine diphosphate galactose was absent in brain
tissue. The formation of the appropriate galactose nucleotide from
galactose- 1-phosphate occurred only in the presence of catalytic
amounts of uridine diphosphate glucose which indicates the presence
of a novel transferring enzyme in brain tissue called galactose- 1-
phosphate uridyl transferase. It should be indicated .Jiere that when
glucose is employed as substrate, it is actually incorporated into
cerebrosides as galactose confirming the presence of the enzyme
uridine diphosphate galactose epimerase in these preparations.

Sii--"-^':!: .

In addition to the fact that cerebrosides are important
constituents of the myelin sheath, there are several disease states
associated with an overabundance of such compounds, particularly
Gaucher 's disease or Tay-Sachs' disease. In the latter condition
related materials called gangliosides accumulate in pathologic
quantities in the brain. We are at present investigating the
metabolism of cerebrosides using tritiated galactocerebrosides in
these studies. Furthermore, we are exploring the effect of certain
antimetabolites such as deoxyglucose and deoxygalactose on cerebro-
side formation.

Since cerebrosides contain long chain fatty acids as well as
sphingosine and a sugar molecule, we wish to investigate the incor-
poration of fatty acids into ceramides (sphingosine-fatty acid) or
cerebrosides (NINDB-NC5) . A search for the appropriate tissue
source and enzyme system will be initiated shortly.

Another important class of cerebral lipids under investiga-
tion in this laboratory consists of inositol lipids. These
materials are particularly interesting because they have been found
to exhibit the highest rate of metabolic turnover of all of the
cerebral lipids. We have demonstrated for the first time the
enzymatic incorporation of inositol into this type of lipid and
have identified the particular cytidine nucleotide cofactor required
for this process (NINDB-NC7) . This process was investigated with
the use of tritiated inositol and in the course of these investiga-
tions several new techniques for the handling and radioactive assay
of tritiated compounds have been developed (NINDB-NC8) . Of partic-
ular interest in this regard was the innovation of the use of
silica counting vials which improved the low level counting of
tritiated samples immensely. Another technique developed here was
the extraction of lyophylized tissue samples with an appropriate
solvent system for direct radio-assays of tissue specimens. These
techniques proved to be particularly feasible for the study of
metabolism of meprobamate, a tranquilizing agent currently in wide
use (NINDB-NC9) .

The availability of liquid scintillation counting techniques
suggested a method which has been successfully employed for the
ultra-micro determination of the enzyme glutamic decarboxylase
(NINDB-NC2) . This enzjnne catalyzes the formation of y-amino butyric
acid, a compound found to exert striking neurophysiological effects.
We have succeeded in identifying three particular regions where this
enzyme is predominantly found in the central nervous system. Thepe
areas comprise the reticular formation of the midbrain, the optic
sensory area of the cortex, and the nucleus proprius of the dorsal
horn of the spinal cord. Such a distribution where a localized
production of 7-amino butyric acid can occur may be of considerable
significance for mediating certain control mechanisms character-
istically exhibited by nuclei such as are found in the reticular
formation. This project is continuing by investigating the meta-
bolic fate of Y-amino butyric acid produced by the decarboxylase
reaction. It undergoes transamination to form succinic semialde-
hyde which is subsequently oxidized. The enzymes catalyzing these
reactions have been demonstrated and an assessment of the quantita-
tive importance of this alternate pathway of cerebral metabolism
will be undertaken.

- 35 -

The investigations of neurohumoral agents led us to the
observation that under certain conditions, compounds such as
serotonin which contain an aromatic benzene ring are not necessarily
formed via the 7-carbon sedoheptulose-diphosphate pathway. Accord-
ingly, we wish to try to identify alternate enzymatic routes for
aromatic ring formation (NINDB-NC6) . These experiments are
pertinent because of the finding that compounds such as benzoquinone
capable of giving rise to free radicals have a profound effect on
the conduction of nerve impulses. This observation was made in the
course of experiments on the intra-axonal injection of enzymes and
other biologically active materials (NINDB-rNCS) . These investiga-
tions also revealed that the application of compounds having
sufficiently high oxidation potential cause drastic changes in the
conduction properties of the squid giant axon. The results seem to
indicate that the axon membrane is normally in a reduced state, a
condition known to require energy obtained through metabolic reac-
tions, and that the appropriate alteration of this condition permits
the investigator to predetermine any number of repetitive responses
to a single stimulus that is desired. It appears that a delicately
balanced equilibrium is obtained between the oxidizing agent and
the reduced axon membrane which can be destroyed by the agent or by
allowing the nerve to fire repetitively until it has exhausted its
metabolic energy source. Some striking recent observations have
been obtained in this laboratory with regard to the ability of brain
extracts to reduce exogenous triphosphopyridine nucleotide in the
absence of added substrate. Taken together, these investigations
suggest certain experiments which should be undertaken which may
help to clarify the mechanism of production of the resting potential
of a nerve fiber and ultimately, the nature of the metabolic
processes responsible for the phenomenon of excitability.

tcjmifcdty.i'

ADDICTION RESEARCH CENTER
Dr Harris Isbell. Chief

I. ADMINISTRATIVE

Throughout the year the administrative unit of the Addiction
Research Center (ARC) continued to conserve the time of the prof-
essional staff by efficient handling of purchasing, filing, personnel
record keeping, etc. The typing of manuscripts has constituted an
especially heavy load during the current year and the editing and
bibliographic checking by the administrative staff contributed
greatly to smooth preparation of manuscripts and reports. As
experience was gained, property accounting, now delegated to the
ARC instead of the hospital, proceeded satisfactorily.

The additional subprof essional employees who came on duty during
last fiscal year or in the first part of the current fiscal year
are now well trained and oriented in their jobs, We were disappoin-
ted that request for special awards to the psychiatric aides was not
granted. We intend to write another recommendation for a special
award for this group in the very near future.

We have experienced difficulty in obtaining professional
personnel but have succeeded in recruiting a neuropharmacologist ,
Dr. William R Martin, who will come on duty on 1 December 1957.
Dr. Martin will initiate a program of studies of the effects of
acute and chronic intoxication with various drugs on the activities
of single neurons. Studies of this nature are basic to complete
understanding of the addiction process.

Space of the ARC has now become inadequate. The animal house,
which is a temporary structure, is very crowded and can barely house
all of the animals needed. It does not have floor drains, is not
sanitary, and should be replaced as soon as possible The addition
of a neuropharmacologist means that crowding in the animal building
will be further intensified It is hoped that the hospital will
make an additional ward available to us. This would permit us to
convert one of the present wards to additional office and laboratory
space .

II. ADDICTIVE PROPERTIES OF NEW ANALGESICS

This is a technological project which is carried on for the
protection of the public, As new analgesic drugs are developed
that are likely to come into clinical use they are referred to the
ARC by the Committee on Drug Addiction and Narcotics of the National
Research Council, After the addictive potentialities of these. new

Page 2

- 37 -

drugs have been determined, by methods previously described, the
findings are referred to the Committee on Drug Addiction and
Narcotics, NRC, who in turn informs the Section on Addiction-
Producing Drugs, World Health Organization. These bodies advise
the United States Government and the United Nations concerning
appropriate legal action regarding control of these drugs at
national and international levels.

It is now hoped that in the future most drugs can be tested in
animals. Currently, initial tests of addictive properties of new
agents are carried out by the Department of Pharmacology, University
of Michigan, using monkeys. All drugs are referred to this unit
prior to being tested by the ARC. It seems very likely, however,
that at sometime in the future some unit of the government (Public
Health Service or Food and Drug Administration) may have to take
over this animal-testing program.

During the year five new analgesics were tested. Three of
these had sufficient addiction liability to justify placing them
under the controls of the Harrison Narcotic Act. D-propoxyphene,
-though possessing some addiction liability, was judged not to be
sufficeintly dangerous to require control by the narcotic law.
No decision has been made in the case of the fifth.

The demethylated congener of morphine (normorphine) was
especially interesting. This drug, which is one of the metabolic
products of morphine in the body, has been presumed to be rela-
tively inert on the basis of animal tests. Axelrod and his
collaborators at the NIMH have shown that ability of the liver to
demethylate morphine declines during experimental addiction in
male rats. Axelrod felt that this change might be a model of
effects on receptors within the central nervous system and might
lead to a theory of tolerance. For this reason, normorphine was
reinvestigated at the ARC.

In single dose, normorphine is less potent than is morphine
in inducing behavioral changes in man. In repeated dose, however,
normorphine has accumulative effects and is more potent than
morphine. For this reason, the dose cannot be elevated as rapidly
as the dose of morphine. Tolerance to the sedative effects of
normorphine appear to develop more slowly than does tolerance to
the sedative effects of morphine. Normorphine completely suppressed
symptoms of abstinence from morphine. Following withdrawal of
normorphine after direct addiction (or after substitution for mor-
phine) J abstinence appeared slowly and was quite mild as compared
with abstinence from morphine.

Although normorphine has definite addictive properties, its
addiction liability is the least of any potent drug in the morphine

38 -

Page 3

"■to

series. If normorphine is a good analgesic, it will represent

a considerable advance toward the goal of a nonaddicting analgesic.

During the coming year this project will be continued, as
it must be, in order to protect the public. Primary emphasis
will be placed on demethylated derivatives of morphine and
meperidine.

III. CHRONIC BARBITURATE AND ALCOHOLIC INTOXICATIONS

A. Substitution of Alcohol for Barbiturates. The project
on equivalence of chronic alcoholic and barbiturate intoxications
was completed during the year. Alcohol was substituted for
barbiturates in a sufficient number of chronically intoxicated
dogs to warrant the following statements: in sufficient dose,
alcohol reduces the nember of seizures after withdrawal of
barbiturates, but does not eliminate them entirely. Alcohol
suppresses the barbiturate withdrawal delirium completely.
Following withdrawal of alcohol after substitution for barbiturates,
convulsions were observed in occasional dogs and delirium in the
majority of the animals. These findings indicate that chronic
intoxication with alcohol and barbiturates are partially but not
totally equivalent.

B. Substitution of Chlorpromazine for Barbiturates.
Chlorpromazine did not suppress abstinence from barbiturates
in dogs .

C. Meprobamate. Special studies were carried out on
chronic meprobamate intoxication. Patients who entered the
hospital with histories of taking large amounts of meprobamate
were maintained on their accustomed dose of meprobamate while
opiates were withdrawn. After allowing a week for recovery
from abstinence from opiates meprobamate was abruptly withdrawn.
A convulsion occurred in one of 3 patients and an abnormal EEG
was observed in another patient.

Five dogs were chronically intoxicated with meprobamate.
The doige was increased as tolerance permitted to 5-6 grams
daily, divided into two or three doses. One of the dogs died
during the period of chronic intoxication. Following abrupt
withdrawal of meprobamate all 4 surviving dogs had severe ab-
stinence. All 4 had seizures and bizarre behavior, and 3 of the
4 dogs died after repeated seizures ("status epilepticus") .
These findings show that meprobamate can cause a type of addiction
similar to that caused by barbiturates or alcohol.

Page 4 - 39 -

During the coming year we hope to test the equivalence of
intoxication with paraldehyde, chloral, meprobamate, doriden
and barbiturates ,

IV„ BIOCHEMISTRY OF ADDICTION

The biochemical unit shifted from clinical biochemistry
into the field of drug metabolism during the year. Methodolo-
gical problems in this area are particularly difficult because
of the relatively low doses of analgesic drugs given human
subjects, and because of the high incidence of interference by
the various foodstuff and other drugs often ingested by the
subjects. A great deal of progress was made in developing
paper chromatographic methods for isolation of drugs from
body fluids. Methods for quantitative determination of morphine
and normorphine were developed. The normorphine method has
been particularly troublesome since the solubility of normorphine
in organic solvents is less than the solubility of morphine.
Quinine appeared to have no effect on the conjugation of morphine,
Less normorphine is conjugated than is the case with morphine.
This last finding may explain the difference in the length of
action and addictiveness of morphine and normorphine.

Addiction to and withdrawal from analgesics and barbiturates
had no significant effect on the excretion of 5-hydroxyindol-
eacetic acid.

During the coming year we hope to complete a project on
comparison of the metabolism of morphine and normorphine, and
to determine the changes in excretion of epinephrine and
norepinephrine during cycles of addiction. We also hope that
another chemist can be obtained to initiate a study on the
effects of addiction on enzymological processes at the cellular
level.

V. NEUROPHYSIOLOGY AND NEUROPHARMACOLOGY OF ADDICTION

Studies on changes in electroconvulsive thresholds during
addiction to and withdrawal from barbiturates in cats were
hampered by a number of technical difficulties. Although
seizure thresholds are elevated and variable during addiction
to barbiturates J elevations were also noted in control cats that
were receiving no barbiutrates , Apparently, repeated electro-
stimulation causes some change (perhaps anatomical) leading to
elevation in the seizure threshold. No consistent change was
seen in seizure threshold after withdrawal of barbiturates.
Cats addicted to barbiturates had fewer spontaneous seizures if

Page 5 - ko -

stimulated on a regular schedule after withdrawal of the bar-
biturates .

Following withdrawal of barbiturates after chronic adminis-
tration, one spinal dog had grand mal seizures above the level
of the transection but no seizures below. This finding indicates
that the barbiturate abstinence syndrome is mediated at levels
above the spinal cord.

During the coming year we hope to continue the project on
seizure thresholds during addiction to barbiturates, using
electroencephalographic changes instead of clinical seizures
as the end point. We also hope to begin experiments with
animals with chronically implanted electrodes, in the hope of
obtaining information on changes at various levels of the nervous
system during morphine and barbiturate addictions. It may be
possible to begin studies on the relationship of systems sub-
serving synthesis and destruction of acetylcholine in relation
to addiction to barbiturates. It is also hoped that studies on
the effects of acute and chronic intoxication with various drugs
on the activities of single neurons can be initiated by Dr. Martin.

VI. PSYCHOLOGY OF ADDICTION

Physician addicts show less elevation on the Pd (psycho-
pathic deviate) scale of the MMP 1 than do either nonphysician
White or Negro addicts. Physician addicts are higher than normal
on the neurotic scales. Unfortunately MMPP 1 profiles on non-
addict physicians are not available and must be obtained before
this study can be interpreted properly. We hope to obtain control
profiles on a sample of Army physicians.

A great deal of progress was made in the construction of
psychological tests for differentiating between the subjective
effects of various classes of drugs. Questions which differentiate
between the effects of a marihuana-like drug, LSD, morphine,
pentobrbital, and amphetamine have been assembled. A general
inventory is to be constructed from these items and tested more
throughly during the coming year on a number of classes of drugs.
It is hoped that these inventories will provide quantitative in-
dices of the effects of the drugs which addicts regard as pleasant
("euphoria") so that a more exact statement on relative addictive-
ness of different agents can be made.

Studies on the effects of drugs on conditioned inhibition of
a feeding response in rats (pain-anxiety) were continued. It was
found that different types of drugs produce specific patterns of

Page 6 -kl-

unconditioned bar-pressing, time-action rates, and conditioned
inhibition of feeding responses. It was also found that very
exact control of the strength of the auditory stimulus used is
essential to this particular method. The studies indicate
that morphine abolishes anxiety in anticipation of a painful
stimulus .

A number of studies on the effects of drugs on "mental
set" were completed. In this work visual-hand reaction time
is determined under two conditions: (1) when various fore-
periods (warning periods) are administered in a regular order,
and (2) when foreperiods are administered in an irregular
fashion. It is known that in "normal" subjects curves obtained
with the regular and irregular procedures are well separated.
In schizophrenic subjects, the curves cross, indicating a dis-
turbance in ability to profit from the regularization of the
foreperiods. This test was administered in random balanced
order to 10 former addicts who received morphine, pentobarbital,
LSD, placebo, and amphetamine. Amphetamine and placebo. had
little effect on reaction time or on mental set; morphine and
pentobarbital slowed reaction time but did not impair mental
set; LSD slowed reaction time, but did not cause any statisti-
cally significant impairment of mental set (crossing of regular
and irregular curves) in spite of the presence of marked per-
ceptual distortion, hallucination, and depersonalization. These
findings indicate that LSD is possible only indirectly related to
the natural psychosis, schizophrenia.

During the coming year we hope to complete the study on
physician addicts, to develop the inventory for measuring
subjective effects of drugs further, to investigate the
significance of drug-produced internal changes in controlling
animal behavior, and to begin studies of the effects of drugs
and addictions on discrimination.

LABORATORY OF NEUROPHYSIOLOGY
Wade H. Marshall, Chief

The productivity of the Laboratory of Neurophysiology
continues at a high level and xs in the van of some crucial
arguments, . One of the most important current questions is
the participation of soma and dendritic membrane in activa-
tion of the efferent axons. Nearly 20 years ago it was
recognized that sufficient depolarization of the dendrites,
or other components, of a neuron could cause the cell body
to discharge without actual complete depolarization of
said component structures. It was further recognized that
sustained depolarization of these structures might result
in repetitive firing of the cell body and axon. However,
physiology of the neural network has been slow to sufficiently
divorce itself from axonology . This is to say that the
compulsion to fit CNS ganglion physiology into "the existing
framework of knowledge" (which was largely axonology) has
acted as a conservative brake on advancement . During the
past several years great progress has been made toward
liberating thinking from the simple axonology concepts.
This has been particularly true of the dendritic components
of the neuron. During the past 2 or 3 years it has been
quite vociferously argued that the dendritic membrane is
entirely passive. It has further been argued that all
synaptically covered parts of the neuron membrane are
passive and electrically inexcitable (that is they are
somehow not capable of complete all-or-none regeneratively
propagated discharges) and that the polarization modula-
tion of these parts of the neuron is entirely accomplished
by neurochemical means. Whether or not the latter point
is correct is not completely proven. But the best evidence
so far obtained for the passive nature of the soma-dendritic
membrane has been developed during this year by Dr. W. H.
Freygang working on the lateral geniculate nucleus of the
cat. Using very small pipette electrodes, excellent
electrical technics, and superb mathematicax analysis,
he has developed strong evidence that only a very small
area of the neuron soma is electrically excitable. All
other parts of the neuron react passively, acting as sinks
of current which causes activation of the low threshold
axon hillock region. This experiment depends on placing
the microelectrode very close to the active membrane so
that it measures the IR drop due to the total membrane current
at that locus . The only decernible reservation about this
experiment devolves on the inevitable Heisenberg uncertainty
principle. Has the electrode, because it is so near the membrane
rendered that locus inexcitable? There are many reasons to
discard this objection. This experiment is the best and probably
the only valid evidence for the electrical inexcitabiiity of the
soma-dendritic membrane in the mammalian CNS. So far as it is

possible to accurately judge current events this paper constitutes
a revolution and a major breakthrough.

Tests of this theory on the motor neuron (anterior horn
cell") done in collaboration with Dr , Karl Frank have more clearly
substantiated it Very recently a concentric pair of electrodes
have been used to record simultaneously from inside and just
outside the anterior horn cell This has likewise confirmed

Dr. Freygang s observations on the lateral geniculate,

'xsrit'Lul aB^f^ J-I nonoqxnioo i)i£s

Drs, Tasaki and Spyropoulos, in the Section on Special
Senses, have made an important advance in axonology . They have
found that when the squid nerve is clamped, i e an attempt is
made to fix an imposed potential difference across the membrane;
that the membrane does not respond uniformly but that erratic
patches contribute the current and that these patches have the
characteristics of local all-or-none reactions. This fact indi-
cates that the normal membrane as a whole is not clamped but
that only the electrodes are clamped. This demands re-evalua-
tion of the basic Na-K exchange theory because obviously the
current measured and the apparent resistance change are not
properties of the total membrane undergoing a smooth continuous
function, but are instead the more or less chance resultant of
reactions in random patches on the membrane. This change in
current flow and pat I .em of same as a function of the imposed
voltage is now regarded primarily as an increase in total area
of active patches Again the inevitable Heisenberg uncertainty
principle must be considered Has the placement of electrodes
inside the squid nerve and other items such as dissection of the
nerve, produced significant local changes in patches of membrane?
However, Dr . Tasaki has acquired considerable collaborative
evidence in recent years from the single node of toad A fibers
and his two stable state experiments All these items suggest
that the normal axon membrane does not exhibit partial states
in its reactions except transiently In the case of the squid
nerve under voltage clamp the membrane resistance changes only
under the active patches and this current has heretofore been
considered to be uniformly conducted by the entire membrane If
the sodium current is not a uniform function of membrane voltage,
for instance, the Hodgkin-Huxley theory must be modified,

Drs. Spyropoulos and Tasaki are investigating active
chemical processes to account for the action potential They
have used the methods of intracellular injection into the squid
nerve and also the single node preparation. In their hands
these methods are exquisitely sensitive tools for study of ■■ - >■
many biochemical problems. Their thesis is that the action '^^■^^
potential as well as the recovery process probably involves
biochemical events and that the ion exchange is not merely a
passive result of a regeneratively propagated action current

-hk _

They have made very substantial progress in this direction and
we can look forward to decisive and comprehensive conclusions
during the coming year.

Drso Tasaki and Spyropoulos have also determined that the
Bekesy potential is generated in the stria vascularis and not
by the brain cells of the ear „ This confirms or perhaps, is
concurrent with similar studies done at Institute for the Deaf
at St o Louis, Mo 0 The source is not in the hair cells

Recently Drs. Tasaki and Chang have gone to Dr. Pomerat's
famous tissue culture laboratory at Galveston. They are making
an intensive investigation of electrical reactions in cultured
CNS cells.

The program of the laboratory has been considerably
broadened and strengthened by the recruitment of Dr. Paul MacLean
(Section on Limbic Integration and Behavior) . His broad
general knowledge in several fields and his work on the limbic
system well fills a gap in the program. Dr. MacLean is setting
up his laboratory and has already underway a valuable project
concerned with use of genetically and chemically induced sub-
cortical lesions in rats.

The Section on Cortical Integration has continued work on
the remarkably successful chronic monkey technic , Stop stimulus
and start stimulus regions have been partially mapped and work on
this aspect is continuing. Regions concerned with pleasurable
and compulsive activity are being clarified as well as regions
concerned with negative emotions and pain, anxiety, and fright.
The importance of such work for problems of mental health needs
no elaboration.

A new technic for implanting of electrodes has been
developed and successfully used on the monkey and the porpoise.
The latter animal (2 preparations) has shown learning processes
faster than the monkey by an order of magnitude. Considering
the fact that the porpoise possesses one of the most elaborately
developed of the mammalian brains, this fact constitutes a very
interesting observation.

Work is continuing on a practical method of portraying
and analyzing activity from 256 electrodes. The section enjoyed
the opportunity of collaborating with Dr. H. Magoun for a few
months .

It is gratifying to note that Dr. Lilly is one who is
actively engaged in chronic electrode work in primates and that
he is deeply conscious of medical and social responsibility
involved. He is not encouraging brash clinical work and is
attempting to do constructive work to encourage only conservative,
well considered activity in that direction.

- ^5-

The Section on the Spinal Cord has continued with elegant
work. It is to be remembered that this laboratory by virtue of
its technical excellence was the first to demonstrate that an
accurate intracellular record of antidromic activation showed
two components o Dr. Frank's consultation and collaboration
with Dr. Freygang has been particularly valuable and gratifying.
This has j.ed to important comparisons of records taken from
within the cell and just external to it by means of a double
concentric electrode system.

They have discovered a "remote" inhibition process which
operates without any detectable change in the polarization of
the cell membrane as measured by intracellular electrodes. This
laboratory is "tooling up" for transmission of neurochemical
agents through their pipettes.

Work has been continued on spreading cortical depression o
It has been determined that neuronal reactivity of the superficial
layer of the cortex is not necessary for this phenomenon. This
is a curious result because while spreading depression is a
dendritic like reaction in the sense that it is completely graded,
a fully developed reaction probably represents the most complete
depolarization the dendrite ever undergoes.

A new technic for study of the superficial cortical
electrical reactions has been developed which permits much
more accurate experiments, and which also permits accurate
observations in drug experiments in face of extreme changes
in blood pressure and which also eliminates other artifacts
such as spreading cortical depression.

_ 46 -

LABORATORY OF CLINICAL SCIENCE
Seymour S. Kety, Chief

The Section on Pharmacology under Julius Axelrod
has continued its studies on the fate, metabolism, and
mechanism of action of drugs which act on the nervous system
with several notable achievements in the past year. In
collaboration with Schmid and Tomkins of NIAMD, he has found
enzymatic mechanisms in the synthesis of N-glucuronides and
in the formation of bilirubin glucuronide, leading to the
elucidation of a biochemical lesion in congenital non-
obstructivOj non-hemolytic jaundice. He has added
significantly to knowledge concerning the metabolism of
epinephrine by elucidating the enzymatic process involved
in the o-methylation of catecholSj characterizing its
requirements and demonstrating it in a number of organs
including the brain o He has shown that this process plays
a key role in the metabolism of epinephz'ine and norepinephrine
in vivo . In collaboration with Agranoff of NINDB^ a method
for the estimation of meprobamate in body fluids was
developed and applied to a study of the disposition in man
of this widely used ataractic agent .

The Section on Biochemistry under Marian Kies, in
collaboration with Alvord of Baylor and Roboz of Georgetown
medical schools, has for several years been concerned with
a better characterization of the materials in brain tissue
responsible for experimental allergic encephalomyelitis.
In the past year they have further purified their active
preparation, obtaining a protein fraction with a ten-fold
increase in activity, A collagen-like material was also
isolated from brain, characterized and found to have moderate
activity .

The Section on Cerebral Metabolism under Louis
Sokoloff has, as part of a cooperative study on aging, made
a substantial contribution to the physiology of aging in
their finding in over 50 normal elderly men that a decrease
in cerebral blood flow is not a concomitant of the aging
process. The decrease which has often been found by previous
investigators appears to be limited to those with evidence
of gross mental changes. These findings are about to be
extended in studies at St, Elizabeths Hospital by Lassen and
Lane with a modification of the technique which employs
radioactive krypton as the tracer gas. The section has
continued its development of techniques for measurement of
blood flow continuously and locally and their application to
physiological and clinical problems. The studies by Sokoloff ,
in collaboration with Kaufman of the Laboratory of Cellular
Pharmacologys on the mechanism of action of thyroxine continue
to produce promising and significant results, indicating an
important effect of thyroxine on protein synthesis.

- h7 -

Public Health Service

National Institute of Mental Health

Laboratory of Socio-environmental Studies

STATEIv^lNT OF FROGFJIM (DBJECTIVES AND .

SIM^iARY OF OPERATIONS DURING 1957

The research goal of the Laboratory is the investigation of
the ways in which social processes bear upon the production- and
course of psychic disturbances. Included with this goal is a wide
range of research areas; the nature and distribution of mental
illness and behavioral pathologies, social and cultural variations
in defining and treating behavioral disturbances, social and
cultural patterns influencing personality development, interpersonal
processes within the faraily, and social processes in the treatment
setting of the mental hospital. This range of interests is repre-
sented in the current projects of the Laboratory'",

With the growing., recognition of the importance of social
a%),ects of illness and with the realization that relationships between
social and medical or biological factors are more complicated than
has been assmued, there has been an intensification of research
interests and efforts in conceptual and methodological issues and
in ,c6llab oration across disciplinary lines,

. , During 1957, the organization of. the Laboratory has been
coEf-leted with the staffing of the Section on Social Studies in
Therapeutic Settings,

Social Developmental and Family Studies

Research in this Section,, under the direction of Dr, I-Iarian
Radke Yarrow, is devoted to systematic study of socialization
influences at various stages of individual development. The greatest
enphasis is ;:f)on the period of childhood, but critical developmental
periods or shifts in social roles in adult life, such as in old age,
are also considered.

The assiinptions that personality is significantly shaped by
the social interactions in which the individual participation from
infancy on through life, and that adult outcome bears a significant
relation to early experiences are readily accepted, though research
knowledge has not succeeded in defining precisely these relationships
or in explaining the processes by which antecedent conditions affect
siiisequent behavior. Advances toward this knowledge rest partly on
refinements in methodology as well as on systematic investigation of"
research hypotheses.

- kS -

Some of the efforts of the Section are directed toward method-
ological problems . Several scientists have begun work on techniques
for obtaining more detailed and, hopefully, more valid data on the
child's social learning environments. One such approach is the
development of techniques for the study of the family in its natural
setting, malting use of direct observational data. Tliat this is a
very difficult problem is reflected in the scant research which has
been done thus far in the field. A second project concerns the
investigation of processes of recollection and reporting of earlier
childhood and family conditions. Much of cujrrent research concerning
relationships between early experience and later development rests on
retrospective data; an understanding of memory changes is lacking.
This factor is believed to be of particular significance in investigat-
ing retrospectively such problems as family relationships in the
childhood of schizophrenics, where the recall of past events may be
markedly modified by the subsequent developments.

In the investigation of family and societal influences upon
the child, seldom has research given consideration to the level of
the child's perceptual and cognitive understanding of the experiences
to which he is exposed. That is, what are the developmental stages
in children's sensitivities to and discriminations in interpersonal
relationships? A project has been carried out which is concerned with
the child's sensitivities to the personality, characteristics and
motives of the persons with whom he interacts, and his modes of causal
thinlcing about interpersonal relationships. Much of the analysis of
these data has been completed during the past year and reporting of
findings has begiin.

Attention to the interplay of social and biological factors
in developmen-".- has been part of the focus of two of the projects of
this Section^ one, a study of family and community influences in the
development of identical quadruplets, and the second, a study of social
characteristics and problems of old age. Both projects were undertaken
collaboratively with other disciplines. In both, data collection has
been completed. The interrelationships between social and physiological
conditions is demonstrated in the study of human aging, in a relation-
ship occurring between various behavioral indices in the aged and the
subjects' combined status on raeasi-ires of O2 consumption and environ-
mental impoverishments.

The work of the next year will be devoted to the completion of
the just preceding projects and to the expansion of the methodological
studies described above.

Community and Population Studies

This section, directed by Dr. Melvin Kohn, studies the relation-
ship between broader aspects of the social order and mental health or
illness. The long range program includes: (l) research on social
factors in the etiology of mental illness and behavior pathologies;

(2.) studies of th^. prc^ess-^.s by whi:;h mental illness is recognized
or defined ar,d the channels th.roi5.gh whi'?h it is brought to treatment
(whether by ,foriua,l "therapeutis agents or other means) j and (3) studies
of GoiDi?i".ni ty crga.nizationj social strnjt'are; and cultural dynam.i?.3
basi.-; to these aims.

Much o.f what ve should like to ac">JomplJsh .i,n the ,fir.3t two
areas is -jn.attainabls at presf-n* .for la?k of basi'" knoxjledge. For
example^ in tb'j: research dCiie by Kohn and Clausen on social factors
i.n the de'^elopment of schi3ophren1a_B .vt became appa-^ent that further
progress awaj.ted a fii!',.ler unders^tanding of the relati 'nshlp between
social class and family structure in the normal populationo Thpreforej
for the i.TEmed.iate future., much of the sect.ion's work will ha'^" to be
.focused on problems o.f basi.j in^Dortance to social psychology. Before
we can discover too much abcu*- social favvto-'S in the etiology of
schizophrr.nia we .shall have to study,., for e^xample.,-, sc-ial -mriation
in child-rearing practices and pf-^snna].ity development, Basic to
our ijnderst/anding of the pro:e?59s by which mental illne.BS is defined
and dealt with is research on th; processas by whi.ch de'."is.tion .from
sub-cultural norms is handled. For the present, the third aspect of
the long-=range program is the most important.

Following a study that showed a relationship be^-ween 30':..io=
economic status, parental authority beh.av.iory and schizophrenia 3
ef. forts have been directed toward securing a more ad.equate knowledge
of the stru.cturing of family relationships in .middle and workd,ng class
families „ The fieldwork on this s'*udy is now eoBiplete,- as is the
first portion of data analysis, a coirparison of the values of parents
in the two social classes. It was found that mi.ddle class parents
are more la,k6ly to attach primajrj'" value to self=control_„ considerationj
curiosity,, and. .happiness | working class parents to obedience ,, neatness
and cleanliness. It was al.so found that the parent's values are very
directly related to the ways th.at they ra.ise their children.

In line witii the Section's .interest .in the processes by which
mental illness is recogn.ized or de.fined and the .-.bannels through which
it is brought to treatment. Dr. Stephen Boggs has been developing a
study of cultural differences in the ways that community resources
(formal and informal) are utilized by people witJi problems. He has
conducted prelimi.nary fieldwork and i.s now i.n process of developing
a systematic research design for th.e investigation.

A third, -study has been undertaken to ascerta.in the relationship
between social background and dnag therapy for prognosis among
functionally psyciiotic patients, Dr, E;rwin Linn has been abstracting
the re,levant data from^ Saint Elizabeths Hospital records to be able to
determine whether or not prcgnosi.3 is improved with drug therapy .-. s..nd
to what extent patients of varying social backgrounds react differ-
entially to drugs.

-5C -

There follow summary statements of the objectives of each
of the projects to which appreciable amounts of staff time were
allotted during 1957.

Office of the Chief
■t-ro.iect lio. H-S-C-1

Title: Analysis of Theoretical and Methodological- "ssues in the
Sociology of Mental Health and Illness

Project Staff: John A. Clausen

To exp line current research within the Laboratory and within
the larger t'i.ld, searching for theoretical convergences and for
problematic issues in empirical findings, especially bearing upon
the relationship between social structure and personality develop-
ment.

Iroject Ko. M-S-G-2

Title: The Impact of Mental Illness upon the Family

rt-oject Staff: John A. Clausen, Leila C. Deasy, Harriet S. Murphy,
Eleanor E. Carroll

To study the effects upon the family of the father's or
mother's mental illness, by focusing on a limited number of hypotheses
and questions raised by an earlier study within the following areas:
(l) the effects of mental illness upon the personal relationships with-
in the family and the family organization, (2) the family's understand-
ing and perspectives of the illness, and (3) the social implications of
the illness. Fajnilies under study are to include both parental and
conjugal families of schizophrenic patients.

rro.ject No. M-S-C-3

Title: The Adaptation of the Mental Patient to his Family Upon
Return from Hospitalization

Project Staff: John A. Clausen, Leila C. Deasy, Harriet S. Murphy

To study the rehabilitation process following the patient's
discharge from a mental hospital, in terms of two interdependent sets
of dimensions: (a) the patient's progi-ess toward mental health, and
(b) the changing structure and functioning of the family of the patient.

- 51"

Social Developmental and Family Studies
Project Mo. M-S-D-1

Title: The Formation of Children's Peer Relationships
Project Staff: Marian R. Yarrow, John D. Campbell

To investigate the process by which children form impressions
of each other and develop patterns of interactions in social situ-
ations, '^o .".udy the effects of developmental, personality and social
factors or .his process.

Pro.iect No. M-3-D-2

Title: Adult Leadership in Children's Groups: A ^tudy of leader's
Sensitivity and Functioning in Relation to the Social-
Cultural Composition of the Group

Project Staff: Marian R. Yarrow, John D. Campbell

To study the adult leader's role in children's groups, assessing;
(a) congruencies and diacreoancies in leader's .nd children's per-
,, ceptions "i interperijonal processes in the -roup, (b) bases and con-
sequence;, of discrepancie;j between leader '>:■ and children's perceptions,
and (c) leader','' '^ehavior and sensitivities regarding the individual
child and the group in relation to the social class and racial cora-
position of the group.

Project Mo. M-S-D-3

Title: The Validity of Retrospective Data on Parent-Child Relationships

Project Staff: Marian R. Yarrow, John D. Campbell.

'To study the extent to which valid information about early
aspects of a child's development and parent-child relationships can
be obtained from parents' retrospective reports. Specifically: (l).
To assess the nature of differences between earlier events and parents '
recollection of such events. (2) To determine how retrospection is
influenced by such factors as the time interval between events and recall,
intervening events, and the current social-jjsycho logical situation.

Project Mo. M-S-D-/i^

Title: Life-styles in Aging

Project Staff: Marian R. Yarrow, Olive U. Quinn, E. Grant Youmans

This project is part of a larger research on the functioning of
physically healthy aged persons, which brings the perspectives and

-52---

raeasurement of physiology, psychiatry, psychology and sociology,
both singly and in combination, to the examination of the problems
and factors in aging. The primary objective of this part of the
total research is to exaraine relationships between the demands and
supports of the aged person's social environment and his functioning
— as it is defined in terms of the organization of his daily behavior,
his planning for the future, his attitudes toward himself and his
relationships with others. Environment is assessed in terms of (l) the
social expectations and stereotypes imposed upon old age, and (2) the
impact of common changes or crises of old age, such as retirement from
employiuent, family losses, and social isolations.

A second research objective is the investigation of inter-
relationships between the social psychological variables described
above and physiological, psychiatric, perceptual and cognitive data.

Project No. M-J-D-5

Title: The Identification of 3elf in Identical Quadruplets: A

Special Case of the Problems of Jibling Rivalry and of Multiple
otatus

Jrroject jtaff; Olive W. Quinn

To analyze (l) interactional patterns, and (2) incompatible
statuses in a group of mentally ill identical quadruplets, in an effort
to understand the inaividual's struggle to establish a uefinltion of
self in relatioii to the group. This problem is seen within the frame-
work of stresses arising from or exaggerated by the fact of multiple
birth.

Project No. K-iS-J-b

Title: The "A" Family as Seen by the Com:nunity

Project Staff: Olive U. Quinn, Leila C. Deasy

This is one part of a larger study of the "X" family from the
points of vle\-i of various disciplines, with the intent of deriving or
exaiviplifying hypotheses regarding nature-nurture contributions to the
aevelopaent of schizophrenia. In this regard, the influences of the
faiiiily on the community and of the comjiunity on the family comprise an
area of information essential to a full unaerstanding of how mental
illness in the "X" quadruplets developed.

Project lio. K-S-D-7

Title: Exploratory Stuuy of Methodology for Assessing Interpersonal
Relationships within the Faraily

Project Staff: Marian R. Yarrow, Thomas L. Gillette

-5J-

To develop techniques of inveiitigating interpersonal re-
lationiihipa within the family, in the natural family setting.

Com,fiunity and i-opulation Studies ,
irro.iect IJo. M-:i-P-l

Title: A Comparison of the Social Relationships of Children in the
Middle and Lower Socio-economic iStrata

i-roject Staff: Melvin L. Kohn, John A. Clausen, Eleanor E. Carroll

To ascertain whether or not there are consistent and patterned
difference'^' between the social relationships of children from the
middle and lower socio-economic strata of urban society.

rro.iect No. M-S-1--2 ^

Title: Exploratory Study of the Use of Local Community Resources
for Handling Mental Health Irdblems

Project Staff: Stephen T. Boggs

To evolve and test hypotheses about the utilization of formal
agencies and informal resources (family, friends, associates and
strangers) by people v/ith personal problems j the social -factors in the
community affecting this utilization j and the consequence^ of various
ways of handling problems for the subsequent career of the individual.

Iro.iect Ho. M-o-l:-3

Title: rt'e-hospital Social Factors, Treatment with the Tranquilizing
Drugs, and Behavior as trognosticators of Successful Release
from a Mental Hospital

Project Staff: Erwin L. Linn

To determine the relationship between (a) the patient's pre-
hospital social background, (b) his course of treatment in the hospital
(with particular interest in reserpine and chlor promazine) and (c) his
behavior while in the hospital and the duration of hospitalization and
probability of readmission, for functionally psychotic patients. Among
the questions to be asked are the following:

1. Are patients treated with chlorpromazine or reserpine more likely to
be released during the first year of hospitalization and more likely to
remain out of the hospital one year after release than a comparable group
of patients admitted to the hospital before the use of tranquiliaing
drugs?

2. Have the tranquilizing drugs increased the probability of release of
patients not treated with drugs because of the generally "calmer"

atnos]..here of the hospital durin^ the current j^eriod of drU(j therapy?
3. To what extent do patients of varyin,^ social backi^rounds react
differentially to the drugsV

JrToject lio, Ii-S-l-'-/i

Title: A Twin Fauiily Study of hental Deficiency

Iroject Staff: Dr. Franz J. Kallmann, Dr. Gordon Allen

To assess the frequency with which mental subnormality can
clearly be ascribed to non^^enetic factors and to elucidate the inter-
action of genetic constitution with environmental causes of sub-
noririality. Also to develop better methods for the collection and
interpretation of twin data in medical research.

Iroject Ho. M-S-P-5 '

Title: Social Mobility and the Milieu of the Psychiatric Hospital

Iroject Staff: Leslie Schaffer, Leila C. Doasy

The study is an attempt to exi;ilore the relevance and impli-
cations of some theoretical work by Harold Lasswell concerning social
structure aiid social nobility - particularly his notion that there is
a significant negative relationship between the extent to which a group
achieves solidarity and hijjh morale and the incidence of mobility
ar.ion^ its members. It is hopped to clarify in theoretical terms a
particular perspective concerning the value context of the psychiatric
hospital and, in particular, some of the problems concerning respect
as a value. Among other questions is whether there is a significant
difference between the incidence and intensity of vertical mobility
in a psychiatric setting as compared with conventional medical and
surgical settin^^s.

55 -

PHS-NIH
NIMH"=STD
Individual Project Report
Calendar Year 1957

Kesearch isranch 3

Section on Technical Development.
Bethesda, Maryland

During the past yearj, the functions of the Section on Technical
Development have been qixLte varied. Included are consultation on the
instrumentation problems of laboratory personnel^, design and development
work on these problems <, construction^ repair and maintenance ^ internal
operation^ and administrative activi.ties»

In the area of design and development., several items of equipment
have been built as the result of a request by an investigator* Some of
thesej to be listed here_, are potentially of widespread interest. For
the Laboratory of Psychology^ a device for putting discriminations on
magnetic tape, and during playback^ having these filtered from the sound
system and used to give a visual indication, A system for communication,
stimulation, and recording from mthin a sound-proofed room to an outer
roomo For the Laboratory of Neuroanatomical Sciences, a device for
photoelectrdcally counting urine drops and reinjecting an equal amount
of saline solution into the animal. For the Laboratory of Biophysics,
numerous high impedance amplifiers^ power supplies, data boards and
control circuitry to aid them in preparing for the annual trip to the
Marine Biological Laboratory in Woods Hole, Massachusetts. For the
Director of Basic Research, a slave scope assembly to facilitate photogra-
phy of an observed waveform on an oscilloscope. For the Laboratory of
Neurochemistry, an "Automatic Sample Changer and Ptadiation Register" for
the sequential counting of blood samples for predetermined amounts of
time. For the Laboratory of Neurophysiology, a technique for mounting
and using thermistors in measuring the temperature of the cortex.

The Section on Technical Development has been engaged in repair
and maintenance to the limi^ that staffing idll permit. Responsibility
is naturally assumed for all equipment built by this facility, or modified
by this facility. Repair of commercial equipment is undertaken when an
economic saving can be effected.

Assistance is often asked for and given in the form of consultation.
First the feasibility of a problem is determined and then the mechanics
are worked outo This may take the form of the proper commercially avail-
able item to purchase, or it may result in a project best done by this
Section, or a combination of the two. The result of consultation may
also be a set of specifications that will be sent out on bido

Internal activities include projects considered worthwhile by the
Section which are pursued further on the initiative of the Section Chief,
One such project is a miniaturized high voltage supply, powered by an

_ ^5 - Research Branch

Section on Technical DevelopmentL
Bethesda, Maryland

air jet. This will be described further in a later report. Another
activity was the expansion of the Technical Development facilities which
carried over into the first part of this year. Stocks were rearranged
for better accessibility and work areas were made more efficient by the
installation of power distribution panels at each position. Files were
expanded to inclade the year's newest electronic equipment pertaining
to medical research and continue to be available to investigators desiring
to use them. Stock requisitions and equipment loans were continued to
provide components and instruments to laboratory personnel on a minimal
delay basJs. The procurement of supplies extends well beyond the Section's
own needs in order to forestall long delays when an investigator needs a
component quickly.

- 57 -

LABORATORY OF CELLULAR PHARMACOLOGY
Giulio L, Cantoni, Chief

During the year 1957 the Laboratory of Cellular Pharmacology
has continued its favorable development. The Laboratory has not
yet reached its maximum potential size and there has been considerable
difficulty in the recruitment of technical and supportive personnel ,
From the standpoint of professional personnel the year has seen
relatively little change, Drs . B, Levenberg and G. Jamieson have
joined the staff of the Laboratory as Commissioned Officer and
Visiting Scientist respectively, while Dr. J. Durell has gone to
the Department of Psychiatry at Yale University on a Training Grant
from the National Institute of Mental Health. On the other hand
several vacancies at the technical level have not been filled and
cannot be filled because of lack of applicants. While the reasons
for these recruitment difficulties are probably beyond the scope of
this report they are pointed out, in the hope that some action may
be possible to remedy this unfortunate situation.

Very little progress has been made as yet towards the estab-
lishment of a Section on the biology and biochemistry of medicinal
plants. Developments in this area depend on the construction of a
greenhouse facility which is in the planning stage. It is hoped that
progress will be more rapid in the next year so as to allow us to
proceed vigorously in the development of a program on alkaloid synthesis
and plant biochemistry, since these areas are of great interest to a
balanced program in cellular pharmacology.

The scientific efforts of the Laboratory have continued to
center along three main lines:

1. Studies on biological methylation,

2. Studies on amino acid metabolism,

3. Studies on comparative biochemistry.

It has been pointed out in earlier reports that these three
broad areas have been selected because of their central importance
in basic biochemical research and because of their special relevance
to problems of cellular and neuro pharmacology. Since the Laboratory
is a relatively small and tightly knit research group, we favor close
and frequent exchange at the intellectual as well as at the technical
level between the various staff members. The development of an
atmosphere of mutual interchange has been facilitated also by the
fact that the chosen areas of study represent different facets of
a broad, continuous research spectrum rather than exploration into
entirely separate fields. It will be seen from the detailed analysis
below that many of the projects are listed as belonging to more than
one of these three areas .

- 58 -

Biological methylation; As has been pointed out in earlier
reports"^ the wide biological significance of transmethylation reactions
is reflected in the universal distribution of methylated compounds
in great variety and at all levels of biological organization.
The central role played by the amino acid methionine in transmethyla-
tion reactions has been emphasized in recent years by a series of
discoveries from this Laboratory and others throughout the world.
Transmethylation reactions are involved or play a part in the bio-
synthesis of substances of particular interest to neuropharmacology
such as the neurohormones, the alkaloids and some of the vitamins
and steroids.

It has been recognized that transmethylation reactions
in particular, and transalkylation reactions in general, have some
features which may be considered of general interest in energy
metabolism and possibly cellular transport mechanisms. This might
be of particular relevance to basic research in neurology since
cellular transport mechanisms play such a key role in mechanism of
conduction and transmission of the nervous impulse. While Projects
1, 2, 3, 4, 11, 12 and 15 contribute particularly to this general
area they also contribute to other important areas of biochemical
research. For instance Dr. Durell and Cantoni's studies on the
synthesis of methionine by enzymatic transmethylation are of parti-
cular interest to students of protein chemistry since the purified
homocysteine thetin methylpherase has been found to undergo a
sulfhydryl dependent polymerization reaction which is essentially
without precedent but which is potentially of very great significance
in our understanding of the cytochemical architecture of the cell.

Amino acid metabolism: A study of the intermediary metabolism
of amino acids and of proteins offers great possibilities for contri^
butions at the basic level of biochemical research and for the
development of a program on cellular regulatory mechanisms. It
has become increasingly clear in recent years that many among the
physiological cellular regulators such as neuro hormones, polypeptide
hormones, and plant hormones are derived directly from amino acids.
Studies on the metabolism of amino acid are also related to com-
parative biochemistry because one of the characteristic features
of mammalian metabolism as opposed to the metabolism of lower species
is the relative inability of the mammal to synthesize amino acids.
Finally, studies in the areas of amino acid metabolism are of
particular interest to mental health since in nvimerous mental and
neurological diseases there is evidence of derangement in the
metabolism of amino acids. It is particularly noteworthy, in "t;his
connection, to emphasize the important contributions of Dr. Kaufman's
studies on aromatic hydroxy lation reactions. These studies have
lead to the discovery that a hitherto unrecognized cofactor is
involved in the conversion of phenylalanine to tyrosine. Much progress
has been made towards the elucidation of the structure and function
of this cofactor and it is of interest to note that progress at the basi(
level has been paralleled by increased interest in the biochemical

- 59 -

etiology of the disease oligophrenia phenylpyruvica, a disease which is
characterized by a genetically determined inability to metabolize
phenylalanine. Dr. Kaufman's important contributions have advanced
our understanding of the disease and contributed greatly to the general
area of neurochemistry .

Another area of research which relates, in part at least, to
amino acid metabolism is protein synthesis. In the course of the
last year the Laboratory has developed a major interest in this rela-
tively new area of research, and is gradually attempting to find its
own experimental approach to it.

At the present time it appears possible to make a fruitful
beginning at an enzymatic level by studying systematically the various
steps which are postulated to occur between free amino acids and a
completed biologically-active protein. In reality only the very
initial phases of this complex sequence of reactions can be visualized
and studied in detail and it is hoped that as progress is made the
next steps will become clearer. The overall problem is a most diffi-
cult and challenging one, for proteins are the most complex and fragile
polymers known in nature. The problem of protein synthesis is in-
timately related to the problems of protein structure, of biosynthesis
and function of the nucleic acids, and less directly to the challenge
of biochemical genetics, chemical morphology and biological evolution.

Although practically all of the work of the Laboratory deals
with amino acid metabolism in general, Projects 5, 8, 7, 8, 9, 10,
,13 and 14 contribute more directly and specifically to this field.

Comparative biochemistry: As was pointed out in earlier reports,
the relationship of comparative biochemistry to cellular pharmacology
is one of the foundations of the scientific philosophy of this
Laboratory. A research program in comparative biochemistry can be
developed favourably through a long term general interest supplemented
with intermittent specific contributions.

Thus implications for comparative biochemistry constitute a
recurring, albeit minor, theme in many of the projects which can be
specifically classified as contributing to the problem of protein
synthesis, aromatic hydroxy lations , enzymatic transmethylation, etc.
More directly pertinent to comparative biochemistry are Dr. Mudd's
studies on the MAE in yeast and Dr. Jamieson's studies of sulphate
utilization in Chlorella as are Dr. Kaufman's studies on the metabolism
and enzymology of phenylalanine in man.

BIOMETRICS BRANCH
ANNUAL REPORT FOR CALENDAR YEAR 1957

General

The Biometrics Branch has made continuing progress in each phase of
its program which consists of the following activities; (a) collecting,
processing, and analyzing data on the extent of the problem of the mental
disorders , particularly with regard to patients under treatment in mental
hospitals , in outpatient psychiatric clinics , in general hospitals with
psychiatric services, and in public and private institutions for mental
defectives and epileptics; (b) providing consultative services to State
research bureaus on the organization of statistical services on the design
of follow-up, evaluative and other special studies; and (c) providing con-
sultative services on design of experiments, analysis of experimental data,
development of mathematical models to the other Branches and laboratories
of the Institute, particularly to personnel engaged in basic and clinical
researcho

During the year a reorganization of the Branch was carried out in
line with recommendations made in the recent Manpower Utilization Study
of the Branch's activities. The Current Reports Section was subdivided
into three separate sections so that the Branch now consists of the follow-
ing: Hospital Studies Section, Outpatient Studies Section, Consultation
Section, Section on Applied and Mathematical Statistics, and Community
Studies Section,

The Branch has made considerable progress in the collection of data
on patients under treatment in mental hospitals and clinics , Nevertheless ,
the task of collecting data on the fate of patients admitted to such faci-
lities remains an extremely difficult task because of the lack of certain
essential knowledge on the etiology and epidemiology of the mental disorders
and the absence of instruments that can be used in comparable fashion from
institution to institution to determine severity of illness and to characterize
the psychologic status, the degree of psychiatric disability, social and
familial adjustment and physical condition of patients at various intervals
following onset of disease. As more new therapeutic programs (drugs, use
of day and night hospitals, half way houses, open hospitals, etc) and
treatment facilities are introduced into hospital and community programs,
the task of obtaining data on people under treatment becomes increasingly
difficult and complex, and data derived from separate treatment facilities,
such as public mental hospitals and clinics and psychiatric services in
general hospitals, become increasingly difficult to interpret. It has become
quite apparent that state mental health and state mental hospital authorities
must develop statistical reporting programs that will coordinate basic data
on patients tinder treatment in all known psychiatric treatment facilities
in their jurisdictions and will include appropriate follow-up data
on the various classes of patients. The Branch has been working with states
to iB^rove reporting within public mental hospitals and clinics. This job

- 2 -

is far from complete and we plan to continue our work with states to improve
hospital and clinic reporting, to de-rolop nrethods that will reflect changes
resulting from new treatment programs and concepts. In addition we will
intensify our efforts to devise methods for collecting coordinated data on
patients under treatment in all psychiatric facilities within defined
geographical areas c

The Branch is also taking step$ to program certain of its operations
for the IBM electronic computer „ The availability of this machine will
make it possible to produce more quickly certain data on patients under
treatment in psychiatric facilities and to permit more detailed and rapid
analysis of certain types of data involving computation of decrement tables,
rates, correlation coefficients and other types of coniputations ,

The services of the Section on Applied and Ifethematical Statistics
continue to be in increasing demand by the investigators in the basic
laboratory and clinical research programs of the National Institute of
Mental Health. Tlirough a'n arrangemeirt iiltli 'the "oicnetrics Branch' of tEe
National Institute of Neurological Diseases and Blindness, this section
also proviies similar services for the scientists of that Institute.
This section has carried out its own research activities developing several
new techniques in multivariate analysis which are helpful in the analysis
of profile data and in the analysis of variation c The Section intends to
provide liaison services between investigators in laboratories and branches
of NIH who plan to collect extensive data and personnel in NIH developing
programs for the electronic calculator scheduled to start operating at NIH
during 1958<, This section is also contemplating the possibility of initiat-
ing investigations into mathematical biology and information theory becs.use
of the significance of such research in various aspects of tha raeistal hef.lth
field o

The Coramurxity Studies Section has not, as yet, been activated due to
difficulty in recruiting a staffs particularly a person to direct its acti-
vities o Active attempts will continue to recruit appropriate personnel for
this important aspect of the Branch's activities,

A problem that makes the achievement of results in the biometrics
field slow is the shortage of well-qualified personnel to fill positions
both in the National Institute of Mental Health and in the field. Not
all states have bureaus of statistical research within state departments
of mental hospitals and mental health, and only a few of the states with
these departments have well-trained people. To improve this situation
at least two things are needed. First, directors of state mental hospital
and health programs must be willing to give strong support to the develop-
ment of adequate statistical research programs. Second, they must be
willing to pay salaries at a sufficiently high level to attract well-
trained and imaginative people into the field. Third, steps must be taken
to increase the pool of trained analytic and mathematical statisticians
to fill the increasing need for such personnel in action and research
programs in the mental health field. The NIH has taken steps to attempt
to alleviate the shortage, starting a grant program designed to develop
training centers for biometricians throughout the Nation and for giving
fellowship support to promising students.

- 3 -

The major part of the Branch has been separated from the National
Institutes of Health reservation for somewhat more than two years. Although
the office space in the Perpetual Building is satisfactory, there are still
many problems involved in developing an efficient office arrangement because
of the separation of the offices over three floors of the building and the
fact that even on the same floor all offices are not contiguous. The staff
in the Perpetual Building feels keenly the separation from the Institute
because of the lack of frequent contact with the professional and other
personnel in the various branches of the Institute and the lack of contact
with personnel in the other Institutes on the NIH reservation. The Chief
of the Branch spends a fair amount of his time traveling between T-6 and
the Perpetual Building to attend executive staff and other meetings on
projects in which the Biometrics Branch has a definite interest. The
Branch hopes sincerely that steps can be taken in the not too distant
future to bring it back onto the NIH reservation.

The reports of the individual sections follow;

HOSPITAL STUDIES SECTION

During the year the Hospital Studies Section continued its work in
further developing the Model Reporting Area for Mental Hospital Statistics,
carrying out cooperative studies with individual hospitals and state mental
hospital systems on methodology of cohort studies and developed new tech-
niques needed to gather information which would permit more meaningful
analyses of trends in the movement of mental hospital populations.

Seventh Annual Meeting of Mental Hospital Statisticians. The 18
states in the Model Reporting Area held their 7th Annual Conference in
Washington, D, C, in May 1957, The conference concentrated on interstate
comparisons of cohort studies giving probabilities of first significant
release during the first 12 months following admission, re-evaluation of
basic definitions of patient movement terms, and the need for more specific
annual and monthly data on the movement of patient populations in mental
hospitals.

Cohort Studies , Implementing a recommendation of the 1956 meeting,
11 states completed cohort studies in which groups of first admissions in
specified age, sex, and diagnostic groups (schizophrenia and mental disorders
of the senium) were followed during each of the first 12 months of hos-
pitalization to determine probabilities of release, death, or retention.
The data showed considerable variation among states in release, death, and
retention rates for each category of patients. A committee reviewed these
findings during a meeting in January 1957 and developed a list of factors
which might account for these differences, such as screening facilities
in the community, legal requirements, administrative policies, type of
patient admitted ana severity of illness. The committee recommended that
these cohort data be published including data from each state that might
make it possible to partial out the effect of some of these variables and

- K -

emphasizing the problems inherent in interstate comparisons of mental hospital
datao The Conference approved the recommendations of the committee and the
Section staff is now preparing these data for publication.

It is significant that eleven states have now carried out these
studies when as recently as five years ago no valid measures of mental
hospital release rates were available on a statewide basis.

The Biometrics Branch has continued to work with the Warren State
Hospital, Warren, Pennsylvania. Data are being obtained that will make
it possible to analyze the experience of cohorts of first admissions to
this hospital during the period 1916-55, not only by age, sex, and diagnosis
but also by such variables as urban-rural residence, occupation, marital
status, therapies, etc, and to determine readmission rates to the hospital
after specified periods of time following release by these variables. It
is expected that some analysis of the data for the period around 1950 will
be completed within the next few months .

The Branch continued its cooperative study with the Department of
Mental Hygiene of the State of Virginia of first admissions to state
mental hospitals of that state over the period 1952-55. Cohorts of
released patients will also be studied to determine probabilities of
return to the hospital within a specified number of months after release.
In order to obtain a~more adequate base for computing such probabilities,
a search of the death certificates in the Virginia Department of Health is
being carried. out for all patients released alive from the hospitals. This
will also permit the computation of death rates within specified periods
of time after admission regsirdless of whether the patient died in the
hospital or outside of the hospital. Preliminary analyses have indicated
some very interesting differences between the various age, sex, and racial
groups.

Another cooperative study with the California State Department of
Mental Hygiene on the ejqserience of first admissions to the Pacific State
Hospital during the five-year period, 194-9 to 1953, was completed during
the year. The study was the first cohort study ever conducted on patients
admitted to institutions for the mentally deficient. The findings indicate
that thdre were striking differences in release rates by age, I.Q., and
diagnosis. For patients with I.Q. under 20 only 1% were released within
4- years following admission, whereas for patients with I.Q. of 70 or over,
12% were released within 4- years. Among patients in the age groups 14.-
17 years, 60-70^ were released in the first 4- years, while among those
under 5 years of age, only 12^ were released. Patients with diagnoses
of undifferentiated or familial mental deficiency had release rates of
55-60^, while those with diagnoses of mongolism and developmental cranial
anomaly had release rates as low as 10-15^ but had high death rates of
27-28^, A paper Incorporating the methodology and results of this study
was prepared cooperatively by the Biometrics Branch and personnel from the
Pacific State Hospital and was presented at the annual meeting of the
American Association for Mental Deficiency in May 1957. The results of
this study fiave served as a starting point for a more Intensive research

- 5 -

project on the factors influencing the prognosis in mentally deficient
patients admitted to Pacific State Hospital. The National Institute of
Mental Health is supporting this research through a special grant.

Trends in Public Mental Hospital Populations. A study was carried
out in which the movement of patient populations in public mental hospitals
in 1956 was compared to what would have been expected on the basis of
the trend over the period 194-5-1955. While the analysis of the gross
data indicated that the number of resident patients in public mental
hospitals of the nation at the end of 1956 was lower than would have
been expected on the basis of the trend in the period 194-5^1955, data
needed to assess the factors responsible for this decrease were not
available. The gross hospital data on the movement of patients must
be made specific for such basic variables as age, sex, diagnosis, and
length of hospitalization, etc., and state mental hospital systems
have, with minor exceptions, never developed techniques to produce
such tabulations. The section developed a method to solve this problem
using data at Saint Elizabeths Hospital to determine release ana death
rates among groups of patients according to such variables as age, sex,
diagnosis, length of stay, marital status, race, and type of commitment.
It is planned to work with several other states to develop similar analyses
so that more adequate interpretation of interstate comparisons of trends
in mental hospital population movement can be made. Indeed, this studjr
emphasized that obtaining the facts necessary to quantify the impact of
tranquilizing drugs and such other therapies and programs as mav be
developed in the future on the mental hospital requires the revision
of existing statistical systems in mental hospitals to provide appropriate
intrahospital data. But equally as important, programs must be developed
which will coordinate data on utilization of all community treatment
facilities so that the role played by the mental hospital can be studied
in relation to that played by these other community facilities in the
treatment and rehabilitation of the mentally ill.

Monthly Reporting. Monthly reporting of gross public mental
hospital population movement by the states in the Model Reporting Area
was begun in December 1956 to obtain mental hospital population move-
ment data on a more highly current basis and to see whether striking changes
are occurring, to consider the effect of seasonal variation in the analysis
of changes in the movement of these populations. Examination of the data
collected during the first 10 months Indicates considerable variation in
the movement of these populations from one month to the next and also
considerable variation among states. However, until data have been
accumulated for more than one year it will not be possible to determine
what proportion of the change from one month to the next is due to
seasonal variation and what proportion is due to other factors . Such
information will begin to emerge during early 1958.

Mortality Studies. Tabulations of the niunber of deaths occurring
in public mental hospitals in 1955 were made available to the Biometrics
Branch by age, sex, mental disorder, and cause of death by 17 states in
the Model Reporting Area. An analysis of the data is presently under way,
using the IBM 65O computer, to determine age and cause specific death rates,

- 6 -

percentage distributions of deaths by cause and the ratio of hospital
deaths and death rates to deaths and death rates in the general popula-
tion. Preliminary findings indicate a marked variability in the distri-
bution of causes of death between the various age, sex, and mental
diagnostic groups and considerable variation by state. However, certain
patterns do emerge. Deaths due to arteriosclerotic and degenerative
heart disease account for the greatest percentage of all deaths, with
deaths from pneumonia the next highest. As would be expected, over 3/5
of all deaths occurred in the age group 65 years and over. The death
rates in the mental hospitals are higher than the corresponding rates
in the general population.

In addition to studying the death experience of the mental hos-
pitals of the 17 states, this study provided valuable experience in the
programming of vital statistics calculations on the IBM 650. This ex-
perience will be particularly useful in programming data for the pre-
paration of the annual census of patients in mental institutions.

The Third Midwest Conference on >fental Health Statistics. This
conference was held at Lansing, Michigan, in October 1957, Much of the
discussion centered around a refinement of interstate comparisons of
gross data on mental hospitals ana institutions for the mentally deficient
in the Midwest. In addition, the following were among the topics dis-
cussed; analysis of mental hospital population data; measures of effective-
ness of hospital programs; recommendations for consideration by the
Committee on Definitions of the Model Reporting Area and reports of
research projects in the various states. These meetings are an outgroT^h
of the annual meetings of the Model Reporting Area and since representatives
from midwestern states who are not members of the Model Reporting Area are
also invited, interest in sound statistical procedures in mental hospitals
has been stimulated in these states

CONSULTATION SECTION

The objectives of the Consultation Section are to establish
efficient records systems, to promote use of comparable terminology and
definition, and to facilitate data reporting and data analysis. Imple-
mentation involves providing consultative services in setting up a records
and reports system or reorganization of out-moded and ciimbersome records
systems .

By furnishing advice and assistance in research design and data
analysis, the Section not only aids in procuring much needed information
but stimulates other states to engage in research by establishing working
models, methodological techniques, and, occasionally, resources.

The following states requested and received consultative services
regarding improvement of their central office, mental hospital, or out-
patient psychiatric clinic records systems or on matters regarding research
design, program evaluation, and data analysis: Delaware, Florida, Georgia,
Kentucky, Maine, Jfessachusetts, Michigan, and Ohio.

- 7 -

Specific examples of assistance furnished by the Section upon request
of state or local mantal health agencies or facilities are briefly presented
be lows

The Institute in Jackson Memorial Hospital, Florida, and the clinic
attached to Tampa General Hospital, Florida, requested assistance on develop-
ing methods to furnish the Biometrics Branch with the data requested annually.
The problem stemmed from the fact that the out-patient psychiatric clinics
were part of a generalized medical care program and the record systems used
in these clinics were part of the total hospital record system. A plan was
devised for incorporating a form for psychiatric clinic data into the basic
record system.

Assistance was given to the superintendent and staff of South Florida
State Hospital with regard to setting up a records and report system. The
request was unique inasmuch as it was tendered by the superintendent before
the official opening of the hospital. Consultation in this case was parti-
cularly satisfying since discussions regarding a records system were
unencumbered by an existing records system.

At the request of the superintendent of Plneland Hospital and Train-
ing Center, Maine, a school for the mentally retarded, their ciur-rent records
and reports system was reviewed. The superintendent was Interested in
establishing an IBM machine punched card system to be used for administra-
tive and research purposes, A statistical system utilizing an IBM key punch
and card count sorter with schedules, coding and punching instructions was
provided for his use.

Consultation services were also provided to the Kentucky Department
of Mental Health and the hospitals they supervise in the revision of its
records and reports system. This reorganization was to a large degree
prompted by their desire to qualify for admittance to the Model Reporting
Area. This state has applied for admission to the Area.

Several projects on the evaluation of drug therapy in the hospital
setting and' in a home care program were reviewed with the Clinical Director
of the Delawai^e State Hospital and members of his staff. Suggestions
regarding use of cohort methods in analysis of follow-up data were made.
Discussions were also centered about the use of concurrent and historical
controls in clinical trials. A form was designed to be used In a visible
file register to guide follow-up of patients and to present. Information
rapidly on the status of patients in the project.

The Chief of the Research Section of the Michigan Department of'"'"'^
Jfehtal Health requested- advice on' t'hfe collection: and analysis of research
data on patients under' treatment in the... hospitals and clinics of that '
state.'- Among the studies- .that .were reviewed v/ers ones on rates' of first
jadmission to their hospitals and another on the evaluationbf the' public
^alth nursing' services to t'he families of hospitalized, mental patient
and to the patients themselve^s wheja ihey are released to the community.

Consultative service was requested; by the Georgia Departm&nt of
Health in relation ..to the evaluation -of "two ■■programs. .One program'
Involved public health nursing services to families of the mentally llx;

the other program pertained to general hospitals providing diagnostic and
treatment facilities for the mentally ill. The fornEr program had been
in operation for several years. The problem was to devise forms and set
up procedures which would enable them to collect certain basic data that
would enable them to ascertain to what degree such services were being
utilized as con^Dared to an optimiim utilization. Reasons for low utilization
in given areas could then be investigated. Modifications in the existing
methods of collecting data and in maintenance procedures were made which
would permit the above requested administrative information to be readily
collected. Further recommendations were made concerning the collection
of individual patient and family data for research purposes.

So as to insure some built-in evaluation techniques into the other
program, the state department of health requested consultation in the
planning stage in order to include items which might indicate the degree
to which the program objectives were being met. Briefly stated, these
objectives were to reduce the number of patients going to the state mental
hospital from counties participating in the program, to return such patients
to the community more quickly than could the state mental hospital and
decrease the number of readmissions. Since randomized controls which would
permit direct evaluation of these objectives was not feasible, several other
approaches in analyzing the accomplishments of the program were suggested.
These measures would throw some light on shifts in patterns of hospitali-
zation for communities with and without such mental health facilities.
Some revisions in the data forms and data collection procedures were made.
Models for data presentation and analysis were also presented.

The Chief of the S'ection is also supervising a contract study being
done by the Harvard School of Public Health for the Biometrics Branch.
This study will determine probabilities of release and return using two
different points in time ("significant" release or return and "standard"
release or return) for cohorts of admissions in the years 1900, 194-0, and
1950. The follow-up period is limited to five years after admission and
will consider such variables as age, sex, mental diagnosis, education,
marital status, etc.

The 1900 cohort has been coded and punched and some preliminary
analyses have been made by age, sex, and type of admission (first and
readmission) for l) entry hospital, 2) legal status, 3) marital status,
4.)birthplace , 5) occupation, 6) education, 7) usual type of household,
8) place from which admitted, 9) in hospital during year preceding admission,
10) cause of death. A detailed cross -tabiolation by age, sex, diagnosis,
and type of admission was also made. These analyses formed the basis for
determining how to group certain variables and which cross -tabulations
would be practicable for the more detailed analysis.

The Section also reviewed the records system of the Ohio Depart-
ment of Mental Hygiene and Correction. As part of this review, data
on first admissions during the years 194-8-1952 are being correlated with
pertinent 1950 census information enabling the computation of admission
rates by such factors as age, sex, color, marital status, education,
occupation, resident (urban-rural, metropolitan-non-metropolitan, county),

mental diagnosis, etc. Proximity to state mental hospital facilities
and the effect of other mental hospital facilities on admissions to
state -operated hospitals is being considered. A portion of the find-
ings will be presented in a regional research conference to be held in
Ohio early next year. Subsequently, data involving discharge and
readmission will be analyzed.

OUTPATIENT STUDIES SECTION

Activities in this year have concentrated on the analysis of the
data being reported in the annual statistical reports from out-patient
psychiatric clinics and providing assistance in extending reporting of
information on patients to an increased proportion of the clinics in
all states, furthering the standardizing of definitions, putting into
effect the plan that is to provide the National Institute of Mental Health
for research study, duplicate standard punch cards that include data on
each terminated patient, and on the development of a plan for a special
study on the socio-economic characteristics of clinic patients in I960.

A conqjrehensive analysis of data on clinic characteristics and the
number and type of clinic staff and man-hours reported by 95 percent of the
1,234- clinics in 195^-55 was completed and is being published in December
1957 as a Public Health Monograph.

"A Manual on Recordkeeping and Statistical Reporting for Mental
Health Clinics" has been published and is being made available to Regional
offices, states, and clinics,

A resToms of the xjorkshop on "Concepts in Mental Health Reporting"
at the annual meeting of the Aisrican Orthopsychiatric Association was
published in the Journal of the Association and reprints made available
for distribution to the states by the National Institute of Mental Health.

The subcommittee on Reporting of Diagnostic Classification for
Children attended by representatives of the American Psychiatric Associa-
tion Committee on Nomenclature and Statistics, American Orthopsychiatric
Association, and several other child guidance clinic representatives and
representatives of the Children's Bureau and other branches of the National
Institute of Mental Health met on September 12-13 to discuss problems on
reporting diagnoses for children.

Data on the patients and services they received in outpatient psy-
chiatric clinics for about 380 clinics were reported for the year ended
June 30, 1955. The reporting clinics, comprising about one-third of the
total number of clinics in the country, do not represent a probability
sample of all clinics and generalization from the findings cannot be
made to the total clinic patient population in the nation. These first
reports on the charactieristics of patients and their services, however,
provide within this important limitation some preliminary information on
patients. Briefly summarized, some of these data show the following;

- 10 -

1. Of each 10 patients terminated during the year, 3 received
diagnosis and treatment, U received diagnosis only, and 2 had received
other services only, that is, only an application interview, partial evalua-
tion, psychological testing, etc.

2. The bulk of the terminated patients - about 8 of each 10 - left
clinic service after less than 10 interviews with a professional staff
member. More than 2 in 10 had only one interview, and almost U in 10 had
2 to /+ interviews .

3. When the patient was an adult, most interviews were with the
patient; only 1 in each 10 interviews was with a spouse or other person
about the patient. When the patient was a child, only half the inter-
views were with the child patient; U in each 10 were with the parent or
parent substitute, and 1 in 10 was with some other significant person
about the patient.

U. Not quite a fovirth of the terminated patients, either because
they came for services other than diagnosis and treatment or because they
did not continued their visits, were iindiagnosed when terminated. For
children with a psychiatric disorder, transient situational personality
disorder was the most frequent diagnosis - 36 percent. Personality
disorders (21^); mental deficiency (18^); and Psychoneurotic disorders
(13^) also comprised fairly large groups. Among the patients 18 years
and over with psychiatric disorder, personality disorders (29^); psycho-
neurotic disorders (28^), and psychotic disorders (24-^), were most
prevalent.

5. The 1955 data on patients made possible for the first time an
estimate on total patients using outpatient psychiatric clinic facilities.
On the basis of the number of clinic patients served per man-hour of pro-
fessional staff time in the reporting clinics and earlier reports on
man-hours of service in all clinics, it has been estimated that 197,000
patients under 18 years of age and 166,000 patients 18 years of age and
over used clinic service sometime during the year ended June 30, 1955,
in continental United States. These very rough estimates provide a
clinic usage rate of 355 for each 100,000 pop\ilation under 18 years of age
and 155 for each 100,000 population 18 and over.

Data on patients for the year ended June 30, 1956, were reported
for almost 500 clinics --about 100 more than reported for 1955, and these
represent about two-fifths of the 1,294- clinics in the United States in
1956. These reports are being processed for tabulation and analysis. Of
the reporting clinics , 237 also prepared special tables that provide
additional detailed information on some items and cross tabulations of
other data that will make possible a more complete analysis of the data
for 1956.

- 11 -

The uniform duplicate punch card plan designed to provide data
on each terminated clinic patient to NIMH to facilitate national research
was put into effect. Thirty-six states with punch card procedures are
participating in the program. Approximately 100,000 cards, that is, data
for 100,000 patients terminated during the year ended June 30, 1957, in
4.77 clinics will be received by NIMH during the last quarter of 1957.
Plans are being made for taking national samples of patients with selected
characteristics for special analysis. Plans are being considered for
additional studies to be made in cooperation with the states in order to
obtain further information on these patients. Present plans include the
submission of duplicate standard punch cards again in I960.

Plans are being developed for the collection of information on
socio-economic characteristics of patients admitted to clinics for a
specified period in i960 to be related to the population census in I960.
To date 20 States have indicated an interest in participating in such
a study and additional states are expected to indicate interest; 5 have
reported that they cannot participate. Some of the socio-economic charac-
teristics of patients for which information may be collected are education,
employment status, occupation, income, mobility, urban-rural (and census
tract) residence, marital status, nativity, family size and composition,
housing, etc. The data will provide rates of admission from the various
socio-economic groups as well as relationships between socio-economic
characteristics and diagnosis, outcome after treatment, services received,
number of interviews, etc.

SECTION ON APPLIED AMD MATHEMATICAL STATISTICS

During the year the section has continued to assist and consult
with investigators on statistical, mathematical, and biometrical problems
arising in various investigations carried out by the laboratory and
clinical scientists at NIMH as well as scientists who are working in
mental health problems outside NIMH. These services provide the scientists
with the most efficient and valid statistical techniques available in the
design and analysis of data. The section has been consulted on a large
variety of subjects including experiments on the effects of various drugs
on psychiatric and sociological functions in animals and in man 5 investi-
gations in electrical conductivity, sections and resections, and vascularity
of nerve tissue; studies in reaction time; continuous performance tests
on various groups of people; surveys on interactive patterns among socio-
economic groups and among the emotionally disturbed; and continuous con-
sultation has been provided to the multidisciplinary aging project.

The section has developed new techniques in mathematical statistics
especially in multivariate analysis which are helpful in the analysis of
profile data and in the analysis of variation. Advice has been provided
to various committees with regard to grants, surveys, and proposals in
the field of mental health. The Section has also reviewed manuscripts
arising within the Institute and has served as referee on papers submitted
for publication in statistical journals .

- 12 -

The section proposes to continue consultations with these investi-
gators already begun and to continue to aid the Psychopharmacology Service
Center to obtain definitive evaluations of new drug therapies in mental
illness. Next year we intend also to provide liaison services between
investigators in the laboratories and branches of NIMH who plan to
collect extensive bodies of data and the machine programmers of the
electronic calculator which has been procured for NIH. The section is
also contemplating the possibility of initiating investigations in
mathematical biology and information theory because of the significance
of such research in various aspects of the field of mental health.

In addition to providing a variety of statistical and mathematical
services to research and clinical investigators of NIMH, this section has
also been called into consultation by investigators outside NIMH working in
mental health. These services include consultations in the design of
experiments, the analysis of data, and mathematical models underlying
the data. The section has served on and provided advice to various com-
mittees in NIMH as well as reviewing and refereeing papers in the dis-
ciplines involved in mental health.

Some examples of the investigations in which this section has par-
ticipated by providing consultations in design and analyzing data are:

1. Experiments on the effects of various drugs on psychological
functions in animals and man.

2. Experiments on the effects of certain nerve sections and
resections ,

3. Studies of various social and psychological relations in
socio-economic groups.

4-. Studies on a maternal attitude test.

5. Ecological investigations in animals.

6. Investigations of blood vessel density in various spinal
neur-al regions .

7. Studies in the methodology of behavioral observations.

8. Reaction time experiments in normal controls.

9. Experiments on the effect of tranquilizing drugs on
certain psychological and biochemical functions.

10. Comparison of brain damaged with normal groups on
Continuous Performance Tests.

11. Leadership studies in childrens camps.

12. Survey on job satisfaction at NIH.

13. Studies on the interactive patterns of emotionally dis-
turbed children.

- 13 -
14., Investigations on electrical conductivity of nerve tissue,

ACTIVITIES OF THE CHIEF OF THE BRANCH

During the year, the Chief of the Branch engaged in certain activi-
ties that might be noted. He was invited to lecture to the students and
faculty of the Department of Public Health of Yale University and to
conduct a seminar on problems of research in the epidemiology of mental
disorders o He was also invited to participate as a member of a study
group convened by the World Health Organization in Geneva from November 4-
to 8 to consider problems of the use of ataractics and hallucinogenic drugs
in psychiatry. While in Europe he was also invited to lecture at the
Institute of Psychiatry of the University of London at the Maudsley Hos-
pital on the collection of data on the mentally ill in the United States,
geographical variations in the availability of psychiatric personnel and
facilities, and the other activities in which the Biometrics Branch has
been engaged.

He also participated in the following conferences? l) A con-
ference on patterns of patient care called by the Joint Commission on
^fental Illness and Mental Health, Boston, March, 1957, 2) Conference
on coordinating community resources in psychiatric after-care sponsored
by Pennsylvania Mental Health, Inc, Philadelphia, April 1957, 3)
Conference on research in mental health sponsored by the Florida Con-
ference on Training and Research in ^fental Health, April 1957,

The Chief of the Branch has been designated to provide liaison
between the National Institute of Mental Health and the Epidemiologic
Intelligence Service Training Program at the Communicable Disease
Center in Atlanta, Georgia, In this connection he presented a paper
at the ^fe.y conference of the EIS and lectured to a training class of
EIS officers during August 1957 on problems of research in the epi-
demiology of mental disorders. The NIMH is supporting this training
program, and it is hoped that through our active participation we will
attract some of the trainees into epidemiologic research on the mental
disorders.

The Chief was also asked to confer with the personnel responsible
for the mental health training and research program being implemented
by the Southern Regional Educational Board. In this connection he
reviewed types of data that are available on the prevalence of mental
disorder and distribution of personnel and facilities in the seventeen
states that are members of the Board and made recommendations concern-
ing the development of adequate statistical services within the state
mental health programs of that region, the training of medical record
librarians, and the need for extensive studies within the states of
that area to throw greater light on regional differences in the utiliza-
tion of psychiatric facilities.

- 1^ -

The Chief of the Branch provides liaison between two special grants
being carried out in the California State Department of Mental Hygiene
and the NIMH. The first project, a study of suitability of out-patients
for treatment was completed in 1957 and a report has now been published on
this study by the California Department of Mental Hygiene. This report
has been issued as Research Report Number 1 of the California State Depart-
ment of Mental Hygiene,* The second project is being carried out at the
Pacific State Hospital at Pomona, California. This project includes both
an extensive research program investigating individual, familial, and
commiinity factors related to admission to and release from the institution,
and evaluating the effect of specific treatment and rehabilitation programs
within the hospital on the prevention of disability and the training of
patients for community employment. In addition, this project is being
used as a training center to attract into the field of mental retardation
high caliber research personnel in psychology, psychiatry, biometry,
sociology, and epidemiology.

Both the Branch Chief and the Chief of the Section on Applied and
Mathematical Statistics serve on the Psychopharraacology Advisory Committee.

A list of the publications of the Branch follows.

^Sampson, H., Ross, D., Engle B., Livson, F., A Study of Suitability for
Out-patient Clinic Treatment of State Mental Hospital Admissions. State of
California, Department of Mental Hygiene. Research Report No. 1, 1957.

Publications of the Branch

Bahn, A. K., and Norman, V. B,, Outpatient Psychiatric Clinics In the

United States: Characteristics and Professional Staff, 195/k-55. Public
Health Monograph No. U9 . Due December 30, 1957.

Bahn, A. K., and Norman, V. B., Outpatient Psychiatric Clinics in the

United States: Characteristics and Professional Staff, 1954--55. Resume
in Public Health Reports , December 194-7.

Geisser, S., The Distribution of the Ratios of Certain Quadratic Forms in
Time Series. Annals of Mathematical Statistics, Volume 28, Number 3,
pp. 724.-30, September 1957.

Geisser, S., A Note on McQuitty's Index of Concomitance. Journal of
Educational and Psychological Measurement. In press.

Geisser, S., and Greenhouse, S. W., An Extension of Box's Results on the
Use of the F Distribution in Multivariate Analysis. Submitted to the
Annals of Mathematical Statistics .

Halperin, M. , and Greenhouse, S. W. , Note on Multiple Comparisons for
Adjusted ^feans in the Analysis of Covariance. Biometrika. In press.

Hill, J. H., and Greenhouse, S. W. , Analysis of Plasma Proteins by
Turbldimetry: An Unsuccessful Aid in Cancer Diagnosis. Journal of
the National Cancer Institute. Volume 18, Niimber 2, February 1957.

Hospital Studies Section, Mental Health Statistics, Current Reports:
Patients in Public Hospitals for the Care of the Mentally 111, 1956
and 1957. Series MHB-H-3.

Hospital Studies Section, Jfental Health Statistics, Current Reports:

Patients in Public Institutions for Mental Defectives and Epileptics.
Series MHB-I-2, 1955. Series MHB-I-3, 1956.

Hospital Studies Section, Mental Patient Data for Fiscal Year 1956.
Public Health Reports , Volume 72, Number 1, January 1957,

Hospital Studies Section, Patients in Mental Institutions, 1953, Part III:
Private Hospitals for the Mentally 111 and General Hospitals with
Psychiatric Facilities. PHS Publication No. 495, Part III.

Hospital Studies Section, Patients in Mental Institutions, 1953, Part IV:

Private Institutions for Ifental Defectives and Epileptics. PHS Publication
No. 495, Part IV.

Hospital Studies Section, Patients in >fental Institutions, 1954, Part I:
Public Institutions for Mental Defectives and Epileptics. PHS Publi-
cation No. 523, Part I.

- 15 -

- 16 -

Hospital Studies Section, Patients in Mental Institutions, 1954-, Part II:
Public Hospitals for the I^ntally 111. PHS Publication No. 523, Part II.

Hospital Studies Section, Patients in Mental Institutions, 195A, Part III;
Private Hospitals for the tontally 111 and General Hospitals with
Psychiatric Facilities. PHS Publication No. 523, Part III.

Hospital Studies Section, Patients in Mental Institutions, 1954-, Part IV:

Private Institutions for Mental Defectives and Epileptics. PHS Publication
No. 523, Part IV.

Hospital Studies Section, Progress in Reporting Ifental Hospital Statistics.
Public Health Reports , Volume 72, Number 9, September 1957.

Kramer, M. , Problems of Research on thf Population Dynamics and Therapeutic
Effectiveness of >fental Hospitals. Chapter IX, pp. 145-172, in The
Patient and the >fental Hospital. Greenblatt, et al., editors. Free
Press, Glencoe, 111., 1957.

Kramer, M. , Statistical Studies of Mental Hospital Populations. Chapter
8, pp. 68-83, in I^ntal Health and the World Community. Prof, F.
Brockington, Editor. World Federation for lyfental Health, 19 Manchester
Street, London W. 1., 1957.

Kramer, M. ; Person, P. H.; Tarjan, G.; Morgan, R.; Wright, 3., A Method
for Determination of Probabilities of Stay, Release, and Death for
Patients Admitted to a Hospital for the Mentally Deficient: — the
Experiences of Pacific State Hospital Dincing the Period 19^8-1952.
American Joirrnal of Mental Deficiency, Volume 62, Nvmiber 3, pp. 4-81-4.95,
1957.

Kramer, M. , and Pollack, E. S., Problems in the Interpretation of Trends
in the Movement of Mental Hospital Populations. Presented at the annual
meeting of the American Public Health Association, November 15, 1957.

Kroll, B. H., and Goldstein, H., Methods of Increasing Ifeil Response.
Journal of Marketing. VoIuhb XXII, Number 1, July 1957.

Outpatient Studies Section, A Manual on Recordkeeping and Statistical
Reporting for Ifental Health Clinics. PHS Publication No, 539.

Pasamanick, B., and Kramer, M. , Designs for Scientific Studies to Estimate
Need for Beds for Psychiatric Inpatient TreatnKnt Facilities for Children.
Chapter 6 in Psychiatric Inpatient Treatment of Children. American
Psychiatric Association, Washington, 1957.

NATIONAL INSTITUTE OF MENTAL HEALTH

Biometrics

BUDGET SHEET

Total: $329,253
Directs $316,478

Reimbursements ! $12 , 775

Axmual Report - 1957
Clinical Investigations
Ifeitional Institute of Mental Health

Previous assnual reports have described in considerable
detail the rationale for the current organization of the
Clinical Investigations program. Our research efforts 'have
been directed on the one hand towaird improvenjents in treat-
meat methods for a variety of psychiatric disorders, and on
the other toward making contributions to a better iinderstand-
ing of the factors which influence normal personality develop-
meat and behavior,, Certais studies from each of the branches
and laboratories were described in order to indicate the scope
of their research, ajsd particularly the areas in which collab-
oration between several disciplines was involved.

In the four asd. one -half years since the first ward was
opened to patients^ the general areas of interest of each
research group have grad'^oally beea defined » These axe still
subject to change, depending as they do upon developments in

the field, on the Eatiire of the Clinical Center setting^ ajad
on the special skills of the staff. Nevertheless, all the
branches have by EOt^' decided upon one or m&i'e major projects
to which they have committed their resources. The mala
portion of this r-sport is devoted to descriptions by their
chiefs of the aetivitiss of the branches asd laboratories.

Duriag the past year we have bees fortunate in the
appoiatments of outstanding investigators to fill the two
major sta^f vacaacies. Iia September Dr. Joel Elkes reported
as Chief of the Clinical leuropharmaso.los'' Research Cemter,
which is being developed isa eollaboration with St. Elizabeths
Hospital. Dr. Elkes v&s Profsssor of Experimeffl'bal Psychiatry
at the University of Birmingham^ Eagland;, where he initiated
a remarkably well-iategratsd program of psychiatric research
ramging from the psychological to the aaaatcaiaical bases of
behavior. At t&e end of Deeerober at the teirroisatiom of his
fellowship at the Center for Advamced Study in the Bskavioral
Sciences^ Dr. David. Baffiburg will, come as Chief of the Adtilt
Psychiatry Branch. Frier to Ms fellowship. Dr. Haiuiburg had
served as Asisociate Director of the lastitute for Psychosomatic
&a& Psyckiatrls Research asd Training of Michael Reese Hospital.
Both Dr. Elkes aad Dr. Hambirg have made sigslficasit coatribu-
tions in their ispesial fields j is addition;, they are particularly
interested and essperiesc^d in the problems of int-ardisciplinary
researchi asd, fi'Ea.H^p they are ususually ccaapeteat admin-
istrators wfe-3 have dem-Dsstrat^d their ability to achieve a high
standard of research sophistication while at the same time
naitttaiaiag a sensitive aad effective clinical opsration.

-2-

Although it will obviously take at least two or three
years for Drs„ Hamburg and Elkes to build their branches to a
state of maximum efficiency, there are many immediate ad-
vantages which result from their arrival. They bring to the
group of laboratory and branch chiefs who are responsible for
the development of the Clinical Investigations program the
much-needed resources and the unique points of view gained
from their wide clinical and general research experience.
Further, it is now possible for the first time to make long-
term commitments of the clinical facilities which it will be
their responsibility to operate. This will open the way to
a whole range of studies within the clinical branches them-
selves and in collaboration with others, which have hitherto
been held in abeyance or pursued on a more or less intensive
pilot basis „

In a sense, we can say that the first phase in the or-
ganization of Clinical Investigations is nearing successful
completion. We now have within the group strong representa-
tion of the various disciplines which we conceive to be neces-
sary for the further development of theories of behavior and of
personality development,, Although later we should like to see
our clinical facilities expanded to include a small therapeutic
community- type hospital and a child institute, we already have
in the Clinical Center and in St. Elizabeths Hospital access to
reasonable flexible facilities which will enable us to set up
many situations for critical study » We are at last nearly
ready to essay an answer to the question of how best to organ-
ize and utilize these personal, professional, material, and
structural resources.

It should be made clear that we recognize, that there
are areas of autonomy for each of the behavioral sciences, and
we assume that certain advances will be possible only after
further progress in the individual disciplines. But in any
review of this total field it does appear that the areas be-
tween disciplines have been relatively neglected, and our
unique resources for collaborative studies impose upon us a
responsibility to pursue them where there is reason to believe
that they might be profitable. Even a cursory scanning of the
reports which follow will indicate that up to the present time
we have, at best, carried out some multidisciplinary rather
than interdisciplinary research - that is, in some studies
representatives of various disciplines working side by side
have collected data in certain experimental situations. This
I regard as a step in the right direction, and I believe that
we have done about as well as could be expected. In the early
life of most groups there is first the formation of a number

-3-

of sub-groups. Not only do the members of these sub-groups
tend to identify strongly with each other, but there is often
a tendency to exclude those vho do not share their point of
view. With varying intensity this has occurred among our
branches and laboratories. To some degree the breaking down
of these barriers will reflect the success the group of lab-
oratory chiefs achieve in finding some common ground.

Circumstances related to the necessity of starting a
clinical operation before some of its key personnel were ap-
pointed have resulted in two types of administrative organi-
zation within Clinical Investigations = Some of the branches
contain representatives of various disciplines: Child Research,
Clinical Sciences, and the Clinical Neuropharmacology Research
Center, Others are largely unidisciplinary: Adult Psychiatry,
Psychology, and Socio-Environmental Studies, The advantages of
the unidisciplinary type of organization are that it facilitates
strong identification with one's own discipline; evaluation of
proposed projects or of work in progress is apt to be more
sound; observations made in one area of the group's concern
are readily correlated with data gathered in others. A poten-
tial problem of this type of organization, however, is that it
may foster a relative lack of that type of commitment which is
absolutely essential in a clinical project where treatment
responsibilities are assumed in order to afford research
opportunities.

The multidisciplined branch does not have this problem
of commitment to the project; and since all of the investigators
are responsible to the same chief, the organizational lines for
efficient operation are clear. This may make for the earlier
effectiveness of such a group. On the other hand there is a
definite tendency to in-group formation with the resulting loss
of contact with others in the larger operation who are similarly
engaged. Sometimes in the interest of promoting mutual good-
will potentially productive differences are ignored; each
discipline becomes too "understanding" of the others; the
special competences of each tend to become blurred; and the
level of performance may sink to the lowest common denominator
in a setting where a pseudo-equality becomes a goal.

I do not believe that such problems as these can be
legislated out of existence by adopting a particular pattern
of organization. A continuing alertness to their development

-k-

is essential to their resolution, and our ultimate success
will depend on our frankness and our willingness to face them
when they do arise. But these are matters for the future.
The current status of our work is reported in the following
pages by the chiefs who are responsible for the development
of the studies in which we are engaged.

Robert A. Cohen, M. D.

Director of Clinical Investigations

National Institute of Mental Health

-5-

Adult Psychiatry Branch

Section on Ward 3-W

Dr„ Lymaji C. Vfynne

For the Adult Psychiatry Section working on Ward 3-W,
the past year has on the whole been transitional; it has in-
volved the rounding off of previous phases of research and
the planning of a new program which will be both more focused
in research objectives and more varied and expansive in the
approaches used to reach these objectives. The program of
this ward, viewed in over-all perspective since the opening
of the Clinical Center, has now completed a rather distinct
evolutionary stage. The program began with a rather large
number of psychiatrists using the ward individually for
quite numerous and heterogeneous projects. This permitted
a considerable variety of fruitful pilot studies, but a shift
to a more consolidated program seemed to have three major ad-
vantages: those studies which are continued can then have a
larger and more adequate sample of patient material, more
focused staff participation permits a more inclusive and
thorough penetration into questions which are particularly
significant; and the clinical operation of the ward can be
more readily integrated with the research.

Arising out of ongoing research on this ward has been
a heightened conviction that a crucially strategic area for
increasing our understanding of mental disorder lies in the
examination of family relationships. This conviction is in
accord with general clinical and statistical studies from a
half-dozen countries which have repeatedly confirmed the find-
ing that schizophrenics emerge almost exclusively from severely
disturbed homes — a finding which provides perhaps the most con-
sistent lead concerning etiology that has been found in any
kind of investigation of schizophrenia. In addition, early
familial experience has long been accepted as a pivotal factor
in determining personality development and deviation. However,
it is only recently that the details of how this generalization
applies to the genesis of schizophrenia has begun to be sub-
jected to systematic research scrutiny.

Research in this section has led to a preliminary speci-
fication of the nature of these familial influences in the
development of schizophrenia. This research has progressed from
clinical observations and an intensive pilot study of five

-6-

families of schizophrenics to the formulation of a series of
hypotheses which can be summarized as follows:

1. The parents of potential schizophrenics have
had serious difficulties in their own person-
ality development in achieving a sense of
personal identity — that is, a self-concept in
which they can clearly differentiate themselves
from others and which they can maintain over
time in a variety of relationships. Clinical
observations indicate that difficulties in
identity formation and threats to one's sense
of identity prevoke intense anxiety and strenu-
ous efforts to reduce the impact of such anxiety.

2. One way of dealing with such personality strain
is for the person to seize upon an interpersonal
relation that can have the continuity that per-
sonal identity lacks. Obviously, the parent-
child attachment offers an opportunity for such
a relation during the child's growing years,
especially if the child is relatively passive
and malleable for "constitutional" reasons.

The need to maintain such a relation in a parti-
cular form acquires all the emotional intensity
that is ordinarily associated with the mainten-
ance of personal integrity and identity.

3. Such relations, like all others, become structured
through interactional processes into par' icular
complementary or reciprocal roles. In relations
of the quality and intensity described, deviations
from expected roles have come to represent a threat
of explosive anger and recrimination.

l^.» The intense need for a sense of relatedness, to-
gether with the threat of its disruption, leads to
a particular kind of relationship in which open
recognition of even ordinary, inevitable divergence
from expected roles is strenuously avoided. The
resultant quality of relatedness has been summar-
ized in the concept of pseudo-mutuality. Pseudo-
mutuality involves a characteristic dilemma: di-
vergence from expected roles is perceived as lead-
ing to disruption of the needed relation, but if
divergence is avoided, new ingredients that would
permit growth of the relation and of the individ-
uals' personalities are excluded.

-7-

5. In the families of potential schizophrenics, it
is hypothesized that pseudo-mutuality of an
especially intense and enduring form character-
izes the acknowledged family relations » Legal
members of the family may be psychologically
excluded from the internally acknowledged family
role structure as it is perceived by the rest of
the family who are involved in pseudo-mutual
relations. However, the resultant quarrels and
schism between the acknowledged family and the
ostracized legal family member may be highly
functional for the organization of the family

as a whole as seen by an outside observer, who
can regard the scapegoat ing of someone as essen-
tial to the continuity of the pseudo-mutuality
in the rest of the family. In other instances,
other persons or events outside the family may
be scapegoated as a way of avoiding recognition
of internal family divergence. In still other
instances, legal outsiders, such as hospital
personnel, may be psychologically incorporated
into the family pseudo-mutuality and role
structure in order to facilitate its maintenance
for a time,

6. In addition, in the families of potential schizo-
phrenics, it is hypothesized that the intensity of
the necessity of maintaining pseudo-mutuality has
led to the development of a particular variety of
shared, family mechanisms by which deviations from
the family role structure are delusionally re-
interpreted or excluded from open recognition.
Further, the effectiveness of these mechanisms is
enhanced by a pervasive familial subculture of
myths, legends, and ideology which stress the dire
consequences of openly recognized divergence from
a relatively limited number of fixed, engulfing
family roles. ■'"- -ji-'.,':

7. In the families of schizophrenics these shared
mechanisms act at a primitive level in preventing
the articulation and selection of any meanings
that might enable the individual family member to
differentiate himself from the family role structure.
It is hypothesized that the resultant patterns of
interpersonal perception and communication become a
part of the offspring' s personality structure and
involve a kind of fragmentation and confusion of

-8-

experience and thought which is a central feature
of schizophrenia. Also the offspring ha? come
to develop only those ego skills which have been
■" valued within the special constrictions of the
family role structure, leading to a personality
impoverishment that becomes clearly apparent when
the offspring needs to assume extra- familial adult
roles.

8. Further, it is hypothesized that different family
members will occupy different positions or roles
within the family social organization, leading to
differing consequences for the personality develop-
ment of the offspring, (This hypothesis has been
confirmed by a detailed examination of very exten-
sive material on a family in which the offsprings
are monozygotic quadruplet schizophrenics.)

In the planning of further empirical research in this
section, these hypotheses have served as a fruitful focal point.
The section planning has been interdisciplinary, with the parti-
cipation of psychiatrists, social workers, nurses, sociologists,
and psychologists. More recently, a committee consisting of Dr.
Lyman C. Wynne of Adult Psychiatry as Chairman, with Dr. Joseph
Handlon of Psychology and Dr. Leonard Pearlin of Socio-Environ-
mental Studies, has been working out a specific research plan for
consideration by the total staff which will be taking part in the
ward program.

The intent in this research is to examine three especially
significant unsettled problems: (l) The degree of constancy of
familial disturbance in schizophrenia in relation to such variables
as: type of schizophrenia, age and type of onset, family social
class, and kind of family constellation; (2) The degree of
specificity that some aspects of family disturbance may have for
schizophrenia, or for varieties of schizophrenia, compared to the
generality of some other features of family disturbance which may
also occur normally or in other disorders; (3) The question of
the extent to which the family disturbance is a primary factor in
the development of schizophrenia or, alternatively, a secondary
consequence of the individual's pathology.

The implementation of this long-range program is at present
planned along two main lines: (l) Intensive studies on Ward 3-W
of the family relations of schizophrenics and, in comparison
studies, of neurotics. Current plans include the trial, in
a variety of settings, of a group therapy approach to each

-9-

family as a whole, the use of quasi-experimental family group
test procedures, and the detailed evaluation of the extent to
which features of family interaction carry over to the in-
dividual family member's relations with others, especially in
observed ward behavior; (2) Extensive studies, off the ward,
of a larger and more varied sample of families, including
"normals", in order to check specific items in statistical
comparisons. Such work, interdisciplinary but with a sociol-
ogic emphasis, has been usefully considered in over-all
planning, even though it will not be operationally practicable
to proceed with it until the more intensive studies have been
advanced.

In September 1957, Dr. Chsirles Savage departed for a
year' s leave of absence, after having completed a number of
papers on his studies of psychodynamic processes in the
therapy of schizophrenics, especially the effects when ther-
apy is conducted in a research setting and when the patient
receives psychotomimetic and tranquillizing drugs.

Despite the emphasis upon family studies for the future,
certain investigations which have continued to seem valuable
and which do not use separate inpatient material are to be
extended; a study of the extent to which social mobility of
various professional groups contributes to difficulties in
interdisciplinary collaboration; a study of role conflicts in
the clinical investigator arising from the difficulties of
integrating research and therapy values; the development and
clarification of the role of psychiatric ward administrator;
the linguistic study of emotional expression; and the effects
of certain perceptual and imaginative impairments upon learn-
ing capacity, for example, in reading.

-10-

Adult Psychiatry Branch
Section on Ward 3-E
Dr. L. Murray Bowen

General Statement

The work of the section is devoted almost entirely to
cne project, the title of which is "The Study and Treatment of
Schizophrenia as a Family Problem." It is anticipated at a
later stage of development that there will be several projects
in the section.

This project was started thirty- eight months ago to bring
normal family members into a living situation in the Clinical
Center with hospitalized schizophrenic patients. This was con-
sidered a potentially rewarding area for study. It is well known
that there is a vigorous emotional process when a psychotic
patient is in living contact with his family. A theoretical
plan had been worked out which, it was hoped, would make it pos-
sible for the families to live in the hospital setting for in-
definite periods, and also for it to be a practical and possible
venture in the Clinical Center, The intensity and specific
characteristics of the intense emotional conflict between the
family members had not been anticipated in the plan. Clinical
experience was that the conflict between family members could
transfer itself into a conflict between staff members. This
transfer took place in the context of ordinary treatment rela-
tionships between staff and family members. Changes in both
the theoretical formulation and in the treatment approach were
made during the first two years. The changes went toward find-
ing families in which the tendency to transfer their problems to
others would be less, and in developing concepts and techniques
to help the staff to work with the families without becoming in-
volved in the family problems. The immediate motivation for the
change was to make the clinical operation into one that was
liveable and operable both for families and for staff and that
also seemed to offer some hope for treatment successes. While
these changes were empirical and made in service of the clinical
situation, they had also a direct bearing on the theoretical
formulation. By the end of the second year, the ward operation
seemed to have reached a controllable and workable level. No
further changes have seemed indicated since that time. The plan
includes fathers, mothers, and patients as the minimal family
group for study. Schizophrenia in the patient is regarded as
a symptom manifestation of an active process that involves the
entire family, and the family therefore treated as a unit.

-11-

A characteristic of the operation has been the diffi-
culty in making accurate predictions of the project course.
For instance, each year there has been an impression that
the project staff had reached a workable capacity to deal
objectively with the emotional problems of these families.
Each time staff again encountered an unexpected situation
which required further resolution. One error in predication
seems to have come from the application of criteria from in-
dividual psychotherapy to the work with the more intense and
involved family group problem. Another error has been the
lack of experience with family groups and the fact that it has
not yet been possible to follow a family through to completion
of treatment.

The year 1956 ended with a fairly stabilized clinical
operation. There were no upsets between staff and families
that could not be understood and controlled within a few days.
This stabilized period was seen more as a calm period between
crises than the beginning of a sustained controlled clinical
operation.

Developments and Trends in 1957

The year 1957 is seen as a transition year for the pro-
ject. This was the first year in which there were no major
changes in either the hypothesis or treatment operation. The
more stabilized clinical operation, which began in 1956, con-
tinued throughout 1957, The clinical operation was much more
able to "run itself." Clinical problems required less time
and a corresponding increase in staff time was devoted to ef-
forts to more accurately structure and define the research
problems.

The first efforts to perceive the family as a unit
began as a clinical necessity. When a staff member related
individually to a family member, it could be the point at
which the family problem could become transferred to an intra-
staff problem. It is believed that "family unit" concept made
it possible for staff to see the family in a different way than
would have been possible observing fathers and mothers and
patients. The presence of the family group in a setting where
they could be observed constantly provided a source of detailed
objective data that would be hard to obtain in any other setting.
Many promising observations were marked "for future study" and
passed over during the early stages when the main effort went to
stabilizing the clinical operation. Early in 1957, when there
was more time for research efforts, some of these areas were

■12-

selected for detailed study. The effort was not successful.
The details seemed out of place in the absence of more pre-
cise overall concepts » The effort was then directed to a
more detailed thinking through of the overall project. This
resulted in four papers written during the year. The result
of this has been far from satisfactoryo Another effort is
now being made to define some of the more specific observa-
tions.

Progress in 1957

The changes in the project have the characteristics of
a growth process in which it is difficult to describe a change
as belonging to one period. Some patterns do stand out. There
are three principal areas of activity and interest, all inter-
dependent. This includes relationships within the family group,
relationships between family and staff, and relationships within
the staff. An interference in one area has a potential of show-
ing almost immediately in all three areas. Interference in
staff- family relationships seriously threatened the project
during the first year. There was careful structuring of the
conditions under which staff members would relate to family
members the second year. This brought enough control over
staff-family relationships to stabilize the clinical operation
and to make possible more accurate observations in the intra-
fajnily area. The focus of research observations during the
second year was on relationship patterns between family members.
The third year the main changes have been in intrastaff rela-
tionships, A year ago very strict structuring was still
necessary to prevent staff-family relationships from involving
the operation in an undefinable emotional turmoil. As the
staff began to understand itself better, the structure becajne
more of a natural process than a necessary set of rules.

The staff effort to understand intrastaff relationships
has been accompanied by a much clearer perspective of the
family as a unit. There was a beginning perception that the
family unit had group characteristics just as the individual
has individual characteristics. The evolution in the staff
seemed to permit enough detachment from the individual to see
the family.

The concept of the family as a unit may be one of the
more important concepts in the project. There are events in
the family when the activity, the intentions, or even the at-
titude in one member can set up changes in another member.

-13-

An exsimple is the mother who developed physical illnesses in
response to a change in her daughter. When one's interest and
focus is on the individual, there is a much greater tendency
to see the family in relationship to that individual than to
see family relationships as a phenomenon. The development of
psychotherapy for the family group was also developed as a
clinical necessity but it appears to have some advantages over
individual psychotherapy that are worth exploring.

Another major clinical change in 1957 was developed to
deal with a clinical problem. The interchange between psychic
and somatic problems is intense in these families. Over a
year ago the project assigned itself the task of combining
psychotherapy and general medical care within a single physi-
cian. This has brought into focus a number of problems pre-
viously missed when psychic and somatic problems were divided
between two physicians. To handle the anxiety situation, the
^ysician who operates the two areas has gone in the direction
of structuring medical practice in a psychotherapy frame of
reference. This area has presented a number of promising
clues for further study.

The following outline by Dr, Warren Brodey illustrates
concretely some aspects of the narcissistic relationships and
reality testing observed during the study of these families.

Family- Staff Mechanisms

1, The staff and family by the nature of this study
maintain close proximity. It is necessary for
family and staff to negotiate with one another
in dealing responsibility with such situations
as, obtaining a pass to leave the unit, periodic
physical examination, passing food at the dinner
table, etc. These families were chosen because
of the primitive intensity of their intra family
relationships. It has been found that this in-
tensity readily spills over into family-staff
relationships, and that even simple negotiations
frequently break down in an atmosphere of intense
family-staff emotions. This capacity to evoke
powerful responses in others is historically a
characteristic of these families.

-14-

2. Examination of this process of evocation in the
family-staff relationship indicates a specific-
ity in the positions that are assumed by the
staff members in relation to the family. These
positions, when compared to the intra family roles,
are seen as "stand-in" positions — the drama being
reenacted is tradition for each family, and has
been called the family nythology. This mythology
has a control axis or leit motif along which all
the parts are played, i.e., good-evil, powerful-
weak, praised-criticised, competent-incompetent,
sick-well, etc. Autonomous stimuli from staff
members or other extra familial figures are re-
sponded to in terms of this central axis- -the de-
gree to which this occurs is directly related to
the degree of lack of coincidence of the stimulus
with expectation and the level of anxiety that
prevails. The process of putting the autonomous
stimuli or the person emjtting them into line, is
called polarization.

3. Examination of this process of polarization indi-
cates that the family responds so as to reinforce
the possibility of getting in return a response
closer to its own projected expectation. This is
accomplished by the fragmentation of the total
reality into accurately perceived parts, and then
utilizing for response these accurately presented
parts, without reference to their relationship to
the whole or each other, i.e., with altered per-
spective. Thus a statement is responded to in
terms of its symbolic meaning without reference
to its reality component, as a long term general-
ization with reference to its immediate intent,
etc. The staff member who responds to the frag-
ment is pulled toward the sixis of orientation of
the family member. The alteration of perspective
in the staff member is a subtle process. It is
often effective in altering the orientation of
the staff member in the direction of the family
nythology, particularly as it is made clear that
this is the only way to obtain or maintain rela-
tionship.

-15-

4. The concept of circular causality if found use-
ful in considering the effect of the above noted
process, in the creation of an altered reality.
Thus conflict {A) in the family evokes the
response in the staff (B) which is closely re-
lated to the DQTthological expectation of (a).
The response in the staff (B) then reinforces
the validity of the projection of the conflict
(a). This process of creating an altered reality
which is valid in fact, as well as in keeping
with the family n^rthology, is called the process
of externalization,

Intrafamily Mechanisms

1, Each family has a specific set of family roles.
These roles are not specific to the individual
family members though one member may habitually
play a particular role. Family members can trade
roles with each other provided that the constella-
tion of roles remains unchanged,

2. The roles can most obviously be described in terms
of the central axis or leit motif of the family.
Each role embodies a major extreme position such
that persons interacting from these positions will
reenact the issues of the central conflict,

3« Grossly at least, the issues of these central con-
flicts embodied in the family mythology are readily
related to the major deep and highly energized un-
conscious conflicts in each family member. But
the conflicts highlighted in the central axis, the
leit motif, and the major roles are those conflicts
which in addition to being in each individual, in-
terlock between important individuals.

4. The major structure of these families can be viewed
as the result of a process of externalization,
similar to that observed in the families' relation-
ships to staff. One can observe the same evocation,
polarization, and fragmentation of reality occurring
within the family as was seen in staff-family rela-
tionships. In observing the family in ordinary
operation it is harder to be aware of the external-
ization process for it is so pervasive. In the
families, externalization is facilitated by marriage
choice, child-rearing practices, etc. Though ongoing
process of externalization is not as readily seen - the

-16-

previous findings point up that the externali-
zation of internal conflicts has taken place.
Also, when an individual family member, perhaps
through his therapeutic work, makes an effort
to introduce into the family relationships as-
pects of himself which do not coincide with the
image projected from other fajnlly members, then
the processes which maintain externalization are
observed to become more evident.

Considering the above observations the intense
close relationships apparently between family
members can be seen as relationships based on
the cathexis of that part of the other family
member which coincides with the projections
from self and is essentially then not removed
from self except to acted out mirror reflections.
The term narcissistic relationships seem specif-
ically descriptive of this phenomena,

5. In practice this system of narcissistic relation-
ship is maintained by the suppression of recog-
nition for relationship purposes, of autonomous
behavior which does not coincide with the family
nythology. Each family member is related to by
the others in terms of the part of this person
symmetrical with the role in which he is cast.

It is considered that autonomous behavior other
than than symmetrical as noted above is not given
a negative relationship value, but rather has no
relationship value,

6. There is observed a strict, iron-clad rigidity
about these families. It is considered that this
is related to the need to suppress spontaneity but
more specifically in these families. An important
characteristic is the single-minded pursuit of
concrete reality and corollary abhorence of ir-
rationality. It is considered that this inability
to directly deal with irrationality has much to do
with the effort to alter reality to make the ir-
rational rational, and when this fails, to project
and externalize this conflict setting up the role
in the family iiythology of the irrational one, the
other family roles then being reinforced as the
super rational ones. The role of the irrational

-17-

one is habitually occupied by the family member
who manifests the psychotic symptomatology. It
has been observed that the processes clinically
manifest in the symptomatology called schizo-
phrenia are an accurate caricature of the same
processes which are covert within the family.

-18-

Child Reseaxch Branch
Fritz Redl, Ph.D.

Creation and Operation of a New Research F?icility

A considerable amoimt of staff work during 1957 went into the
planning and opening of the new Children's Treatment Residence and
into the exploitation for research of unique observational possi-
bilities that offer themselves only during such periods of transi-
tion from one setting to another. While in terms of the research
projects reported on in the annual report of 1956, this heavy re-
focussing of research effort during 1957 constitutes somewhat of
a detour, for the long range objectives of the research at the Child
Research Branch it probably constitutes one of the most Important
moves forward.

The purposes served by the Residence are:

1. To make possible the collection of research data on child
patients when they have reached a level of recovery that
makes their treatment in a closed hospital ward setting
Inadvisable, \rtille they are not yet ready for full return
to life in the open community.

2. To explore the nature of the therapeutic milieu, including
social structure and staff roles, that are required during
this phase of treatment and to compeire it with the nature
of environment most conducive to treatment in the earlier
phases in a closed ward setting.

3. To create concepts \rh±ch will enable us to describe the
movement of patients into an improved state of mental health
in terms as specific as one is now able to use for the des-
cription of their pathology while still more fully in the
grip of "mental disease."

The Research Operations which were carried out in 1957 and
\rtiich were closely related to the opening of our new research facili-
ty, the Residence, were the following:

1. Study of a group of "Normal Controls" - matched in I.Q., age,
social background, and racial distribution with our patient
group, while exposed to a week's life in the residence.
Narrative recordings by staff and participant observers as
well as more rigorously planned recordings by trained ob-
servers using systematic observation techniques, were used
as methods in this study.

-19-

2. Study of a group of children of nvirsery school age with
symptoms of aggressive acting out during eight weeks on
4-East, after the patients had been moved into the resi-
dence. These children were exposed to a planned siimnier-
nursery school program -t^ile under study and the material
gathered on them should peirait comparison with similar
behavioral expressions observed during two very differ-
ent developmental phases.

3. Study of child patients on 1<-East - eight children of aji
age range around eight years, brought in for the purpose
of a temporary stay on the ward for differential diagnosis,
for a limited period of observation, ^fith two objectives
in mind:

a. widening the clinical data on children with similar
symptoms by studying a larger number for shorter peri-
ods of time I ajid

b. selection of a group of new long-range child patients
with a high degree of homogeneity in a number of variables,
to be chosen on a more thorough basis than the usual fonns
of direct intake into the ward would otherwise allow.

Operation 1. and 2. were discontinued after the end of the sum-
mer; operation 3. will continue for the rest of the year.

The exploitation of the data gained during this period and com-
parisons with data gained on previous control normals, as well as on
our long-range patient group, is now being worked on but is not yet
at a stage of completion tdiich makes a detailed report possible.

Abstract of selected research activities as contained in the
Project Reports for 1957°

Individual Ttieareipy and Psychopathology

While two children have been without a therapist since July 1957 >
intensive recording has been done on the other four, who are being
seen four hours a week in individual therapy. While much of this is
still in the process of ongoing data collection, the materials avail-
able now for the development of hypotheses of the children's pathology,
as well as for the basic trends in problems of technique, are being
worked on by the therapists, their consTiltants, and other research
staff. Comparisons of later phases with data produced in earlier
stretches of therapy, organized collation of therapy data with obser-
vations gained from other sources, including the more strictly de-
signed research projects, and with data gained about the pre-histoiy
of the children, are among the tasks on which part of the effort of
research staff is being focussed at this time.

-20-

Tentative findings:
Psychopathology :

1. Hyperaggressive children display a ja,thology ¥111011 combines
aspects from childhood neuroses and psychoses to constitute
a special syndrome. Although individual children differ in
aspects of this syndrome, in all cases there are profound
ego disturbances centering around problems of impulse con-
trol, and particularly around the control of aggression. The
ego disturbances are reflected in conceptual lacks, learning
difficxilties, disturbances in conceptions of space and time,
low tolerance for frustration, hyper -distract iMlity hy en-
vironmental props, readiness for contagion, pai-anoid-like
suspiciousness and projections. Despite these features, the
children being studied here differ in many features from
psychotic children. In particular, they do not show the
autistic behavior and fantasies of the latter, they are gen-
erally in communication with the environment, and under spe-
cial circumstances they show marked ego-intactness.

2. In all cases oral themes seem to play a major part in the
underlying fantasies of these children. The children seem
to interpret experiences via orally incorporative or des-
tructive modes. Even material that seems initially to be
predominantly phallic in tone, can be readily seen as a de-
velopmental phenomenon superimposed on an anlage of primary
oral concerns.

3- Related to the above, one finds in these children intense
anxiety over the possibility of dependency, and intense de-
fenses erected against both behavioral and fantasy expres-
sions of dependency. With progress these defenses seem to
(diminish both in behavior and in fantasy productions.

k. All of the children show severe problems in the formation of
a sense of identity. These problems seem related to the ab-
sence of or failure of figures who might serve as transmitters
of cultural or subc\iltural values. In all cases there is ab-
sence of a father, failure of the father to fulfill a role
that might provide a source for social identification, or in-
adequacy of the father as communicated to the child through
the mother's perceptions. With all children the opportunity
for establishing any relationship (even an anti -social one)
with a social order seemed lacking.

-21-
Problems of Technique ;"-;!fr;j;

1. Foremost among these is the broad observation that, contrary
to beliefs popular in the field, individual psychotherapy
with the hyperaggressive child is more like than unlike psy-
chotherapy with other categories of disturbed children. As
in all cases where ego development is weak or distorted,
there is, especially in the early phases of treatment, great-
er necessity for the therapist to function as an aiixiliary
ego for the patient than is true in more classical neurotic
cases; this , however, is no more than a difference in em-
phasis, since it is well kno\m that child therapy always
requires that the therapist play a partially educational
role more than does adult therapy, by virtus of the fact
that no child's ego is fully formed.

2. A second impression is that the therapeutic process, while
similar in course, is more prolonged than is the case with
other kinds of children.

3. Third, while limit setting plays an important role in all
child therapy, it becomes partictilarly significant in treat-
ing children vfhose most crucial problems lie in the area of
control, fear of loss of control, and distrust of the adult's
dependability and integrity in controlling both himiself and
the child. Since fear of seduction (in both the narrow sexu-
al meaning and the broader sense of seduction to Impulsivity
of any kind) plays a major role in the psychodynamics of
these children and seductive experiences often figure promi-
nently in their history, it becomes a vital problem for the
therapist to avoid confusing the wish to demonstrate his bene-
volent intent %-rt.th seduction. Particularly in the earlier,
more disorganized phase of therapy (which may be prolonged
for many months and even a year or more), it may be a dis-
quieting e:cperience for the therapist to find himself re-
sponded to as though he were a dangerously hostile figure,
and it is easy to become unxri.ttingly seductive in the effort
to correct this projection.

k. Many countertransference problems also have become apparent
in this project. While the particular content of the counter-
transference will no doubt vary \-ri.th the personality of each
therapist, all those participating here have had to deal with
feelings aroused by the need to meet such explosive barrages
of raw destructiveness and with those aroused by the under-
lying oral demandingness of such children, whose own fantasy
certainly seems to be one of eating up the therapist.

-22.-

5- Impressions axe beginning to emerge as to specific interpre-
tive techniques. In the earliest phases of treatment, \dien
these children communicate largely through gross motor be-
havior and acting out, it seems necessary to accompany the
traditional resistance interpretations with fairly concrete
behavioral responses to the child; it is as thou^ actions
speak loudly while words at best mean little or, at worst,
signify oral sadistic attack to this kind of child. later,
as the child moves into a phase of more symbolic communica-
tion, the interpretations also seem to need to shift; at
this phase communication seems best to be achieved by cor-
responding symbolic gestures on the part of the therapist,
much as one answers a schizophrenic child's fantasy communi-
cations within the framework of his own fantasy rather than
by interpretive translation. It seems only to be in the more
advanced phases of therapy, as the child becomes able to ver-
balize directly about himself, that the weight of the inter-
pretive effort can be shifted to direct discussion of the
child's problems and their origins and remain effective.
While all three levels of communication are present through-
out therapy, there is a difference in their relative useful-
ness at various phases.

Milieu Therapy

Under this heading are summarized a variety of research activities.
The "level" on which research is carried on in this specific aspect
varies all the way from naturalistic styles of data collection, the
production or or^nized research data as part of projects with a special
design and focused on limited variables and the development of con-
cepts to the formulation of theories and hypotheses preparatory to
later more rigorous selection of variables. Without going into detail
the following highlights may be given special emphasis:

Tentative findings:

Concept of Milieu smd Breakdown of Vajiables

1. It is possible to isolate about thirteen to fifteen distinct
and relatively independently researchable sub-units of the
milieu which seem to have behavioral impacts on the cMldren
under study.

2. At least seven quite distinct meanings are customarily in-
voked when the adjective "therapeutic" is attached to the
milieu concept, each one of them relevant in its own right,
but in need of sharp separation for the utilization in an
organized research approach.

-23-

3. A considerable list of properties of games, materials, props,
tools involved in activities such as arts emd crafts, etc.,
can be isolated as of clinically distinct importance, and the
therapeutic variation of these factors can be described in a
considerable amount of detail. Effects of some technic[ues of
employing such activities and of handling child behavior dar-
ing the process can be distiactly seen as differing in their
effect on the children from others, so that the groundwork
for a more organized pharraacopaea mentioned as one of our ob-
jectives, can be seen to emerge. Such factors as have been
Isolated by now can be described in sufficient detail and
precision to make them teachable to others and approachable
in sharper research design in later studies.

k. Techniques for the clinically geared observation of surface
behavior on the spot can be developed so that they avoid the
traditional gap between obser^-uble surface data on the one
hand and depth-psychological dynamics on the other more suc-
cessfully than in the past.

Life Space Interview

Copious material collected for the piirpose of exploring eind
struct\iring this technique, described in 1956, has been added to.
A preliminary fonmilation of basic theory and technicaJL principles
were submitted for discussion to professional groups at the 1957
Orthopsychiatric Conference; parts of this are in the process of
publication in the American Journal of Orthopsychiatry.

Tentative findings:

1. Bie variety of purposes for which treatment staff uses Life
Space Interview techniques can be ordered around the follow-
ing sub -goals which emerge most frequently in in-patient
treatment of children with aggressive disturbances:

a. Clinical Exploitation of Life Events, under vihich dis-
tinct categories have been temporarily singled out under
the following labels: (l) reality-rub -in, (2) symptom
estrangement, (3) revitalization of numb value areas,
(k) new tool interpretation, (5) manipulation of the
bo\uidaries of the self.

-2/r-

b. Emotional First Aid on the Spot with subcategories

temporarily classified under the following code labels:
(l) drain-off of frustration annoyance, (2) communica-
tion mainteimnce in moments of relationship decay, (3)
support for the management of panic, fury and guilt,
(k) regulation of behavioral and social traffic, (5)
umpire functions in decision crises and in cases of
loaded transactions.

2. In terms of exploration of Criteria for the indications
or contraindications of holding Life Space Interviews in
a given situation, and of the choice of a specific tech-
nique, the following 6 subcategories of areas of major
relevance have emerged:

a. central theme -relevance

b. ego proximity and issue clarity

c. role compatability

d. mood manageability

e. timing

f. Impact of terrain and props. ■' ■

3. On the basis of preliminary work a number of similarities
were found between techniques employed by interviewer in
Life Space and in Play Therapy Interviews. Among the dif-
ferences in the techniques employed in the two types of
interviews were the following:

a. As expected, play is used less frequently in Life
Space Intei*views.

b. Techniques of control were used more frequently by
Life Space Interviewers.

c. While there were no differences in the amoiint or spe-
cific techniques of interpretation used in the two
types of interviews, there were differences in the
direction of interpretation: In Play Therapy Inter-
views interpretations were directed more frequently
toward impulse, whereas in Life Space Interviews in-
terpretations aimed relatively more frequently toward
resistance and defense.

Learning Dibourbances

The major objective of the research on Learning Disturbances
carried on at the Child Research Branch is to arrive at a sharper
differential diagnosis between those disturbances of learning which
are intimately linked -up with the basic pathology of the children
and those which are a result of previous learning failixres or of im-
portant behavioral or cognitive learning blocks.

-25-

In order to isolate the variables that go into the success or
failxrre of a specific learning task and •sdaich make a given learning
sitiiation either destructive or supportive for the learning process,
our study focused especially on the problem of motivating the children
toward learning activities, of exploriixg the type of "situational in-
gredients" at work and of assessing the nature of certain specific
leaming disturbances that seem to occur with frequency in the type
of hyperaggressive child patient under study here. School records
distributed over a 27 month period were sampled, rated in terms of ^
variables involved, and later reliability was checked by use of judges
not connected with IHIMH. Chajiges in school behavior of 6 children
were studied by comparing ratings for two halves of the sample by
time. ClinicaJ. analyses were undertaken on the learning problems of
each child and on special sources for anxiety in both, children and
staff, with respect to the learning situation. With the new group
of child patients on 4-East, methods are being developed on the basis
of the previous studies and are focusing aroimd the following:

1. Planned variations of school program to provide examples
of behavior in different settings (individual, group;
formal, informal), with different materials (verbal,
manual -manipulative, etc.), and different content.

2. Participajit and non -participant observation.

3. Analysis of observations to isolate variables and to devel-
op systematic methods of describing the variables.

Tentative findings:

1. A behavior Rating Scale, which can be used reliably in
judging school incidents for adjustive behavior, was developed.

2. Over the period of 27 months the children changed significant-
ly in the direction of better school adjustment.

3. Categories for describing clinical factors accounting for
school behavior and behavioral change were developed, and
it was demonstrated that they could be used reliably in
judging school incidents. ISae clinical factors in the
learning situation cam be subsumed under three major
categories :

a. Self (self picture; inner pressures and forces; infan-
tile needs and frustrations)

b. Relationships (to adults; to peers)

c. School (subject matter, methods, material; teacher
personality.

Behavioral Measurements and the Assessment of Change

An Important part of our research effort has always been geared
in the direction of better methods for observing and describing child
behavior and toward the development of categories of recording that
would make it possible to catch the clinically relevant issues of
"change." Several studies in that line were reported previously. Dur-
ing 1957 several additional methods were tried. Among the studies
undertaken during this year are the following:

1. Systematic observations in a variety of settings and coding

of individual interactive behavior during two treatment phases.

2. Systematic observations done on a control group of children,
matched for age, I.Q., race, socio-economic status.

3. Categorization derived for detailed descriptions contained
in clinicaJ. records and case conference materials.

U. Periodic interviews and collections of clinical incidents
from Child Care Staff.

5- Exploratory interviews with child care and therapy staff
directed at staff's concept of change and improvement g^rif^
matched with their actual statements about observed func-
tioning of their patients.

Tentative Findings:

Among them is one, especially, that makes it possible to list
"findings" gained so far, as a result of investigations by means
of the Leary-Ossorio technique ;diich were made in two series, a
year and a half apart, and from idiich the following suggest themselves:

1. Changes in behavior interaction patterns. From the inves-
tigation of two series of observations made a year and a
half apart, the following major conclusions can be drawn:

a. The interpersonal behavior of the children has changed
considerably in the course of treatment.

b. Over the period there is a decrease in inappropriate
behavior toward peers. Most children show a trend
toward more friendly peer relationships.

-g7-

c. Changes in relations with adults are much more marked
than changes in relations with peers. Hostility to-
ward adults decreases considerably. Particularly there
is a decline in hostile -dominant Isehavior and an in-
crease in friendly -passive behavior toward adults, with
a major increase in trusting, dependent expressions.
Inappropriate behavior also decreases considerably. The
distinction between behavior toward peers and behavior
toward adults gets sharpened.

d. The behavior that the children evoke from others shows
corresponding changes. Children are less hostile than
they were in response to a particTilar child. Adults
show an increase in the proportion of friendly, giving,
supportive behavior with the children.

e. Different behavioral settings produce different quali-
ties of interpersonal behavior.

f . There is an interaction between person and situation
that goes beyond what either contribute independently
to ovir ability to predict behavior. That is, althou^
there axe generalizations, settings also operate differ-
entially for different children.

g. The effects of settings differ in the two phases. Ten-
tatively, it would seem that in the later phase of treat-
ment the situation comes to play a greater role as a de-
terminant of behavior than it did previously.

h. Changes in interpersonal behavior appear more readily in
some settings than in others.

i. A paper on some of these findings was presented at nation-
al meetings and is in process of publication. Data analy-
sis is near completion and another paper is being worked on.

2. Concepts of Improvement:

a. Formulations of clinically relevant concepts of improve-
ment are xindergoing continuous change as onxr study pro-
ceeds, and temporary findings axe as yet too volatile
to be reported this year.

b. A pilot study for the collection of data on the staff's
concept of improvement as related to our present child
patients is in a state of partial completion. Preliminary
impressions indicate that the children have improved in a
number of areas. Especially, hostile interactions between
children have decreased and acceptance by the children of
staff interventions has gone up. Other details about im-
provements are too varied from child to child or require
too much background data to be summarized here.

Next Step Plans

The activities reported oa here s.re ?iot really to be considered
as a nimber of research projects with relatively independent objectives.
They are, with some exceptions, more is, t!he :aature of a research pro-
gram rather than a sequence of projects o

During the next years it is intended:

1. To bring to a state of closui-e those phases of the program
and to finish up -those studies ^±dch ai'e i^, the nature of
relatively limited "project type" investigations and to
publish them in form of a paper or article for a scientific
journal during 1958 or 1959 »

2. To pull out of the larger material such sections as can be
reasonably closed out as independently reportable findings
and to publish them as articles cr books. Among these,
some will be on the level of articles in scientific periodi-
cals or books on therapy techniques directed primarily to-
ward the research field. Others, by the very nature of the
program will combine research findings with directives to

be used for staff traini??^ or for application by practition-
ers in the field of Psychiatric In-Ifetieat Trea-bment of
children, and will be addressed to ee.ch of the disciplines
involved in psychiatric Residentisl Ttierapy.

3. In order to fulfill the major objective of the research
program, namely the study of the t.veatment process during
its full duration from hospitalisation back to reinstate-
ment into normal comnroriity functiorrLag, several groups of
children with similar pathology i^^Lll be taken through their
full course of therapy. TH-iis is a condi.tioa sine qua noa
for coming closer to the task of creating diagnostic con-
cepts which will either verifj' our hypothesis tJaat these
child patients constitute a specific nosological entity.

If the findings should cjiae out in terms of e preference
to maintain them as if a ''borderline" category, to fill this
category with enough specific content to make prescriptions
and predictions more reJJ-able aad to separate them more
sharply from borderline cases of other types. We plan to
use the next years for the completion of this task.

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CLINICAL NEUROPHAEMACOLOGY KESEAECH CEMER CLINICAL INVESTIGATIONS,
NATIONAL INSTITUTE OF MENTAL HEALTH MD SAINT ELIZABETHS HOSPITAL,

Joel Elkes, M.Do

The Clinical Neuroptiaimacology Research Center, now in the pro-
cess of being established as a Joint project between the National. In-
stitute of Mental Health and Saint Elizabeths Hospital, is a Clinical
Laboratory intended primarily for the study of the action, and the
mode of action, of drugs on mental function in man, with special, re-
ference to their bearing on problems of mental disorder.

The location of the Center at Saint Elizabeths Hospital was
thought appropriate for a number of reasons. In the first place, it
was felt from the outset that such a program would gain greatly by
being initiated and maintained in a large modern mental hospital,
where abxindant and varied clinical material would make for the con-
duct of controlled large scale trials of pharmocotherapeutic agents,
as well as the ready selection of suiitable case material for special
intensive investigation of individual conditions and syndromes.
Furthermore, it was thought desirable to expose the investigators
working in the field to the, in many ways unique, phenomena present-
ed by mental illness in a mental hospital; and thus familiarize them
with the special research problems presented by a mental hospital
population. Equally, it was hoped that the contact of the clinical
staff of the Hospital with scientists working amongst them would make
for a more ready appreciation of the role of each in a common research
program. The Saint Elizabeths setting, with its long tradition of
clinical care and teaching, and its high standard of resident staff
therefore seemed to provide a unique opportxmity for the pursuit of
such collaborative research into the biology of mental illness. Its
location within the Washington area, and within ready access of the
Clinical Center will, make for ready interaction between it, and the
resources and special services of the Clinical Center. Essentially,
therefore, the functions of the CNPRC" and the work of other labora-
tories at the Clinical Center are envisaged as complementary and in-
terdependent. It is, in fact, plajmed that a number of long range
programs will be conducted with the active and sustained collabora-
tion of the laboratories of Clinical Science, Psychology, Adult Psy-
chiatry, Socio Environmental Studies; the Biometrics Branch of NIMH;
and the Psychopharmacology Service Center. The full yield of the
scheme of necessity hinges on the degree and the intimacy of this
interaction.

A further featiore ^ich, with increasing experience, may grow
in importance may be the steady defixiition and growth of methodologi-
cal tools specially adapted for the study of large mental hospital
populations and their interaction with the community. It is hoped that,
in time, coiirses in Research Method in these special fields will emerge

-30-

as a direct outcome of collaborative studies between CHPRC, Saint
Elizabeths, and. the appropriate laboratories of KIH.

For the present, three broad Sections are envisioned for the
CHPRC. These are the sections of Clinical Psychiatry, Chemical Phar-
macology and Behavioral Sciences. Only the broadest indications of
the programs of each can be given at the present stage.

1. SECTION OF CLIHICAL PSYCHIATRY

One of the early functions of the Section of Psychiatry will be
a systematic survey of the existing population of Saint Elizabeths
Hospital, with special reference to the assessment of the impact of
pharmocotherapies on the existing services of the Hospital. It is
common knowledge that the immediate management and treatment of the
acutely ill patient has been altered. Large groups of chronic pa-
tients heretofore secluded in the continuous treatment wards of the
hospital have been mobilized, and new categories of patients, with
special needs of their own, may well be emerging. Also, such reha-
bilitative measures as have been empirically achieved have increased
and made more urgent the contacts between the mentaJ. hospital and
the commimity. Acciorate figures in all these respects, however, are
not readily available at present. Nor has the impact of the new
therapies on staff attitudes and staff skills and on the emergence
of novel responsibilities for ward personnel been systematically as-
sessed. In conjunction with the Laboratory of Socio-Environmental
Studies, the Psychological Laboratory, and the Biometrics Branch of
NIME, it is hoped to give early thought to the design of a series of
documents aimed at answering certain specific questions relating to
these various areas; to test and recalibrate these in different
therapeutic settings of the hospital; and, in the light of experi-
ence, adopt some dociunents \&Lch would with reasonable accuracy
measure subjective and objective change in the patient and the en-
vironment within which he functions. It is hoped to reduce these
data to a statistically manageable form, and to apply them to wider
populations than the one for which they were originally intended.

The design of the above documents will proceed pari passu with
the design and calibration of documents used in a study of the placebo
response, and the systematic trial of new agents. It is hoped that
these studies will be conducted in conjunction with the Psychopharma-
cology Service Center.

A further function of the Section will be to determine and classi-
fy the mental and somatic responses to established and new dr-ugs in
relation to the nature of the individual illness, the phases and the
changing patterns of the course of an illness and the genetic back-
ground of the individual patient. Relatively little is known of the
relation of drug reactivity patterns, in either mental or metabolic

-31"

terms, to genetic factors. It is intended to single out a few selected
syndromes^ such as the depressive syndrome^ certain phasic mental dis-
orders, and stable schizophrenic states., for intensive clinical, psy-
chophysiological and metabolic studies.. "Hiese will be conducted in a
metabolic ward and will, aim at establishing correlates between clini-
cal, somatic, biochemical and endocrine responses to graded doses of
individual drugs and metabolites | and by the use of suitable techniques
(including animal techniques - see below) at defining the relationship
between biochemical events in tissue fluids, and intra-cerebral events.
•The interplay between the nervous, and the endocrine systems may be
particularly relevant in this context; and may perhaps, in time, con-
tribute to a definition of prognostic indicators in the choice of indi-
vidual drugs for particular syndratnes. Furthermore, it is hoped that
drugs discrimlnately used may lead to the recognition of pharmacologi-
cal and biochemical cleavage planes between syndromes bearing a super-
ficial clinical resemblancei and thus contribute to a clearer classi-
fication of the phenomena of mental disorder than has been possible on
clinical grounds alone.

2. SECTION OF CHEMEGM. FHABMACOLOGY

The activities of the Section will be closely related to both
the functions of the Section of Psychiatry and the Section of Beha-
vioral Sciences. In the clinical field, this Section will be responsi-
ble for the conduct of hiunan studies in intermediate metabolism, and
the establishment of the biochemical correlates of drug reactivity
patterns in the individual patient. Also, using tracer techniques, an
attempt will be made at a clearer recognition of the relationship of
systemic biochemical events to events within the central nervous sys-
tem. The precise metabolic pathways affected by selected drug, and
the metabolic fate of drugs will also be studied.

In the experimental field it is intended to carry further the
examination of the effects of drugs en enzymatic processes concerned
in the synthesis, storage and release of neurohumoral agents within
the brain, with special reference to the possible existence of three
types of drug receptors related, respectively to a naturally occur-
ring choline ester, catecholamine, and indole. It is hoped that
attention will be directed toward the effect of drugs on the opera-
tion of hormonal mechanisms, within and outside the central nervous
system, with special reference to pituitary function; and, at a more
cellular level, to an examination of drug effects on carbohydrate and
nucleotide metabolism in the central nervous system. The fluorimetric
and tracer methods used in these studies wi3J. be intimately related
to pairallel pharmalogical and electrophysicologieal studies in the
Section of Behavioral Sciences.

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3- SECTION OF BEHAVIORAL SCIENCES

The work of the Section of Behavioral Sciences will be closely-
related to the work of the other Sections, and also to some studies
currently in progress in the laboratories of Clinical Science and
Psychology at the Clinical Center. In the human psychological studies,
particular attention will be paid to the processes of attention, 'set',
sensory discrimination, and learning in the schizophrenic and depressed
patient in various phases of illness, and the effects of drugs upon
these processes. An attempt will also be made to establish objective
measiores for those aspects of thought disorder \diich are characteristic
of the schizophrenic syndrome, and which are measurably affected by
drugs. Somatic measures will center on vaa:ious aspects of autonomic
and fine motor function, and the spontaneous and induced electrical
activity of the brain.

These studies will be linked to studies of the effect of drugs
on the function of sensory pathways in the experimental animal, with
special reference to the coding and transformation of information
along various levels of integration within a sensory pathway. Micro -
electrode techniques will be used in these studies, emd an attempt
will be made to link concepts of modem information theory to data
obtained in physiological eind pharmacological experiment. The opera-
tion of highly patterned inhibitory fields operating within the central
nervous system may be relevant in this context. The capacity of the
brain as an information-storing, matching and predicting organ is dis-
turbed in certain stress states, in drug induced states, and in schizo-
phrenia. These disturbances may have their chemical corollaries. It
may, therefore, be appropriate to carry out these studies in a hospital
setting where clinical disttirbances in the hajidling of sensory informa-
tion, though not uncommon, have not so far received the experimental
scmitiny they merit.

A further aspect which it is hoped to pursue in this Section is
the systematic study of the electrophysiological equivalents of learn-
ing in the normal animal, and in animals subjected to either anatomi-
cal or biochemical lesion. Techniques in this regard, though still
at an early stage of development, promise well, and may gain by being
linked to the techniques used in the studies in the sensory physiology
field.

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lABORATORY OF CLINICAL SCIEHCE
Seymour S. Kety

The area of interest of the Laboratory of Clinical Science lies
in the application of the biological sciences to the problem of mental
disease. The individual sections of which the laboratory is com-
posed, representative of the various biological disciplines, work
freely within this broad field concentrating upon certain clinical
or basic studies which they pursue independently or in collabora-
tion with each other or with other laboratories and institutes.
In July of this year a second ward was placed under the direction
of this laboratory, making possible the initiation of a long-range
multidisciplinary program of studies in the biological aspects of
schizophrenia. Since this is expected to be the central program of
the laboratory for the next several years, some discussion of its
historical backgroimd and methodological approach seems warranted.

Biological Aspects of Schizophrenia

There is a long history of theories and findings which postu-
late or purport to demonstrate characteristic biological changes
which operate at a fundamental level in this important field of
neuropathology, where definite pathological change in the brains
of schizophrenics was reported by Alzheimer in 1897 and by Mott in
1920. More carefully controlled studies by Dunlap in 192U and Conn,
ten years later, failed to reveal significant changes from the normal,
so that at the present time there is no pathological change general-
ly accepted as characteristic of this disease. More cogent has been
the evidence acquired by studies of its genetic aspects. Studies by
Kallmann of a large population of schizophrenics had shown a high
incidence of mental illness in their immediate families, an inci-
dence which increased progressively with consanguinity, making it
compatible with but by no means proof of the genetic factor. Studies
on uniovular and biovular twins by Luxemberger in I928, Rosanoff in
193^^ Ballmann in 19^6, and more recently. Slater in 1953 have shown
a concordance rate in the imiovular twins varying from 60 to 86 per
cent, with a concordance rate in the biovular twins identical with
that in siblings, which is about 10 to ik per cent. Although none
of these studies is free of important methodological defects which
would tend to exaggerate the concordance rate in uniovular twins,
the close agreement in the concordance rates by several investiga-
tors using somewhat different approaches and studying patients in
different coiintries strongly suggests an important genetic element
in at least a large fraction of schizophrenics o

-34-

In the field of electrophysiology, as eaxly as 19U1 Finley
reported a higher incidence of elect roencephalographic abnormali-
ties in schizophrenia (28 per cent as compared with 7 per cent in
normals). A series of reliable investigators have confirmed this
high incidence with frequencies rajiging from 23 to 60 per cent in
this disease. These findings are compatible with the reports by
Heath and by Sem-Jacobsen of pajT'oxysmal spiking activity in deeper
cerebral structures in a large percentage of schizophrenics. The
electroencephalographic evidence has formed the basis for the cur-
rent project by Evarts, McDonald, Pollin, Snyder, and Butler on
behavioral and biochemical correlates of the electroencephalogram
in schizophrenia, \diere preliminary studies have revealed at least
one positive correlation with biochemical changes in the blood.

Although there has been some emphasis on the endocrinologic
changes in schizophrenia in the past, there is little confirmed evi-
dence of endocrine disturbance in this disease which cannot readily
be explained as being secondary to the anxiety and stress vhich
characterize this condition. The same comment is true of circula-
tory changes. In his current project in this area. Garden has foiind
little cardiovascxxlar deviation except for a diminished ballistocardiogram.

There has been much speculation concerning distvirbances in the
circulation and energetics of the brain in schizophrenia. The Section
on Cerebral Metabolism and the Section on Psychiatry have confirmed
and extended previous work in this field in showing that although
there may be a correlation between certain mental states emd cere-
bral oxygen consumption, there is no abnormality either in circiila-
tion or total oxygen consumption of the brain in schizophrenia.

Much of the biologicsLL work and many of the findings have been
in the field of biochemistry as related to schizophrenia. There is
some agreement in the literature of some disturbance in carbohydrate
metabolism, i.e. a reduced glucose tolerance and an increased insulin
tolerance, although to ■vdiat extent this is primary is in doubt.

Many of the biochemical studies in the recent past have concen-
trated on various aspects of protein and amino acid metabolism. Gjes-
sing in Norway first showed -a correlation between nitrogen balance and
the mental chemges of periodic catatonia. More recently, there have
been reports of altered excretion patterns of amino acid and phenolic
amines in schizophrenia by Williams and by McGeer and their respective
associates, findings which have not generally been confirmed. One
major program of the laboratory is a systematic examination of the
metabolism of certain amino acids (e.g. phenylalanine, tyrosine, tryp-
tophane, histidine, glutamine) in normal man and in patients suffering
from schizophrenia.

-35-

There are at the present time three hypotheses^ widely held, if
poorly supported, for a significant biochemical mechanism in the patho-
genesis of schizophrenia. Iliese involve, respectively, epinephrine,
ceruloplasmin, and serotonin. The epinephrine hypothesis postulates a
disordered metabolism of this hormone in schizojiirenia with the produc-
tion of toxic schizophrenogenic substances » It is based upon the un-
confirmed finding of Osmond, Smythies, and Hoffer of hallucinogenic
properties in adrenochrome and adrenolutin, and on the finding by Leach
and Heath of a more rapid oxidation of adrenaline in vitro by schizo-
phrenic serum. McDonald and the Section on Medicine have confirmed the
latter finding but have shown further that it is related to and probably
explained by the low levels of ascorbic acid usually found in unselected
schizophrenics. Since there is no evidence for the formation of adreno-
chrome or adrenolutin in vivo in normal or schizophrenic man, a project
is under way in the laboratory which is studying the effects and fate of
this important hormone in these two popislations .

An elevation in the copper -containing globulin, ceruloplasmin, in
the serum of schizophrenics was first reported in 1955 "by Ozek in Ger-
many, and in 1956, Leach and Heath demonstrated that it was the impor-
tant enzyme in the in vitro oxidation of epinephrine. In 1957 Akerfeldt,
in Sweden, applied the dimethyl -paraphenylenediamine test for cerulo-
plasmin to schizophrenic serum and showed that the positive reaction
was related both to an increased ceruloplasmin and a decreased ascorbic
acid. In the past year, McDonald and his associates in the Section on
Medicine have shown further that ceruloplasmin is not characteristically
high in schizophrenia, and that the positive Akerfeldt test in this di-
sease is more the resxilt of a low ascorbic acid v±iich is probably on a
dietary basis, since he was able to demonstrate normal levels of this
vitamin and a negative Akerfeldt test in schizophrenic patients at the
Clinical Center kept on an adeq.\iate normal diet. This interest in cerulo-
plasmin has prompted the initiation of a project by Hansen in the Sec-
tion on Cerebral Metabolism on copper metabolism in normals and schizo-
phrenics. An outgrowth of the ceruloplasmin hypothesis has been the
reported isolation by the group under Heath of a substance, taraxein,
reported to be an altered form of ceruloplasmin which they find capable
of producing certain of the manifestations of schizophrenia on injection
into prisoner volunteers. Bobbins aoad Smith, on the other hand, have
been unable to confirm these findings. The laboratory awaits better
characterization of this substance and more reproducible techniques for
its production before attempting to eval\mte these reports. Interest
has also been aroused in the laboratory by the preliminary report of
Winters of the ability of small doses of schizophrenic serum to pro-
duce behavioral chaages in the rat. A discussion has been arranged
with Winters for the purpose of working out some eollabozative vali-
dation of these findings.

-36-

The hypothesis that an abnonnality in the metabolism of seronto-
nin occurs in schizophrenia stems from the discovery by Hofmann in 19^3
of the hallucinogenic properties of lysergic acid diethylamide and the
demonstration by Gaddum and Woolley, independently, of an anteigonism
between this substance and serotonin. Rirther support has been found
in the demonstration by Udenfriend, of the National Heart Institute,
of the presence of enzymes for the formation and destruction of sero-
tonin in various parts of the brain, the isolation by Homing of the
NationaJ. Heart Institute of dimethyl -serontonin from the cohaba bean,
and the demonstration by Isbell, of the NB4H Addiction Research Center,
that dimethyl-serontonin possesses hallucinogenic properties. This
hypothesis is compatible with findings of Brodie's group in the Nation-
al Heart Institute of a release of brain serontonin on the administra-
tion of reserpine and the behavioral effects reported in animals and
man of the administration of marsalid which increases the brain sero-
tonin content. The only evidence at hand, however^ for an actual dis-
turbance in serotoain metabolism in schizophrenics is the finding by
Zeller that such patients fail to show the normal increase in 5-
hydroxyindoleacetic acid which he has found to follow the administra-
tion of tryptophane. Several projects contemplated or initiated as
peurt of the amino acid metabolism program of the laboratory propose
to test the metabolism of tryptophane and serotonin in schizophrenic
patients .

Even a casual review of the literature reveals no dearth of
positive findings in schizophrenia from every biological discipline.
On the other hand, it is extremely difficult to find any T^rtiich have
been confirmed by others or for which there is evidence that they are
characteristic of a si^iificant proportion of schizophrenics and fun-
damental to the process rather than being completely secondary to the
disease or to present methods of its treatment. TSiere appeatr to be
at least two factors operating to produce this unfortunate state of
affairs, in addition to the emotional domination and tendency to re-
port preliminary results quiclsly and widely which seem to character-
ize research in those diseases which constitute important national
problems. The diagnosis of schizophrenia, being entirely phencmeno-
logical and clinical and without etiological bases, is apt to include
a number of different diseases with a common symptomatology. This
would introduce major sampling errors in studies on relatively small
samples, especially idaoee limited to a population at a single institu-
tion as practically all of lihese studies have been, and might help to
explain the extremely large variability in biological data obtained
on "schizophrenics" and the infrequency with wfeich these are confirmed
by subsequent investigators. Perhaps a more important factor has been
the general fall\ire to control the impoirtant non-disease variables,
which are either secoaadary symptomatic featxzres of the disease or
which £ire associated with the chronic hospitalization to which most
of the patients are subjected. Dae "controls" for most of the
studies in schizophrenia have been hospital or laboratory staff under
normal conditions of life.

-37-

We feel, nevertheless, that this is a particularly propitious
time for a major effort in this field, hopefixLly avoiding or, at
least, attempting to minimize some of the methodological pitfalls
to which previous studies have been subject. The recent twin studies
of Kallmann and Slater, confirming and extending those of previous
workers, strongly suggest an important role for biological factors
in the etiology of many types of schizophrenia. In the past two
decades the field of intermediary metabolism has been largely xra-it-
ten and a wealth of basic information made available on possible
biochemical mechanisms which have been studied only partially in
normal man and practically not at all in schizophrenia. There are,
furthemiore, certain new techniques which were not available to
previous studies: chromatography for the separation of large num-
bers of constituents, various techniques of spectrophotometry v.Gi-
lizing ultraviolet, infrared, or fluorescence for the sensitive
detection and quantification of chemical substances, and the use
of isotopic techniques for the tracing of metabolic pathways in man.

Dr. Perlin and the Section on Psychiatry has given considerable
attention to the problem of selection of patients, in an effort to
minimize the incidental and non-disease variables in the sample and
to maximize within the sample the incidence of those fonns of the
disease in which genetics and biological factors operate signifi-
cantly. These patients are housed in the Clinical Center and main-
tained under optimal dietary and therapeutic care in conditions
which tend to provide a normal amotmt of activity, and with appro-
priate psychotherapy designed to minimize the disturbance snc- the
anxiety associated with the institutionalization and with tlie obser-
vations themselves. The schizophrenic group is controlled by means
of a population of normal individuals, maintained as much as possi-
ble under similar conditions of diet, activity, and management.

These two controlled populations offer to the members of the
laboratory and to other interested investigators a unique opportu-
nity to test various hypotheses relating to schizophrenia and to
correlate their findings with those of others in different fields
who have studied the same population. Reference has already been
made to some of the specific projects now under way or being initia-
ted which include studies on electroencephalographic changes, the
effects and fate of epinephrine, blood levels and metabolism of
glutathione, copper, ceruloplasmin, and ascorbic acid, and the meta-
bolism of such amino acids as tryptophane, histidine, glutamine, and
tyrosine .

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KESEARCH OF THE SECTIONS

The Section on Psychiatry under Seymour Perlin has concerned
itself with psychiatric variables and their correlations with hio-
logical measirrements o In the past year an interesting relationship
has "been discovered between cerebral oxygen utilization and certain
personality traits or the psychological state of the individual at
the time of the procediire. These studies are being extended to de-
termine whether the relationship is maintained. A careful psychia-
tric study by Pollin and Perlin of normal volunteers has elucidated
a very high incidence of significant psychopathology which was high-
ly and inversely correlated with the extent to which external factors
operated in the volunteering process o This represents a contribution
of considerable significance in clinical investigation on volunteer
populations. Reference has already been made to the excellent theo-
retical study and practical achievement in the problem of selection,
of an adequate population for biological research in schizophrenia.

The Section on Physiology under Edward Evarts has continued its
program of studies related to the correlations between drug action,
behavior, and electrophysiology. By meajis of chronically implanted
electrodes in trained, conscious animals, clear-cut differences be-
tween the cortical effects of hypnotic and ataractic drugs have been
demonstrated. The absence of cortical depression by the latter group
may help to explain the selective behavioral effects of these drugs.
Clinical psychological studies by Kornetsky on a number of centrally
acting drugs have revealed significant effects on intellect^^al, motor,
and perceptiial skills by meprobamate in normal subjects. In schizo-
phrenic patients single therapeutic doses of chlorpromazine or seco-
barbital produced similar impairment of intellectual, motor, and per-
ceptual functioning, but during chronic administration of these agents,
the deficits associated with chlorpromazine disappeared.

One of the major interests of the Section on Medicine, headed by
Roger McDonald, has been the interrelationship between the nervous and
endocrine systems as Indicated by the hypothalamico-hypophysial sys-
tem. In the past year McDonald has evaluated a widely held concept
that pitressin is the neurohormone which directly stimulates ACTH re-
lease from the anterior pituitary gland. In a series of crucial ex-
periments he has shown that pitressin and ACTH release can occur inde-
pendently of each other and that morphine, which acts on the central
nervous system, effectively blocks the ACTH release associated with
pitressin, thus demonstrating that the pitressin effect is not a direct
one upon the anterior pituitary gland. The studies of McDonald and
this section on many of the biochemical dist'urbances thought to be
associated with schizophrenia, highlighting nutritional factors as
their probable cause j have already been mentioned. They have brought
a new and critical approach to the field of the biology of schizo-
phrenia, an approach much needed lest this Important interest be
stifled in its very reawakening by overenthusiastic and undercritical
conclusions.

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Laboratory of Psychology
Dr„ David Shakow

As has been pointed out in previous annual reports,
the program of the Laboratory, despite having certain clear-
cut areas of activity such as is represented by the separate
Sections, is best viewed as a whole and in mutual context „
I shall therefore combine the report on the activities of
the seven Sections which comprise the Laboratory without mak-
ing a distinction as to source of support — Clinical Investi-
gations or Basic Researcho I shall concern nyself first with
reports on the status of various studies and then consider
other material of relevance as an annual report o

Although there are still four important programs which
have not reached the stage where they may be considered as ,
actually launched, the rest of the work of Laboratory in this
fourth year of activity is well under wayo This, despite the
fact that two Section Chiefs, those in Personality, and in
Learning and Perception, have not as yet been appointed,, It
appears, however, that the first problem will be solved as
of the middle of next year, and various plans are afoot to
solve the secondc In the meantime, the Acting Chiefs of the
two sections have worked most conscientiously at their tasks
of keeping the administrative machinery going.

Although some work has already started, the major
program in relation to schizophrenia is still to be worked
out. With respect to the research to be carried out on wards
3-V/ and 3-E some preliminary planning is in progress but
largely it awaits the coming of the new Chief of the Adult
Psychiatry Brancho We are most anxiously awaiting this de-
velopment since it will afford us an opportunity to deal with
more molar and social aspects of schizophrenia — a necessary
complement to other kinds of schizophrenia research we are
carrying on and planning. Since this summer we have been
carrying out a series of studies on wards 4--W and 2-W, but
these have been considered largely pilot projects to develop
methodology and refine our concepts. The principles for the
selection of patients and controls on these wards having been
established, we are now ready to enter with a more definitive
program. The schizophrenia program to be carried out at
St, Elizabeths Hospital is in part awaiting the completion
of the construction which is going on there at the present
time and the period of basic relation-building which
Dr, Elkes is now in process of carrying out in this new
set-up. By the beginning of the next year it is hoped that
a program of research utilizing this unusual facility will
have been formulated.

-^0-

Although minor sub-projects have been carried out, the
central Psychotherapy Sound-Movie Program has suffered serious
delays over a three-year period because of the slowness with
which construction of both the room and projector equipment
has proceeded. However, it looks as if the major construction
work will shortly be over and with the coming of Dr. Bergman
plans have already been laid for actually carrying through a
full psychoanalytic psychotherapy. The problem of freeing more
time for this study for the two major investigators now becomes
acute.

In presenting the present programs, I plan in general to
follow the organization of last year's report; that is, to pre-
sent the work of the various sections separately in order that
the stage of development they have reached and what they are
engaged in will be clear. It is important, however, that the
section reports should be presented in the context of the general
program of the Laboratory because there is a certain kind of
artificial separation which derives from the section organization.

The general goal of the Laboratory, stated in its broad-
est terms, is the study of psychological function - both normal
and pathological - in the context of specific behaviors or in
more generalized structures of personality. In many instances
these functions are studied explicitly in relation to nervous
and other somatic systems. In other instances they are studied
independently and with only an implicit acceptance of such re-
lationships, either because these relationships are not immedi-
ately relevant, or are not presently available for study. This
broad but focal concern with psychological function is approach-
ed through various avenues, each of which contributes to the
total picture. These approaches may be roughly designated as
the study of the developmental, aging, mature, and pathological
aspects of the organism. The last is considered both with re-
spect to the character of the pathology and with respect to
efforts at its modification, whether through individual psycho-
logical, psychosocial or physiological means.

Against this background I shall first consider the work
of the three sections of the Laboratory in the Clinical Investi-
gations area: Child Development, Personality, and Section of
the Chief.

-a-

Child Development

The Section on Child Development has continued its re-
searches along the general pattern set in previous years, an
emphasis on the study of basic processes and developmental
aspects of behavior in infants and young children. Several
studies have been carried through to completion, and new ones
have been initiated. The five senior members of the staff
all continue in the program. One psychologist at the Ph.D.
level. Dr. Yvonne Brackbill, was added to the staff in August,
to assist Dr. Gewirtz with his studies on infant learning.
Dr. Belinda Straight, as a guest investigator, has continued
cooperative work with Dr. Bell in the study of one-month old
infants and their mothers.

Research in the section is directed toward evaluating
the inherent, maturational and environmental determiners of
personality and development in infancy and the persistence of
early emotional and behavior patterns, as they relate to mental
health. At present several fundamental methodological and pro-
cedural studies are under way. Some of these studies are con-
cerned with devising tools for use in a more general longitudi-
nal study of personality development. The children selected
for study are presumably normal, although some selections of
subjects are made on the basis of specific conditions that
could affect mental health. For example, in addition to
babies in normal homes, we are studying infants living in in-
stitutions and infants whose parents have contrasting and
possibly psychopathogenic personalities or attitudes toward
child rearing practices. One group of studies is concerned
with available data from the Berkeley Growth Study, in which
characteristics of the mothers' personality are related to the
personality and development of the children (on whom records
are available from birth to 18 or 25 years). Significant re-
lations from this study are utilized in devising tests and
procedures for further studies of infant development.

The researches of Dr„ Gewirtz are concerned with the
etiology and conditions of dependency and attention-getting
behavior, an area of importance because it is an aspect of the
central problem of how social learning takes place. Working
with nursery school children he has experimentally observed this
behavior under conditions of social reinforcers (approval), and
their effect in situations of satiation and deprivation, and
has demonstrated significant relationships, (l) Brief social
isolation (equated to a condition of deprivation of all social
reinforcers) increased reliably the reinforcing power (i.e.,
the importance) of adult approval for children (aged 4-0 to
5-6) as a positive function of the degree to which they typically

-42-

sought such approval in other settings; and older children
in this age range were affected to g, greater extent than were
younger children. (2) In children aged 6-6 to 9-0, it was
found that brief social isolation (deprivation) enhanced the
effectiveness of social reinforcers representing approval and
social contact relative to a control condition (no treatment);
and that a brief condition of satiation for approval and social
contact decreased the effectiveness of those social reinforcers
relative to the control condition. Dr„ Gewirtz's current program,
with Dr, Brackbill, is directed toward observations of infants
under one year of age.

Methods are being explored with very young children
which reduce to relatively simple terms the complexities of
the behavior which characterize emotional dependence in later
childhood and which would relate those behaviors to critical
aspects of myriad environmental conditions to which young
children are typically subject. A series of prototype experi-
ments with human infants in a highly controlled institutional
setting represents the core of the experimental program.
Initially, these experiments will attempt to relate effects
in the child's pattern of emotional dependence to variations
in selected aspects of the caretaking process. At first, the
reinforcing aspects of caretaking and adult responsiveness to
the child are employed as variables; and the range of adult
responses which can function as reinforcers for the young child's
behavior will be explored. Selected stimulus events associated
with the caretaker are being set into a variety of contingencies
with different responses emitted by the child. After some of
the more common reinforcers which are provided by adult re-
sponses are determined, selected stimulus events (e.g., the
attention of a caretaker) involved in or attached to the care-
taking person may be set into a vaflety of contingencies with
these reinforcing aspects of the caretaking process; and
selected aspects of this process may be made contingent upon
different responses emitted by the child.

Dr. Rheingold is carrying out a series of studies on
social responsiveness in infants. Her work has been with
children in institutions, with re-tests in their homes of
children originally observed in institutions, and with compari-
sons between behavior in their homes and in a strange place of
the same children. In a monograph now published, she demonstrat-
ed increasing social responsiveness in institutional babies who
were given individualized maternal care, and she (together with
Dr. Gewirtz) has just completed a study in which she was able
to increase vocalizations in three-month old babies by positive
social reinforcement.

-43-

In a pilot study of a few infants living in their own
homes, Dr„ Rheingold has tested the developmental changes in
social responsiveness to known persons and to strangers, and
compared the difference of the infants' behavior In their
own homes and in a strange testing room. She has found evi-
dence of significant differences and plans to extend these
studies to a larger population. Data are now being analyzed
of observations made by Dr„ Rheingold and Dr, Bayley who
re-visited at 21 months of age infants first studied at
6 months while living in an institution. Half of these in-
fants had had an 8-weeks experience of special care-taking
by a single person. The follow-up study was carried out to
look for any evidences of long-term effects of the special-
ized care. Some slight differences of manner of social re-
sponsiveness are suggested,

Dr, Bell is conducting studies of early phases of mother-
child interactions on samples selected on the basis of the
mother's expressed attitudes toward children and child-rearing
(the PARI). Motion picture records of the infants are made of
standardized situations at 3 days of age, and of the mother-
child pairs at one month of age. Ratings of the mothers' be-
havior are being compared with their responses on the Parental
Attitude Research Instrument; the characteristics of the infants
are being rated at three days and at one month of age. Consist-
ency of the infants' behaviors, as well as patterns of mother-
child interaction relevant to the maternal attitudes are being
studied. The data having been collected, they are now in
process of analysis by a variety of methods. The general
approach used appears to have provided quite rich data on the
nature of the early child-mother relationship.

In addition to the PARI, a questionnaire-rating scale
filled out by the mother to express her attitudes to child-
rearing (described in earlier annual repolrts — which, by
the way, has received extensive use over the country),
Drs, Schaefer, Bell and Bayley have prepared for publication
two Maternal Behavior Research Instruments, which were de-
veloped for quantifying descriptive material from the case
files of the Berkeley Growth Study, One of these instruments
is based on material derived from interviews with the mother
about child-rearing and development which is carried out by a
sophisticated child clinician; the other is based on direct
observations of child-mother interactions in a relatively
standard situation, Dr, Schaefer has utilized this and other
material in applying fsctor analyses and Guttman' s radex methods
to the intercorrelations of maternal behavior scores, and has
concerned himself with developing, around the resulting pattern
of maternal traits, a theory of certain aspects of personality

-kU-

organization: the two factors of autonomy- control, and love-
hostility form the frsune in which the traits are organized in
a circumplex.

DrSo Bayley and Schaefer are carrying on a series of
studies of the Berkeley Growth Study material in which the
^^aternal personality scores are being correlated with other
parental data and with the children's scores. Findings so far
show patterns of relationship of maternal traits to socio-
economic status, to children' s happiness and activity and to
children's intelligenve scores, which if corroborated by fur-
ther study would have important implication for child-rearing,

A few of the findings might be mentioned here: Corre-
lations between the maternal traits and socio-economic status
show the higher status mothers to grant more autonomy to their
children, to be more cooperative in the testing situation, and
more equalitarian in their interactions with their children.
Lower-status mothers tend, on the other hand ttJ-oii-iaintain close
contact with and to be more intrusive, irritable, punitive and
ignoring of their children. When compared with characteristics
of the children, those children whose mothers grant autonomy
are equalitarian and cooperating, express affection, tend to
have below-average intelligence scores as infants but to earn
increasingly higher "IQs" to about six years and remain high
through 18 years. In contrast, those children whose mothers
are punitive, irritable and ignoring tend to have high scores
as infants but to develop slowly with even lower "IQs" to about
6 years, after which age they remain low. In both of the above
sets of comparisons the relations are much stronger for the
mothers of boys, than the mothers of girls. Among personality
ratings of the children, cooperative, equalitarian, affection-
ate mothers tend to have babies who are happy, calm (unexcitable)
and "positive", while the irritable, punitive mothers tend to
have infants who are rated as more active. The same relations
tend to hold for the boys after they are as old as 8 years, in
ratings related to their socially responsive, cooperative and
intellectually efficient behaviors in these variables the boys
who score high tend to have cooperative , equalitarian, affection-
ate mothers who had close contact with their babies. The boys
who rated low more often had mothers who were punitive, irrit-
able and ignoring. Further study is necessary to clarify the
nature of these relationships.

As part of a program for studying development in infancy,
Drs, Bayley and Schaefer have been trying out on infants and
successively revising, methods of recording and rating both
maternal and infant behavior observed during the infant develop-
ment tests. In connection with this program Dr„ Bayley is

-is-

preparing her California First Year Mental Scale, for a thorough
revision and restandardization. This revision is being under-
taken as a necessary preliminary to the infant study because
currently available tests for infants are out of date, inade-
quately standardized and procedures and scoring poorly defined.
It is planned to correct these inadequacies and to expand the
test to include emotional and attitudinal scores that will per-
mit a more comprehensive evaluation of the infant as observed
in the test situation.

Theories of the early formation of personality, both of
emotional adjustment and intellectual development are based on
rather general studies with very little experimental work under
specifically controlled conditions. The primary research efforts
of this section are directed on the one hand toward identifying
more or less specific environmental conditions that can influence
the course of development, and on the other hand toward studying
in infants their developing capacities to learn, and the stabil-
ity of both learned (or conditioned) behaviors and of matura-
tional trends in response tendencies. Once these are better
understood it will be possible to state more explicitly the
determining factors in the dynamics of personality formation.

The personnel and program of the section are utilizing
to the fullest extent the facilities available to it. It is--
at present necessary (both for lack of facilities and by demands
of the research designs) to make a large proportion of the ob-
servations in facilities outside of the NIMH, in hospitals,
well-baby clinics, orphanages, and in the infants' own homes.
For certain of the studies it would be desirable to have
accomodations either in the Clinical Center or in a separate
building, for housing normal, healthy infants who could be made
available for continuous study over periods of a few days to
several months, and either with their mothers or on a "Foster
care" basis. It is hoped that such a facility with the augment-
ed staff and caretaking personnel it would entail will be con-
sidered seriously as an important aid to the Child Development
research progi*am.

Personality Section

The program outlined in previous annual reports of this
Section has necessarily undergone some modification with the
resignation of two of the four investigators of the Section,
The remaining two investigators have continued their studies
of the process of change in attitudes, value systems and per-
sonality. The central focus of the Section continues to be
the development, testing and extension of current personality
theory. More specifically, the major effort of this Section is

-46-

the application of personality and social influence theory to
the problems of modification of attitudes, value systems and
behavior.

The ward milieu studies dealing with preferred nursing
roles have been completed this yearo In line with the develop-
ing program on ward 3-W stdflies will be undertaken to analyze
the nature of relationships existing among the hospitalized
schizophrenic and his parents. Although investigation of
psychosomatic disease came to a temporary halt with the re-
signation of Dr, Iflund, it is planned that some studies in
this area will be con*4nued by Dr. Handlon,

In planning the future directions of the Section, an
effort has been made to select personnel who will be able to
work closely with the Adult Psychiatry Branch in research and
case evaluation. Drs, Handlon and Waldman, who came on duty
in September, give promise of fulfilling this goal. They are
already actively engaged in planning collaborative research
programs with psychiatrists, sociologists and members of other
disciplines active on the Adult Psychiatry and Clinical Scieaees
wards.

In the ward milieu studies we have to date been concerned
with one important aspect of ward milieu, namely, the nursing
role as it relates to the treatment of schizophrenia. In this
setting efforts have been made to introduce predetermined ward
philosophies on the experimental basis. Under these conditions,
it is necessary for the experimenter (the ward administrator)
to communicate his concepts to the nursing staff and to help
them accept and apply them in order that the desired experimental
condition be achieved. The problems inherent in this mode of
research have offered a very practical and real-life situation
in which to investigate conditions affecting attitude change.
Over a period of two years data have been gathered concerning
the impact of five unique ward pilosophies on the psychiatrists
and nursing personnel. It has been found that psychiatrists and
nurses show consistently different concepts of the preferred
psychiatric nursing role and this offers a basic problem for
collaboration. It was further noted that although nurses may
show attempts at modification of their nursing concepts in the
direction of the new ward philosophy, these changes are unstable
and disappear over time. It was concluded that the less accept-
able a ward administrator's philosophy was to nurses initially,
the less it was finally accepted by them even after as much as
21 months of exposure to it. These studies have not as yet
been extended to measuring the effect of a given ward milieu on
patients inasmuch as the desired ward atmospheres, i,e„, the

-47-

experimental conditions have not been achieved. Other studies
of the development of psychiatric nursing attitudes were under-
taken with nurse trainees, graduate nurses and experienced
psychiatric nurses « It is clear that with the greater crystal-
lication of the nurse's identity as a professional individual,
her amenability to roles quite deviant from her own preferred
nursing role becomes progressively reduced.

It is anticipated that this Section will become increas-
ingly involved with ward studies particularly as the contemplated
studies of patient-family interactions get under way. Efforts
will be made to investigate the premorbid and postmorbid patterns
of interpersonal communication unique to families having a
schizophrenic member. It is planned that carefully controlled
studies will be made using a variety of techniques including the
quasi-groups technique where unknown to the subjects, the process
and substance of interpersonal communication can be systematical-
ly manipulated.

Two major investigations have been conducted in the area
of psychotherapy. One involves research regarding moment-to-
moment changes in the ego organizations of patients in the course
of psychotherapy. Current work is mainly concerned with the in-
vestigation of a speech disruption measure adapted from Mahl in
its relation to these ego states. Currently attempts are being
made to determine the influence of rate of speech on the incidence
of such speech disruptions. The continuing aim of this investi-
gation is to use these and other measure to define shifts in a
patient's ego state. The second investigation in the area of
psychotherapy relates to the communication of therapist's values
and preferences for types of content and emotional expression in
the course of therapy. This was investigated in the treatment
of two schizophrenic patients. This particular study was com-
pleted in its writing stage this year. It has, however, given
impetus to a broader program of study. It is planned that some
of the implications regarding values and expectations of patient-
therapist pairs will be the basis of a program of research re-
garding "drop-outs" from therapy. It is becoming increasingly
evident that a sizeable proportion of the total number of patients
referred for psychotherapy drop out of treatment without benefit
during the initial phases of therapy. These patients are describ-
ed in sociological terms as coming predominently from the lower
socio-economic groups. It is hypothesized that with further
analysis of these individuals, it will be found that an important
variable affecting drop-out rate is the nature and degree of dis-
^^repancy between therapist's and patient's values and role ex-
pectations. It is proposed that a study of the psychological
variables resulting in such communication failures will be in-
vestigated. The next step of the proposed program would be the

-4-8-

utilizatlon of the identified variables in treatment and in
quasi-treatment groups in order to facilitate communication
and the adaptation of the psychotherapy situation to the
special needs of this large group of patients. Such a
program would have both theoretical and practical signifi-
cance.

Another aspect of the "values" studies is a two year
study regarding the communication of "moral" values in the
course of psychoanalytic treatment which is being brought
to a close. This may provide data related to the question
of whether the intensive analytic relationship affects the
moral values of a patient in the direction of those held by I
the therapist. An analysis of the pattern of change in moral
values of each of the four patients studied will be under-
taken,

Dr, Handlon plans to investigate the relationships
among physiological states, individual personality structure
and susceptibility to the various psychosomatic diseases in
a program tentatively planned with Dr, Hamburg.

To date there have been but few attempts to develop
instruments that permit the simple and economic assessment of
the mental health of large segments of the population. Dr.
Handlon is collaborating with members of the Socio-environ-
mental Laboratory in the attempt to apply the Guttman Scalogram
technique to the development of valid and reliable measures of
"mental health".

The Section is also occupied with a research project
which may perhaps be classified most appropriately as "service
research", but which carries much wider implications. This
involves the evaluation of the NIH Research Associates Training
Program. The project touches on a very basic administrative
question: How best to facilitate optimal interaction between
the inherent capacities of the investigator and the stimuli
provided by the setting to promote creative productivity.
This project may develop into such scope that it may be neces-
sary to bring in researchers on a contract basis or to assign
investigators full time to this particular project.

Section of the Chief

The major areas of research in this section are
schizophrenia, psychotherapy, and the psychological aspects
of physical illness. In many respects the activities of this
section overlap with those of the Section on Personality.

-49-

It is our expectation that when the Chief of the Personality-
Section is appointed, some reorganization of the two sections
will take place looking towards further integration of the
activities of the two groups.

At the present time the members of the section who are
concerned with the problem of schizophrenia are Drs, Rosenthal
and Zahn in addition to the Chief. One continuing study by
Dr. Shakow involves the analysis of a large body of already
existing experimental data on the psychology of schizophrenia
as a basis for the development of theory in this field. Dur-
ing the year some progress was made on the analysis of this
material. In part this was used for a paper presented at the
Second International Congress of Psychiatry in Zurich. It is
hoped that eventually this work will result in several mono-
graphs on the psychology of schizophrenia.

The major group of studies consists of four parts and
will involve the members of this section who are working in
schizophrenia as well as members of other sections working in
this general area. It is essentially the over-all program in
relation to Clinical Center wards and St. Elizabeths wards
which is being planned as described in the introductory re-
marks to this report. Many of the studies will be carried out
concurrently and collaboratively with other Laboratories of the
Institute.

One series of studies deals with responsivity patterns
in schizophrenics. For this Dr. Rosenthal has the major respons-
ibility. Patients are being studied '£pr their responses at both
the autonomic and molar behavioral levels when confronted with a
variety of orienting situations. This is in part an outgrowth
of previous studies on reaction time and on response to other
forms of simple stimulation which have indicated the existence
of deficits in schizophrenic patients. For a preliminary study
a group of 13 schizophrenic patients selected on the basis of
alpha patterns have been under study since July 1957, The ex-
periment is still in process but the analysis of the material
should be begun shortly,

A second series of studies in which Dr. Shakow is par-
ticularly interested and which will be carried out with Drs.
Rosenthal and Zahn might be terms "capacity" studies, A con-
siderable variety of psychological functions have in previous
studies been found to normalize themselves under conditions
of either repetition or optimal conditions of cooperation.
There are however some functions in which such a tendency to-
wards normalization does not appear to exist at least in the

■50-

contexts in which they have been studied thus far. This
persisting pathology appears particularly prominent in sit-
uations where speed of response is called for by the environ-
ment . It is the purpose of the planned series of studies to
find out whether with repeated exposure to the same task over
a long period of time and with the setting of optimal conditions
for performance it is possible to achieve the same normalization
as is found in the other group of psychological functions. Some
preliminary studies have already been started in this area on
our wards here but mainly they are awaiting the development of
the wards at St, Elizabeths,

Still another group of studies, as yet not clearly de-
lineated, involve affective situations where attitudes of
acceptance or rejection by the environment enter prominently.
These derive in many respects from studies carried out by
Garmezy and Rodnick at Duke, dealing with patients having good
or poor prognosis, and should help to make more understandable
the incongruence between cognitive and affective functions as
characteristic of this type of patient,

A fourth group of studies subsumed under this general
program are the family and social studies now in process of
planning to be carried out by members of the Section on
Personality in association with the Adult Psychiatry Branch.
(See Project No, M-P-P-(C)-9)

Dr, Rosenthal has carried the administrative responsibil-
ity for the general aspects of the scientific investigation of
a group of identical quadruplet girls who have been under study
by investigators from various laboratories for a period of
several years. A large amount of data in different areas have
been accumulated. The integration and evaluation of these data
are to begin on a formal basis shortly. The psychological material
is in process of analysis by Drs, Rosenthal, Parloff and Waldman at
the present time.

The psychotherapy activities of the section center around
Project No. M-D(C) 1, and as far as this section is concerned is
being carried by Drs, Dittmann, Shakow and Bergman, Both methodo-
logical studies aimed at making the substantive attack on the
problem easier and a systematic theoretidal exposition of the
area as a field for research are included.

During the year Dr, Dittmann has been involved in two major
studies having to do with the micro-analysis of the complex data
of non-verbal communication provided by the special technique of
sound-movies which we are using. In one project Dr, Dittmannand

-51-

Dr. Lyman l.^nne of the Adult Psychiatry Branch have attempted
to find ways of coding speech in order to identify disturbances
which may be used as an index of psychological disturbance.
Pitch, stress, and juncture patterns were first studied with
the conclusion that these microlinguistic phenomena were too
closely related to the syntax of language to be carriers of
emotional communication. The next attempt was to work with
hesitations and breaks in speech » Although they could be coded
with fairly high reliability these qualities did not seem tO' be
related solely to anxiety, but to other, irrelevant factors.
During the present year a third set of phenomena were worked
with, the so-called "paralinguistic" phenomena. These include
changes in duration, loudness, pitch, intensity, articulation,
and vocalization as applied to unit of speech larger than the
morpheme. Preliminary study indicates that these phenomena can
be coded fairly rapidly and offer promise of eventual useful-
ness for dealing with one of the non-verbal communication
channels.

Another study being carried out by Dr. Dittmann has to do
with the judgment of facial expression from short sequences of
motion picture film. A previous technique of showing short
series of prints from motion pictures was abandoned as being
too artificial. The present technique involves showing short
sequences of film of about three seconds in length through ?
motion picture projector to the judges. Considerable reliabil-
ity has been obtained across judges, A pilot study was run to
test whether these scores could be related to other variables.
Using sequences of film of a patient following either leading
responses or confrontations by the therapist facial expressions
showed greater relatedness and calm following leading responses
and greater discomfort and apprehension following confrontations.
Judgments based on speech with meaning filtered out and on con-
tent alone showed trends in the same direction. The technique
appears to hold promise as a method of studying emotional com-
munication as mediated by visual cues. Reliability on a very
limited sample is high and the judgments can be related to other
variables. If this method holds up it may give us a beginning
towards the analysis of the visual communication channel.

During the last year Dr. Shakow did some additional pre-
liminary work on the project dealing with the information to be
derived from the repeated viewing of complex'- material. The
purpose of the study was to determine what additional relevant
information necessary for the understanding of various aspects
of the therapeutic process could be derived from successive
viewing of a film from a psychotherapy session and whether there
were major differences in the additional information derived as
between active and passive analytic approaches to the data.

•52-

Due to some lindtations of apparatus and press of time much
"less than the desirable amount of study could be carried out.
However, with the acquisition of our new projector it ought to
be possible to carry this project out with greater facility.
It is therefore being planned for the next year.

Another area of research is an psychological factors
related to physical disease that is being carried out by
Dr, Kendig in association with various of the other Institutes
and with some outside agencies „ Her major project is on the
self-concept and body-image as related to disease suscepti-
bility and organ choice. In this study she is exploring the
attitudinal factors insofar as they affect health and longevity.
She is particularly interested in early childhood attitudes
which may be instrumental in determining the nature of the self-
concept and the body-image, especially in relation to suscepti-
bility to illness, organ choice, course and outcome of disease.
At first Dr, Kendig used an extensive series of self-concept
tests and a variety of projective techniques on a group of
physically ill patients. However, these proved unsatisfacgory
since they seemed mainly to reflect the present self-concept
and body-image as unfavorably modified by years of illness.
It therefore seemed necessary for her to develop an elaborate
detailed questionnaire or interview schedule which would dis-
close the attitudes towards the self and the body inculcated in
early childhood, explicitly by direct instruction and implicitly
by the emotional climate of the home and family reactions to
illness. During the past year such an instrument has been de-
vised and pre-tested on two patient groups and on one group of
normal controls. The scales are now being drawn up so the data
can be coded and treated quantitatively. In the course of the
current year the expected coding of the interview schedule
which has already passed through a number of forms will be com-
pleted and a weighted scoring system devised. It will then be
used with groups of patients in five of the other Institutes
and with normal control groups.

Partly in relation to this study and partly as an out-
growth of her association with the other Institutes at the
Clinical Center Dr, Kendig has become involved in a study of
intractable (phantom) pain with Dr, John Van Buren of NINDB
and on precocious puberty and pseudo-hermaphroditism with
Dr, Roy Hertz of the National Cancer Institute, Both of these
studies throw light on the body- image and the self-concept and
therefore contribute to her major project. She is also seeing
a group of patients who are being studied for the effects of
various drugs by Dr, Conan Kornetsky, Again in these patients
she is interested in problems of body- image and self-concept.

■53-

There are a few other studies going on in the Section
which are not directly related to these three major areas.
One is a further development of the study which Dr„ Dittmann
has been carrying out with Dr. Wells Goodrich on interaction
patterns of normal and hyperaggressive children, a project
reported upon last year. Their work during the present year
has been chiefly concerned with further reliability studies
of the methods developed. In this connection Dr. Dittmann
has undertaken a study of dimensionality of psychological
variables using non-metric techniques. This is an attempt to
deal with certain problems in ordering data derived from per-
sonality material.

Dr. Paul Bergman, who has recently arrived and who is
to participate as therapist in the psychotherapy sound-movie
project, will also undertake a program of research of his own.
These are of course only in the planning stage at present.
They are to be along the lines of the relation between the
effects of psycho somimetic drugs and psychotherapy, and on
the interaction of other adjuvants and psychotherapy.

In closing this summary of the work of the Laboratory
of Psychology I should like to point up succinctly and without
elaboration a few tentative but important generalizations which
derive from the preparation of the reports of the several
Sections, These refer to common trends which appear independent-
ly despite the diverse approaches to the study of psychological
functions by different methods and with different subject matters.

The first of these is a methodological point — that of
the value of the comparative method. It is through the com-
parative approach that we become impressed with the tremendous
potentialities which lie in the interaction of the complicated
psyche of the human (and its associated nervous system) with a
stimulative complex social environment. We get an inkling of
what such an interaction does for the full development and exer-
cise of the organism's capacities. This picture is made even
more vivid when we see these same principles reflected in lesser
degrees in lower orders of animals, in the aged, in psychoses, etc.

Thus, we see in the report of the Aging group evidences
for the potentiality of the organism for maintaining a high level
of psychological function despite some biological decline. The
difference between younger and aged rats is in many respects
small or even non-existent. Also, this time in human subjects,
similar scores are obtained in a variety of functions when the
aged come from active rather than from limited institutional
environments.

-5V

In the report of the Section on Animal Behavior we find
that even when the human organism is damaged physically in an
important part of its brain, the potentiality for recovery is
great. Thus after frontal lobe damage monkeys seem to be
permanently affected in delayed- response type tests, chimpan-
zees are also impaired but are able to recover with retraining;
in man there does not seem to be any consistent damaging effect
on problem- solving behavior. We also see a similar phenomenon
in studies we have made of schizophrenics where optimal environ-
mental pressure frequently brings patients close to capacity
levels which are not far from the normal „ We find it at another
level in Dr. Calhoun's report of the importance of social
factors in space utilization by mice and shrews living in wood-
lands. And we may have similar data from Dr. Kendig' s studies
soon in still another area — physical disease and organ choice
as related to the self-concept and the body image.

All of these studies seem to be leading in the direction
of saying that despite the genetic factors which may be playing
a role in either normality or pathology, the human organism has
a tremendous range of potentiality which neither psychosis, nor
age, nor brain damage can more than partially stay in its course
if a social environment is provided which is sufficiently rich
and appropriate to make demands on its potentialities. It is
in this context that our developmental studies in handicapped,
normal and superior subjects (both animal and human) become so
important, for it is there that we can ask ourselves the im-
portant question: What is the process by which these potenti-
alities are most effectively built up for optimal use, for re-
sistance to destroying factors, and for recovery from such
destroying factors?

-55-

Laboratory of Socio-environmental Studies
Dr. Marian Radke Yarrow

The research goal of the Laboratory is the investi-
gation of the ways in which social processes bear upon the
production and course of psychic disturbances. Included
with this goal is a wide range of research areas: the
nature and distribution of mental illness and behavioral
pathologies, social and cultural variations in defining
and treating behavioral disturbances, social and cultural
patterns influencing personality development, interpersonal
processes within the family, and social processes in the
treatment setting of the mental hospital. This range of
interests is represented in the current projects of the
Laboratory o

With the growing recognition of the importance of
social aspects of illness and with the realization that re-
lationships between social and medical or biological factors
are more complicated than has been assumed, there has been
an intensification of research interests and efforts in
conceptual and methodological issues and in collaboration
across disciplinary lines.

During 1957, the organization of the Laboratory has
been completed with the staffing of the Section on Social
Studies in Therapeutic Settings.

Social Studies in Therapeutic Settings

In recent years there has been an increasing recog-
nition of the therapeutic significance of the mental patient' s
social environment. The mental hospital is more than simply
an auxiliary setting within which therapy goes on; it is a
relatively long-term and all-encompassing life experience
which, by virtue of the special nature of mental illness,
necessarily has therapeutic consequences. This fact has led
to an interest in studies of interaction among patients and
between patients and staff, social role definitions of patients
and staff, lines of communication and patterns of decision-
making in the hospital, values, norms, and behavior of adminis-
trators, physicians, nurses, attendants, and patients, and
various other aspects of hospital structure which appear to
have consequences for the course of mental illness.

■56-

In 1957s for the first time, the Clinical Investiga-
tions Branch undertook to support the operation of such studies
through its budget o This decision was followed by a period of
active recruitment of social scientists who were motivated and
equipped to cope with the problems in this field o This has
been accomplished successfullyo Since five of the seven pro-
fessionals (including one Visiting Scientist) have entered
this Section within the past two or three months, the general
section program is still in its early stages of development.
Dr„ Morris Rosenberg has recently assumed direction of this
Sectiono

Active planning is currently under way for the collabo-
rative research witn other units of the Clinical Investigations
Brancho Mr, Turk and Mr„ Lefcowitz are currently developing
plans for research designed to form an integral part of the
Neuropharmacological Program at Sto Elizabeths Hospital c
Dr, Pearlin and Dro Rosenberg are collaborating with members
of the Adult Psychiatry Branch and the Laboratory of Psychology
in the development of a research program in Ward 3-West of the
Clinical Centero Dr, Wallin is currently working with the
psychiatric group in Ward 3-East of tne Clinical Center in
the intensive study of families of schizophrenics arid is using
this information for the development of scales about parent-
child relationships associated with the development of schizo-
phrenia o Such collaborative undertakings, to which a large
part of the staff time is likely to be devoted, are pursued in
the faith that the pooling of skills and perspectives from
different fields will pro^ilde fruitful insights and valuable
data bearing on the therapeutic process,

MPo Perry j, in his work at the Clinical Center, has
provided a detailed demonstration of how the objective
positions of staff members in the ward structure influence
their attitudes and behavior toward the patients. These
studies are scheduled for completion this year.

During the past year Dr, Goffman has continued his
intensive investigation of the social life of the mental
hospital patient at St, Elizabeths Hospital, Using partici-
pant observation J unstructured interviews ^ and case record
sampling, he has succeeded in specifying some of the thera-
peutic implications of the pattern of involuntary incarcer-
ation and stigmatization which characterizes life in the
mental hospital.

PUBLICATIONS NOT RELATED TO A SPECIFIC PROJECT

Ader, R, and Clink, D„ W„ Effect of chlorpromazine on the acquisi-
tion and extinction of an avoidance response in the rat.
J„ Pharmacolo & Exper, Therap, 121; 1957 (In press).

Bayley, N.s National Parent-Teacher Quiz Program - Questions and
Answers, Nat'l Parent-Teacher. 51, #5, 28. Jan. 1957.

Bayley, N.: On the Growth of Intelligence, Translated into Japanese
and reprinted in Americana. A monthly J, of Humanities, Social
Sciences, and Natural Sciences, _2, #11, Nov. 1956.

Bayley, N.: A new look at the curve of intelligence, Proc. of
1956 Invitational Conf. on Testing Problems. New York:
Educ. Testing Service. 11-25, 1957.

Bayley, N,: Data on the growth of intelligence between 16 and 21
years as measured by the Wechsler-Bellevue Scale, J. Genet.
Psychol, , 90, 3-15, 1957.

Bayley, N,: Predicting children,! s Intelligence, Nat'l Parent-
Teacher. In press.

Carlson, 7,R,: Effect of lysergic acid diethylamide (LSD-25) on
the absolute visual threshold. J. Comp. Physiol, Psychol.
Submitted for publication,

Dittmann, A.T,, and Moore, H.C.: Disturbance in dreams as related
to peyotism among the Navaho. American Anthropologist. 59.
6^-64.9, 1957.

Dittmann, A. T,: Review of Harry Stack Sullivan's Clinical

Studies in Psychiatry, Contemp. Psychol.. 2, 127-129, 1957,

Glasner, P.J., and Rosenthal, D,: Parental diagnosis of stutter-
ing in young children, J. Speech & Hearing Disorders. 22.
288-295, 1957,

Handlon, J. H., and George, F.H.: Language for perceptual analysis.
Psychol. Rev.. 6^, U-25, 1957,

Handlon, JoH,; Personality changes following alteration of
external genitalia in female pseudohermaphroditism,
Psychosm. Med, . 1957. In press, (with I.K.Rosenwald and
I, M .Rosenthal ) .

- 51 -

-2-

Publications (Cont'd)

Kelmanj H„C„, and Parloff, MoB„: Interrelations among three
criteria of improvement in group therapy: Comfort,
affectiveness, and self awareness. Jo Abn, & Soc.
Psycholo 5^, 281-2S8, May, 1957.

Kendig, I,V.: The Un-Merry Widow. Book Review, Cont. Psychol.
In press,

Kety, S„S.: The implications of psychopharmacology to the
etiology and treatment of mental illness. Ann, N.Y.
Acado Sci,, 66: 836-8^0, 1957,

Kety, S,So: Recent studies in psychopharmacology, A,M,A.
Arch, Neurol, and Fsychiat., 77: 278-279, 1957.

Kety, S.S,: The cerebral circulation in man. Triangle, 2.'
47-52, 1957,

Kety, S.S,: The general metabolism of the brain in vivo.
The Metabolism of the Nervous S'/'stem, edited by
D. Richter, Pergamon Press, London, 1957 (In press),

Kety, S.S,: Determinants of tissue oxygen tension. Fed. Proc,
16: 666-670, 1957.

Rheingold, H.: The modification of social responsiveness in
institutional babies. Mono. Soc. Res, Child Develop.
21, Serial No, 63, #2, 1956,

Rosenthal, D.: Drug research design in a psychiatric out-
patient setting. Proc, of Conf. on Evaluation of
Pharmacotherapy in Mental Illness. In press,

Rosvold, H.E,, Mirsky, A.F., Sarason, I., Bransome, E,D,,

and Beck, L,H,: A continuous performance test of brain
damage. J, Consult. Psychol. . _^, 34-3-350, 1956.

Sternberg, R,, Chapman, J., and Shakow, D. The problem of
intrusions on privacy in psychotherapy research.
Psychiatry. In press.

Streicher, E. Biochemical investigation of the aging nervous
system. In press.

58 -

-3-

Publications (Cont'd)

Streicher, E. The neurobiological research program of the
Section on Aging of the National Institute of Mental
Health. Proceeding of the Conference on the Process of
Aging in the Nervous .System, Bethesda, January 30,
February 1, 1957.

Sokoloff, L., Perlin, S., Kornetsky, C., and Kety, 3,3.:

The effects of d- lysergic acid diethylamide on cerebral
circulation and over-all metabolism. Ann. N.Y. Acad.
Sci., 66, 4.68-^77, 1957.

Schaefer, E.S., and Bell, R.Q.: Patterns of attitudes toward
childrearing and the family. J. Abnorm. See. Psychol..
5U, B, 3S1-395, 1957.

Schaefer, E.S. and Bell, R.Q.: Development of a maternal

attitude research instrument. Child Develop. In press.

Waldman, M.: The application of developmental theory to problems
of social adaptation, (with L. Phillips and 3. Kaden)
In press.

- 59 -

NATIONAL INSTITUTE OF MENTAL HEALTH

Clinical Investigations

BUDGET SHEET

Estimated Obligations for FY 19*^8
Total: $^61,389
Direct: $353,652

Reinibiarsements: $107,737

Project: Neuropharmacology Research Center

ANNUAL REPORT

f SERVICES BRAT

January 1, 1957 - December 31, 1957

COMMUNITY SERVICES BRANCH, NIMH

INTRODUCTION

States and Territories have been receiving Federal men-
tal health grants-in-aid and technical assistance for ten years.
A major objective has been to help them establish sound adminis-
trative organizations at State level and to provide a well-trained
multidisciplinary staff for leadership. This was essential to
bring more direction to the scattered and often ineffective efforts
in community mental health programs and to insure continuity of pro-
gram. As a results most States and Territories now have a profes-
sional staff developing a program aimed at public education, preven-
tions treatments, and rehabilitation. An increasing amount of train-
ing and research is being built into these programs.

The recent broad-based legislation for State grants-in-aid
to localities for community mental health services to California,
Connecticut 5 Florida, Minnesota, New Jersey, New York, and Vetmont,
follows many of the concepts included in the "Program Guide"
issued by the Public Health Service in 1954, This type of legis-
lation seems to be setting a pattern for other States to follow.
Implied in these new programs are more organized efforts by State
administration to meet the demands of the public for preventive
and corrective services in the mental health field x^hich are equal
in quality and scope to general medical services. It recognizes
that institutional care of the mentally ill has been designed
chiefly for committed patients and does not meet the major needs of
early treatment and prevention. The growing emphasis on comrni^nity
services is likely to continue at a rapid pace, greatly increasing
the demand for trained personnel, coordination of medical and so-
cial services, insurance coverage j, and for research on the effec-
tiveness of programs.

State programs were developed by constant teamwork of com-
munity. State, and Public Health Service staff, based on the fol-
lowing assumptions;

Poor social adjustment and mental illness is
widespread, involving especially children, young
adult males, middle-aged females and the aged of
both sexes;

Syroptom complexes have many causes based on
imiltiple etiological factorSj even perhaps in an

individual cases

The public is inclined to view mental illness in all
ages as a single disease with a "mystical or unnatural"
cause. Methods of dealing with the mentally ill are
largely responsible for the lack of public understanding;

The public is increasingly concerned with the threat
of mental illness, and is extremely interested in preven-
tion. It is interested in utilizing all available know-
ledge in prevention and treatment programs even though
scientific knowledge is limited at present;

There are so many social and economic implications
in mental health and illness that the mobilization of
family and community resources are essential for an ef-
fective mental health program. With more involvement of
citizens in educational, preventive, and treatment pro-
grams, they would gain a better understanding of the na-
ture of mental illness and of the components of mental
health and would be in a better position to support re-
search, training and services.

Current research findings and improved treatment
techniques tend to increase rather than decrease the
need for more professional staff and organization; and
finally.

More effective and complete coverage of preventive,
treatment and rehabilitative services would be a tremend-
ous factor in preserving the manpower pool of the nation,
in addition to cutting down the morbidity and cost of men-
tal illness.

The increasing interest in healthy psychological develop-
ment of the child at home and in the school, and his ultimate
performance as an adult in a job and as a parent, has made the
public acutely aware of the need for corrective services. Be-
sides the general mental health services ordinarily provided,
there is increasing demand by organized groups for special ser-
vices to meet needs for particular areas of distress, i.e., alco-
holism, drug addiction, and juvenile delinquency. Maintaining an
organization which can integrate staff activity to provide all of
these special services and at the same time utilize scarce profes-
sional staff most effectively is a challenge to community, State
and Federal Governments. There is the danger that States, as well
as the Public Health Service, may respond to special areas in mental
health programs at the expense of a comprehensive approach, thereby
weakening the organizational structure which has been built so pa-
tiently in many States during the past ten years. In effect.
State leadership responsibility could be scattered again, as it
was in 1947.

Another problem is the frequent conflict about who will
be responsible for the total mental health program in States.
One group demands a Department of Mental Health with Cabinet
status, another expects the Health Department to become respon-
sible, and a third group advocates that mental hospitals be
given total responsibility. At this time there is insufficient
evidence that any one of these ways of organizing State mental
health services is the best for all of the States and Territor-
ies, Time and experience should help solve the problem and the
Public Health Service should advise caution despite the need for
stronger and more centralized leadership in some States. In any
event, there is little doubt about the need for hospital and
community programs to coordinate their efforts in serving people.

The more serious test of whether or not State and com-
munity programs will continue to develop in a healthy fashion
is still to come. Almost half the States and Territories have
considerable dependence on Federal grants for their continued
existence. Most of the other States use grants very effec-
tively in testing new methods and evaluating the effectiveness
of their programs, which generally would be impossible on State
resources. The morale and pace-setting value of grants is ex-
tremely important for all States and Territories. With so many
pressures for categorical health programs in States, leadership
is inclined to stay with those programs that are national in
scope.

The shortage of personnel is still serious but not dis-
couraging even though turnover is very great. The Public
Health Service regional office staff are more permanent than
many of the State program staffs and in many instances they
are depended upon to lend continuity to State programs. With
State leadership staff struggling to hold on to its gains and
to meet the increasing demands of the public for program
coverage throughout the State, there is great need for the
Public Health Service to continue technical assistance, es-
pecially for assessing community needs, introducing new meth-
ods, developing new areas of service, and in program evalua*
tion.

If the Public Health Service and the States are to
participate effectively in preserving the manpower pool of
the nations, so essential to national defenses more suitable
and widespread community mental health services, acceptable
to the public, m^ast be provided. Practically every profes-
sional person in his lifetime will face a serious social or
psychiatric problem, either in himself or his family, which
will partially or completely incapacitate him in his work
for a significant length of time. This time could be short-
ened if there were convenient and acceptable mental health
facilities available which were equal, for example, to the

-4-

facilities available for physical disabilities. When physical
illness or injury strikes it is usually recognized quickly and
facilities acceptable to the family are usually waiting to
serve. With mental disorders, it is often the reverse.

The Community Services Branch plans to assist States in
holding on to the gains made in community programs by providing
mental health consultants in every regional office to give sup-
port to State staffs, and assist in getting wider coverage of
services to all parts of the State. Specialists in special pro-
gram areas from within and outside the Public Health Service
will be provided to States to help them incorporate the latest
practices into their programs. Through technical assistance,
conferences will be held with State and community staff for the
exchange of knowledge and program development in new areas, es-
pecially in the field of alcoholism, drug addiction, school
mental health, and aging.

The Public Health Service will cooperate with the State
mental health authorities in conducting orientation conferences
to acquaint the staff of national. State, and local mental
health associations with public mental health programs. These
conferences should encourage voluntary and public organizations
to work together on common objectives and probably will result
also in increased support of official programs by citizen
groups.

The staff will work with individuals, groups, organiza-
tions, and institutions who are interested in new approaches
for prevention^ treatment, and rehabilitation of the mentally
ill. Besides providing consultation, in some cases, the devel-
opment of projects will be encouraged. More effort will be
given to improving hospital administration and treatment pro-
grams. This will be done by providing expert consultants to
hospitals, supporting conferences for the exchange of ideas,
special studies to improve operating procedures, demonstra-
tions, and small grants to hospital staff members in Isolated
areas so that they may spend time learning of new procedures in
more modem treatment centers.

Demonstrations will be continued in the aftercare of drug
addicts, mental health activities in a county school system, and
health education in a State mental health department.

Branch staff at the Study Center will continue to study,
at close range, one county in Maryland, to keep abreast of com-
munity organization and dynamics, and their influence on new
mental health serviceso These studies are important for devel-
oping in Branch staff a progressively deeper and sharper under-
standing of community mental health services, which is so essen-
tial for the staff role as consultants to States and local pro-
grams.

An effort will be made to assist States in transmit-
ting their training needs to universitieso At present,
universities tend to emphasize training for clinical ser-
viceSo State and local mental health staffs need training
in working with groups and community organizations in the
consultation process,, training techniques, administration,
and research design. Only by communicating their needs to
the training institutions can the universities begin to
meet the demands of modern mental health programs.

In order to keep abreast of developments in the men-
tal health field and maintain a leadership role^ staff will
continue to participate in inservice training, in national
and regional conferencesj and some will have special as-
signments to States. Staff will also participate in the
Public Health Service graduate training program. Next
year. Dr. Alan Miller mil return from a year's study in
England^ His special knowledge of the open hospital and
how it is integrated in the community will be utilized
widely by the Branch. A m.ore complete analysis of State
program activities will be made, including scope of pro-
grams, methods used, effectiveness, cost, legislation, and
program activities common to all communities. This infor-
mation is essential for redefining the role the Public
Health Ser\?ic8 should piay in the expansion of community
mental health ser\'lces throughout the nation. The States
have already laid the foundation.

FEDERAL LEGISLATION AND APPROPRIATIONS

No major Federal legislation directly affecting

the operations of the Coxsmunxtj Services Branch was enact-
ed during the year. The appiopriations for grants to
States for community ir-ental health services was continued
at $4j000i,000s as in the previous year., but Guam was added
to the States and Territories lAiich share in the grants.

For the first times appropriations ($2,000,000)
were made available for mental health project grants
(Title Vg Piiblic Law 911) ., covering the fiscal year end-
iEg June SOj 1958.

The total operating budget of the Branch for staff
, and admiaistration for fiscal year 1958 was $1,116,450,

slightly more than a year before.

BRANCH STAFFING

There were 62 professional staff members, plus sup-
porting secretarial staffg employed in the Branch at the

end of 1957. Recruiting additional staff for the Branch was a
major, time-consuming activity but was more successful in 1957
than in previous years. Despite the acute shortage of mental
health staff, 19 new professional employees were added to the
staff. Three professional employees left the staff leaving a
net gain of 15 employees. Ths three staff members who left the
Branch were psychiatrists, who are most difficult to recruit.

In central office, a public health physician was employed
as a specialist on alcoholism. For part of the year a new psy-
chiatrist worked on industrial mental health before her transfer
to a regional office. Also, an administrative assistant was re-
cruited.

The regional offices filled positions for two psychiatrists,
two clinical psychologists, two psychiatric social workers and one
mental health nurse, helping to complete the mental health teams
in the regional offices.

At the Mental Health Study Center, Dr. Alan D. Miller
was transferred to England for advanced study and research.
Dr. Stanley F, Yolles, formerly the Associate Director is the
present Director. In addition, a clinical psychologist was re-
cruited.

The two new demonstrations launched during the year (the
New York City Drug Addiction Project and the Volusia County-
Florida School Mental Health Project) were able to recruit a
full staff ccmpleiment (six social workers in New York City, a
psychologist and nurse in Volusia County). During part of the
year, the staff member conducting the demonstration on mental
health education in Ohio was reassigned to work on the Asian flu
program.

As in previous years, the Community Services Branch contin-
ued to be responsible for staffing the mental health clinic at the
D,C. Juvenile Court on a reimbursable basis, A psychologist was
recruited but the position of psychiatrist remains vacant. Plans
are bsiitg considered for the eventual transfer of responsibility
for the clinic to the District of Columbia,

During ths year, t>:.i?o psychiatrists on the staff completed
training in public health. A staffing innovation in 1957 was the
"Career Davslopment" plan. The purpose of this plan is to employ
young, promising, fully-traiaed professional people and provide
them with an opportunity to obtain a broader or higher level of ex-
perience in order to prepare them to fill the regular positions in
the Branch. I'toder this plan, a social worker was added to the re-
gional office staff and .assigned to work as the State- level social
work consultant in tb,s Arizona mental health program.

By ths end of 1957 there ^jrere only ten professional posi-
tions vacant and definite prospects or commitments for over half

of the positions. It seems quite likely that in 1958 almost
all of the Branch positions will be filled.

In 1958s, orientation of new staff will continue to be
an important activity. With the completion of the period of
rapid growth and expansion, 1958 should see a period of con-
solidation and, alsoj, the consideration of new ways in which
a larger staff can work together effectively.

In the Spring of 1957 9 most of the central office
staff of the Branch moved from the National Institutes of
Health grounds in Bethesda to Silver Springy Maryland. The
Hospital Consultation Service of the Branch remained on the
Institute reservation. Branch staff recognize the critical
space shortage at the National Institutes of Health reserva-
tion and also that the physical space a\7ailable in Silver
Spring is superior to the Branch space previously occupied on
the reservation. Howeverj the physical separation of the Hos-
pital Consultation staff from the rest of central office staff
tends to retard the development of a fully integrated Branch
program, despite the strenuous efforts that have been made to
maintain lines of communication. Similarly, the staff at
Silver Spring have lost many of the benefits of the easily ac-
cessible contacts with staff in other parts of the National
Institute of Mental Health,

DEVELOPMENTS IN STATE COMMUNITY MENTAL HEALTH PROGRAMS

The major function of the Community Services Branch is
to improves extend^ and strengthen State and local community
mental health services and mental hospital services. Federal
grants to States, irental health project grants, consultation,
technical assistance projects, field demonstrations are some
of the ways that are used to achieve this objective. A com-
prehensive program including prevention, clinic and hospital
services has been the goal. Of course, progress or lack of
progress in individual States and localities result from a
complex of factors and forces but the Federal program for men-
tal health services has proved to have significant impact in
moving programs ahead.

Plans submitted by States to the Public Health Service
show that on the T.'jholej State programs for community mental
health services continued to expand in 1957, moving toward
meeting the many large areas of unmet needs. Although some
States have suffered set-backs, by and large^ the coverage and
quality of State and local mental health programs are improv-
ing. More clinics have been establishedo Efforts are being
made to do more mental health education and to provide consul-
tation to other programs and agencies. In some States, it has
been possible to develop and expand a program of training sti-

-8-

pends and research. Stronger ties are developing between commun-
ity and hospital programs. Nationwide, increasing attention is
being given to specialized mental health services for particular
groups, such as alcoholics, aged, mentally retarded^ and patients
released from mental hospitalSo The regional mental health con-
sultants have had a continuing and important role in working with
States on these developmentSo

Organization

Relatively few changes in organization resulted from
State legislation in 1957. West Virginia was the only State
that had a major reorganization. The community mental health
program was transferred from the Department of Health to the new-
ly created Department of Mental Health which is responsible also
for the mental hospitals, the State Training School for the Re-
tarded and the Alcoholism program. Connecticut abolished its
Mental Health Council replacing it with a Mental Health Board and
gave the Commissioner of Mental Health more authority to direct
the program. Idaho changed the size and membership of its Board
of Health, and Missouri created a five member State Mental Health
Commission responsible for appointing the Director of the Division
of Mental Diseases in the Department of Public Health and Welfare.

Divergent organizational changes were made in relation to
alcoholism programs, Texas and Utah set up new independent alco-
holism agencies. However, two States (California and Indiana)
abolished their Alcoholism Commissions and integrated the alco-
holism program into the existing public health departments.
Illinois created a Division of Alcoholism in its Department of
Public Welfare and Washington established an alcoholism program
within its State Department of Institutions,

State Grants-in-aid to Localities

Probably the most f^ir-reaching development in 1957 was the
legislative action in four States (California, Minnesota, New Jersey,
Vermont) which followed the pattern of Connecticut and New York in
providing State grants-in-aid to localities for community mental
health services.

This type of legislation is highly significant in its im-
pact on the future development cf community mental health programs.
At the local levels theavailability of State matching funds makes
it possible for more e-eumil'^fcees co initiate .qew programs of commun-
ity mental health services. Where ^^aob^itcQsarh already complete-
ly supporting mental health services. State matching funds release
local funds which can be used to expand and improve existing services.

At the State level, the legislation indicates the acceptance
by the State of responsibility for helping to finance local mental
health services on a continuing basis. State appropriations for com-
munity mental health may be expected to increase. An eventual devel-

-9-

opment of local services throughout the State is implied.
Also State funds act as a binder in bringing closer working
relationships of State and local mental health staffs.

The use of Federal grant~in->aid funds is also af-
fected. Part of Federal grants are now being used to init-
iate mental health clinics in communities. With, the avail-
ability of State funds for this purpose,, Federal funds can
be used increasingly for demonstrations of new types of ser-
vices, pilot projects, training and research.

According to the Minnesota mental health authority,
"The recent session of the Legislature enacted the Community
Mental Health Act which provides basically for state match-
ing of local funds so that the communities can develop their
own local mental health services. Within four years we ex-
pect to liquidate the state financed clinics in favor of
this community operationo This new program is an example of
the use of the demonstration technique. The existing state
clinics were established several years ago and their ser-
vices expanded by the use of Federal funds. They have dem-
onstrated their value and the communities are now willing
to share in this cost."

Using a different approach to the development of lo-
cal community mental health services j three Midwestern
States (Iowa, Kansas and South Dakota) authorised their
counties to levy taxes or appropriate funds to support lo-
cal community mental health centers or clinics.

Funds

According to the plans submitted by States to the
Public Health Service for the fiscal year ending June 30,
1957, States budgeted $45.4 million of Federal, State, local,
and private funds for community mental health services, 76
percent more than a year before. Excluding New York State
which accounted for $14.1 million of the total increase of
$19,5 million, funds budgeted by the States increased by 28
percent. The largest gro^irth was in mental health clinical
services which rose from $18.1 million in 1956 to $37.8
million in 1957.

Of the $45.4 million budgeted in 1957 the large majori-
ity (83,3 percent) was for clinical services. Of the remaind-
er, 4.4 percent ($2,0 million) was budgeted for the State men-
tal health program administrative unit, 2,9 percent ($1.3 mil-
lion) for the control of alcoholism,, 2,0 percent ($0.9 million)
for trainings '^"^ percent ($0,7 million) for research, and the
rest for other types of services. Federal funds ($4 million)
constituted only 8,6 percent of the total funds budgeted,

-10-

State and local community mental health programs have
expanded tremendously following the availability of Federal
grant-in-aid funds beginning in fiscal year 1948. In 1948,
$3 million of Federal funds were available and $2,4 million of
State and local funds. In fiscal year 19575 Federal funds had
been raised slightly to $4 million but State and local funds
had skyrocketed to $41,4 million.

Preliminary tabulations for fiscal year 1958 indicate
a continued increase in funds budgeted by State Mental Health
Authorities for community mental health services. Available
data for 45 States reveal that 34 States have more funds avail-
able in 1958 than in 1957 and 11 States have less funds. For
the 45 States combinedj 20% more funds were budgeted in 1958
than a year before. New York State, which alone spends about half
of the total funds budgeted In the nation, reported a tremendous
increase of $6,4 million between 1957 and 1958, Other States re-
porting large increases included Alabama (747,), Delaware (537,),
Louisiana (307,), Ohio (407,), Oregon (837,), West Virginia (1217,),
and Wyoming (847,), States reporting decreases included Kentucky
(107,), New Mexico (187,), Washington (157,), and Puerto Rico (427,).

Three States (Colorado^ Washington, Wyoming) for the
first time in 1957 voted specific State appropriations for com-
munity mental health services, thus joining the large majority
of States which already have identified mental health appropria-
tions. Such action by a State legislature is concrete recogni-
tion of the State's responsibility for community mental health
services, and usually sets a precedent for additional and more
adequate appropriations in future years.

Staffing

The development of strong State-level mental health teams
to provide leadership in the States has been a long-time objec-
tive of the Branch, The Branch has especially encouraged a basic
State level team which includes representatives from the four men-
tal health disciplines of psychiatry, clinical psychology, psy-
chiatric social work and mental health nursing. During 1957,
States slowly expanded their State-level mental health staff.
At the end of the year^ 12 States and Territories had State-level
teams representing the four disciplines, 18 States had teams re-
presenting three disciplineSs and 24 States had representatives
of only one or two disciplines. In some States, only part-time
services of staff were available.

As of December Ij 19575 there were State level psycholo-
gists carrying administrative or consultative responsibilities in
community m.ental health programs in 29 States, psychiatric social
workers in 40 States and mental health nurses in 27 States, Three
States (Californiaj Marylandj New Hampshire) passed laws on cer-
tification of psychologists. Several States (Califomias Georgia,

-11-

Pennsylvania^ Texas) are developing regional staffs of psy-
chiatric social worker consultants who serve several coun-
ties within a State» Several States have increased State-
level nursing positions (e.g., Florida, Kentucky, Massachusetts,
New Yorkj, North Carolina). Vacancies for personnel in State
and local positions continue to increase faster than such
personnel are being trained.

Heavy turnover in the top-level State staff continued
to plague mental health programs. Almost one- third of the
States and Territories had changes during 1957 in the direc-
tors or commissioners of community mental health programs
(Colorado, Connecticut, District of Columbia, Georgia, Idaho,
Indiana, Kentucky, Missouri, North Dakota, New York, Ohio,
Pennsylvania, Puerto Rico, Utah, Virginia, Virgin Islands,
West Virginia), Without attempting to evaluate whether the
staff changes strengthened or weakened State leadership, the
fact of change alone interrupts the continuity of program.
Also the high "mortality rate" in these top jobs tends to
deter many high caliber, career-minded people from seeking
positions in State service.

Mental Health Education and Consultation

All States have programs of mental health education
and consultation for lay and professional groups and agencies.
To brief general practitioners in the diagnosis and treatment
of mental disorders as well as in referral processes,
Nebraska is using Federal funds to develop a special film
for this purpose. Federal funds are also being used in a
Bridgeport, Connecticut mental health clinic to experiment
with the employment of a psychiatric social worker in a posi-
tion called "Educational Director."

Local Services

New local mental health centers or clinics continue
to be organized (e.g., Alabama, Illinois, Massachusetts,
New Hampshire, New York, Ohio, Tennessee) but sparsely set-
tled areas have great difficulty in recruiting staff. Clinic
services are especially scanty in large areas in the South,
Southwestern, and Mountain regions of the country. According
to the Oregon Public Health Service plan, "The most vociferous
demands in'the field of mental health are for increased mental
health clinical services for both adults and children." Some
States are using traveling clinics, some are trying to organ-
ize multi-county clinics^ and others are trying to provide
mental health consultation services Oiere no direct treatment
facilities are available.

To meet the need in rural areas, Florida has evolved a
new kind of mental health staff person called a "mental health
worker." These "mental health workers" (whose background may

-12-

have been in nursing-, teaching or social v/ork) are stationed in
the rural countieso They refer people to the clinics in the
urban counties and try to carry out the recommendations made by
the clinics in conjunction with community agencies. They also
conduct a program of mental health education and community or-
ganization. The program of the "mental health v/orker" has re-
ceived strong legislative support in Florida, and the idea may
spread to other States even though the effectiveness of the plan
has not been established^ Alabama, for example, has indicated
that it is seriously considering initiating such a program in
1958.

Mental Retardation

State legislatures showed high interest in mental retar-
dation, Idaho and Minnesota made it mandatory for local school
districts to provide instruction for handicapped children. State
funds were appropriated for the establishment of a diagnostic
and training center for the mentally retarded at the University
of Washington. The Delaware legislature authorized the establish-
ment of day centers for children with an I.Q, of less than 35,
who are living with their families. New York is making a State-
wide census of mentally retarded children and will be developing
plans for a State research institution on mental retardation.
Massachusetts received a new appropriation of $150,000 for com-
munity nurseries for retarded children.

Examples of mental retardation projects, which are sup-
ported by Federal grant-in-aid funds, include the multidisci-
pline training program of the New York Medical College at the
clinic for the mentally retarded of the Flower-Fifth Avenue
(New York City) Hospital, and the day care program for young
mentally retarded adults of the Retarded Children's Aid Agency
of Chicago, In many States (e.g,, Arizona, Nevada, Oklahoma,
Rhode Island) State mental health staff have been actively in-
volved in the establishment and development of nex7 clinics for
the mentally retarded which are supported through Children's
Bureau grants.

State and Local Surveys

Surveys of State or local mental health needs and resour-
ces are another indication of the stir and ferment on mental
health. The American Psychiatric Association completed surveys
of Iowa and OhiOo State-wide surveys are planned or underway in
Michigan, Hei-j Hampshire and Nevada. Los Angeles, California, and
Montgomery County, Maryland^ are examples of the more numerous
local communities in the midst of a survey.

Training and Research

Training and research were being stepped up through the
action of State legislatures. The Iowa legislature set up a new

.13-

fund for training and research at the Psychopathic Hospital.
The appropriation for Florida's Council on Mental Health
Training and Research was raised to $363^000 for the current
biennium as compared with $250^000 in the previous period.
Texas will be organizing a new community hospital for train™
ing and research in mental illness, to be located near the
Texas Medical Center in Houston. In 1958a Illinois will be
opening its new training and research centerj the Illinois
Psychiatric Institute in Chicago, Louisiana appointed a new
Director of Training and Research and got its new training
program in operations after making agreements for the train-
ing of mental health personnel with Louisiana State Univer-
sity, Tulane University and two State hospitals. The Medi-
cal Center at the University of North Dakota was directed by
the State legislature to encourage the training of psychia-
tric personnel for staffing the mental health agencies of
the State and training stipends were provided.

Alabama made its first effort to attract mental health
trainees to the State when it set up a training unit in
Birmingham, Massachusetts has set up a project for training
community mental health staff. A curriculum is planned for
public health nursesg school psychologists and school social
workers, AlsOs by offering second-year fellows in child
psychiatry, part-time experience in the mental health center
programg the Massachusetts Department of Mental Health hopes
to interest more of them in the community mental health field.
Under the Division of Community Mental Health Services in
New Yorkj about 50 stipends are being awarded to mental health
trainees J about 45 stipends to employees of the mental hospi-
tal program, Indiana will be using about $50,000 of its
Federal grant-in-aid for training stipends.

Sparked by a consultation request from a State, a
staff member of Region II., with the cooperation of staff in
other regions, conducted an informal survey of the educa-
tional leave policies for psychiatric nurses in State mental
health programs in June, 1957. The survey revealed a paucity
of State financial support for the professional training of
psychiatric nurses. Of the 44 States reviewed, only 12 had
State funds available for training stipends. These 12
States were; California, Florida, Illinois, Kentucky,
Louisiana, Michigan, Minnesota, New York, Ohio, Pennsylvania,
South Carolina, and Virginia, The level of training sup-
ported by the States varied and raiaged from single courses
to training for the Master's degree. Without exception,
everyone of the 12 States expected the trainee to accept
State employment for a specified period in return for the
financial aid provided during training,

A second staff member in central office supplemented
this survey with a narrative report which included a discus-
sion of the problems resulting from the frequently inadequate

-14-

amount of the stipend and from the requirement for obligated
State employment in return for the training stipend.

In the area of research a program of research in alco-
holism was established at the College of Medicine of Ohio
State University. The California Department issued its first
research report on a study which found that there are few pa-
tients arriving at the State mental hospitals who could be
cared for better in an outpatient clinic. The General Bacon
Health Center in Delaware is working on a study of the rela-
tionship between behavioral adjustment and the emotional a-
rousal pattern in children. The Michigan Department is con-
ducting an analysis of the characteristics of audiences par-
ticipating in mental health education programs. Minnesota
is supporting a study of the reasons for the breakdown of re-
covered or partially recovered mental patients. New York is
studying schizophrenic children in outpatient settings.

In its official plan submitted to the Public Health
Service, Connecticut reported that 5 "A grant of Federal funds
was made in 1956-57 to a psychiatric clinic for children in
Bridgeport to enable its staff to do a preliminary survey and
evaluation of some of the work done in that clinic over a
five-year period. As a result of this preliminary survey,
the clinic expects to undertake some more intensive research
activities in the coming year supported by funds from other

During the year a member of the Region V staff issued
a compilation of mental health research conducted or support-
ed by State mental health agencies in that region during
1956-1957. Of the 122 research projects reported, 467o were
biological, 337, clinical, and 21% were psycho-social. Four-
teen of the projects were in mental retardation and five were
on aging, .

Needs

Although progress is being made on many fronts, the
States report many gaps and inadequacies in over-all commun-
ity mental health services. In the plans submitted to the
National Institute of Mental Health, State after State indi-
cates the need to set up more mental health seirvices for peo-
ple living in geographical areas now without ser-s/ices. States
are seriously concerned with the need for more treatment and
rehabilitation services, mental health education, consultation
to community agencies, training opportunities for mental health
staff, and research and evaluation. Over and over again States
report that the bottlenecks are inadequate funds for community
mental health services, shortages of professional mental health
personnel, and low salaries.

-15-»

MENTAL HOSPITALS

Mental Health Project Grants

A major effort of the Hospital Consultation Service
of the Branch has been in providing staff services to the
new Mental Health Project Grants program. Legislation es-
tablishing this program was passed by Congress (Public Law
911) in 1956o This legislation was based upon the recog-""
nized need for encouraging effective ways to improve pro-
grams for the care of the mentally ill, for experimenting
with new methods of care,, and for helping isolated hospi-
tals to demonstrate the feasibility of methods already suc-
cessfully in use elsewhere. It was believed that, in many
instancesj the secondary gains to the institution because
of the stimulation of working on a project would in itself
improve the quality of care in that institution. When
Public Law 911 was passedj no appropriation was made, How-
everj steps were taken to establish the groundwork for the
grants program. A Review Committee was established with a
membership of thirteen outstanding professional persons
from the field of psychiatry, clinical psychology, psychi-
atric nursing, psychiatric social work, sociology and
hospital administration. Applications were received be-
ginning in January 1957 in anticipation of the availability
of funds. The response to the announcement of the grants
program was enthusiastic and immediate. Two million dol-
lars were made available for grants during fiscal year
ending June 30, 1958.

The Review Committee has met three times during
1957 and has considered 137 applications. Applications
have been received from 34 States and three Territories,
including States in every region of the country. Organ-
izations submitting applications have included State de-
partments of mental health. State hospitals. State insti-
tutions for the mentally retarded, private hospitals,
clinics, universities, residential treatment centers for
children, rehabilitation centers, and professional organ-
izations.

To date A4 projects totalling $1, 385,306 have been
approved by the National Advisory Mental Health Council.
Examples of the initial projects which are just now get-
ting underway are;

1, Demonstration of a day hospital service in a
child gujidance center setting.

2, Demonstration of a special group program for
acting-out children in a residential treat-
ment home for children.

-16-

3. Demonstration of a day hospital program for psy-
chotic children. as part of the state hospital unit
for psychotic children.

4. Utilization of a public health nursing service in
the supervision of convalescent psychiatric patients.

5. Coordination of community services to facilitate
the hospitalization of patients.

6. A study of preadmission services and alternatives
to hospitalization.

7. Establishment of aftercare services and the coor-
dination of community services in a rural area.

8. A study of the various techniques for the care
and treatment of chronic psychotic patients.

9. The improvement of medical records in a large
state hospital.

10. The provision of comprehensive psychiatric ser-
vices in a geographically isolated area with max-
imum utilization of local facilities.

11. A project to develop ways and means to sustaining
the geriatric patient extramurally and cut down,

if possible, the admission of the nonpsychotic geriatric
patients to the public mental hospital.

12. A study of the language and communication problems
of mentally retarded children.

13. Demonstration of a psychiatric rehabilitative ser-
vice for young inmates of a county jail.

14. An evaluation of treatment methods for schizophren-
ic patients selected from chronic wards of a state

hospital.

15. A demonstration project which would set up a suici-
dal referral service in a large urban area.

16. A study of the role of practical nurses as a possible
solution to the problem of the shortage of nurses in

state hospitals.

It can be seen that the approved projects cover a wide
range of problems in intramural and extramural care.

In the course of the review and approval of the projects,
the Review Committee has been working on guide lines for the pro-
gram. Early in 1958 the Committee plans to review the progress

-17-

of the program and to see if there are uncovered areas which are
in need of further stimulation and development.

As in many new programs, the working out of relationships
has been an important factor in the initiation of this program.
This had included the clarification of the responsibilities be-
tween headquarters and regional office staff. Some questions
have come up concerning the confidentiality of grant applications
and the role of the State mental health authority in relation to
applications from voluntary agencies. Efforts have been made to
interpret the basic features of the Mental Health Project Grants
program.

Headquarters and regional office staff have received nu-
merous requests for consultation concerning the program. The
staff members and members of the Review Committee have made site
visits and have given consultation. Applicants have indicated
that these consultations have been most helpful in clarifying
the potentialities of their own program as well as stimulating
the development of better patient services.

Currently approved projects will require over $1,200,000
of grants in order to continue in fiscal year 1959, Unless ad-
ditional funds are available, very few new projects can be added
during fiscal year 1959. The staff will make visits to the
approved projects and will be available to help project direc-
tors in their recruitment of personnel and in their working out
of the projects.

Hospital Consultation

The year 1957 has seen an acceleration in the amount of
consultation given to State hospital programs. The regional
office consultants as well as the staff of the Hospital Consul-
tation Service have been active in this area. The Hospital Con-
sultation staff have visited 36 states to meet with hospital
and other mental health personnel and to visit mental health
facilities. Through these visits new program ideas are being
communicated widely. The content of these consultation visits
covered a wide variety of subjects and some new patterns in the
care of mental patients seem to be spreading rapidly.

Several States attempted to modernize their laws in re-
gard to the commitment, detention and care and treatment of
the mentally ill (e.g., California, Colorado, Kansas, Minnesota,
Montana, North Dakota, Texas), Alaska enacted a comprehensive
mental health act following the framework of the Alaska Mental
Health Enabling Act passed by the Congress.

Of special interest was the 1957 legislative action in
seven States (Connecticut, Maine, Minnesota, New Hampshire,
Oregon, Rhode Island, West Virginia) which ratified the Inter-
state Compact on Mental Health, Together with Massachusetts,
New Jersey, and New York which ratified the Compact in 1956,

-18-

ten States are now participating in the inter-State agreement
which was first issued in 1955. The Compact makes the patient's
welfare the cardinal consideration in deciding whether he shall
be kept in one State or sent to another. The prompt action of
the ten States suggests that the Compact meets a long recognized
need and also that inter-State agreements may be a useful admin-
istrative device for helping to solve other problems of providing
mental health services.

The establishment of psychiatric facilities in general
hospitals seems to be a definite trend. For example, Georgia
asked for help in developing its program for establishing such
units and using them as screening centers for patients prior
to admission to the state hospital. The State plans to reimburse
the local hospitals for the care of the patients.

The philosophy of the "open hospital" is receiving wide-
spread attention. This philosophy implies the creation of a
therapeutic milieu, greater patient freedom, a different concep-
tualization of the status of the patient with, in turn, differ-
ences in the staff-patient relationships, a fuller integration
of the hospital into the community, and a broader , use of commun-
ity resources. Most hospitals are trying to achieve this goal
one step at a time. Mental Health Project Grants are being used
by a few hospitals for this purpose.

Many hospitals are asking for help on how to achieve im-
provements in patient care with "what they have at hand now" and
without either extensive building programs or recruitment of
hard-to-get professional personnel.

Several States are taking action to provide special care
and treatment for emotionally disturbed or psychotic children.
The Minnesota and Virginia legislatures authorized the establish-
ment of resident treatment centers for emotionally disturbed child-
ren while Nevada and Washington will be establishing special treat-
ment facilities for children as part of the State hospital program.

Interest and activity in mental retardation continued at a
high level, Arkansas, Nebraska, Texas, and Wisconsin authorized
the construction of new institutions for care and treatment of the
mentally retarded.

Aftercare facilities and programs are becoming increasingly
important. These are being developed as a part of hospital programs
and as a part of community programs administered by voluntary or pub-
lic agencies. Two conferences on aftercare were held as Technical
Assistance Projects and involved participation of regional and head-
quarters staff. Three regional conferences were held with the Of-
fice of Vocational Rehabilitation and mental hospital personnel on
the rehabilitation of the mental patient. These were held in Re-
gions rv, V and VI, Another conference in California enabled the

-19-

hospital and aftercare staff to meet together. All of these
conferences have contributed to the better understanding be-
tween the intramural and extramural programs and better com-
munications in the interests of patients.

The half-way house as a method of care is receiving
widespread attention and interest. As in any new development,
there is much experimentation and considerable variation in
the various programs. Some see the half-way house as meeting
a need for an interim facility which avoids the dependent se-
curity of a hospital ward and yet offers an individualized as
well as a group program. It is possible that in some commun-
ities the already established facilities^ such as the YWCA
and the YMCA, may provide this kind of opportunity fot the
discharged patient. Some hospitals are setting up rehabili-
tation wards that provide interim care to the patient and as-
sist him in his integration back into the community. Patient
clubs or social therapeutic clubs are becoming more widespread
and are another assist to the patient in his resocialization.

The interest in the development of half-way houses and
patient clubs is very closely related to the growth in scope
and importance of the volunteer movement. Volunteers are an
important factor in the closer working together of hospitals
and communities. Volunteers are being used in many roles in
working with the institutionalized patients and are sponsor-
ing some community efforts such as ex-patient clubs and half-
way houses. A conference on the work of volunteers with men-
tally ill patients is to be held in June 1958 under the spon-
sorship of the American Psychiatric Association and four other
national organizations. This conference is being supported by
a grant from the National Institute of Mental Health. Four
preparatory commissions are gathering material to be used as
the basis of the conference. This conference will consider
the present status and purposes of volunteer programs for the
treatment, care, and rehabilitation of the mentally ill; the
delineation of the functions of volunteers; the unique pro-
grams in the field of community rehabilitation services; and
the existing administrative patterns and personnel policies
governing the operation of volunteer programs. Problems of
recruitment and training of volunteers will also be considered.

The care of the aged in nursing homes and in mental
hospitals is getting increased attention nationwide. Crowding
in other community facilities often makes the State hospital
the only place for the disabled old person. In some States,
county homes are used for this purpose. Visits have been made
by staff to the county homes in two Mid-Western states and a
workshop is to be held in December 1957, with nursing home
operators in another State, Branch staff are participating
in the planning of a national conference of nursing home

-20-

operators in February 1958, which is being sponsored by the Bureau
of State Services, Public Health Service.

The community care of the mentally ill and the early dis-
charge of patients from State hospitals together with treatment
in the community in lieu of hospitalization have many implica-
tions for other community health and welfare programs. Consul-
tation has been provided to national and State agencies on ways
of coordinating services of hospitals, public health and welfare
agencies. Community workers such as public health nurses and
welfare workers are key figures in providing care for the pa-
tient and his family. Many efforts are being made to familiar-
ize these workers with the problems of the mentally ill, and to
interest them in expanding their services to this group. There
are also indications of the need for change in agency policies
which may exclude a person from service by reason of his mental
illness. Conferences have been held with personnel in the Bureau
of Public Assistance and Old Age and Survivor's Insurance to
point up some of these questions. The fact that the American Pub-
lic Welfare Association devoted part of its "Round Table" to a
consideration of the problems of mental health and mental illness,
is a very encouraging indication of the interest of welfare admin-
istrators in this area.

The upgrading of the existing staff through staff develop-
ment activities and the use of the psychiatric hospital as a train-
ing resource Ihave important implications for improvement of patient
care. The Hospital Consultation Service staff have contributed to
a number of different kinds of staff development efforts, including
regional meetings, summer institutes, hospital staff seminars and
staff consultations. Special consultation was given to one State
concerning the development of its hospitals as training centers.

It has not yet been possible to work out adequate informa-
tion collection procedures in order to answer the requests for in-
formation on such subjects as State commitment laws. State licens-
ing laws for private mental hospitals, architectural plans, trends
in aftercare programs and personnel standards. It is hoped that
during the coming year further progress can be made in the collec-
tion and analysis of such data.

One of the needs voiced by many States is for small amounts
of money with which they could initiate a variety of developmental
projects. Such money could be used for consultation, for staff de-
velopment, for sending staff teams to visit other hospitals, or for
experimental purposes. It may be that this need can be met through
the Mental Health Projectv Grants Program; if not, ways need to be
found to assist States in this kind of effort.

SPECIAL AREAS OF MENTAL HEALTH

Alcoholism D

Branch activities relating to alcoholism during the past

-21-
year have expanded in two important respects. The first is
the increased amount of service given by the regional mental
health staffs to program developments relating to alcoholism.
The rising number of requests for such services reflects a
growing awareness of the relatedness of alcoholism to the
broad field of mental health problems. Regional staff were
being asked to meet the following kinds of requests: planning
for and participating in State or regional institutes on alco-
holism; development of more effective treatment and rehabili-
tative measures in State mental hospiitals and mental health
clinics; consideration of alcoholism in relation to tuberculo-
sis, diabetes and other chronic diseases; problems of alcohol-
ism in industry; consideration of excessive drinking among
Indians. Regional mental health staff also consulted with
other regional staff of the Public Health Service and of the
Department (such as the Office of Vocational Rehabilitation)
on problems of alcoholism.

There are currently 37 official State alcoholism pro-
grams in operation, with others in various stages of organi-
zation. A commonly cited factor relating to these programs
is that they have relied entirely on State initiative rather
than on Federal support. The desirability of effecting more
formal working relation between these presently independent
programs on alcoholism and the Federal-State operations per-
taining to other public health activities, is a matter now
receiving attention on both State and Federal levels. Re-
gardless of the natute of such a relationship, it is practical-
ly inevitable that the participation of the regional mental
health staffs will continue to grow in significance.

The return of Dr. Paul H. Stevenson to active duty
as Concultant on Alcoholism marks the second advance during
the year in the Branch's activities relating to alcoholism.
This event provides for more effective consultation services
to and through the regional office staffs and also for the
reactivation of certain headquarters activities. Most impor-
tant will be the renewal of active liaison relations with the
major organizations operating on the national scene in the
field of alcoholism, and the maintenance of rosters and current
summaries of State and local programs and facilities, thus
serving again as a clearing house for information. In addition,
through the procurement of the recent annual issues of the
Classified Abstract Arthive of the Alcohol Literature, the
Institute is now one of the limited number of depositories of
this service in the country. This archive will be kept cur-
rent, and arrangements made to make it available to a wide
circle of research workers and program staff working in the
field.

In March 1958, the National Institute of Mental Health
and the Bureau of State Services, Public Health Service, will
jointly sponsor an ad hoc conference of about 25 national ex-

-22-

perts in the field of alcoholism. They will be asked for their
suggestions on the future role and program of the Public Health
Service in regard to alcoholism.

Industrial Mental Health

At the 1956 Conference of the State and Territorial Mental
Health Authorities with the Surgeon General, the mental health
authorities requested that the National Institute of Mental Health
make available information dealing with mental health in industry.
For several months in 1957, a Branch psychiatrist was assigned to
work in central office on mental health in industry. This staff
member prepared the publication, "A Review of Mental Health in
Industry" which contained a review of the literature, a bibliog-
raphy of some 150 titles, a description of several programs in
large companies, and a list of films on human relations in indus-
try. The review of the literature covered recent history, func-
tions of the psychologist and psychiatrist, relationships of men-
tal health programs to general industrial health programs, atti-
tudes of management and labor, and training and research. The
special problems presented to industry by absenteeism, accidents,
alcoholism, and the elderly worker were also considered. The re-
view found that the participation of public health agencies in the
industrial mental health field has been limited and fragmentary
and suggested the need for development and expansion of the total
field of mental health in industry.

Mental Retardation

A member of the central office staff was the joint author
with Dr. Seymour B. Sarason of a major report (in press) on mental
retardation. The report entitled, "Psychological and Cultural
Problems in Mental Subnormality, A Review of Research," was spon-
sored by the National Association for Retarded Children under a
National Institutes of Health grant.

The report points out that the bulk of cases of intellec-
tual deficit are identified and become problems during the span
of years children normally attend school. Therefore, reported
prevalence of retardation in the population reaches its highest
point at age 14-16. These children and adolescents who have been
labelled retarded leave the school system and merge successfully
into the adult population because their post- school life places
different kinds of intellectual demands upon them. There is no
present reason to assume either organic or hereditary etiology in
most of these individuals; rather, they suffer from learning defi-
cits often introduced by the subcultural patterns of living and
child rearing characteristic of the groups into which they were
bom. The report urgently recommends research on the nature of
the intellectual processes learned in the «srious sectors of our
population, on better means of identifying learning deficits at

-23-

the preschool level so that corrective action may be taken be-
fore it is too late, and on the intellectual requirements of so-
cial living outside of the school situation.

Narcotic Addiction Demonstration

A Demonstration Center to work with drug-addicted pa-
tients discharged from the Lexington Hospital was launched by
the Community Services Branch during the year. The Center was
set up in New York City in an attempt to prevent relapse among
discharged drug addicts by helping them utilize the facilities
of community health and welfare agencies and by providing con-
sultation to the agencies so that they will better be able to
meet the needs of former addicts. The program of the Center
is based on the general premise that an increased use of com-
munity resources will help to rehabilitate narcotic addicts.
Experience has shown that there are obstacles both in the pa-
tient and in the community that interfere with the full use of
community services for this group.

A staff of six psychiatric social workers has been em-
ployed and arrangements have been made for part-time psychia-
tric consultation. The Center staff have been contacting com-
munity agencies and, somewhat surprisingly, have found that
agencies are willing to cooperate with the Center and to pro-
vide service to selected addicts. In many instances, this
has involved a reversal of previous agency practice.

The Center will also be continuing a previous project
of the Bureau of Medical Services, Pwblic Health Service, to
maintain contact with a sample of drug addicts, without at-
tempting treatment intervention, in order to find out about
re-addiction rates after discharge. In addition, a study is
being planned of the social and psychological factors that
distinguish those who successfully discontinue taking drugs
from those who become re-addicted.

School Mental Health

The number of school mental health activities of the
Community Services Branch increased in 1957 in response to
greater interest in this area by the States and the greater
emphasis given these programs by our staff. The year 1957
is the first time the Branch has had a full-time consultant
working in this special area. The provision of a full-time
consultant in this field enabled the Branch to work more
closely with other Branches of the Institute also involved
in mental health in education activities and to provide in-
creased consultation to national organizations. States, and
teacher-training colleges.

Colorado, Mississippig Idaho^ Missouri, and South
Dakota, were among the States which utilized Branch staff

-24-

to develop joint conferences of State mental health and education
personnel on school mental health program development. Region III
reviewed the school mentalhealth activities of its States as a
part of a regional study of school health programs. Seventeen
Southern States under the Southern Regional Education Board ini-
tiated a project to increase the utilization and training of school
psychologists. Considerable effort was expended on establishing
closer liaison with the Office of Education, Department of Health,
Education, and Welfare, and the National Education Association*

During 1957, the Branch, in cooperation with the Florida
State Department of Health and Education initiated a school mental
health demonstration in Volusia County, Daytona Beach, Florida.
Two members of Branch staff, a clinical psychologist and mental
health nurse, were assigned to this county to study the present
and potential local health department's school system teamwork
on the screening and local management of minor emotional problems
in school children. It is anticipated this fetudy will help to
formulate the elements of a basic school mental health program
that can be adapted and field tested for use in other rural coun-
ties.

TECHNICAL ASSISTANCE PROJECTS

Technical assistance projects were initiated in 1955.
These projects are special conferences focussed on a particular
mental health problem of a State. They are designed to assist
the States in building their mental health programs and are seen
as an extension of the consultation and technical assistance now
provided to the States through the professional staff of the Com-
munity Services Branch. They have been particularly valuable in
helping States explore and develop new mental health program areas.

In 1957 there were 12 technical assistance projects carried
out as a joint endeavor by the States, Regional Offices, and the
Branch, at a total cost of approximately $45,000. This represents
an average cost per project of approximately $3,700. Generally,
at least one outstanding national consultant is employed to par-
ticipate in the project. The following is a listing Ijy title of
the projects carried out this year:

California - "Coordinating Treatment Services for
Mental Patients in California"

Colorado - "Development of Better Social Services —
Family, Patient, Hospital, Conmiunlty"

Colorado - "Mental Health Through Coordinated
Efforts of Education, Mental Health
and Public Health Personnel"

•25-

Connecticut

Iowa

Mississippi

Missouri

New York

Pennsylvania
South Dakota
Texas

Utah

"Applications of Management Theory
to Administrative Psychiatry"

"Rehabilitation and Post-Hospital
Care for the Mentally 111"

"The Schools the Childj and Mental
Health"

"Leadership Training for Community
Mental Health Promotion"

"In-Patient Psychiatric Units for
Children - A Program Designed to
Prepare the Child for Return to
the Community"

"Conference of Community Mental
Health Clinics"

"Leadership Training for Mental
Health"

"Maximum Utilization of Community
Agencies in Treating Emotionally
Disturbed Children"

"Development of Collaboration be-
tween State Agencies to Promote
Better Mental Health Programs"

CONFERENCES OF CHIEF STATE PSYCHOLOGISTS. SOCIAL WORKERS.

AND NURSES

As in previous years s Branch staff helped to sponsor and
plan conferences for top State- level community mental health
staff in each of three disciplines: psychology, social work, and
nursing. These conferences provide an opportunity for the State
staff in one discipline to exchange ideas and information on pro-
gram developments in the various States. The meetings of the
chief State psychologists focussed on the need for psychologists
to have training in consultation and administration. The social
workers' meetings discussed the philosophys methods, and tech-
niques of mental health consultation. At the nurses meeting, re-
source books, containing mental health materials and publications
of special interest to State- level nursing consultants, were dis-
tributed. Several members of university nursing faculty, who
were present at the meeting, requested copies for their use in
teaching. The shortage of mental health nurses was a major sub-
ject of discussion.

-26-

ORIENTATION COURSES FOR COMMUNITY MENTAL HEALTH
STATE PROGRAM DIRECTORS

In accordance with recommendations made by the 1956 Conference
of State and Territorial Mental Health Authorities, the Community Ser-
vices Branch has assigned two staff members to be responsible for de-
veloping a course of instruction and orientation on community mental
health programs for State-level mental health staff. Following comple-
tion of a preliminary plan for such a course, an advisory committee will
be established, including representation from the Community Services
Advisory Committee, members of the National Institute of Mental Health
staff at headquarters and regional offices, and consultants outside of
the Public Health Service.

It is anticipated that an initial pilot course will be given for
the States in three regions where the problems are fairly similar. Em-
phasis in the course will be placed on program planning, coordination
of coiranunity agency activities, and administration. Experienced people
from State mental health program staffs, as well as others, will be
drafted as faculty members to discuss and present aspects of these prob-
lems.

It is planned to have this first course early in 1958; a second
course in another area of the country is planned for the Spring of
1958. Later courses may provide more intensive training in special
areas, such as administration. Vhere possible, such subsequent units
will probably be arranged through contracts with appropriate university
graduate departments, schools of public health, graduate schools of so-
cial work, etc.

REPORT ON FEDERAL MENTAL HEALTH ACTIVITIES FOR CHILDREN

At the request of the Joint Commission on Mental Illness and
Health, a statement was prepared on the impact of Federal mental health
activities on services for children. Although the statement focussed
primarily on activities of the National Institute of Mental Health, the
review revealed the tremendous range of activities and the substantial
investment of the Federal government in the mental health of children.
A surprising number of Federal agencies are active in this field, includ-
ing the Cooperative Extension Service of the Department of Agriculture,
Department of Defense, Bureau of Public Assistance, Office of Education,
Children's Bureau, Department of Justice, and many programs of the Public
Health Service.

Within the Community Services B ranch j , activities directly related
to children included the following: (a) About 10% of the time of region-
al consultants was devoted to school mental health, (b) a psychiatrist
is assigned full-time to work on school mental health, (c) a school men-
tal health demonstration has been launched in Volusia County, Florida,
(d) four of the twelve technical assistance projects conducted in 1957

-27-

were directly concerned with children, (e) Federal grants-in-aid
for conmunity mental health services have helped State programs
grow from $2.4 million of State and local funds budgeted in fis-
cal year 1948 to $41 million in 1957. Federal grants have been
an important factor in the tremendous spurt in the number of
outpatient psychiatric clinics established since 1946. Prelim-
inary tabulations reveal that 72% of the persons served in out-
patient psychiatric clinics were under 18 years of age. Feder-
al funds have been used in many States for "growing edge" ac-
tivities for pilot projects, experimental services, demonstra-
tions, and research. A frequent pattern is the use of Federal
funds to demonstrate a new mental health service which, after
the success of the demonstration, is taken over and supported
by State and local funds, (f) under the National Health Pro-
ject Grants program (Title V), eight projects totalling
$278,000 (October, 1957) were approved which were concerned
with children.

CONSULTATION ON RESEARCH AND EVALUATION

Increasingly, as programs in State mental health agen-
cies expand and develop, requests are made for consultation ser-
vices relating to program research and evaluation. With the
pioneering stage passed, interest has turned to justification
of existing programs and increased evidence that services are
actually accomplishing the results for which they are intended.

To supplement resources in the regional offices, during
the past year a Section on Program Research and Evaluation with-
in the Community Services Branch was established in central of-
fice. Two staff members are presently serving in that capacity.
Regional consultants can request assistance from this Section
as occasions and problems warrant. Also through this Section,
the various technical research resources in the many laborator-
ies and branches at the National Institute of Mental Health may
be made available to the regional offices and State mental health
programs.

As an illustration of the activities of this Section, at
the request of the mental health consultants in Region VIII,
the two staff members of the Section participated in a meeting
held in Utah to consider possible research studies relating to
the establishment of new communities. This meeting was spon-
sored by the Bureau of Mental Health of the Utah Department of
Public Health and included representatives from the Departments
of Psychology, Sociology, and Anthropology in the three State
universities -- namely, the University of Utah, Brigham Young
University, and Utah State University, This planning group is
interested in a large-scale, long-term study of three new
towns being built near the Utah-Arizona border in connection
with the construction and use of the Grand Canyon Dam, Also,

-28-

a fourth town similarly related to the Flaming Gorge Dam on the
Utah-Wyoming border may be included. Any such studies would be
multi-disciplinary and would involve all three universities.

Questions were raised and discussed with reference to
Public Health Service research grants, administrative problems
within the universityj collaboration, research design and grant
procedures.

THE MENTAL HEALTH STUDY CENTER

The Mental Health Study Center, a field station of the
Community Services Branch in Prince Georges County, is a clin-
ical unit whose general function and purpose is to provide a
setting in which studies can be conducted on various aspects
of community mental health. It functions in four major areas,
operation; (1) a research program ranging from studies on the
structure, function, and operation of mental health units to
epidemiological studies of problems in community mental health;
(2) a mental health consultation service for Prince Georges
County service agencies concerning family problems and commun-
ity mental health activities; (3) a limited all-purpose psychi-
atric outpatient service restricted to residents of Prince
Georges County; and (4) in addition, the Center engages in
training activities for various professional personnel. The
staff of the Center are also called upon from time to time to
act as consultants outside of the County,

Epidemiological Study of Reading Disability

This project is now in its fourth year. It is a product
of the basic interest in the problem of locating emotionally
disturbed and maladjusted individuals in the community and in
identifying some of the psychological and sociological factors
associated with such maladjustment. As a resident mental health
research team that also offers service in the county, the staff
became aware that one major concern, in the schools, in the
homes, and in the courts, was the apparent high frequency and
ubiquity of serious reading problems among children. The staff
recognized that this community problem was remarkably suitable
for epidemiologic inquiry, Reading disability is a definable
phenomena. Accurate and complete case finding, one of the mqre
difficult problems in epidemiologic studies of mental disorders,
is an approachable goal. It is possible to know with reasonable
accuracy how many children have serious disabilities, to know
where these children live, and if only crudely at first, who
they are and how they live. It is also possible to know these
things about average readers and good readers.

In spite of the fact that this phenomena is defined in
educational termSj it is almost certainly of great mental health
relevance. The syndrome of reading disability is clearly a

-29-

final common pathway Tdiich may have many origins. Reading
is a basic and highly valued communication skill and a dis-
ability in this area, whatever its origins, limits the in-
dividual's capacity in many areas. As with so many chronic
disorders, the consequences reduce the probability of its
correction and may, in fact, lead to its entrenchment and
even enhancement. The staff are interested in exploring
and documenting this apparent destructive potential. It is
the impression of the staff that such a disorder, together
with its sources, constitutes an important reservoir of
psychopathology from which a variety of disorders may e-
merge. Should this be demonstrated, the presence of read-
ing disability in an individual or an unexpectedly high in-
cidence of reading disability in a family or neighborhood
or community could serve as a flag calling attention to the
need for more intensive examination^ This may be, in short,
something like a "coliform count" for a public health
screening device for mental health problems. The staff ap-
proach to the problem is a multi-dimensional one; some of
the areas of interest are described below:

a. A profile of reading performance by school dis-
trict will be completed during the first half of 1958 based
on data collected over the past three years. Earlier inter-
im studies have demonstrated the reliable performance of
most school districts as well as increasingly reliable differ-
ences between discreet geographical and sociological units

in the county. The profile will provide a basis for the
study of the meaning and significance of these differences
as well as offer some clues to the nature and direction of
performance changes in specific localities and in the county
as a ^ole.

b. A series of longitudinal studies based on three
years of data from 1954 to 1957 v;ill be completed during the
winter of 1957-58, These studies provide a crude sampling
of children along a broad spectrxim of reading achievement
and covering grades one through nine. They describe, with-
in sampling limits, a picture of the range and variability
of reading achievement over these grades. The three stud-
ies have provided a good estimate of the reliability of the
data-collecting instruments including the "reading quotient,"
a statistic that permits comparison of reading achievement of
children at different age levels. They will also permit the
evaluation of impact of agej, sex, and certain psychological
and socio-cultural forces on achievement.

These longitudinal studies will also serve as pilot
projects for a Cohort Study of the entire sixth grade school
population of 1954-55 (approximately 5,000 children), to be
started during 1958, This study is planned first as a test

-30-

of the hypothesis that reading disability identified early can
act as an indicator of psychopathology. In addition to collect-
ing data on the total school careers of this group, information
will be gathered from the Health Department, the Courts, Welfare
Department, and other community sources. Second, and perhaps
more importantly, the study will allow the development of methods
for the effective and meaningful handling of large amounts of in-
dividual .mental health data.

c. The clinical study of the first group of boys with
reading disability and of their parents was completed during
1957 and a second group has been in treatment for eight months.
These intensive studies of families seen in collaborative group
therapy have contributed heavily to staff understanding of the
intra-personal, familial, and cultural dynamics that appear to
be so significant in this syndrome. One of the methods of deal-
ing with the problem may be collaborative group therapy, a by-
product of the research operation.

d. Current plans, in addition to the Cohort Study,
call for the completion of the survey of individual and family
life, originally planned for 1957 and postponed. This survey
will seek to examine the social matrix in tAich the syndrome
appears through surveys of individual and family life in sever-
al of the communities pinpointed as high and low incidence a-
reas by the demographic study.

Post -Hospital Project

This project, begun in 1955, is a survey of a group of
mental hospital patients returning to their homes in Prince
Georges County, It was felt that people who had experienced
hospitalization could contribute to the understanding of ad-
justments during the post-hospital period. This information
could be useful in planning for service programs for the post-
hospital patient.

During the twelve-month period of August 1955 through
July 1956, 77 patients returned to the county. Forty-six of
the 77 were interviewed; 24 had moved, 4 were not available
for interview and 3 refused interview. Patients were inter-
viewed once after they had been at home for approximately six
months. Information was obtained about their experiences since
returning home and from whom, if anyone, they had looked for help
in the family, neighborhood, or from professional resources. In-
terviewing began in January 1956 and was completed in March 1957.

A preliminary analysis of the data calls attention to two
facts. First, the total number of patients returning to this com-
munity was numerically less than had been expected. Secondly, pet-
haps similar to many communities, staff had anticipated a total
post-hospital population composed primarily of psychotics and were

-31-

surprised at the large number of patients with an alcoholic
or non-piaychotic diagnosis. It would seem logical, there-
fore, that one of the first practical steps in planning a
followup program would be to review carefully with the hos-
pital the y^riety of patients admitted and discharged.

Other significant activities and projects of the Study
Center include;

1. A pilot project aimed at trying out brief family-
oriented service. The procedure being tested is to offer
families a series of three family group therapy conferences
after the usual diagnostic evaluation has been completed.
The goal in this approach is facilitating communication with-
in the family.

2. A followup study has been initiated of patients
seen for diagnostic services only and then referred to other
community agencies.

3. A study and evaluation of general clinical pro-
cedures has been initiated. The traditionai 'technique of
an intake interview followed by a psychiatric diagnostic
session, followed by a psychological evaluation, followed
by a staff conference will be under review as will be the
voluminous dictation, recording and transcription of each
step of the diagnostic and treatment process.

4. The Center continues to work on the development
of a way of classifying and filing the varied kinds of data
about the county in which it works - its social structure
and forces, its sub-cultures and neighborhoods, and agencies,
A detailed cross-indexed classification was completed in
July 1957.

5. The record system project, begun in fiscal year
1952, had as its objective the design of an integrated set
of mental health clinic records, including a coding system
for IBM cards. After this record-keeping system had been in
operation for five years, the Center staff, this year, com-
pletely revised all of the recording methods in use after
evaluation was made of each item on each form as to its ap-
plicability, practicability of completion and usefulness.
Together with the Biometrics Branch, Center staff plan to
analyze the five years of data acctimulated on IBM cards.

WORK WITH REGIONAL. MTIONAL, AND IHTERNATIOmL ORGANIZATIONS

Continued efforts have been made to develop program
relatedness with national and international official and vol-
untary agencies. This type of relationship is particularly

-32-

iraportant in a preventive mental health program. Mental health
programs rather uniquely demand the close working relationship
of many individuals, groups, and agencies.

The following are some examples of how the Branch has
been working with both national and international official
and voluntary agencies in further developing mental health
services to people: (1) Joint planning was initiated with
the UoSo Department of Agriculture in an effort to take ad-
vantage of their interest, and ongoing activities related to
mental health. This agency has a tremendous potential for
preventive mental health, particularly in rural areas, (2)
A staff member of the Branch represented the National Insti-
tute of Mental Health at the Third Pan American Congress of
Social Service in San Juan, Puerto Rico. (3) Regional of-
fice staff have participated actively in the deliberations of
the National Social Welfare Assembly regional meetings. These
meetings cover a wide range of activities including services
to the aging, juvenile delinquencyj and mental retardation,
(4) Two staff members participated in the 1957 National Asso-
ciation for Mental Health Assembly as leaders of workshops on
rehabilitation of the mentally ill, and the relationship of
the community and the hospital in the care and treatment of
the mentally ill, (5) Both regional and central office staff
participated in the 1957 National Health Forxim which was de-
voted to mental health. Regional and central office staff
were also active in professional organizations such as The
American Psychiatric Association, National League for Nursing,
American Psychological Association, National Association of
Social Workers, etc.

Working relationships with the Office of Vocational Re-
habilitation, Children's Bureau, Public Assistance, and the
Office of Education have been greatly strengthened through nu-
merous joint activities. For example, the Branch co-sponsored
with the Office of Vocational Rehabilitation a series of re-
gional conferences throughout the United States on the rehabil-
itation of the mentally ill.

The regional offices concerned (Atlanta, Charlottesville,
Dallas, and New York) continue to work with the Southern Region-
al Program in Mental Health Training and Research of the Southern
Regional Education Board, which, with a grant from the National
Institute of Mental Health, was successful during the year in em-
ploying a mental health staff. Southern Regional Education
Board's Council on Psychological Resources in the South has re-
sulted in the first regional program to train school psycholo-
gists. Likewise the regional offices in the Western part of
the country (Dallas, Denver, San Francisco) continued their work
with the Western Interstate Commission on Higher Education to es-
tablish a Western Regional Council on Mental Health Training and
Research, which received during the year a grant from National
Institute of Mental Health to establish, operate and staff the;

-33-

above council. The New York Regional Office continued its
cooperative work with the Northeast States Governments Con-
ference on Mental Health.

As in previous years, many of the regional offices had
a meeting of the State program staff in their regions gener-
ally to exchange information and experience about program
problems and developments. In Region V a regional meeting was
held which was focussed on the single subject of mental health
education.

COMMUNITY SERVICES COMMITTEE

Recruitment and training of community mental health
staff were the major subjects discussed in the two day meet-
ing in March 1957 of the Community Services Committee of the
National Advisory Mental Health Council. The Committee dis-
cussion was centered about the problem of; (a) how to in-
crease the supply of persons enrolled in professional schools,
and (b) how the people in the training centers could be
channeled into community mental health programs.

Among the suggestions made were the following: (1) A
more intensive, aggressive, and better organized recruitment
program is needed, beginning with the high school student,

(2) If part of the medical residency took place in a commun-
ity agency rather than in a hospital, the interest of stu-
dents in entering community services might be stimulated,

(3) A study was prpposed to determine the motivational fac-
tors which lead an individual to select either private prac-
tice, work in a mental hospital or in community mental health
services. (4) Community work needs to be made more attrac-
tive through such devices as career plans, inservice train-
ing, providing maximum responsibility and professional free-
dom to staff. (5) Special project funds are needed to encour-
age State hospitals to orient themselves community-wise. (6)
Mental health associations should be encouraged to emphasize
preventive services and community mental health programs as
well as the mental hospital programs. (7) Increased utili-
zation should be made of public health nurses in community
mental health programs.

In addition, the Committee took formal action in unan-
imously approving the recommendation made at the 1956 confer-
ence of the State and Territorial Mental Health Authorities
that the National Institute of Mental Health provide courses
of instruction for orientation of State- level staff on commun-
ity mental health programs.

I -34-

ANNUAL CONFERENCE OF THE SURGEON GENERAL WITH THE STATE AND
TERRITORIAL MENTAL HEALTH AUTHORITIES

Preceeding the formal Conference of the Surgeon General
with the State and Territorial Mental Health Authorities, the se-
cond annual two-day "Technical Session" was held for community
mental health program directors. These informal meetings provide
an opportunity for program directors from all parts of the country
to exchange information and experiences about program developments
and activities. The manpower problem - recruitment, inservice
training, retention of staff - was the major subject discussed in
the meetings but other subjects discussed included research.
State-level program planning and regional programs for sparsely
settled areas.

At the formal Conference on November 5;, 1957, the Mental
\ Health Authorities passed thirteen recommendations. Three of the

■j recommendations were concerned with training. The first asked

; for Public Health Service grants of training funds on a matching

I basis to the Mental Health Authorities to support interstate

training centers for professional training in mental health. The
second encouraged the training of more personnel for community
i mental health programs by providing more funds for training grants

i to operating agencies that are carrying on community laental health

I programs. The third asked for liberal stipends to general prac-

I titioners and non-psychiatric specialists for periods of three to

! six months of intensive training in mental health,

i Two recommendations requested increased Federal grant-in-

! aid funds for community mental health services. Surprisingly,

\ these recommendations were submitted by New York and California,

I both large, high- income States that contribute more in taxes

I than they get back from a Federal grant,

I Two recommendations were concerned with meetings of men-

' tal health staff. One asked the National Institute of Mental

Health to set up a series of regional conferences for State men-
tal health staff and the second asked for a continuation of the
1 annual meetings of community mental health program directors usu-

) ally held in conjunction with the annual Conference of the State

1 and Territorial Mental H&alth Authorities Td.th the Surgeon General.

I
I

Additional recommendations requested that (a) Hill-Burton
funds be extended for use in the construction and equipping of men-
tal health facilities established for cooperative ^se by several
States, (b) the Public Health Service explore with the National
Association of Mental Health possible plans for providing orien-
tation for executive secretaries of State mental health associ-
ations on the Federal and State community mental health programs,
(c) a study be conducted of the present structure of mental health
clinics, (d) exploration be made of the possibility of notifying
the mental health authorities of Federal grants in the mental

-35-

health field made by agencies other than the Public Health
Service, in the Department of Health, Education, and Welfare,
(e) the Public Health Service prepare and publish a monthly
Mental Health Digest. As a recommendation to themselves,
the Conference endorsed the principle of establishing after-
care programs for released mental hospital patients.

NATIONAL INSTITUTE OF MENTAL HEALTH

Cotnrniinity Services Branch

BUDGET SHEET

Estimated Obligations for FY 1958
Total: $1,367,667
Direct: $l,31''J-,600

Reimbiir sements : $53 » 067

ANNUAL REPORT OF PROFESSIONAL SERVICES BRANCH, NIMH

CALENDAR YEAR 1957

The Professional Services Branch continued to fulfill its function
in the fields of program planning, program development, the administra-
tion of special grants, budget review, specialized assignments with re-
spect to program problems faced by the Institute, and the provision of
consultation within the Institute to other governmental and non-
governmental groups.

The major activity of the Branch continues to be research and
development in program areas and problems. Special grants are used in
this connection to extend, temporarily, the facilities of the Institute.
Analysis of the state of knowledge and programs of action, consultation
with other groups or agencies concerned with the same problem, and feed-
back of new knowledge and understandings, especially to State mental
health programs, also constitute important parts of this activity. These
areas form an over-all pattern, as indicated in the outline and stsmmaries
which follow.

Studies Concerned with the Prevention or Reduction of Disability in
Pathologic or Deviant Populations

Rehab i 1 i ta t ion

Progress continues on two large-scale studies of psychiatric re-
habilitation and a third project has been initiated. The Boston State
Hospital Pilot Study of Rehabilitation and Rehabilitation Personnel is
in the final stage of analysis of data. Dr. Ralph Notman, Principal
Investigator, and Dr. Richard H. Williams of the Professional Services
Branch, are assuming joint responsibility for preparation of a major
report to be published in book form. The study of the post-hospital
experience of mental patients is currently in full operation with four
more years of committed support. Dr. Ozzie Simmons and his staff at
the Harvard School of Public Health have published several papers based
on the study, A study of the adjustment patterns of married patients
admitted to a mental hospital for the first time, during hospitaliza-
tion and the post-hospital period, has been initiated in the Department
of Mental Hygiene in California. Drs. John Clausen, Morton Kramer and
Williams are acting as liaison.

Feedback activities from the rehabilitation studies have in-
creased markedly during the past year. Drs. Notman, Simmons and
Williams have consulted with the staffs of several State hospitals and
State mental health programs and have participated in regional con-
ferences on psychiatric rehabilitation sponsored jointly by the OVR
and the NIMH. A book has appeared. The Patient and the Mental Hospital
(Milton Greenblatt, M.D., Daniel J. Levinson, Ph.D., and Richard H.
Williams, Ph.D., Editors), which summarizes current research on the
social and psychological aspects of treatment and rehabilitation.
Dr. Williams is serving as Chairman of an Advisory Committee at the

Massachusetts Mental Health Center (Boston Psychopathic Hospital) which
is concerned with a group of studies on rehabilitation, alternatives to
hospitalization and the relation between drug and milieu therapies. He
also serves on a Panel on Patterns of Patient Care, for the Joint Com-
mission on Mental Illness and Health, and prepared an analytical sum-
mary of the deliberations of this group.

Mental Retardation

Concern for the mentally retarded throughout the country has been
greater during the past year than previously. The amount of research
and program development has increased markedly with much improvement of
both the quality and quantity.

Activities within the NIMH staff and special grants made in this
area have played an important stimulating role.

The American Association for Mental Deficiency project on Techni-
cal Planning in Mental Retardation has been working on many problem areas.
The primary ones this past year have been: reorganization of the American
Journal of Mental Deficiency; development of an abstracting service which
has been appearing regularly in the Journal; publication of review articles
(the NIMH supported survey of the etiology of mental retardation done by
Drs. Masland, Satason and Gladwin will be published in the spring of 1958).
Dr. Leonard J. Duhl is serving as the Associate Editor for Medicine for
the Journal.

Conferences have been held with medical school deans and heads of
the departments of psychology and psychiatry to discuss the inclusion of
teaching of mental retardation in medical schools. It is believed that
it should be incorporated along with the general program of child develop-
ment, rather than as a special entity and specialty.

A basic revision of the presently existing nomenclature is in
process. This nomenclature will fit the standard American Medical
Association version. The revision is being made in cooperation with the
American Psychiatric Association committee, the NINDB as well as other
Government organizations.

Institution-university cooperation studies are being made to de-
termine how to improve the working relationships between these two groups.
Institutions offer a wealth of subjects for research purposes; the uni-
versities can both actively participate in research and offer much to im-
prove the institution.

The grant to the National Association for Retarded Children on
the etiology of mental retardation is being prepared for publication.
One version will appear in the Genetic Psychology Monographs and the
other in the American Medical Association Journal of the Diseases of

children. They are both being reprinted in the American Journal of
Mental Deficiency and will subsequently be circulated by NARC and various
Government agencies. This survey has already had a marked impact on
researchers.

The third special grant in this field to the pacific State Hospital,
to study the factors involved in institucionalization of the mentally re-
tardedj has begun. In addition to doing cohort studies of the population,
attempts will be made to develop m.easures of Individual change. This
grant has also allowed for the development of the Pacific State Hospital
as a center for research in mental re tarda Si on. Major cooperative re-
lationships have developed with University of California at Lcs Angeles,
California Institute of Technology and the University of Southern
California. Various departments such as bio-statistios^ public health,
psychology, psychiatry and chemistry have become Involved, Various
groups of graduate students have been brought into the program. In addi-
tion, many persons not previously interested have been attracted both
to the hospital and to work with the retarded themselves. This project
ably demonstrates how effects of a research project car. spread beyond
the research itself,

Cooperatio!!. has continued with other agencies in Governmentj
especially the Office of Education. Dr. Duhl has continued to consult
on m.ental retardation, and served as a member of the Office of Education's
Research Advisory Board. The Pvesearch Advisory Board is responsible for
evaluation of research projects in ed^acation and has given special em-
phasis to mental retardation.

Drug Addiction

A major study of drug addiction among m-inors at New York University
is in its terminal year of support, M'ach has been learned about the cir-
c'jmstances under which young people become drug users, the way they are
initiated, and the kind of people they are. There has been basic clari-
fication of the delinquency-drug use relationship. We now know the social
psychology of drug addiction quite well, even though we cannot control
all contributive forces in this field, as we cannot in other problem areas.

There is still concern about this field. The Professional Services
Branch is currently exploring the possibility of developing; (1) a
sophisticated doc^jment on the measures necessary, in terms of commuriity
action, to reduce and control addiction, and, (2) a small-scale demonstra-
tion effort, aimed at the reduction of drug addiction in a part of a large
city, with another part of the same city used as a control area. Such a
formulation, based upon the research done in the last six years, plus a
demonstration, could well lead to similar efforts, on a large scale, vjith
local and/or State financing. It is now felt that basic social science
research should be followed by action research.

4 -

Juvenile Delinquency

Three special grant projects in delinquency research have been
under \<iay during 1957, with Dr. Raymond Gould as the Branch liaison per-
son. The first, at the Thorn Clinic in Boston, involves an intensive
diagnostic study of hyperaggressive, uncontrollable boys and their
families as preparatory to a larger study ivhich is to include both in-
tensive diagnostic study and intensive investigation of the treatment
process over a period of several years. The special grant covered che
pilot phase of the project, with the understanding that the investi-
gators would apply for a regular grant for the next phase. The appli-
cation for the regular grant was approved in June of 1957 and the
investigators are moving into this phase of the study in December of
1957. At the same time they are completing the analysis and the re-
porting of the pilot phase. The project is already supplying methodo-
logical innovations in the content analysis of interview materials and
a deepened understanding of the dynamics of the problem of the hyper-
aggressive child and his family, with valuable clues regarding effec-
tive treatment.

The second project, at the South Shore Guidance Cenier in
Quincy, Massachusetts, has concentrated in its pilot phase on develop-
ing a typology of a sample of 50 delinquents who came to the juvenile
court in 1957. The tjrpology is designed so as to be relevant for treat-
ment purposes. A first draft of the analysis of the pilot phase has
just been submitted to NIMH. The study has included the design of an
extensive schedule for accomplishing the social and psychiatric diag-
nostic study and has involved reliability checks on the observations
of the psychiatrist by one or more other psychiatrists. It has also
included a specification of the ideal treatment, the recommended
treatment, and the actual treatment or disposition prescribed by the
court, x^7ith predictions regarding the probability of recidivism in each
instance. This group is planning to apply for a continuation grant
of several years' duration early in January 1958. This project will
involve enlarging the sample so as to permit more refined analysis and
a program of intensive treatment where appropriate, and intensive
follow-up of the sample so as to test the predictions and deepen the
diagnostic understanding of the cases.

The third project, with Dr. Lippitt and Dr. Withey at the
University of Michigan, is in its pilot phase, using a social-
psychological approach to develop a clinically meaningful typology of
delinquents, with a focus on the social situation of the child as well
as on significant attributes of the child and his family. They are
also conducting pilot investigations of significant agencies in the
community, such as police, juvenile court, social agencies, and schools.
Application for an expansion of this project will be submitted in the
spring of 1958,

- 5 -

Dr. Gould has been active as a consultant in delinquency research
during the year, and has an article on the present state of delinquency
control and research in the December 1957 issue of Federal Probation.

Other Areas

Consideration is being given to the promotion of research and
development activities in other areas, under this general heading, in-
cluding alcoholism, sex deviancy, suicide, family disorganization and
the problems of gifted children. No actual work has as yet been under-
taken in these areas.

Studies of Fundamental Processes Affecting the Mental Heaich o£ Popu-
lations of Entire Communities (Local, State and National)

Communication of Mental Health Concepts

A major study in this field, at the University of Illinois, has
shown what the population thinks about mental health problems, how
these beliefs compare with those of the experts, and v^hat is being said
about the theory of mental illness in the mass media. The project has
terminal support, and is currently addressing itself to experimental
studies of change phenomena in this area, as well as to an analysis
of the factors determining how mental health information is secured,
screened and transformed by the media. The demographic factors are
pretty well understood. The final results should be useable tools for
those who want to achieve specific mental health education objectives.

Child-Rearing Practices and Beliefs - The Parental Role

The Illinois studies on communication highlighted a specific
problem area--education concerning child rearing or rather the fac-
tors responsible for parent behavior with respect to their children.
There had been many studies of what kinds of problems children showed
as a consequence of particular parent behaviors and child-rearing
practices. One of the most definitive was an extensive study by
Robert Sears at Harvard with regular research grant support. It be-
came increasingly clear, however, that little was kno^^m about the
total set of factors that determine parent behavior. The interaction
of parent personality structure, beliefs, concepts and hypotheses
about child development, value structure and goals for the child,
sub-cultural influences, etc., had not been explored for all parents
and only in a limited way for those who have produced children needing
clinical attention. In short, vjhat is the total set of influences that
determine parent behavior? Which of the influences are raanipulable by
non-clinical methods? l-Jhat is the natural history of parent role de-
velopment? The emphasis here is on basic understanding of hov7 a role
is developed in our culture. The answers should help greatly to deal
with the more applied problem of parent education. This study is
being supported on a five-year basis starting in April 1957. The
principal investigators are Robert Sears and VJilbur Schram at
Stanford University.

6 -

Aging

Progress continues on the study of Psychological and Sociological
Factors in Successful Aging on a special grant to the University of
Chicago, being undertaken in Kansas City. Dr. Williams provides the
NIMH liaison. Excellent relations have been established with a panel
of about 150 persons between the ages of 50 and 70, with all of whom
the staff has conducted four intensive interviews to date. A compara-
tive study has been made of a group of people in their 80' s.

A special grant to the University of California Institute of
Industrial Relations was recently approved to complete a study of
social and psychological aspects of retirement, with Dr. Else Frenkel-
Brunswik as Principal Investigator. Dr. Williams has effected liaison
between this project and the Kansas City study.

Papers have been presented to scientific meetings by members
of the staff of the Kansas City study and Dr. Williams prepared a paper
for the 4th International Congress of Gerontology. Dr. Williams is
currently preparing a chapter on "Changing Status, Roles and Relation-
ships" for the Handbook on Social Gerontology being prepared by the
Inter-University Training Project in Social Gerontology, financed
jointly by the NIMH and the NHI. Materials will be drawn from the
Kansas City and California studies as well as from the multi-
disciplinary study being conducted at NIH. Dr. Williams also is main-
taining liaison with the Center for Aging Research at NIH.

Community Decision Making

The staff of the Professional Services Branch has felt it would
be valuable to make an analysis of factors in decision-making processes
which may affect the mental health of comraunities. Approval was given
by the Executive Staff to develop a project in this area, and a pro-
posal was submitted for consideration by the National Advisory Mental
Health Council in November. The Council was divided in its opinion of
the proposal, and the majority felt that the time was not ripe for the
particular proposal presented. It was therefore disapproved. However,
it was clear from the discussion that the Council felt research and
development in this area vjould be important, and undoubtedly further
explorations of this field will be made.

The Utilization of Space

The Branch has had a continued interest in the physical and
social environment as it relates to mental health. An informal group
of consultants from varied disciplines has met regularly to discuss
this problem. They have, as part of their discussions, aided in the
formulation of several projects. An interesting concept has been de-
veloped called population potential, which states that a community
closer to centers of population density will react quite differently

from communities at some distance from major population densities. Using
this concept and the mathematical formulations associated with the pre-
liminary xi?ork has shown, that the prevalence of alcoholism, for example,
is greater nearer the centers of population potential than in areas dis-
tant from it. Work with city planners has led to their ability to utilize
a new dimension in consideration o^ plans being made for connriunities.
Dr. Duhl has been asked to speak at both the City Manager's Association
and the American Municipal Association on topics related to mental health.
The interest seems to lie less in concern about mental health clinics
and facilities and more with problems of the general iinpacf. on the pro-
motion of health of a population. The general importance of human
ecology is being recognized. It is becoming evident how difficult it
is to deal with a specific problem vjithout considering the multiple
factors involved in the community.

Other Areas

Some consideration has been given to problems of creativity, but
no systematic v/ork has yet been started. The Branch also hopes to under-
take a basic study of the logistics of mental health services in the
future.

Studies of Fundamental Processes Affecting the Mental Health of Specific
Populations in Organizational Settings

Mental Health in the School

The school is repeatedly alleged to be the community structure
next to the home that plays a dominant role in determining the mental
health, character, and personality structure of children. In spite of
this repeated assertion no careful studies have been made o£ the mental
health influences of the schools. Nearly all of the studies to date
have dealt with efforts to identify disturbed children in the school
at any one moment with little effort to show the school's etiological
relationship. These studies have been valuable as ways of shovjing the
treatment problem faced by the school, the ccmxiuatty, or the home; but
they have not dealt with the day-to-day psychological et-ents of the
classroom and school in such a manner as to give a clear understanding
of how the school can play a constructive role in the promotion of
mental health and prevention of mental illness while maintaining its
social mission as a teaching institution.

The thinking that led to the formulation grew out of the con-
siderations over the last two years of an NIMH ad hoc Committee on
School Mental Health and of the work in this area of the Professional
Services Branch. The basic idea-~that the psychological events of the
school and classroom can be directly observed and studied--is a new
departure in school mental health. The validity of the formulation
has been checked with outstanding child psychologists.

The relationship of the events studied to educational and achieve-
ment indices must be a matter of concern since the school's socially
designated function is education. The primary concern here, however,
is with the nature of the psychological events and their relationship
to educational outcome. If they are functionally related, the degree
to which one set of variables should be manipulated to affect the
other becomes a value judgment which is not determined by research but
which may be made by those responsible in the light of research find-
ings. In other words, research in this area is not directed toward
arriving at value judgments- -rather providing a well docijmented basis
for them.

The National Advisory Mental Health Council at its meeting in
November approved a grant to the Bank Street College of Education for
five years of support to pursue research along these lines.

Preliminary exploration has started to develop a project con-
cerned with mental health in college settings.

Mental Health in Work Groups

In our highly competitive and expanding economy the work situa-
tion is particularly important for mental health, both as a source of
support and of health as well as a source of pathology in some instances.
Dr. Rajmiond Gould is the Branch liaison with projects in this area. The
National Advisory Mental Health Council approved the initiation of pro-
gram development in this area in June of 1957 and authorized support
for a project of Dr. Chris Argyris of the Department of Industrial
Administration at Yale University. In this project he proposes to in-
vestigate the observation that the needs of the individual worker tend
to be in conflict with the needs and policies of the work organisation.
In this connection he proposes to conceptualize and develop measures
for optimum mental health of the worker (involving a constructive com-
parison between worker needs and organization needs) as opposed to
maximum mental health for the worker (in disregard of organizational
needs). Argyris has now completed over 60 interviews with management
and workers in a silver manufacturing plant and has prepared a state-
ment of his study design which was approved with enthusiasm by an
ad hoc advisory group on November 29.

An application from Drs. French, Kahn, and Mann at the University
of Michigan was approved at the November meeting of the National Ad-
visory Mental Health Council. In this project the investigators propose
to develop their theory of the dynamics of work organizations, V7ith a
more intensive focus on the mental health aspects of these dynamics.
They expect to be assisted in this research by Dr. A. T. M. Wilson,
industrial psychiatrist of the Tavistock Clinic in England. This de-
velopmental phase is to be followed by the submission of applications
for specific projects to test hypotheses related to the theory.

- 9 -

Studies of the Mental Health Aspects of Traumatic or Stressful Events
in Various Populations

Disasters

The Institute's interest in disasters grew out of early (1949)
inquiry by the FCDA concerning the management of populations in event
of attack. The Professional Services Branch staff prepared extensive
documents on this subject at that time. Later the NRC Committee on Dis-
aster Studies asked for support of some of its work by the Institute.
Since it was felt that behavior under extreme circumstances is related
to personality and mental health status, the Council made a grant for
the partial support of their work. Recently (1957) this grant was re-
newed. There has been serious consideration of staff representacicn
in the disaster and extreme circumstance area as part of the Community
Research Facility Plans.

Epidemics

There has been no real program development work in the epidemic
field. The PHS was requested in the summer of 1957 by the Army Chemical
Corps to make a study, primarily of industrial reaction, of the impact
of the anticipated Asian influenza epidemic. The Service felt that any
study made should not be limited to industrial production offices but
should encompass as many aspects of community reaction as possible.
The participation of the NiMH was requested. Several staff members par-
ticipated in the planning of the over-all study which is being administered
by the Behavioral Studies Section, Public Health Education Branch, BSS.
Field studies in selected communities before, during, and after the epi-
demic period are being conducted. Various aspects of community planning
and reaction to the epidemic at various stages are being measured. The
NIMH is helping in three ways: (1) Personal services funds equal to
one man year at the GS-11 have been transferred to the study to help with
field work and data analysis of temporary employees; (2) One social
scientist is on detail to the project; (3) A grant was made to support
the field interviewing work by National Analysts, Inc. The work in this
area has had to be done quickly and without a large amount of preliminary
study. It is congruent with the Institute's interest in reaction of
populations to conditions of threat.

Urban Relocation

A study has recently begun of the impact of urban renewal and re-
location in relation to slum clearnace, under the direction of Dr. Erich
Lindemann at Harvard. This study, like all studies of human behavior
under stress, should highlight some of the mental and emotional components
of ecological and social change generally.

Accident Prevention

The Department, and PHS became highly interested in accident pre-
vention in early 1956. NIMH participation in the program of the Service
was requested. One PSB staff member was assigned responsibility in this

- 10 -

area. The Service has centered its Accident Prevention Program in
the Division of Special Health Services, BSS. The Institute is supply-
ing one staff member to the Accident Prevention Program, Dr. Bernard
Fox, a psychologist specifically recruited for the. work and tscbnically
a member of the PSB. A special grant has also been developed to support
a forthcoming conference on research on accident prevention with em-
phasis upon the possible contribution of the behavioral and social
sciences. Regular research grant support of accident prevention studies
by NIMH and other parts of the NIH has been encouraged. Tnare is cur-
rently some concern being expressed over the basic relevance of soEe
kinds of accident prevention research to the NIMH program.

Establishment of Research Settings

Carefully established and planned research settings for studies
of human populations, in which basic demographic data are well known
and samples of the population may be systematically draxTO; can facili-
tate a variety of studies of special problem areas. Also, results can
more readily be made cumulative, and the interrelations of problems
more thoroughly understood.

The Community Research Facility Plans, which the NIMH have been
developing, would be of much value in relation to most, if not all, of
the specific areas discussed above.

The California State Department of Health is interested in the
establishment of a "community population laboratory" in the Oakland bay
area. It is possible that the NIMH will wish to assist in the effort,
in collaboration with other Institutes, and to utilize this laboratory
for special studies in the fields of aging, alcohol, and possibly others.

Conclusions

All of these areas are being approached from the general perspec-
tive of operations research. There is another, and more fundamental
element which they have in common. All of them are tendlag to broaden
the basic conceptions of public mental health by analysis of the inter-
personal and societal matrices within which each problem occurs. An
understanding of these matrices is proving to be basic both to an ^under-
standing of the nature of the problem and to the development of methods
for its solution.

- 11 -

Several of the studies are explicitly concerned with alterations
in social circumstances which go far to overcome other deficits, inclu-
ding deficits of a physiological nature. There is a growing body of
evidence that this approach to problems of mental illness and health
is both feasible and highly worthwhile.

One of the major efforts in future years should be to consoli-
date gains made to date, and to explore the interrelated and cumulative
aspects of the findings as they are made. It is to be suggested, as
a major recommendation, that new areas not be explored at the expense
of following through on work already begun.

NATIONAL INSTITUTE OF MENTAL HEALTH

Professional Services Branch

BUDGET SHEET

Estimated Obligations for FY 1958
Totals $157,055
Directs $150,961

Reimbursements s $6 , 09^

Project included: Community '^tudy Project

PUBLICATIONS AND REPORTS SECTION

NATIONAL INSTITUTE OF MENTAL HEALTH

Annual Report
Calendar Year 1957

During calendar year 19579 raore than diaring previous years j the
information and public education activities of NIMH's P & R were weighted
in the direction of interpreting and presenting the findings of funda-
mental research in the basic medical sciences that contribute to the
field of mental healtho A niajority of the major radio and TV programs
and magazine and newspaper articles which P & R prepared ^ or otherwise
cooperated and participated in, irere on mental health research subjects
rather than on needs and services or interpretation of basic mental
health subject-matter. The same trend was noticeable in some of the
special events sponsored by P & R during 1957 and in consultative and
other types of assistance provided to other branches of the Institute and
to outside organizations during the yearo

In part, this trend was a reflection of the Institute's generally
increased research programs, particularly intramurallyj, as well as of
NIH's intensified concentration on research accomplishmentSs as evidenced
by the almost exclusively research character of the weekly report and the
call for special reports dealing 'with various phases of reseai°ch develop-
ments. As a consequence, there have been more demands on P & R staff
for studying and keeping abteadB of research developments in a wide
spectruni of- technical areas j and of actively seeking out new developments
in theccourse of preparing articlesj reportsj speeches^ and responses to
inquiries. To meet these demands as well as increasing demands on the
Director for professional and lay presentations on mental health research,
P & R has had the responsibility not only for handling this material
accurately and comprehensively but also for presenting it with a keen eye
to the broad policies, as well as the public relations problems that
might be involved.

In part the trend during 1957 '^^s a conscious effort on the part
of P & R to stress mental health research increasingly during the past
year or two. Work done during past years., and the increasingly effective
activities of the mental health voluntariesj have awakened public interest
in, and understanding of, mental health problems to the point where the
Institute no longer needs to devote major effort to stimulate inclusion
of mental health material in the mass media. The major task now is to
direct and channelize existing interest and to stimulate attention to
neglected areas. This P & R has attempted to do during 1957«

Another important trend in P & R's activities was the greatly
increased number of special jobs and special events performed and sponsored
by P & R in a partnership role (rather than in an assisting or independent
role) with other branches of the Institute. The over-all number of such
special jobs greatly increased during 1957= So did the amo-ont of con-^
sultation to and work with outside organizations. Some of tliis special
work was done on request. Much of it vras actively solicited and performed
by P & R in recognition of the essential role of public information and
education in the over=all goals and objectives of the Institute and its
program.

Work in

A large part of NIMH's activity during 1957 'was devoted to such key
areas as psychopharmacologyc, agings mental retardation, and rehabilitation
of the mentally illo Much of the work done ty P & R, as an integral part
of over=»all Institute work;, can be described most conveniently under such
subject headingso

P sychopharma c ology

All of the mass media and the general public were intensely concerned
with the tranquilizers, the energizers, and other phases of psychopharmacology
during 1957o The year had scarcely opened before NIMH ijas barraged by press
and magazine inquiries stimulated by unfavorable publicity about the Institute's
psychopharmacology program, P & R spent considerable time in handling these
inquiries, preparing special reports j and otherwise counteracting the adverse
results of a public attack on the Institute's program in this fieldo

To help counteract the effects of this publicityj and to withdraw the
Institute from the strategically poor defensive position in which it had
been placed, P & R arranged with Jules Billard for placement of a major and
authoritative positive statement of NIl'IH's position on psychopharmacological
agentso This appeared, as the lead interview^article by the Director in the
June 21, 1957 issue of Uo Se NEWS AND WORLD REPORT. The article, entitled
What You Ought To Know About Tranquilizers 9 met with immediate and unqualified
approval by the psychiatric profession, the medical professions special
interest groups, and the general public, and the Institute was unifonnly
congratulated on its firm stand in the field of psychopharmacology. Uo So
NEWS AND WORLD REPORT , generously supplied several thousand reprints to
satisfy requests for copies of the article received from all parts of the
country. It is of interest that Dto Allman, President of the American
Medical Association, quoted from the U<. S« NEWS piece in his art.icle on
tranquilizers that appeared in AMERICAN WEEKLY late in 1957 «.

Another major article on The Tranquilizer Question was a piece with
that title by Frank Bello in the May 1957 FORTUNE magazine. Based in large
part on information supplied by the Institute's Psychopharmacology Service
Center, through arrangements made ty P cS: R, this was a comprehensive article
on the subject of psychopharmacologyc P & R made arrangem.ents to procure
reprints and has been using this piece 5 along with the U. S« NEWS piece, as
a regular part, of its informational materials.

A number of important press articles on psychopharmacology, prepared
with assistance from P & R, appeared during 1957<> The more important of
these included several articles in a series on mental health by Howard
Whitman in the COLE NEWSPAPER SYNDICATE, several by Selig Greenberg in his
series on New Horizons in Medicine in the PROVIDENCE JOURNAL-BULLETIN , a
SCOPE piece on the NIMH program of clinical research on anti-depressive
drugs, a NEW YORK TIMES piece on tranquilizers by John Finney, and a lead
article on the 'Psychopharmacology Service Center in SCOPE WEEKLY. In
addition, information on psychopharmacology was provided to writers from
the AAA magazine, REPORTER, CHEMICAL AND ENGINEERING NEWS 5, PHYSICIANS
MAGAZINE, READEife DIGEST, CAPITOL TD-ffiS, WASHINGTON POST, GANNETT NEWSPAPERS,
N. Y. DAILY NEWS, WORLD-WIDE NEWS, NEA SYNDICATE, NEWARK EVENING NEWS,
SCIENCE SERVICE, and INS.

Three major TV shows j in which P cS: R had an important role in
selecting topics and making arrangements, were devoted to psychopharma-
cology. One, the American Association for the Advancement of Science
hour-long NEW FROOTIER program, appeared on the CBS-TV Network at the
very close of 195^1 the Chief of NIMH^s Psychopharmacology Service Center
was guest panelist on the section of the program dealing with the biological
scienceso Arrangements were made for the Chief of the Center to give a
medical exposition of tranquilizers on Howard Whitman's special half -hour
program on tranquilizers produced as pairt of a national hook=up NBC-TV
HOlylE shoWo Toward the end of the year arrangements were again made for
Dr. Cole to appear on TV — this time the McCaffrey CELEBRITY PARADE
(WMAL-TV) in a discussion of tranquilizers and tensions.,

In addition^ P & R provided information and arranged for consul-
tation to an independent film maker who is currently preparing a medical
fil::n on tranquilizers addressed to the general physicianj and assisted
Editorial Research Associates on their new pamphlet on psychophamiacologyo
During the year, the Chief of P & R served as a member of the Committee of
Editors in a Working Conference on the Status and Improvement of Clinical
Drug Evaluation Reports sponsored jointly by the Institute's Psychopharma-
cology Service Center and the American Psychiatric Associationo

Gerontology Conference

P & R's major activity in the field of aging for 1957 was complete
coverage and handling of the press relations and publicity program for the
Tenth Annual Scientific Meeting of the Gerontological Society held in
Cleveland on October 31 - November Eg 1957«. Carried out by P & R staff at
the request of the Chief of NIMH's Section on Aging, who was Program
Chairman for the meeting, this was a highly successful and extremely
important undertaking which increased P & R's prestige with NIMH and out-
side scientists in the field of agingj as well as NIMH prestige for its
leadership in this field. Preliminary to the meeting^ contact was made
with and publicity materials distributed to 22 editors of metropolitan
newspapers with large national circulations j 22 selected science writers
with a known interest in gerontology;, program managers of all the principal
radio and TV stations in Clevelandj and the CBSg NBC, and \^ESTINGHOUSE
radio and TV Public Service departments* T'wo advance press releases, one
a general anno\incement and the other on a special synposium of European
gerontologists, were sent to 200 large dailies plus some professional
journals. The K,Y. THESj the NeY, JOURNAL-AMERICAN, and AP sent reporters
from headquarters? INS and UP were covered by the Cleveland bureaus. In
addition, requests for all releases and papers were received from SCIENCE
SERVICE; Roland Berg, Medical Editor of LOOK; the Managing Editor of MEDICAL
NEWS; Earl Ubell of the N,Y, HERALD=TRIBUNE; Tom Henry of the WASHINGTON
STAR; the editor of the PITTSBURGH STOI-TELEGRJill; Robert P. Goldman of PARADE;
Ray Bruner, Science Editor of the TOLEDO BLADE; free=lance -writers; Richard
C. Bostwick of Sl'IITHj KLINE and FRENCH; and Fred Freed of CBSo

As part of the press coverage, condensations of the major papers to
be delivered at the Conference were prepared and these were made available
at the press room, along with suggested leads, biographical sketches of
the principal speakers, photographs, and printed programs. P & R staff
members were in Cleveland for the meeting, set up the press room, and took
care of all public relations for the Conference o Three days ahead of the

meeting a staff member went out to do advance publicity xd-th the managing
editors of the three Cleveland papers, the three id.re services, and the tiro
radio stations and one TV station which had expressed interest in interview
programs with gerontologists attending the meeting. In addition, P & R had
an NIMH exhibit at the Gerontology meetingo

Immediate results of P & R's publicity work at the Gerontology
Conference included:

1) Two radio interviews with gerontologists on Cleveland's VGAR and
KYWo

2) One TV interview with Dto BourHere of France on WJW.

3) Advance stories in No ./T. TIMES and other papers.

k) Daily stories in N. Y. TIMES and over AP and INS. AP stories

were carried on front pages from N. Y. HERALD TRIBUNE to SEATTLE
TIMES, from Great Falls (Mont,) LEADER to Louisville (Ky.) TIMES,
from Ithaca (NeYo) JOURNAL to Idaho Falls POST-REGISTER, and many
others, both large and small. INS coverage was also widespread.

5) Daily stories by medical xjriters in CLEVELAND PLAIN DEALER, and
daily feature stories xd.th pictures in CLEVELAND PRESS. Also
publicity in CLEVELAND NEWS.

6) Round-up article by WORLD WIDE NEWS in November 20 issue of
SCOPE WEEKLY.

In addition to these immediate res'iiltsj, various featiire articles will
no doubt result from this public relations work. Two of the reporters who
covered the meetings write columns related to gerontology, and many of the
free-lance and magazine writers who requested materials will probably use
them as source data for future articleso

Other Work on Aging

Mental Health of the Elderly, a new pamphlet prepared by P & R, was
issued describing NIMH's varied activities in the field of aging. It was
also translated into French and Italian, and copies (including those in
English) were sent to Italy for display and distribution at the Inter-
national Gerontology meeting. GPO has reported relatively high sales of
this pamphlet (a total of I5OO being sold in the 3 months from June to
September) , and a second edition was run off in 1957.

As part of its assistance in the press room at the annual meeting of
the American Psychiatric Association in May, P & R staff prepared press
announcements on papers delivered by NIMH personnel on their research in
aging, and arranged for a press conference with two of these scientists.
This activity resulted in a n\amber of press articles on NIMH research on
aging and mention, of this work on 3 network radio programs. Several months
after the meeting,. P & R wrote an article on the research work of one of
these scientists for Tom Henry in the WASHINGTON STAR, During the year,
information on aging was also given to Fishbein of WORLD-WIDE NEWS, to
Beach of U. S. NEWS AND WORLD REPORT, and to Cassels of UP.

- 5 -

Another major informational event in the field of aging was the Johnsi
Hopkins FILE 7 TV show, in the fall of 1957, devoted to the sociological
and psychological aspects of aging, with the Chief of KIMH's Section on
Aging as guest speaker, P & R worked with the script writer and helped
make arrangements for this program.

Mental Retardation

During the year, P & R was called upon to assist in revitalizing the
JOURNAL ON MENTAL DEFICIENCY, published by the American Association of Mental
Deficiency, the principal professional organization in the field of mental
retardation. At the request of a member of NIMH's Professional Services
Branch who had become Medical Editor of the J0I3RNAL, a P & R staff member was
assigned to develop magazine policy, to set standards for manuscripts, to
develop editorial guidelines and procedures, and to get the JOURNAL operating on
a journalistically professional basiso A major policy statement, prepared
by this P & R staff member, was adopted by the JOURNAL, as were the editorial
guidelines. She also edited a nijmber of highly technical professional
articles in order to provide the Medical Editor and other JOURI\!AL staff with
prototypes and practical guides.

At the close of the year, P & R worked closely with the National
Association for Retarded Children, the principal voluntary in this fieldji,
in preparing releases and other advance publicity as well as in making
arrangements for a special meeting and press conference (held in New York
City in January 1958) in connection mth release of two major reports on
research on mental retardation, prepared under the sponsorship of NARC
with the aid of a grant from NIMH and NINDB. Firm relations were established
•with the information, publicity and executive directors of NARC, and P & R
plans to work closely -with that organization in planning appropriate joint
activities.

During 1957s WGAY, a local radio station, carried a taped interview
on retardation with the Professional Services Branch specialist on this
subject. P & R also prepared a number of speech materials for top level
speakers on retardation diiring the year, and assisted a writer from the
N.Y. DAILY NEWS with a story on patients in hospitals for the mentally deficient.

Mental Health of Children

P & R prepared three speeches dealing with mental health of children
diu'ing 1957» one for the Director of NIMH on Services and Programs for Mothers
and Children (delivered at the annual American Public Health Association
meeting in Cleveland) , and two for the NIMH specialist on school mental health
(delivered at the National Education Association Centennial Convention and
Syracuse University's Second Annual Conference on Secondary Education).
P & R is assisting this school mental health specialist on a regular basis,
collecting pertinent research data for his use, evaluating the usefulness of
such material, and advising him of its potentialities for articles in various
types of outlets. P & R -will prepare some of these articles and provide
editorial assistance on all of them.

P & R prepared a statement for and assisted in an open house, held hj
NBlH's Residential ,Tj?eatment Center for emotionally disturbed children, for
members of Montgomery County citizens' associations. Also coincident with

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the opening of the Center, a series of still pictures showing normal controls
were taken for subsequent public relations and other informational uses»
Some of these pictures were used for an INS story. MEDICAL NEWS carried a
major picture story on the Treatment Center and the January 1958 issue of
HARPERS carried an excellent major article on the work of NIMH's Child
Research Branch; P & R assisted with both of these articles o In addition,
information was provided to LOOK for a major article on emotionally dis-
t\irbed children, and to Eve Edstrom of the WASHINGTON POST on treatment
facilities for such children.

Arrangements' were made for NIMH's Chief of the Section on Child
Development to discuss IQ testing on ABC-TV's OPEN HEARING, a Network
program. P & R wrote 3 articles in collaboration with this Section Chief 5
(l) a guest column on IQ testing for Jane Eads AP column, (2) a 3>000 word
story on adopted children for CHILDREN magazine, and (3) an article on
predicting children's intelligence for the NATIONAL PARENT -TEACHER magazine.
Information on IQ testing was also provided for a WASHINGTON DAILY NEWS
story.

P & R helped with arrangements for an article on normal children
in the February 1957 issue of BETTER HOMES AND GARDENS, and for a pro-
spective article on child rearing being prepared by a free-lance writer.
In addition, a statement was prepared for the Director's signature on the
new PIEIRE THE PELICAN series of child-rearing leaflets for parents,
produced by the Louisiana Mental Health Association.

A number of the large meetings at which P & R exhibited and dis-
played materials during 1957 were held by organizations directly interested
in or vitally concerned ^with the mental health of children. These in-
cluded the biennial meeting of the American Association of School
Administrators (17,000 registered attendants), the American Orthopsychiatric
Association annual meeting (5>000), the 12th Annual Conference of the
.'association for Supervision and Ciirriculum Development of the National
Education Association (3»000), the American Academy of Pediatrics (1,000),
the NEA annual convention (20,000), and the New York Congress of Parents
and Teachers (7,000).

Treatment and Rehabilitation of the Mentally 111

As part of its emphasis on rehabilitation of mental patients during
Mental Health Week in 1957> P & R prepared a 4-minute 15-second tape record-
ing of the Director of the Institute on the subject of The Healing Community,
dealing vilth. the role of the community in helping the former mental patient
make a successful adjustment. P & R offered to transcribe this talk onto
blank tapes sent in by any individual or organization. Though the tape was
not available until shortly before the Week, some 20 requests for the tape
were received from radio stations and mental health associations o It is
planned to continue this type of activity, with promotional assistance from
the National Association for Mental Health and the Mental Health Materials
Center.

In this same general area, P & R prepared an outline for a speech
given by the Director at an APA Mental Hospital Administration session,
and drafted a progress report on NDIH's program of Mental Health Projects

Grants, which are awarded for studies and demonstrations of improved methods
of patient treatment and careo

Information was provided to the NBC-TV Public Affairs Department for
a documentary on mental hospitals, and to Howard Miitman for a half -hour
program on rehabilitation on the N3C=TV HOME shoWo Writers for TIMEj READER'S
DIGEST, COSMOPOLITAN;, and INS were helped with stories on day=and night-care
programs, rehabilitation of the mentally illj identifying and receiving help
for the emotionally disturbed;, commitment procedures, and resident patient
populations.

Research

Research, both intramixral and extramuralj was emphasized wherever
appropriate in P & R's work during 19570 The research interest is apparent
in many of the activities already described, and Dd.ll be integrated into the
discussion of activities in subsequent sections of this report. This section
describes some of the more important P & R projects which are of primary
relevance to basic research and which do not lend themselves to treatment
under special subject headings.

Starting in July, the Institute Director's Weekly Report, prepared
by P & R, was heavily weighted in the direction of research. In the preparation
of research items for these reports, P & R has received excellent cooperation
from ND'IH's research programs^ a staff member has been invited by the Director
of Basic Research to sit in on staff meetings. In all, "^S items were included
in NH-IH's weekly reports to NIH from July 1 to December 31, 1957; of these, 53,
or more than txiro-thirds , were incorporated into the NIH reports to the Surgeon
General. This material proved to be extremely helpful in preparation of
Research Highlights of 1957 which, as in past years, iiras prepared ty P & R.

P cS: R prepared a number of releases and research papers delivered by
NBIH staff at professional meetingSj, wrote a speech for the Director on
Current Trends in Psychiatric Research for a Regional Research Conference
of the Araerican Psychiatric Association^ and assisted the American Psychological
Association in planning a press reception for a foreign world-renowned neuro-
physiologist.

During I957 the script for the proposed NDIH fiLii on Mental Health
Research was completed and the project approved for production. The film ^ras
planned as a public relations tool to acquaint the general public with the
nature and scope of mental health research, and thereby to help dispel some
of the prejudices against psychiatry and the field of mental health, as well
as to help relieve some of the ingrained pessimism about the ability to treat
mental illness successfully.

P & R arranged for an NIMH researcher to discuss the physical effects
of emotions on the ASK-=.IT=BASKET WTOP=TV program, and for the Director to
discuss mental health research in the SCIENCE SERVICE series of taped radio
prograras. K3C=TV was given information for a documentary on stress.

In addition to research articles mentioned in other parts of this
report, P & R assisted in arrangements and information for the '^-article
series on alcoholism written by Cassels for UP. Information on research
grants and intramural research projects was provided to free-lance writers
and writers from MODERN l^IEDICINE, TIME, LIFE, READErIs DIGEST, SCOPE, PAGEANT,

SCIEOTIFIC AMERICAN, U. So NEWS AND WORLD REPORT, FORTUNE, N« Yo TBIES,

N. Y. DAILY NEWS, SCRIPPS-=HOWARD, SCIENCE SERVICE, WASHINGTON POST, MEDICAL

NEWS, and IKSo

Work With Voluntaries and Other Organizations

As in past years, P & R worked very closely with the National Asso-
ciation for Mental Health in planning and carrying out public information
and education programs, both in connection vrxth Mental Health Week and in
connection xiTith year-round activitieso In addition, assistance and con-
sultation were provided to an increasingly larger number of other organiza-
tions, such as State and local mental health associations , voluntary and
professional associations in the field of mental retardation, and a wide
variety of civic, service, and quasi-governmental groups with a primary or
ancillary interest inj, and concern with,, problems of mental health and
mental illness.

Mental Health Week

During the first week in May, NIMH and NAMH jointly sponsored the
9th annual celebration of Mental Health Week. With the theme "The Mentally
111 Can Come Back," the Week xras focussed on what citizens and communities
can do to promote the full recovery and rehabilitation of the ex-mental
patiento During 1957j "the Advertising Council again ran messages supporting
celebration of the Week in the May-June issue of their RADIO-TV BULLETIN.

P & R prepared special Mental Health Week kitsj each containing a
careful selection of program, publicity^ information, and educational
materials to be used in celebrating Mental Health Week and in planning
long-range mental health activitieso These kits were mailed out to some
600 mental health voluntaries, civic and service organizations, mental
health agencies, and other interested groupso Selected publicity materials
were sent to science writers and others in a position to promote the over-
all goals of the Week. Included in the kits were a new version of a
Mental Health Fact Sheet prepared for the occasion by P & Rg and announce-
ments of the tape recording of the Director's talk on The Healing Community.
Additional requests for kits and for extra copies of certain materials in
the kits were received prior to the Week and subsequentlyo

The Mental Health Week kit, in the past year- or two, has developed
into an important program item, apart from its use in connection with the
Week. Kits are requested throughout the year by local and State mental
health agencies and organizations for use in planning and conducting
program activities. As an example, the Bureau of Community Mental Health
Services, New Jersey Department of Institutions and Agencies j has requested
kits to assist them in developing community mental health education as a
first step in setting up the County Mental Health Boards required iinder the
newly enacted Community Mental Health Services Act of the State of New
Jersey.

A number of radio and TV programs and magazine and press articles
during Mental Health Week were a direct or indirect result of P & R
activities. In addition, P & R prepared two speeches for use during Mental
Health Week (one delivered by the Director and another by an Assistant
Secretary of DHEW), and the Presidential Message and Proclamation for
Mental Health Week.

Work With NAME

NBffl worked with and assisted the Advertising Cottncil and the NAMH in
the Advertising Council's major year-roiind mental health education campaign
which was launched in 1957<> P & R can claim a good share of the credit for
the fact that this campaign was developedj, since P cS: R established the con-
tact with the Ad Council in 1952^ built up relations and cooperation with
the Ad Council Program Consultant and other staff during the past six years,
and assisted in establishing relations between NAMH and the Ad Councilo In
connection with the Ad Council's distribution of How To Deal With Your Tensions
as part of the general mental health campaign, P <§: R arranged for a foreword
by the Director of NIMH, and is assisting in distributing the booklets

P cS: R continued its periodic consultation with the public relations
and educational directors of HAMH in order to plan joint programs and provide
distribution of each other's materials o P & R prepared the message from the
President to the Annual Meeting of NAIfflo NAFEg in turn, has promoted dis=
tribution of two new P & R publications? Facts About Mental Health and Mental
Illness, and the Barbiturates leaflet <, At the end of the year, P & R was
planning joint publication, with NAlfflg of a series of leaflets and folding-
card exhibits for teen=>age audiences describing the work of mental health
professional personnel and the kinds of training and experience such people
must haveo At the end of the year, alsoj, P & R was planning cooperative
public relations with a newly appointed special liaison representative of
NAI^Ho Contemplated activities include preparation of a series of charts
and leaflets interpreting NH'IH activities to State mental health associa=-
tions, and cooperation mth NAMH field representatives and regional groups
of mental health organizationso

Work With Other Organizations

During the year^, P & R provided consultation to an official of the
Southern Regional Education Board engaged in preparation of a special report
on the work of that organizationo Assistance was given to the General
Federation of Women's Clubs on a popular pamphlet being prepared by the
Federation on what mental health means to the individual and the family.
Consultation and other help was given Editorial Research Associates on
their new pamphlet on psychophaiTOacology,

A speech was -written for delivery by a Government official at the
Rhode Island State Mental Health Associations greetings were sent for the
Director of NIIIH to a meeting of the Louisiana Mental Health Association,
forewords were Tjritten for two pamphlets published by the Westchester
(Ne Ye) Mental Health Association, assistance and advice were provided
an official of the Oregon Mental Health Association;, and a series of film
previews were arranged for a teachers' workshop conducted by the Washington
School of Psychiatryo

Mental health materials prepared by P & R received wide acceptance
and use by key organizations o The Canadian Broadcasting Company purchased
8 prints of Preface To A Life for a nationwide telecast o The Bureau of
Health Education of the American Medical Association requested copies of
a packet of NIMH educational materials for use in their health education
programo The Mental Health Materials Center included copies of P & R's

= 10 =

Reference Guide Noo 3> Introductory Readings in Mental Health, in their kits
which go to 2500 individuals and organizations active in h\:unan relations work.
Two State Health Departments purchased 15s 000 copies of What Is Mental Illness,
the popular leaflet prepared by P & R<, 6,500 copies of Careers in Psychiatric
Social Work and 1^500 copies of Mental Health of the Elderly were sold by the
Government Printing Office from June to September 1957£> and 3*000 copies of
Barbiturates As Addicting Drugs were sold between September and Decembero

Exhibits and literature displays were sent to meetings of a vrlde
variety of voluntary and other organizations which play a key role in promoting
mental healths These organizations included the American Academy of Occupa-
tional Medicine, the National League for Nursing, the National Conference of
Social Workers, the National Education Association, the American Personnel and
Guidance Association, the Cleveland Health Museuia, a number of county mental
health associations, and the National Health Councilo This activity has been
a major phase of P & R's public relations and educational work for 1957*

Other Activities

Many of the activities already described=-speeches5, articles, radio
and TV programs, exhibits, special events, and consultations—are directly
related to public relations work for NII-IH as an institution. The press
releases, annoioncements, and answers to public inquiries are' also integral
to P & R's public relations work for the Institute, In addition to these
activities, P & R vjrote and provided still pictures for an article entitled
Report from NB'2I Xirhich appeared in the October 1957 issue of STATE OF MIND,
the monthly magazine published by CIBA for the general practitioner.

P & R staff also assisted a number of the scientists at KDIH in
organizing, formulating, and presenting their scientific data. In addition
to the Weekly Reports and the Research Highlights for 1957> P & R also
prepared the Director's Budget Testimony and the short=form annual report,
as well as supervising preparation of the long"=form annual report,

P & R, at the request of the Chief of the Training Branch, wrote a
comprehensive historical analysis of NI^iH's training programs which is to
be included in the Institute's report on training being prepared at the
request of Congresso

Recognizing its responsibilities for developing competent personnel
in the field of mental health information and public relations, P & R for
the first time established a position for, and recruited an Information
Traineso A comprehensive training prograra, including evaluation, was
planned and scheduled with NIMH Branch Chiefs, the Office of Research
Information of NIH, and the Special Assistant for Information to the Surgeon
Generalo Under supervision, the trainee developed a new system for cata-
loguing and controlling distribution of publications. This system has been
put into effect with gratifying results.

The number of public inquiries answered during 1957 was e:ctremely
high. An estiniated 1800 letters of more than routine difficulty, including
about 50 Congressional letters were sent out (based on actual count of
891, including 2^■ Congressional, from July 1 to December 3I) , Replies to
Congressional letters require knowledge of NIMH policy, considerable
original research in gathering data for the reply, and a keen sense of

- 11 -

public relations in presenting the materials

Approximately 2^114 telephone inquiries were haxidled from July to
December 1957=

A total of 83s 0^7 pieces of literature were distributed in answer
to 8,3^2 requests during 1957 <> This was about two and one^half times the
volume handled in 195° I the nuraber of separate requests also rose hy about
50 percent. Over 300 clearance papers were handled by P cS; Rj and 1133
film bookings were made during 19570

Rew Publications and Other Materials

Two new pamphlets and two new leaflets were issued in 1957o One
pamphlet. Facts About Mental Health and Mental IllnesSs, was prepared for
Mental Health Week and has proved to be so useful that P & R plans to
reissue it from year to year^ bringing the figures up to date each time«
Mental Health of the Elderly ^ the other pamphlet, was prepared as an
extended printed version of the original NDffl exhibit of the same titleo
This publication, which describes the comprehensive activities of NIMH
in the field of aging, was also issued in French and Italian for use at
the International Gerontology Congress in Italy,

What Is Mental Illness?, the NUffi leaflet which was distributed in
large quantities in its pre-publication edition, was received from GPO
early in 1957° Large quantities of this leaflet have been distributed,
15jOOO copies being sold by GPO to two State health departments in a
single weeko The other new leaflet , entitled Barbiturates As Addicting
Drugs, has filled an urgent need and met with unqualified approval. The
Food and Drug Administration requested IjOOO copies for use in their
District OfficeSj and the GPOj which reported 3sOOO copies sold between
September and December 1957> went back to press for a second edition of
2,000=

Reference Guides Nos<> 1 and 6, Mental Health For Parent and Child
and Advanced Readings in Mental Health were revised, as was the Current
Reading List of mental health pamphlets, reprints, and reports available
from P & Ro

Mental Health Memo Noo I9 the first issue of a proposed series of
digests of significant program activities designed as a means of communi-
cation for operating agencies throughout the coiintry, was prepared and
sent to some 550 individuals and organizations, including State Mental
Health and Mental Hospital Authorities and NIMH regional staff.

Copy xjas prepared for an abridged statement of Institute fxuictions
to be entitled National Institute of Mental Health~=A Summary Statements
This will be issued as a leaflet to be sent in response to inquiries
from students and others who do not need a fully detailed description of
NIMHo

In addition to new NDIH publications, P cS: R purchased distri-
bution stocks of 29 new reprints dxiring 1957<> These covered such varied
subjects as narcotics addiction, delinquency, psychiatric terminology,
treatment of the mentally ill, family mental health, child guidance,

■ s

- 12 -

scientific developments, legal problems in mental illness, tranquilizing
drugs, communication of mental health concepts, and mental retardation.

Prints of three new films were purchased during 1957^ The Kid
Brother, and To Your Health, new films on alcoholism; and The Human Side,
a film on voliinteer programs in mental hospitals o

The Public Relations of Mental Health Education

The special nature of the mental health field, with its attendant
difficulties in communicating information that conflicts with existing
attitudes, and the special role of the NIMH as a leader in mental health
research, training, and service programs, have posed unique problems for
P & R, In meeting its responsibilities, P & R has attempted to develop
its information and public relations activities so that they help promote
the goals of mental health education., Similarly, educational projects
are carefully planned so that they constitute good public relations for
mental health in generalo

During 1957j P & R was involved in a number of activities intimately
related to these public relations aspects of mental health educationo The
Chief of P & R participated in a panel on mass comm\ani cat ions at the
National Health Council's National Health Forum (held in Cincinnati in
March) which was devoted to the subject of Better Mental Health, The
presentation, in addition to being published in the National Health Council's
official report of the 1957 National Health Forum, was published as an
article entitled Mass Communications and Health in the August 1957 issue
of the New Jersey PUBLIC HEALTH NEWS. Copies of this article were procured
by the California State Department of Health for distribution to all State
health educators, to all health educators in training, to mental health
service personnel, and to reference libraries for public health personnel.
The spring issue of MENTAL HIGIENE, the professional quarterly ptiblished
by NAMH, also quoted excerpts from this presentation.

P & R assisted in the preparation and review of the series of five
articles on psychiatry and psychology today, carried in LIFE starting
xd-th the January 5s 1957 issue. In addition to providing information and
materials for the articles, P & R was instrumental in guiding their
development and general approach, both through direct review and thorough
communications xjith the two APA's, who were given major responsibility
for review by LIFE,

In May of 1957 the Chief of P & R participated as discussant in
a sjnnpositun on Public Awareness and Problems in Mental Health at the 12th
Annual Conference of Public Opinion Research held in Washington, D, C,
by the American Association for Public Opinion Research. P & R also
pai^ticipated3in!pr6viding"':"consultatiori:i'to the program" director and' other
officials of the Educational ITV Genter~,i".AnncArbor,.-ivIichigan5 Hho'are 1;,"
planning' aesifeiries of mental health proEr,aihs.v::In:"additiDh, P & R partici-
pated in consultation mth researchers from the University of Illj.nois
Institute of Coiiiiaunications Research who are conducting a special study
of coiiiiTiunications of mental health concepts under a grant ii-om IvIMK,

13 -

NATIONAL INSTITUTE OF MENTAL HEALTH

Publications and Reports

BDDGET SHEET

Estimated Obligations for PY 19^8
Totals $176,229
Directs $169,391

Reimbursement s s $6 , 838

RESEARCH GRAMS AND FELLOWSHIPS BRANCH

Annual Report for Calendar Year 1957

The continuing and rapid growth of the research grants pro=
gram made 1957 a year of sigaificaat deirelopaient and reassessment
in Branch operations « Reaffirmation in the fiscal 1958 "budget of
last year's strong Congressional support for research in mental
health, again testified to a steadily gro"td,ng social concern over
problems related to mental ill-health, as well as to an increasing
public recognition of research as a vital national resource.

I, PROGRAM GROWTH AKD DEVELOPMEJNTt THE ADfffNISTRATIVE PICTURE

Throughout the year the steadily joDunting volume of grant
applications was to necessitate a series of modifications in pro-
gram administration. A glance at the following comparative figures
on new grant applications furnishes a rough index to the growth of
the program.. ScclMing applications relating to previously conanitted
funds (i.e. continuation and supplement applications), the number of
grant applications received has risen from 260 in 1955? "to 457 in 1956,
and reached 683 in 1957. Kuaibers of research grant applications which
were approved rose from I30 in 1955 to 2^2 in 1956, reaching 292 in
1957.

It is apparent at a glance that the volume of work necessi=
tated by the review and approval operation has very materially
expanded in the last two years » Concurrently, the staff of the
Branch has increasingly been called upon to provide advisory and
consultative services to grantees, prospective applicants, and to
university departments in the behavioral, medical, and biological
sciences. Difficulties arising from an acute shortage of staff at
the outset of the year were conrpoTonded by the loss of staff time in
providing repeated and lengthy information statements for budget
justification and other administrative purposes. IM certainty as
to 1958 appropriations iar^jeded Branch planning for many months . It

" 2

has Tseen difficult for Bramcfe staff msmters to ^ma.ertal£e the aeces-
saxy degree of stimulatioa, of special areas of i^searcl^ in whida the
Institute ha-s a priniary interest. While it has "been a eontimsiBg
problem this year to meet o?©rall demaads for service ^ jnembers of
the staff ha-eie teen hard pressed as ¥©11 t© fiBd tiaae to keep abreast
of recent i^searda developsnents ia the m0.ti-disciplined fields ^ieh
mjderlie research in mental health. ^

A loss of e2q)erie3aced BrasGh staff -was ©ceasioaed in April,
1957 with the transfer of the Mental Health Stiidy Section to the
Division of Eeseareh Grants » So hea-vy had the task of reviewing the
increased voltnne of research grant applications become that a sister
Study Section to the Mental Health StusSy Section^ the new Behavioral
Sciences Study Section, was established at this tii^.

Some of the new staff positions established this year to meet
the increase in work- load have been filled - - including those of a
Program Analyst, a new Executive Secretary of the Msntal Health Small
Grants Committee, and an Executive Secretary of the Mental Health
Career Investigator Selection Consoittee, together with the new
con5)lement of the Psychopharmacology Service Center, Other positions
are as yet still vacant. It has proven difficulty as is true in msny
scientific fields today, to locate well-ijaalified applicants. Even
tdien qualified people are hired, a losag period of training and ex-
perience in the Braach is necessary before new staff reach their full
work value within the Bi^mch setting. Sds problem offers n© hope of
iiffinediate solution.

To help in the training of new staff si^a&ers brou^t on during
1957^ an orientation series of "discussioa-cpaestion-aaswer" sessions
have been held at intervals, individual background orieatatioa folders
have been prepared, and, through the medium of week3y staff meetings
and roiEfcine circulation of information materials to all staff stembers,
a strong effort has been made to establish that aecassary inter-
comniuni cation without which few work gro-i^s fimetion successfully.
Furttier effort in this area included a major reorganizstioa and con-
solidation of Branch files to ensure the iaaasdiate availability of
baekgrouad inforaettion to all staff membei's.

Sse gx»5rth is the volume of applications for research grants
has very markedly Increased the number of individual eansultatioas
with i®searda inviastigators, A eoasiderabla shar^e of such consulta-
tion is eoadmeted by smil, but :m^' personal later^ews have been held
by the staff is. ^thesda as well as at eoafereaces and professional
meetings. Diaring 1957, staff sasmbers partieipated ia a variety of eoa-
fereaces, ineli^ding the Conference on Research in ^ntal Health held in

3 "

JacksoHTiUep Florida^ ia April, arf. tie Soutliexn Regional Miaeatioa
Board's Coafei^ace on Jfental Health Research, in the South j, held in
Williams'burgj, Virginia in August^ 1957l amMal aad 3Pggional sneetiags
©f such professioaal groups as the AsBSleaa PsycMatrie Association.,
Anaricaa Psychologieal Associatios,;, ete» Branch staff also visited
SQWB fifteen to tireaty -fflaivsrsity deparfansats in the "biological aai
behavioral seienees as advisors aad eoas'ultaa.ts on researeh programs.

Analysis of Program Meeds

nihe jMieious distrilmtioa of grant fsasds carries with it sosse
reqiairement that those respoasiTble for the program work from a soxmS.
basis of Ifflowing "where jou are^ where jon are ^ing^ and how you can
best get there." 5to acquire such a platfoam for operating necessitates
a eontinuing program aaalysiB. Xaereasisglgr^ ale©;, the Branch has been
called v^n to famish analytic inforaation on the grants program - -
to the Sti^ Sections^ the national Advisory Sfental Health Cotmcil;,
branches ©f the Public Health Ser^ee^ other goveiament agencies aM.
the public. To a greater extent than in the past both the Council and
Study Sections have turned to the Braadi for infonnation on policy, on
program dii^etion and planning.

In an effort to n^et both internal and external derasnds for
ps^grajE aaalysig^ the Branch this year tools a number ©f steps to
develop long-range aiethcsds of adasiaistrativB i^view and critical
examination. A part of this new activity has been dirgcted toward
the establisha^at of a sou^ and workable basis for "categorizing"
grants. Since the spring of 1957 a largB part of -ae tiim of one
staff lEember has been spent In the devBlopaaent of a system of gx-ant
analysis^ ia ■which defined and standardised processes of content
analysis will be combined %-jlth medianieal sorting procedurss to per-
mit of rapid seleetion. It is hoped that the successful estaMisfeEent
of the grants category system will facilitate not only the sort ©f
program analysis which concerns itself chiefly with how srada s^seareh
was^ or was x»t^ s'i^parfced (in terms of atEabers of applications^
aaiDunts of nsney^ distribution by fiscal years^ areas of stMyj, etc.),
but may later assist in iaterprsting comtrtbutions to scientific
toowledge^

Still a fm°ther armmm of program aasljsis was e^lor^ by an-
other staff mamber in a detailed stody of the ©vbesII role of program
evaluation within the Branch, based ia lar^ measure on an historical
analysis of rslated earlier e^erlenee. Siis study indicated the seed
for, and feasibility ©f, pi^paring analytic iBviews ©a subject areas
©f tte x^search grants program, an overall historical review of the ad-
Mnist^tivie development ©f the program, aad additioMil information
articles iaterpr^ting the program to scientific audiences.

k -

While lack of staff tisie this year has limited the preparation
of analytic stiadies, several short reviews of special aspects of the
program were ■unfiertaken, including a statistical analysis of the
i*esearch fellowships program^ a backgroimd paper (for use hy the Study
Sections and Council) considering fluid funds in the award of research
grants^ and a more substantial review of the Small Grant Program.
With an aim of determining the availability and nature of grant sirp-
port in mental health and related disciplines from foundations and
professional organizations, the Branch this year also has prepared a
sxir7ey=guestionnairej, presently in process of clearance^ which will
be circulated to some seven hundred private organizations.

The anall Grant Frogi^m

Ihe year 1957 slso produced a serious review* of the Stoll
Grant Program. Initiated by the Natiosial Institutes of Health on
an across-the-board basis in March, 1956, the program had been planned
as a new method of research support in which the usual deadlines
would be waived. Maximum awards imder the Small Girant Program are
$2,000 plus indirect costs. It was hoped that the program would pro-
vide support for such pvirposes as small-scale pilot studies, modest
assistance to young investigators, assistance for minor iresearch needs,
etc.

In the late fall of 1957, a general assessment of the Small
Grant Program was undertaken in all the National Institutes of Health.
While the Program has been less successful in other Institutes,
K.I.M.H. has found it to be a workable and desirable means of granting
funds in a flexible and rapid manner for certain types of limited re-
search needs.

From September, I956, to October, I957, the Mental Health
Small Grant Committee reviewed 2^9 applications and approved 112 - -
a 45 per cent approval rate. AluBDst ninety per cent of the applica-
tions approved constituted awards to research investigators who had
not had px^vious s^sp^tort from this Institute . More than half of the
approved c.X'i.ixcations eoiild be classified as "escploratory and pilot
gt".aiies." Sixty- four per cent of the applicants were psychologists,
13 per cent psychiatrists, with sizable minorities from sociologists
Bz^ anthropologists.

At its Hovember, I957 meeting, the national Advisory Ifental
fealth Council eadorsed continuation of the Small Grant Program in
this Institute at the same level of fiaaaacial support.

*See ±a this eoaaection "Report of the Jfental Health Small Grant
Oojmuittee, N.I.M.He, to the National Advisory Ifental Health Council,"
October 22, 1957.

5 -

Program Grants aad Flioid Fuada

The gtaestion of haw piibHc Svm&s for research may loost pro-
diictivelj amd equaMy "he distribxited is a coatinuiBg concern to
grast-giving agencies. Since its iaeeption in 19h^^ the Public Health
Serriee program of research graats has Iseea based on the sigiport of
projects axA programs. This year, as in earlier years j the query was
again rsdsad in the National Mvisoiy Ifeatal Health Ctoyncil as to
whether siuppleasental si^port for tSiose research needs which did not
fit into the usual research project or progiBm, mi^t be given through
luaag) mm. "block grants" to institutions or deparbmsnts^ which cotjld
then distribute the funds as ■Siey saw fit aapag departments or in-
vestigators e

As a result^ the whole subject of fluid funds amd program
grants was cojriprehensi-^Tely aired this year^ in cosmiiittee discussion,
administra>tive consultation^ and at tha Council aad Stxsdy Section
meetings. In a final revieW;, the Cotmcil recommended that increased
eniphasis continue to be given to the award of long-term program
grants to investigators of established eoarpetence in the plaiming and
direction of a program of researdi. Applications for such program
si;5)porti, the Ooraacil felt^ should be prepared within the context of
the present N^I.H, grant program aad shoiild be evaluated primailly
on -^.he capabilities of the investigator (together with project-site
visits to review all such applications) j-uther than on the detailed
specifications of projects to be pijrsued, Sie Council suggested that
■ttie staff of the National Institute of Jfental Eealt-h encourage the
submission of applications for progrsm grants whenever it is deemed
appropriate .

II. THE SUBSTANCE OF THE BESEARCH GRAM?S PROGRM

Underlying the seesningly heterogeneous nature of the basic and
applied research supported in the extraBSoral program of the National
Institute of Jfental Health Is a aeeeesarily eoa^tx^hensive view of the
etiology 5 prevention and treatment of mental illness. While ti^saiendous
strides have been taken in twentieth eeat"a3:y reaeareh in the biological
aM behaviosBl sciencesj, our knowledgja of the fundamental processes of
B3aa's functioning in his environcKnt is stiH ve2:y fragmentary. Occa-
sionally^ a researcher's "serendipii^'% that original "gift of finding
agreeable things not solicit for" amy bring long-needed "break-throughs"
where least easpeeteds Jfeanwhile, long-tesm invBStments in the proven
investigator J, in interdisciplinary team rgseardb.^ and in projects for
the ij^rovejEent of methodology and quantification continue to add slowly
to our knowledge.

QSie scope of the researcli stjpporfced in aieatal health crosses
through many fields of specialization — psychiatry^ psychology,
sociology;, anthropology and other social sciences., in addition to
such "biological sciences as neuroanaton^Tj! neusrophysiology;, "bio-
chemistry^ neurochemistry aad genetics. As the meiiber aiid variety
of research grants in these areas preclude any comprehensive suinmary
of the research, the following remarks vill attempt cnly to highlight
some of the research areas.

Basic and Methodological Research

From the early beginning of the research grants program, the
National Institute of Mental Health has "believed strongly in the
sxipporfc of "basic research — defined once as "research where the
primaiy aim of the investigator is a fuller understanding of the
su"bject under study rather than a practical application thereof."
This year a very substantial share of the research grants program
was invested in the support of basic research studies.

Daring 1957 grant strpport was awarded for a nimber of re-
search studies dealing with the functioning and structvire of the
brain. Through the use of iirplanted electrodes in an animal brain,
one investigator hopes to locate neural systems concerned with
basic drives - - hunger, thirst, sex, etc. — a research study of
great potential significance to a neurophysiologieal landerstanding
of behavior. Another jresearch project approved this year seeks to
provide new data on "behavior as related to chronic stimulation of
cerebral structures. The investigator, who carries out much of his
escperimentation with a monkey colony at Yale Ifeiversity, utilizes
an ingenious, transistor-like brain stimulator the size of a
cigarette pack.

Explorations of brain chemistry in asaimals provide further
clues to the sources of behavior, N.I.M.H. research- siipported in-
vestigators at the University of California are examining brain
enzymes in relation to the adaptive problem?" sol'vlng ability of the
animal. It has already been demonstrated that h^tb adaptable
animals, those capable of variability in attempting to solve a
problem, have a higher level of activity in one of their brain
enzymgs - - diolinestera.se - - than do those less adaptive animals,
mors rigid in their "behavior whsn faced with a problem. Another
graatee, foKnerly a U.S. Public Health Service fellow, emplojs "both
chemical and electrical stimulation of tha local brain areas in rats
together with electroencephalograph recordings, in a further effort
to understand the action of neural centers concerned with primary-
drive "behavior (sexual, maternal, etc.).

One of our more important needs in psychosomatic medicine is

a widened understanding of the relation of "behavior and physiological
processes, such as hlood pressure, heart rate, muscle potential and
other processes controlled "by the autonomic nervous system. Modern,
polygraphic equipment offers many new tools for measuring and record-
ing performance in the autonomic nervous system, termed "by some "the
voice of the -unconscious." The Institute, for several years, has
supported a series of electrophysiological studies of the autonomic
nervous system as a mechanism underlying hyperkinetic behavior.

It has long been of theoretical interest whether some persons
show the effect of stress mainly through the increased activity of
one physiological system, as, for example the cardiovascular, while
others reveal the effect of stress primarily in a different functional
system, such as the gastro-intestinal or skeletal -motor . A research
grant, awarded by the Institute this year, provides for further system-
atic study of the specificity of physiological reactions to stress.
Still another research project utilizes electrical stimulation of the
skin in psychophysical studies on man and in parallel electrophysiolog-
ical work on the cat brain, studying space-time interactions in the
somesthetic system.

As yet we have only begun to understand relationships between
man's early learning experience and his later behavior. An N.I.M.H.
grant- supported study with birds and animals on "imprinting --" an
extremely rapid form of learning, which takes place during the early
life of many organisms --is helping to verify and extend some of the
original findings on imprinting. Other research projects with monkeys
and other animals attempt to clarify the role of fearful experiences
with other individuals upon subsequent social behavior, and also in-
vestigate the permanency of physiological and psychological effects
produced by handling (or gentling) in infancy.

In a world made only too conscious of radioactivity, timely
research on the behavioral effects of x-irradiation on animals before
birth is being currently supported at the University of Tennessee and
the University of South Dakota.

As tools for testing and measurement are improved and other
methodological advances made, new roadways of knowledge may open to
the research investigator. One substantial "program grant" at the
University of Washington supports long-term research in the mathematical
analysis of patterns of personal data - investigating such problems
as methods for research on diagnoses, factor analysis, and ways of
improving psychological tests. This year several additional grants
were made in the area of psychometric theory -- including one grant
for the preparation of a handbook of contemporary measurement theory.

A substantial amount of basic research in psychopharmacology

has received grant support this year -- in part as the result of direct
program stimulation by the Psychopharmacology Service Center, and is
elaborated on elsewhere in this report.

Reseaxch in Social Problem Areas

Increasingly, in the last decade American society has come to
recognize the mental health implications of a number of "social problem
areas" -- among them juvenile delinquency, aging, drug addiction,
alcoholism, and mental retardation. Together with the developing
sense of public responsibility for better solutions to these problems
which affect so many of society's members, there has grown an in-
creasing demand on state and national agencies to assist in support-
ing reseaarch in these areas. Last year's Annual Report documented
the Congressional interest in fostering research in these social problem
areas and pointed in detail to the growth of such research supported
by N.I.M.H.

Ihxring 1957 the Institute has continued to encourage the sub-
mission of well-designed projects, both in basic and applied research
relating to the special areas of social concern. Among the more size-
able awards made this year is a grant given jointly with the National-
Heart Institute to establish an Aging Research Center at Duke University.
The Duke program has been especially designed to promote an inter-
disciplinary research approach to the multiform, problems involved in
the process of aging.

A variety of other research projects in aging, juvenile delin-
quency, drug addiction and other problem areas reflect an increasing
interest on the part of research investigators throughout the country
to work in areas of direct social concern. Considerable progress in
stimulating research in psychopharmacology has, of course, been
fostered in the Psychopharmacology Service Center, as is reported
sub se quently .

Other Areas of Research

While the number of grazit applications has increased during the
last three years at a near geometric rate, much of the overall pattern
of grant support has remained relatively stable . An exception, of
course, has been the publicly spotlighted area of the tranquilizing
drugs. But side by side with the growing interest in special social
problem areas, there moves a steady volume of applications for research
into such psychological processes and functions as intelligence,
learning, perception, attitudes, emotional states and their inter-
relations, as well as a large body of research directly dealing with
the etiology and treatment of mental illness.

studies of the causes of severe mental disorders, such as
schizophrenia, are exploring both genetic and environmental factors.
Biochemical approaches, such as research on the metabolism of indole
derivatives in schizophrenics, attempt further to establish the eti-
ology of the disease.

Treatment studies continue to range throughout group psycho-
therapy, psychoanalysis, shock therapy, drug therapy, "milieu" or
social setting therapy and a variety of rehabilitation programs. In
the face of the recognized nationwide shortage of hospital attendants
for the mentally ill, the Institute this year awarded a grant to the
American Psychiatric Association to support a working conference on
volunteer services for psychiatric patients.

History offers long documentation to the thesis that man acts
according to his perception of his environment. Among research studies
to enlarge oixr understanding of the basic featxires of perception, is a
"program grant" to Clark University. Other studies are exploring the
judgemental processes involved in perceiving other people.

Both in 1956 and again in 1957 "the National Advisory Mental
Health Council, conscious of what one leading American medical historian
has referred to as a mistaken modern tendency "to limit the definition
of research to the experimental process," recommended further support of
scholarly research. The Council has also encouraged grant support of
research projects in the history and socio-cultural aspects of psychiatry
and, more broadly, of medicine.

Several current mental health research projects may also con-
tribute to the great American talent hunt today, through supporting
projects for a more systematic analysis of aptitudes. Diiring 1957 the
Institute participated in an inter- agency grant award to set up a new
study on identifying, developing and utilizing h\jman talents, to be
based on a sample of over one million American high school students.

III. THE PSYCHOPHARMACOLOGY RESEARCH PROGRAM

The revival of psychopharmacology, an old science with a new name
and with renewed promise of help for the thousands of mentally ill pa-
tients throughout the country, led to the establishment in late 1956
of the Psychopharmacology Service Center. During its first year the
Center has had to struggle with, and learn to adjust to, the many
administrative problems and growing pains experienced by any young
organization. It came into being at a time when the "tranquilizing

- 10 -

drugs" had caught the attention of the whole American public. Medicines
for the mind and drugs for the soul were — and still are -- not only
the target of cartoons and quips, but also a source of deep concern
to scientists, physicians, and all those responsible for research funds
and a subject of serious editoriaJ. comment by the press and other
thinking laymen. With such an urgent and pervading interest in its
work, the staff of the Center was plunged precipitously into almost
daily crises calling for immediate action and decision. But meanwhile,
in this atmosphere of subdued uproar the staff felt impelled to proceed
deliberately and soberly with a program leading to its ultimate goal.
This goal can perhaps best be stated as the promotion, stimulation, and
support of research and related activities that will result in increased
■understanding of the psychopharmacological agents and their role in the
treatment of psychiatric patients. And clearly, from this greater under-
standing may come the possibility of freeing those with mental illness,
whether serious, debilitating and continuous or slight, bothersome, and
transient, to live more creative, interesting, and happier lives.

Psychopharmacology Service Center Staff
Activities and Program Developments

At its inception the Center was staffed with two professional
persons; at the end of the year there are five professional persons,
plus supporting semi-professional, secretarial, and clerical personnel,
amounting to a total of thirteen. Staff has not been easy to come by,
and much time of those who first came to the Center has been spent in
recruiting and other personnel chores.

Soon after its formation, a Psychopharmacology Advisory Com-
mittee was selected and appointed. This committee, made up of leading
scientists in psychiatry, psychology, sociology, neurophysiology, and
pharmacology is responsible for guiding the staff on general policy
and planning. It also serves as a review committee for grant applica-
tions in psychopharmacology. The staff and the committee have been
working through a period of definition of functions, especially in the
matter of review functions. After trying several different procedures,
it has now been decided that most of the applications for grants in
psychopharmacology will be reviewed by this committee, with related
basic studies reviewed by the relevant Study Sections.

Conference and Meetings

As part of its effort to facilitate and stim\ilate sound research,
the Center held two conferences in 1957- On January 1^+ and 15, in
collaboration with the American Psychiatric Association, it called
together a group of prominent clinical investigators and editors of

scientific joiirnals to discuss problems in the reporting of psychiatric
drug studies. The major purpose was to consider ways in which the
reports of clinical drug evaluations could he made more informative
and useful. The conference resulted in a series of concrete and
specific recommendations on reporting of data ahout patient selection,
evaluation of change, treatment setting, and toxicity reactions. In
addition, the editors recommended that as one means of handling the
flood of psychopharmacological papers a newsletter-type of journal "be
published, containing brief summaries of current research, analytic
review articles, euid bibliographies. An article describing the con-
ference entitled "Recommendations for Reporting Studies of Psychiatric
Drugs" appeared in the July 1957 issue of Public Health Reports .

Later in the year, on September 19 and 20, the Center organized
a working group on anti-depressive or "energizing" drugs. Because
the tranquilizing drugs appear to be of only limited value for patients
who are depressed, withdrawn, or markedly inactive, several new drugs
with potential anti-depressive or stimulant properties are being tried.
The staff of the Center deemed it wise to meet at a time when research
on these drugs was just beginning, with a group of investigators who
have done, or might be interested in doing, such research to exchange
views and information and to lay plans for future research. One
result of the meeting was the conclusion that problems of research
with cases of regressed and withdrawn schizophrenia are quite different
from research on depression. Even though the same drugs may turn out
to be effective for both groups, the patient populations are, in fact,
not at all alike and demand research planning designed for the specific
group under study. The animated discussion and large amount of new
information gleaned by the Center's staff and all those present
demonstrated the value of such working groups as one fruitful approach
to stimulating good research.

Informational Activities

As another approach to research facilitation and stimulation and
as stated in the Research Grants and Fellowships Branch Annual Report
for the Calendar Year 1956, one of the functions of the Psychopharmacology
Service Center is to "serve as a clearinghouse of information." During
the past year the Center has collected, organized, and catalogued about
2,500 articles and reports, both published and unpublished, on psycho-
pharmacology. A coding system has been developed to permit easy and
accTirate identification and retrieval of the documents, and most of
them have been coded. For over 500 of the more important articles,
300-word abstracts have been written so as to provide investigators
with concise, well-organized, and readable summaries of research in

- 12 -

which they are interested. It was originally planned to follow the
recommendation of the editors attending the conference on reporting
of psychiatric drug studies hy starting a newsletter or abstract
journal to serve as one vehicle for the rapid commimication of in-
formation ahout research activities in psychopharmacology. However,
as this notion was explored in more detail, it became evident that
administrative considerations militated against the Psychopharmacology
Service Center itself handling the publication. The present proposal
is to solve this aspect of the communication problem by grant support.
Now that investigators know of the existence of the information
clearinghouse, many requests for information have been received and
answered. These requests have ranged from specific questions about
use of drugs with certain kinds of patients to general inquiries
about all research that has been done in broad areas of psychopharma-
cology. Although much of the scientific information activity of the
Center has revolved around the accijmulation and dissemination of
written research reports and the preparation of reference lists and
bibliographies, all members of the staff have engaged in providing
information by attending scientific meetings, presenting papers, taking
part in discussions of psychopharmacology both at scientific conventions
and with visitors in the office, answering many telephone inquiries
received every day from scientists and administrators both within and
outside the government, appearing on television programs, and being
interviewed by newspaper and magazine writers. Finally, in line with
the request of the 83rd Congress, a comprehensive status report has
been written, describing in detail the developments in psychopharma-
cology during the past year.

Interactions with Drug Companies

Throughout the year the staff has been meeting and corresponding
with representatives from many of the drug companies. At the spring
meeting of the Physiological Society a presentation was made to a
relatively small group of drug company representatives to describe to
them the purposes and activities of the Center. A more extensive
report was given in October to the American Drug Manufacturers
Association. Relevant here also is the fact that the executive
secretary of the American Drug Manufacturers Association is a member
of the Psychopharmacology Advisory Committee. Relations with the
drug companies have been cordial and mutually satisfactory. The
companies have shown a sincere willingness to give information (some
of it confidential and handled in a strictly confidential manner by
the Center's staff) about their drugs, both new and old, and they have
cooperated whole-heartedly with the information clearinghouse. The
Center, in turn, has sent much general infonaation about psychopharma-
cology to persons doing research in the drug companies. It has had

many sessions with driig company representatives to discuss their
research problems and to consult with them on techniques and
methodology, particularly on problems of screening drugs for
behavioral effects and designing of clinical studies. These
discussions illustrate one important facet of the Center's work.
The drug companies do not need financial support, but they often
do want good objective evaliiations and advice. Since much of the
psychopharmacological research is done under drug company auspices,
the Center, through its consulting service, can indirectly but very
significantly contribute to the development of better research and,
thus, to better Tinders tanding of the drugs.

Research in Psychopharmacology

The core and raison d'etre of the Psychopharmacology Service
Center program is stimulation and support of research. During the
fiscal year 195T;> ^2 new grants in psychopharmacology were awarded,
totaling $73^ J 291. These grants range in content from basic
pharmacological and physiological studies through research on the
effects of drugs on animals and normal human behavior, to clinical
studies of drug effectiveness in psychiatric patients. In terms of
amount of support they vary from small, pilot one -year studies of
about $2,000 to five-year support of a major and extensive research
program on the psychopharmacology of schizophrenia totaling more than
$500,000.

The National Institute of Mental Health has for several years
been supporting substantial work in psychopharmacology through its
regular research grants program. This work and emphasis are contin-
uing, with the added impetus of additional fionds specifically ear-
marked by the Congress for both preclinical and clinical research
in psychopharmacology. Although continuing to push basic research,
the staff of the Center and its Advisory Committee have, during the
past year, channeled considerable effort into the stimulation of soimd,
we 11 -controlled clinical studies, and several new grants have been
awarded for such research.

One carefully controlled clinical study in a large state
hospital system is testing the effects of four phenothiazine drugs on
chronic schizophrenic patients. Dosage is individualized and is at
the high upper limit to yield needed information about dosage and
dosage schedules for fut\ire use of drugs in hospital settings. The
research is designed to answer the question of whether or not patients
treated with drugs improve, as compared with untreated patients, in
their social adjustment within the hospital and also to obtain con-
clusive data on the number of patients who improve enough to leave
the hospital. A complementary investigation is studying the effects

- ll^ -

of five phenothiazine drugs on newly admitted, rather than chronic,
patients. Four of the drugs are the same as those being used in the
study of chronic patients, thus allowing a good basis for coordinated
and comparative results on these two groups.

Another investigation on acutely ill patients is evaluating
the effectiveness of both chixpromazine and reserpine. In addition
to increasing knowledge about the comparative value of these two
drugs, this study should extend the generality of the findings about
tranquilizing drugs and the applicability of their use. These
studies will make possible sound conclusions about drug effectiveness
and, also important, will provide information on the best designs to
use in future research in hospital settings.

Preliminary observations of res\ilts with tranquilizing drugs
indicate that some patients respond and others do not What accounts
for this difference? In order to discriminate more clearly the
differences and thus to predict more accurately the effectiveness
of drugs, a study is underway in which patients will be given several
perceptual tests before they begin drug therapy and these tests will
be correlated with results of the treatment This study may well also
point up clues leading to better understanding of the mechanisms of
drug action in the nervous system.

Ifeny clinical studies have indicated, in a general way, that
drugs are of great benefit to hospitalized psychiatric patients, but
there has been little research on outpatients . With the release of
patients from mental hospitals after drug therapy it is essential to
know if these patients are able to take their places as active pro-
ductive members of society. Consequently^ research is being supported
to evaluate cMorpromazine and promazine for use with chronic schizo-
phrenic patients treated in a clinic, rather than a hospital. The
study is assessing the psychological changes accompanying drug therapy
and the patient's social adjustment in the community. Moreover, it is
not basing its conclusions on observations for only a few mont]:s,but
is planning to follow the patients ' progress for several years .

Closely related to the question of outpatient drug treatment,
is the question of how long to continue drug therapy with chronic
patients after their overt symptoms have subsided and they have been
released from the hospital. Is it necessary to continue the drugs
in the same way that diabetic patients must keep on taking insulin
and epileptic patients anticonvulsant medication? Should the drugs
be gradually reduced, or should they be replaced by placebos? A well-
planned study in which neither the psychiatrist, psychologist, and
social worker nor the patients know which kind of treatment is being
used is attempting to answer these important questions.

With the tremendous increase in the number of new psycho-
pharmacological agents it is vital that they receive careful pre-
liminary clinical screening soon after they become available One
of the studies is being supported specifically to subject new drugs
to rigorous testing. Along with the clinical trials, work is being
done on animals to observe any toxic effects after long-term admin-
istration and also to obtain data on the possible sites and modes of
action of new compounds.

It is a truism that the effects of a drug are not produced
just by the drug but by the interaction of the drug with the system
in which it is used. This is even more true of psychopharmacological
agents, where the interactions extend into complex personality and
social variables. One study currently receiving support is comparing
drug effectiveness with patients who are merely given custodial care
with patients who are receiving intensive social therapy from psychi-
atrists, nurses, and other personnel. An interesting by-product of
this study will test the hypothesis that intensive social therapy
may be just as effective as drug therapy.

Not only are the social variables in drug action in need of
study, but it is essential to investigate the psychodynamlc and
personality changes that appear with drug therapy. Therefore, a
study has begun in which the patients receiving drugs are also being
given intensive psychotherapeutic interviews or are undergoing
psychoanalysis .

In such a broad field as psychopharmacology, how shall the
many important variables be determined? One investigator is attempt-
ing to delineate these variables by analyzing the relations between
environmental variables and the effects of drugs . Both animal and
human subjects are being used, and a wide variety of measures and
techniques employed. As specific reproducible results are found in
animals, crucial experiments will be adapted for human beings to
learn the generality of the results.

Several researches on drug toxicity are under way. One is
working on psychomotor dysf xmctions , such as parkinsonism, that occur
with use of tranquilizing drugs. Another is looking into the effects
of chlorpromazine and reserpine on the reticuloendothial system to pin
down the clinical observation that patients on protracted drug treat-
ment seem more susceptible to infections and are less predictable in their
response to antibiotic therapy. Indirectly related to studies of toxicity,
but with definite implications, is a study of the effects of drugs on
the psychological development of young animals. The significance of
this research for the question of using drugs with children is obvious.

In addition to stimulating research and providing support for

- 16

clinical and toxicological studies, the Center has during the year
encouraged many studies of basic research on animals and of the
effects of drugs on the performance of normal human beings .

Plans for the Coming Year

In the process of reviewing applications for research grants ;,
making surveys of past and current research, and consulting on
research designs, the staff and its Advisory Committee have become
increasingly aware that there are no good instruments for assessing
the psychological and social changes that take place with drug
therapy. This is particularly true in studies of drug effectiveness
with neurotic patients or psychiatric patients who are not hospital-
ized. Two recently awarded research grants will be concerned with
this problem as it involves hospitalized patients. In addition, to
meet this need the staff, together with a subcommittee, is devoting
considerable effort to the construction of a valid, reliable rating scale
for use primarily in outpatients . This undertaking exemplifies one of
the practical and significant ways in which staff activity can augment
research being done imder grant support.

Although there is no lack of preclinical research in psycho-
pharmacology, there is a need for compilation and organization of the
data and theories to learn where psychopharmacology has been and where
it is going. A recently-begun staff project will be the preparation
of extensive and definitive working papers to serve as a basis for
program planning and stimulation of research. One of the papers will
emphasize the pharmacological and physiological research; the other
will be primarily focused on behavioral techniques with animals.

The informational activities of the Center will undoubtedly
have to be expanded and extended if the demands of investigators are
to be met, and explorations into ways in which the publication problem
can be solved will be continued. Hopefully, the foreign literature
will also be included in the collection and will be translated and
abstracted.

The success of the first two conferences has led to plans for
additional meetings. Now under consideration is one meeting to discuss
problems of chronic drug administration, including toxic and with-
drawal effects. The other will probably be organized around the topic
of behavioral testing of drugs.

Finally, now that at least some of its staff and administrative
problems appear to be resolved, the Psychopharmacology Service Center
can concentrate more fully on its primary function of research stimu-
lation, planning, and accomplishment.

17 -

Specific plans are being considered for the organization of
single or cooperative studies in the following areas:

1. The testing of nev drugs in chronic schizophrenic populations.

2. The evaluation of newer "energizing" drugs in depression.

3. Drug studies in neurotic outpatients.

h-. Drug effectiveness in "both schizophrenic children and
children with serious behavior disorders.

It is probable that work will be under way in most of these
areas before the end of the current (1958) fiscal year.

IV. RESEARCH TRAIIOiWG; CAREER INVESTIGATOR GRANTS AMD THE
FELLOWSHIPS PROGRAM

Present day shortages of scientific personnel and the spread-
ing range of professional disciplines Involved in mental health
research have accentuated the need for training assistance. Research
training activities of the Branch as represented by both the Career
Investigator grants and the research fellowships program constitute
a vital share of Branch activity. This year, with the addition of
a full-time Branch staff member for fellowships and Career Investigator
grants, a greater degree of planning and program evaluation has been
made possible in these programs.

The Career Investigator Grant Program. Started in 195^ as a new form
of research support designed to assist in the opening of research
careers to qualified young psychiatrists and scientists in related
disciplines, the Career Investigator program has supported seventeen
investigators to date. All but three are psychiatrists. The program,
which aims to enable a limited number of highly qualified young men
or women to spend from three to five years in full-time research and
further development of research skills, manifests considerable stability
by this time.

It is significant, that in the shifting psychiatric world --
where financial rewards for private practice far outweigh any fellow-
ship or training stipend, there have been no resignations from amongst
the psychiatrist Career Investigators.

In December, 1957 past and present Career Investigators to-
gether with members of the Selection Committee gathered together in
a three -day meeting at Arden House in Harriman, New York for a gen-
eral discussion of the program. The role of the research psychiatrist

is a relatively new one in many university settings, and a share of
the discussion vas concerned with the professional future of the
research psychiatrist. Stressed by many of those participating in
the program was the value to the Career Investigator of a strongly
organized university department able to offer research guidance.
The discussions also emphasized the validity of the three to five-
year research training program in terms of the growth of an investi-
gator's research abilities. As a whole, the meeting provided a
valuable opportunity for the interchange of scientific ideas among
this select cadre of research investigators.

The Research Fellowships Program. During fiscal year, 1957? $6^7,000
was earmarked for mental health research fellowships . The Mental
Health Fellowships Board reviewed 206 applications and made ik'J
awards. Applications in this lively program range over a wide
variety of the behavioral and biological disciplines related directly
and indirectly to mental health.

IFb^llowships supported by N.I.M. H. are available to the
scientist whose experience has matured him to train for leadership
in mental health research, to the post-doctoral candidate preparing
for a research career, to the pre-doctoral student whose endowment
recommends him for emphasis on research training, and finally (an
innovation of fiscal 1957) to the medical student whose aptitude
justifies a year or two of application to the techniques of the basic
sciences as an extension of his training for medical work. More than
two million dollars has been invested in over 600 mental health
research fellowships during the period from 19'<-7 through 1957-

Research work in progress by N. I.M. H. fellows extends to a
variety of areas, including the problems of aging, mental retardation,
psychopharmacology, neurophysiology and techniques of clinical psychi-
atry. This year's applications also numbered several studies submitted
by educators which deal with adjustment problems in high school and
college students.

While the fellowships program has repeatedly proven its value
as a sound investment in research training, the administration of the
program has been somewhat hampered by the overall volume of fellowship
applications received at N. I.E. It has been difficult in the past
to provide that individualized attention to fellowship applicants which
might pay dividends in more responsible and selective faculty guidance.
With the addition this year of a full-time Branch staff member to work
with the fellowships and Career Investigator programs, it is hoped this
recognized problem may reach better solution.

NATIONAL INSTITUTE OF MENTAL HEALTH

Research Grants and Fellovfshlps Branch

BUDGET SHEET

Estimated Obligations for FT IQ'^S
Total: $328,353
Direct: $199,307

Reimbursements : $129 , O^t-S

TRAINING AND STANDARDS BRANCH
Annual Report For Calendar Year 1957

During the past year one of the serious problems confronting the over-
I all field of mental health is that of manpower. Because of the expanding in-
terest of the country as a whole in the field of mental health opportunities
for staff appointments are increasing at a rate far greater than the capacity
of the training centers to prepare professional people. The staff of the
Training Branch have been deeply involved in this problem. In additions
attention has been focused upon improving and extending the quality of
psychiatric education. Continued emphasis and support have also been directed
toward training large numbers of clinical personnel for the reason that it is
from this group that we get our people for leadership positions in teaching,
research, public service and administration, and for community mental health
programs at State and local levels. This does not imply that the Training
Branch has neglected giving stimulus to the development of more adequate train-
ing opportunities in the area of research The staff are expending consider-
able effort in this latter direction and it is anticipated in the next several
years more attention and conceivably more grant support will be expended in
the direction of developing basic sciences programs in human behavior. A
number of medical schools are engaged in a study of the development of a basic
sciences department of human behavior at this time.

Aside from the needs for personnel for clinical therapeutic activities
is the need for stimulating the development of community mental health
personnel for administrative leadership at the State and local community
level. These administrative leaders are in extremely short supply and consid-
erable stimulus must be given to the training centers to have them focus their

. 2 -
attention upon the preparation of such professional persons. In the field
of mental health the educational centers are experimenting with various types
of training programs that will prepare a mental health leader analogous to
the general public health officer to deal with the problems of prevention of
mental illness and the promotion of mental health.

In connection with these activities, the staff of the Training Branch
carry on extensive consultation with presidents and deans of universities ,
medical schools, graduate schools and schools of public health as well as
with department heads in psychiatry, psychology , social work and nursing.
Frequently the staff have been called in consultation or have been used as
resource personnel in the broad field of mental health education. The
number of project site visits approximated 300 made by the staff during the
past year.

Grants have been made during the past year for the purpose of im-
proving and extending the psychiatric aspects of training of the medical
and nursing student . These people represent a first line of defense so to
speak and it is desirous from a preventive point of view that they be
adequately prepared to deal with emotional problems encountered in their
respective spheres of activity.

During the past year traineeships were awaurded departments of
psychiatry in medical schools for the purpose of providing additional
clinical experience in psychiatry or experience in psychiatric research
for the medical student. It is anticipated that more physicians will be
recruited into the specialized area of psychiatry, A total of 290 such
traineeships were awarded.

As indicated above there continues an excessive demand for leader-
ship people in teaching, research, public service and administration, and

- 3 -
in community mental health activities. These people come from the programs
of clinical training. For this reason the greatest percentage of the funds
available for training have gone into the preparation of as large numbers
of psychiatrists, psychologists „ social workers, and nurses as is possible.
During the past year frequent consultation has been given to a number of
schools of education concerned with the preparation of the classroom
teacher. These schools have been interested in incorporating material from
the field of the behavioral sciences, including psychiatry, psychology, and
social sciences into the training of the classroom teacher that will be
useful to her in dealing with emotional problems encountered in the growing
and developing child in the classroom setting. It is anticipated that
several of these institutions will apply to the Institute in the near future
for support of programs of an experimental nature to work out the content
and the methods for presenting this material in these training programs.
Special attention continues to be devoted to encouraging the development
of training programs concerned with mental retardation and juvenile
delinquency. Some small encouraging progress can be reported in these latter
areas .

A large number of training centers, widely scattered throughout the
country, appear to have increasing interest in these conditions. We cannot
report the same kind of interest in the training of personnel to work in the
area of alcoholism. It has been a difficult assignment to arouse interest
in training personnel for this health problem.

In a number of medical schools there appeared during the past year
a considerable interest in developing a closer teaching liaison between the
departments of psychiatry and the pre=clinical or basic sciences departments.

_ 4 -
This Interest seems more intense from the pre-clinlcal departments of
pharmacology and physiology „ A number of medical schools are experimenting
with conjoint teaching activities Involving the department of psychiatry and
one or more of the pre-clinlcal departments- It is anticipated that the
Institute will receive in the future requests to support the further elabora-
tion of these conjoint experimental teaching activities »

NATIONAL INSTITUTE OF MENTAL HEALTH

Training and Standards Branch

BUDGET SHEET

Estimated Obl.igat3iQng f«?r .lY 19'i8
Total: $i+10,081
Direct: $278,823

Reimbursements: $131,258

Project included: Training Activities

NATIONAL INSTITUTE OF MENTAL HEALTH

Clinical Investigations
Office of the Director

BUDGET SHEET

Estj.mated Obligations for FY IQ'^S
Total: $221,9'^5
Direct: $170,533

Reimbursements : $51 ,^12

Projects included: I^D(C) 1 through M-D(C) 3

Serial No. M-D(C) 1

1. Clinical Investigations

2. Office of the Director
3" Bethesda, Maryland

PHS-WIH

IndividuaJ. Project Report

Calendar Year 1957

Part A.

Project Title; The Analysis of the Psychotherapeutic Process, Particularly
the Psychoanalytic Process

Principal Investigator; Robert A. Cohen

Other Investigators; David Shakow, Allen Dittman, Morris Parloff , Paul
Bergman, Mabel Cohen

Cooperating Units; Laboratory of Psychology

MEm Years;

Professional: 0.25
Project Description;

Objective; To conduct an intensive study of the psychoanalytic process

Methods Eniployed; \

1. Data Collection; Natiiralistic recording by motion pictxires and

stereophonic souad of portions and of complete courses of
psychoanalytic (and in some cases of other psychotherapeutic)
treatments of adults and children with a variety of emotional
disorders.

2. Data Analysis; Methods will be developed to organize the exten-

sive material which will be gathered by a variety of partial,
total and cimiulative exposxire techniques; to divide it
into units which on the one hand accurately reflect the
nature of the exceedingly complex interactions between pa-
tient and therapist, and on the other are sufficiently
specific and manipulatable to permit an orderly and mean-
ingful analysis of the therapeutic process.

For the past 2 years two training and supervising
analysts have studied very intensively a short series of
therapeutic intearvlews; first using a typescript alone,
then the sound recording and finally the sound motion pic-
ture. These studies were carried out independently at the
beginning, but they are now being combined in order to set
up categories for the individual elements which must be
rated in order to study the therapeutic process.

= 1 -

Serial No. M-D(C) 1;, page 2

Project Descrlptioo, (coEtlEued);

Patient Material;

Up to the present time the material used has been collected at
the University of Illinois where another research group is work=
ing toward the same goalo

Our ow7a phj^sical set-up has finally been completed, and an ex-
perienced therapist has begun a trial series of single inter-
views with a variety of patients and with several normal controls o
In the coming year it is anticipated that it will be possible to
embark on a motion picture recording of a regular psychoanalytic
therapy.

Ifejor Find!.ngs;

None as yet. Much methodological research must be done before sub-
stantive theoretica.1 contributions can be madeo

SignifieaEce;

This is cum of a series of studies of the psychotherapeutic process;
The Process of Change and the Communication of Value Systems in Psy-
choaoalytic Therapy M=P-P(C) 5^ Linguistic Study of Easotional Ex-
pression M-P=G(C) 4| Judgment of Facial Expression fi-om Short Se=
quenees of Motion Pictiara Film M"P-C(C) 5; Analysis of the Psycho-
therapeutic Process; The Cumulative Information Derived from
Repeated Viewing of Complex Material M-P-C(C) 2j Development of
an Ego -Integration Conceptual System for Studying Psychotherapy
M-P-P(C} 6.

Despite the fact that psychotherapy is the major therapeutic device
in psychiatric treatment., our understaxiding of it as a procass is
still very limited » One reason for this is that previously data
could be secTored only by the therapist; his reportdng was limi,ted
both by the fact that he was a participant as well as an obsen/er
in the process and also by the human impossibility of reporting
completely -wb&t had tr8s:is,piredo In the therapeutic situation;, the
relationship is exceedingly complex^, and this is all the more true
since much of the communieation occurs at an implicit le^-^elo Hence,
much of the significant data was not even available to anyone out-
side the rala.tlonship which it was proposed to study. The soui-id
motion pictxire pro'vldes for the first time a sizable and signifi-
cant amount of objective data hitherto \inobtainablej what is
equally important is that this data is collected in a form suit-
able to multiple and repeated analyses.

This series of studies nmy make many contributions methodologically,
it will be possible to study the psychoanalytic process scientifi-
cally to a far greater degree than has heretofore been pcfssible.
Theoretically it is expected that it will make available new and
highly significant data - data which is gathered in a mere or less
naturalistic asttixjLg but which is as objective as those usually
obtained in laboratory experiments.

Beyond the direct contribution to a better understanding of the
psychotherapy process itself, it will aid in the establishment of

Serial Ko. M-D(C) 1, page 3

Project Desci-iption (continued);

Significance (continued);

the scientific bases of psychoanalytic theory. It is safe to
say that psychoanalysis is one of the central socio -psychologi-
cal sciences. It deals with man, born with his drives and abili-
ties, with his slow adjustment to social life through family train-
ing. While it deals with the same kind of data social sciences
deal with, it also provides information on the subjective aspects
of the activity of those parts of the central nervous system which
have recently attracted so much attention, viz. the limbic system
and the reticular activating system. Psychoanalysis should be
able to make fundamental contributions to the understanding of
education in its broadest sense.

Proposed Coxrrse of Project;

It is expected that this program wiU continue for many years.

Part B. included; No.

Serial No. M-D-(C)-2

Office of Director
Clinical Investigations
Bethesda

PHS-NIH
Individual Project Eeport
Calendar Year 1957

Project Title: Development of an Ego Integration Conceptual
System for Studying Psychotherapy

Principal Investigators: D. ¥ells Goodrich, M.D.

Donald S. Boomer, Ph.D.

Other Investigators: None

Cooperating Units: Section on Personality, lahoratory of Psychology

Laboratory of Clinical Sciences
Eniployee Health Service, NIH
Community Psychn.atric Clinic, Roekville, Md.
Washington Institute of Mental Hygiene

Man Years (calendar year 1957) ' Patient Days (calendar year 195?) :

Total: 2.00 Outpatients: k2 patient days

Professional: 1.00
Other: 1.00

PROJECT DESGPJPTION;

Objectivas; (l) Long-tei^i: To develop a theoretical model and

observational tools for the purpose of generating and testing
a network of hypotheses about the conditions of personality
change, (2) Immediate: To organize a loose set of clinical-
theoretical ideas and observations into a coherent model, as
indicated above, and to determine the feasibility of observing
certain critical changes in patient behavior during psycho-
therapeutic sessions .

¥e are concerned with the moment-to-mament le^?■el of ego
integration in the patient in his dealings with the therapist.
¥e have conceptualized and hope to be able to identify in action
four patterns of ego integration among which patients are presumed
to shift duj^ing a therapy session. These have been carefully
spelled out, but for the purpose of this report brief descriptive
simimaries must suffice:

- ^

" '' "* M-r)-(c)-2

page 2

Defended (F) - The patient is controlling anxiety by his
custorasiry means, and is functioning at his characteristic
level, Involimtarily reveal Ing from time to time, the ego-
distorting aspects of his defensive fiinctioning.
PartiaXLy defended (P) - Similar to F but less stable and
comfortable. Patient displeiys some readiness to move
toward a suspension of his defenses, with concomitant
premonitory anxiety.

Self observing (o) - The widely-described "split ego"
state in which the patient is monitoring his own behavior
and considering simultaneously, or in rapid alternation,
his feelings, his behavior, and his defenses.
Deccaiipensated (c) - The overwhelmed ego: Anxiety is so
high as to submerge defenses, disrupt some or all ego
functions and interfere with interpersonal and task-
directed functioning. This may be a clear open panic
state or a transitory disturbance, virtua3-ly unnoticeable
unless reported by the patient.

Methods Itaployed; In order to provide data on personality change dviring
psychotherapy, from two to six patients are maintained in outpatient
psychotherapy continually. The senior investigator is responsible
for maintaining professional relationships with the referring and
collaborating eigencies (see "cooperating units"), for supervising
the diagnostic screening procedures (psychiatric interviews, psycho-
logical tests, physical examinations and laboratory tests), and for
supervising the psychotherapeutic treatment and incidental medical
care provided to the patients while they are subjects. Psychiatric
supervision of psychotherapy is carried out by means of individugil
conferences with the project's therapists (i.e., psychiatrists and
psychologists who donate time to the project) and by use of the
one-way vision screen vhen this is indicated to clarify a clinical
problem.

During the first few weeks of psychotherapy, and periodically
thereafter, each patient's major resistances axe formulated both
in general clinical terms and in terms of specific inter^/iew
behavior. Particular attention is directed to formulating major
current transference resistances, since the reseeirch model focuses
upon the process of patients' attaining conscious insight into
transference experiences. All interviews are recorded for
behavioral analysis, according to the methods outlined in Project
Ho. M-P-P-(G)-6 (Section on Personality, Laboratory of Psychology).

- 5 -

" 3 " M-D-(c)-2

page 3

Interview transcripts are also coded into phases according to

whether the patient's statements demonstrate a blatant resistance

state (f) or one of the other ego states (P, C, or O). It may

then be possible to explore relationships between the clinical

course of therapy, specific ego state phases during interviews H

and the profile of statisticeuLly measurable behaviors. |;i

Ilirough this integration of clinlceil case studies with
the statistically-controlled behavior measures, we hope to be
able to define shifts in the patient's ego state. Subsequently,
it may also be possible in a more detailed theoretical manner to
relate ovir concept of ego state to more general concepts of ego
psychology.

Patient Material; Patients are selected according to the following
criteria: (l) Ages 17 to 40; (2) approximately half women and
half men; (3) absence of psychotic or "borderline" type of
psychopathology; (U) absence of social or family problems or
of severe acting-out tendencies; and (5) likelihood of demon-
strating in a short time some definite changes under the influence
of psychotherapy. A total of seven patients have been studied
to date; the addition of from two to four more patients d-uring
the coming yesir is contemplated.

Significance to HIMH Research; The systematic Investigation of relevant
aspects of psychotherapy is a salient part of the program of NIMH.
This project may contribute directly to this effort with substemtive
findings or indirectly with methodologlC€LL and conceptual develop-
ments which can be utilized in other parallel investigations.

Proposed Course of the Project; Biis work, as ciirrently envisaged, will
continue throughout this yeax and weH beyond. Some csirefully
controlled definitive work will be carried out d-uring this yeso*
with regard to the incidence of speech disruptions and the correlates
of high and low incidence. Bie broader conceptual-theoretical work
of formtilatlng a model will also continue along the lines outlined j

above.

- 6 -

Serial No. M-D-(C) 3

1 . Office of the Director
3 Location: Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

[irt A.

Project Title: Establishment of a Near Zero Level of Physical

Stimulation and of Action Possibilities and its
Effects on Mind and Brain Activity.

Principal Investigator: John C. Lilly.

Other Investigators: Thelma W. Galkin and Jay T. Shurley.

Cooperating Units: None.

Man Years: Patient Days: None

Total: .99 1/3
Professional: .49 1/3
Other : . 50

Project Description:

Objectives:

1. To make a survey of the literature on individuals who
were exposed to environments in which the physical stimuli
were at a minimal level.

2. To devise an environment producing minimum possible
levels of stimuli in terms of light, sound, gravitational
effects, movement, temperature changes, pressures on the
skin, etc.

3. To observe the effect of this environment on monkeys
and human subjects.

4. To obtain fundamental base line data on brain activity
and mind activity during a state of minimal inputs to the
brain from the environment.

5. To interest professional psychiatric and psychoanalytic
personnel in serving as subjects to obtain professional
evaluations of and maximum meaning from this type of experiment

6. To write a book detailing our findings in the literature
on autobiographical accounts as well as experimental results
found by others.

Methods Employed:

1. Library research.

2. Communication with persons who have been exposed to
minimally stimulating environments, i.e., American Speleo-
logical Society, Arctic Institute.

- 7 -

Serial No. M-D-(C) 3

PHS-NIH
Individual Project Report
Calendar Year 1957

page 2

A. (continued)

3. Experimental methods have been under development for the '
last 4 years. The present approach is to suspend the subject i
in quiet water,* in the dark at such a temperature as to be
neither warm or cool (about 34.5°C) with a breathing mask
which gives minimal stimulation The mask has been the major
problem: underwater masks from the Navy Experimental Diving
Unit, the Army Engineers, and Chemical Warfare have been
found to have too high unit pressures on small areas of the
face, leading to (1) pressure stimuli and (2) eventual local
anoxemic pain. Therefore, a program of mask development has !
been undertaken: Model #7 is almost completely satisfactory.
Preliminary designs for a quiet, pressure-balanced respirator
are being done . j

Major Findings: To date, many examples have been found in the,
literature of individuals isolated in boats or in the polar
regions or in prison, but the factors of threat to life, cold,'
hunger, thirst, sun, etc. make it difficult to attribute the
effects solely to reduction of the ordinary levels of stimulat a

The results of experiments done on volunteers show the followii;;

1. Any remaining continuous stimulus becomes extremely
irritating and leads the subject to terminate the experiment.

2. Patterns of activity resulting from previous stimuli
slowly die out in the tank — the "half -life" seems to be about I
1/2 to 1 hour. :

3. A powerful tension may develop in an interval as short as I
2 hours .

4. One experience of the first stages of visual hallucinatory
phenomena has been experienced.

5. At emersion, the subject's appreciation of clock time
was changed so that he felt as if the day was started afresh.

An additional subject has been trained and is about to start
his own series of observations on himself.

* Tank devised and its use loaned by Physical Biology
NIAMD, Dr. Heinz Specht .

- 8 -

Serial No. M-D- (C) 3

page 3
PHS-NIH
Individual Project Report
Calendar Year 1957

(dontinued)

Significance to Mental Health Research: An evaluation of the
significance of the literature on normal individuals who have
been exposed to extreme environments.

This project will provide baseline data on effects of short-
term isolation from the usual levels of stimulation. Since
the work is essentially exploratory, we will be in a better
position to evaluate its significance after satisfactory
apparatus allows better experiments.

This work may allow us to more sharply distinguish between
I the effects on a normal person of purely voluntary isolation

from physical stimuli and that of the involuntary isolation
, experienced by the mentally ill person; no systematic exami-
I nation of such effects has yet been made; it may be that

certain experiences in these circumstances are fundamental
and characteristic for both the normal and the mentally ill
person--the major differences may be due to attitudinal
variables only. If so, the results may add to our basic
understanding of causal factors in mental illness.

A truly surprising amount of interest has been aroused
in scientific and non-scientific circles over the reports
on this project. During this year interest has been expressed
in this project by two groups, one is the submarine warfare
' group with the Navy and the other is the "Far Side" project

group of the U S. Air Force who are interested from the stand-
point: (1) isolation of a man in a space ship, (2) the effect of
weightlessness upon his mental functions. Several laboratories
have expressed enough interest to warrant their starting similar
projects: University of Utah, Mayo Clinic, Holloman Air Force
Base, Fort Ord (Human Resources Board).

Proposed Course of Project: 1. To foster the development of
a new tank more suitable for these experiments.

2. Continue the search of the literature.

3. To collect data from more subjects.

4. To continue to reduce the stimuli.

art B included Yes x No

- 9

Serial No. M-D- (C) 3

page 4
PHS-NIH
Individual Project Report
Calendar Year 1957

Part B: Honors, Awards, and Publications

Publications other than abstracts from this project:

Lilly, John C Some thoughts on brain-mind, and on restraint
and isolation of mentally healthy subjects. (Comments on
"Biological Roots of Psychiatry" by Clemens E. Benda)
J. of the Phila. Psychiatric Hospital, 2:16-20, 1957.

10 -

NATIONAL INSTITUTE OF MENTAL HEALTH

Clinical Investigations
Adult Psychiatry Branch

BUDGET SHEET

Estimated Obligations for FY 1958
Total: $757,^10
Direct: $170,065

Reimbursements: $587,3^5

Projects included: M-AP(C) 1 through M.AP(C) 12

Serial No. M-AP(C)- i
1. Adult Psychiatry Branch

3. Bethesda^ Maryland

PHS-MH

Individual Project Report
Calendar Year 1957

Part A.

Project Title: The Study and Treatment of Schizophrenia
as a S^mily Problem

Principal Investigator: Murray Bowen, M. D.

Other Investigators 5 Robert Dysinger, M. Doj, Warren Mo Brodey, M. D.,

Betty Basaaaania, M.SoW.

Cooperating Units: None

Man Years (calendax year 1957 ): Patient Days (calendar year 1957):

Total: k 2^950 days

Professional: 3
Other: 1

Project Description:

The project was started 38 months agOo The first two years there
were major changes in the hypothesis aad in the treatment approach to
schizophrenia. This is the first year there has not been a major change
to include in the axsnual rsport. To staraBarize briefly^ the first year
was devoted to the study of mother® smd patients » The second yes^ was
devoted to the study of fsaailies with fathers ;, to a redefinition of the
hypothesis, sod to effort® to develop a psychotherapy of the family as
a unit. The third year went to refinement of the psychotherapy and an
effort to define some of tha concepts and to write about experiences
that had been hurriedly pagssd over in the emotional turmoil of the first
two years. When the project was starfesdj, there was no previous litera-
ttire or experience to use as a gaide., There was am intellecttiaL convic-
tion that this area could be profitable. The only blueprint, for an
operation that would make it possible for noraaal family members to con-
tinue to live in the high anxie^ aad for staff to work with the pro-
jectp was a theoretical anticipation of probleiiES along the -m^ and some
ideas about possible solutions o Maajy deeisioas that affected the entire
coTirse were fortuitous ones to deal with the emotional emergency of the
moment. Such was the decision to pat the entire family together into a
family tmit p^ch©th@rapy» Originally conceived as an emergency Measure
to control uncontrolled ©motion, it opened up a n©w area of observations,
techniques a^id cos^cepts.

- 11 -

Serial No» M"AP|'C)~l page 2
Project Description ( continued);

Objective;

The immediate research objective is to attempt to define in more
detail some of the mauj promising clinical findings that were by-passed
in the emotional emergency of the early stages » The therapy objective
is further development and refinement of family unit psychotherapy. A
therapy objective to reach a more predictable and efficient means of
therapy is a crucial part of the project.

Method;

Small complete family gro^ips which include at least father, mother
and schisophrenic patient are hospitalized. The hospital setting permits
around the clock observation of the family group. The daily family-staff
group meetings serve as a means of fort&er cheek emd understanding of the
emotional processes within the group, of the emotional conflict between
staff and families^ of the e2E,oti03ml process i^thin the family, and as a
means of psychotherapeutic comzsKtaication to the family. An inpatient
operation is much more difficult to operate than an outpatient operation
but the added information and observation is considered essential. On
the other hand, there is evidence that outpatient psychotheraj^ caa be
more productive thae in the inpatieat operation. Several outpatient
studies have been carried out in order to observe variations and refine-
ments in family psychotherapy. It is possible to try such variations
as the use of one therapist with one or more families i or two or more
therapists with one or more families.

Patient Ifeterial;

Four family groups participated in the 1957 operation. The first
was a mother and datighter connected with the project since November 195^ •
They lived together on the ward into May 1957 at which time they were dis-
charged from the project. They now live at the family home in another
state. The second was a mother and daughter who lived constantly on the
ward from November 195^;) until discharged to outpatient status on
October 7, 1957- They live in a nearby city. The third was a family of
father, mother, patient, and normal siisling admitted in December 1955 and
still active in the project. The normal sibling has been away at school
most of the year. The family is currently disrupted by the mother's
3 month "business leave" to their home in another state. The fourth is
a father, mother, patient, normal sibling family admitted in Atigust I956.
The family group has been present the entire year except for the normal
sibling's absence at school for six months. This family may terminate
project participation January 1, 1958. An outpatient family of father,
mother, and psychotic teen age daughter have been seen as outpatients
since early November 1957 • The four inpatient families axe the same
referred to in the I956 report.

- 12 -

Serial NOo M"AP(C)-1 page 3
Project Description: (continued)

It is expected that 2 new inpatient families will be admitted by-
December 1957^ that new families will be admitted as vacancies occur
in the ward, and that some outpatient families may be started in I958.

Major Findings;

1. The clinical facts reported in the 1956 annual report, which coxild
be classed as Intrafamily Reaction Patterns are still as prominent and
pertinent as a year ago. These are part of many such observations awaiting
more careful definition and incorporation into papers. There is a new
series of observations to suggest that the psychotic symptom in the patient
is an outward escpression of a regressed impulse in a parent.

2. A new class of prominent clinical findings might be classed as
"Family Group Reaction Patterns". The families all present a group picture
of helplessness and inadequacy. They deal with many life problems as bur-
dens to be endured rather than problems to be solved. Therapeutic emphasis
is directed at this helplessness. When either parent is able to become
active in solving such a problem, the emotional adjustment of the entire
family changes. The schizophrenic patients have responded favorably to
actions by parents that popular concept would call traranatic. This sug-
gests that it is not traumatic action bpt passive lack of action that is
incapacitating to patients.

Significance to Mental Health Research;

It may be that the broader perception of psychological processes pro-
vided when the family is seen as a unit, may be a major contribution from
this project. A medical orientation to help the patient places the fact
of a parent's activities in regard to the patient in a completely different
perspective than when the orientation is toward helping the family unit.
When the project staff is able to achieve a family unit orientation, the
investigator has the experience of observing what appears to be a new
psychological phenomenon. If it is possible to clarify some of the pro-
fusion of clinical facts observable from this perspective, this might be-
come the basis for a different view of inteirpersonal processes.

Proposed Course of Project;

1. Complete the evaluation and organization of data already secured.

2. Continue the inpatient operation with 3 to 4 complete small families
using the same theoretical orientation and treatment approach as

a year ago.

3. Build up an outpatient sejrvice for variation and development of
therapy techniques and to coaiplement the inpatient service.

k. Maie an effort to define and conceptualize some of the major

clinical findings by-passed in the effort to establish the project.

5. Seek help from other disciplines in the further effort to concep-
ttialize and validate findings.

Part B included; Yes

Serial Noo M°AP(C)°l page k

PHS-NIH
Individual Project Report

Calendar Year 1957

Part B: Honors^ Awaxds^ and Riblications

Publications other than abstracts from this projects Hone

Honors and Awards relating to this projects

1. "Study and Treatment of Five Hospitalised Family Groups each with a
Psychotic Member", Invitation to present paper about project to
Section on Intrafamily Relationships o

2o "Family Participation in Schizophrenia", Murray Bowen^ M. !>„, Invitation
to speak to Psychiatric Staffs Phipps Clinic, Johns Hopkins University,
Baltimore^ March 12^ 1957"

3« "A Psychological, Formulation of Schizophrenia"'^ Murray Bowen^ M. D.^
Invitation to speak at a panel discussion on the Etiology of Sehizo-
phrenia., American Psychiatric Association^, Chicago,, Illinois_, May 15^
1957 o This has been elaborated iEto a chapter of a ■book, "St'odies in
Schizophrenia" t<3 be published in the Spring of 1958.

h. "Family Participation in Schizophrenia" j, Murray Bowen, M. Do, Presented
at the Meeting of the Ameritsaa Psychiatric Association, Chicago^ Illinois,
May 15, 1957.

5. "The Action Dialogue" in an Intense Relationship; A Study of a Schizo-

phrenic Girl and her Mother", Robert Dysinger, M. D., Presented at the
Meeting of the American Psychiatric Association^ Chicago, Illinois,
May 15, 1957.

6. Invitation to speak at the Zurich Conference = not accepted.

7. "Schi3£ophrenia and the Family", Murray Bowen, M. D,, Invitation to

present paper about project at lowa-Kebraska Psychiatric Meeting,
University of Iowa, Iowa City, Iowa-, October 26, 1957.

8. "A Working Approach to Schizophrenia and the Family", Murray Bowen, M. D.,
Invitation to present paper on working research concepts at a research
seminar, Yale University, New Haven, Connecticut, October 31p 1957.

9. Group for the Advamcement of Psychiatry, Family Committee, Murray Bowen, M. D.,
April 5j 6, 7, 1957. Invitation to meet with Family Committee.

November 7, 8, 9, 10, 1957, Murray Bowea, M. D., Invitation to become per-
manent member GAP Family Committee <.

Serial No. M-AP(C)-2

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Investigation of the Character Structxire
in the Alcoholic Patient

Principal Investigator: Murray Bowen, M. D.

Other Investigators: None

Cooperating Units: None

Man Years (calendar year 1957): Patient Days (calendar year 1957):

Total: 120 hours
Professional: 120 hours
Other: None

Project Description:

This is a detailed psychotherapeutic study of addictive character
(alcohol and drug addiction) patients. Five patients have been studied
in about six years.

Objective:

Treatment of the addictive patient with a modification of psychoanalytic
technique and a study of the character structure of the patient as revealed
in the transference relationship.

Method:

Psychotherapeutic treatment using a specific modification of technique
based on psychoanalytic theory. The addictive personality is seen as one of
the clearest examples of fixation at the oral passive stage of psychosexual
development. According to the theory, the relationships of a child at this
age centers about the child in the oral receiving role ajid the parent in the
oral giving role. In experience it is very difficult to get a workable trans-
ference relationship with addictive patients. The modification in technique
involves an oral giving attitude on the part of the therapist and the symbolic
oral giving of the therapeutic hour to the point of establishment of a workable
transference which is then resolved in the usual way.

Patient Material:

One patient is currently in the study. She was dischaxged to outpatient
status in July 1957.

Serial No. M-AP(C)-2 page 2

Project Description (continued):

Major Findings:

Treatment goes satisfactorily both in terms of treatment response and
in terms of content material. Indications are that much of the perverse
sexuality content is a defense against oral passivity.

Significemce to Mental HeaJLth Research: >^ •^■^•'

It is hoped that this study may eventually maie some contribution to
understanding the relationship of orsJ. passivity to other very infantile
clinical problems.

Proposed Course of Project;

Continue with this one patient and make a report at the termination of
her treatment. It is proposed to keep the side interest in this problem
for its contribution in the understanding of the oral passive component in
schizophrenia and other infantile character problems.

.yvJLi Hj.

Part B Included: No

- 16 -

Serial Wo. M-AF(C)-3

lo Adult Psychiatry Branch

3. Bethesda^ Maryland

PHS-NIH
Individual Project Report
Calendar Year 1957

Fart A.

Project Title : A S'budy of Clinical and Experimental DepersonsQ-ization :
The Effects of Psychotomimetic Drugs on Psychological Processes

Principal lD.vestigator : Charles Savage ;, M»Do

Other Investigators: Juliana Day, M.D.

Cooperating Units; Margaret Toohey, Research Assistant? Nursing Personnel
on Ward S-West

Man Years (calendar year 1957 )s Patient Days (calendar year 1957)-°

Total? .5

Professional ; .2 500

Other; .3

Project Description;

Objectives;

To stu(Sy artificially induced psychoses and delineate their
relation to schizophrenic processes and depersonalization^ and
their effect on th'S therapeutic process.,

Methods Eniployed;

Psychotomimetic agents such as LSD, mescaline, are given to
patients in psychotherapy and to voliinteer subjects. Their verbal
prccaictions before., daring, and after are recorded, compared and

analysed o

Ma.jor Findings;

A. 1957--Praliminsry trial with one psj'-chotomimetic agent
produced an effect more similar to a natural psychosis by creating
a disturbance of thought processes with relatively little visual
disturbaiic© in contrast to the effects of LSD and mescaline .

B. Data collected from 1955 to 1957 on a single patient in
intsnsix>-a individusJ. therapy who received LSD and reserpine and

- 17 -

Serial Wo. M-AP(c)-3 page 2

Majoi- Findings (eoatinued);

other dr\igs over a long period of time ajialyzed for their effects on
psychotherapy. Findings: Under the influence of LSD the memories of
childhood experiences sind emotions which came to the fore were fre-
quently too highly charged to be effectively dealt with in psychotherapy.

Significance to Mental Health;

A. Drugs which are psychotomimetic are useful adjuncts to the study
of natiiral psychoses.

B. The value of LSD in psychotherapy still remains debatable.

Proposed Course of Project;

Further review of data from study "B" with a view to publication.
Paper to be concerned with the psychodynamic effects of both LSD and
reserpine in the long-term intensive psychotherapy of a single patient.

Part B included Yes / X / No / /

Serial No. M-.AP(C)-3 page

Part B; Honors, Awards, and Publications

Publications other than abstracts from this project;

Honors and Awards relating to this project:

"lysergic Acid Diethylamide and Schizophrenia, " by Charles
Savage, M.D. Presented by Dr. Savage at the Association ox
Former Internes and Residents of Freedmens Hospital, June 6,
1957.

- 19 -

PHS»NIH
Individual Pi'oject Report
Calendar Year 1957

Serial Wo, M-AP(g)-^

1. Adult Psychiatry Branch

3. Eethes'iaj Jferylajad

Part A.

Project Title: A Study of Tranquilising Drugs; The Effects of a Tran-
quiliaing Drug on Psychodynsmic and Social Process

Principal Investigator: Charles Savage., M«D.

Other Irr/estigators : J\iliana Day^ M.D.^ lyman. G« Mtynxxs, McD.^
Leslie Schaffer^ M.D., and Harold A. Greeterg, M.D.

Cooperating Units: Margavet L. Toohey, Research Assistants Nursing
Personnel on Ward 3-West

Man Yeaxs (calendar year 1957):

Total:

1.5

Professional :

Other:

Patient Ds,ys (calendar year 1957):
1725

Project Description:

Objectives :

An intensive study to assess the effe-st of tra^i^uilizing drugs
on the therapeutic process.

Methods Employed;

A. 1955-56. Four regressed patients who had been studied and
treated intensively for a year's time -jjlthout tranquilizing drugs
were selected. They had all px'oven x'esistgixtt to psychotherapy and
intensive nursing cai'e. Their daily livingj, their relations with
others and the resection to the therapist a]J. hs3. haA carefxil
scrutiny. Gross behavioral observations were recorded as well as
i-atings. Contpsi'ison of therapy vrith asid without resei-pine were
Double blind controls were used.

B. 1956-57. A fifth patient ■\irs.s ar^Aad to this study who, in
contrast^ was a borderline neurotic^ who '(ms highly verbal and active
in psychotherapy. This patient '3 therapy had been under observation
for over a year 'vTith a S3.ngle therapist ;, in pasri with LSD (see project
on psychotciEDlnistic drugs ) . T?f70 period:^ of reserpine administration
with differing doss^e we:«?e alternated with periods of placebos and

Serial KOo M-AP(c)-4 page 2:

Methods Employed (continued);

phenoTDarbital administration. Control periods vithout reserpine were
increased over the earlier study frcm two weeks to a month as previous
findings indicated a long lag in reserpine effect.

C« 1957° Two of the patients in study "A" were given clinical
trials with ehlorpromazine and with Trilafon.

Major Findings;

Further study of data from "A"; With reserpine, patients were more
friendly and less preoccupied and showed greater self-control and social
conformity. Delusional material was less frequently expressed in waking
life and appeared in dreams. Individual psychotherapy was a more agree-
able collaboration but sensitive topics were still avoided. Reserpine
had a dramatic effect in a therapeutic milieu affecting favorably not only
the patient but the patient- staff interactions. It did not facilitate
psychotherapy within this sample of patients. Its effect did not last
after reserpine was discontinued stnd could also be reversed by severe
environmental stress.

Findings from study "B": Analysis of behavior charts and psycho-
therapeutic interviews showed no significant beneficial shift during
reserpine periods. In this patient there was an increased preoccupation
with the need for mothering and support during the period of reserpine
administration. The patient's periods of greatest curiosity and re-
sponsibility were when no drug was administered.

From study "C"; The clinical trial with ehlorpromazine was for
too short a period to dracw conclusions and was replaced by Trilafon
because of ehlorpromazine 's undesirable side effects. Neither patient
showed striking changes with Trilafon, one showed little or no behavioral
change, the other, who had had Parkinsonism with reserpine had no such
effect with Trilafon. On maximum doses of Trilafon she was less anxious
and more self- controlled than when on no drug.

Significance to Mental Health;

Both studies "A" and "B" are limited by number of patients and by
diagnostic category and conclusions must be viewed with caution. In the
first study reserpine aids in increasing the psychotic 's self-control
and social conformity and in both studies reserpine appears to strengthen
the patient's repression of conflict, but apparently not facilitate
psychotherapy.

- 21

Serial No. M°AP(c)-^ page 3

Proposed Course of Project:

Further review of data from study "B" with a view to publication.
Paper to be concerned with the psychody^namic effects of both LSD and
resei'pine in the long-term intensive psychotherapy of a single patient.

Part B included Yes [^TJ No l~~~f

- 22

Serial No. M-AP(c)2^+__pageJ+

Part B; Honors, Avraxds, and Publications

Publications other than abstracts from this project:

Savage, C. and Day, J., "The Effects of Reserpine on
Psychodynamic and Sociail Processes . " Presented by
Dr. Savage in May 1957 at the Annual Meeting of the
APA. Accepted for publication in the A.M. A. Archives
of Neurology and Psychiatry.

Honors and awards relating to this project:

- 23 -

ikljll:

PHS-NIH
Individual Project Report
Calendar Year 1957

Serial No. M-AP(C)-5
1. Adult Psychiatry Branch
2.
3. Bethesda, Maryland

Part A.

Total:

1.15

Professional :

.75

Other:

Project Title : Problems of Psychoanalytic Research with Schizophrenics

Principal InvestigatCT? : Charles Savage, M.D.

Other Investigators: Juliana Day, M.D., Harold A. Greenberg, M.D.,
Leslie Schaffer, M.D., Jordan Scher, M.D., layman C. Wynne, M.D.,
Stewart Perry

Cooperating Units: Nursing Personnel of 3-West

Man Years (calendar year 1957) •' Patient Days (calendar year 1957):

1000

Project Description:
Objectives ;

1. To study alterations in psychoanalytic technique which
are iarposed by the research setting.

2. To study the application of psyehoanaljrfcic techniques
to the therapy of schizophrenics.

3. To study the emotional problems of the therapist brought
about by the intensity of the psychotherapeutic relationship with
the schizophrenic.

Ifethods Employed:

Tape recordings of psychoanalytic therapy, staff review and
discussions of recordings.

Patient Material:

Hospitalized schizophrenics.

Maj or Findings ;

The transference psychosis which develops in the course of the
analysis of hospitalized schizophrenics tends to become diffuse and

Zk -

Serial No. M-AP(c)-5 ps^e 2

Major Findings (continued):

projected to other members of the staff, and thus converted into a
formidable resistance. If the staff responds to the transference
distortions as realities, the patient loses the opportunity to learn
the nat\are of the distortion and to develop more appropriate patterns
of reactivity. Close cooperation of the analyst with the rest of the
staff is essential to the handling of the diffusion of transference.

Customary focus in psychotherapy is on the problems of the schizo-
phrenic patient. Yet equaJ. attention should be paid to the problems of
the analyst who is treating him. The analyst's understanding of his own
countertransference to his schizophrenic patient leads to an iinderstanding
of the patient's productions in analysis and the ability to respond to
them appropriately. By identifying with the patient, the analyst is able
to understand and communicate with the patient. This process of identifi-
cation is fraught with anxiety because the analyst experiences the patient's
problems as his own and the anxiety associated with them. In addition, the
very fact of conducting analysis in a research hospital complicates the
transference picture and renders difficult the adherence to a rigid psycho-
anaJyiJic technique.

Significance to Mental Health;

Psychoanalytically oriented therapy is regarded as a major research
tool for the understanding of the schizophrenic process. That which en-
hances our capacity to use these techniques effectively has both research
and therapeutic application.

Proposed Course of Project;

Because Dr. Savage has departed for a year's leave of absence, his
focal interest in this area of inquiry will be missing, but attention
to these problems will continue as part of several projects, especially
the studies of the family relations of schizophrenics.

Part B included Yes /IT/ No / 7

25 -

Serial No. M°AP(c)-3i page 3

Part B; Honors^ Awards and Publications

Publications other than abstracts from, this project:

Savage, C, "The Diffusion of the Transference -Psychos is
in the Treatment of Schizophrenia. " Accepted for publi-
cation in Psychiatry^ 1957 •

Honors and Awards relating to this project:

Savage, C, "Parazneters and Interminable Analysis."
Presented at the American Psychoanalyi^ic Association
Meeting in Chicago, Illinois, May 195?.

Savage, C, 'Ifethodology . " Presented at the Annual
Meeting St. Elizabeths Hospital, May h, 1957.

Savage, C, "The Problems of the Analyst in the
Psychotherapy of Schisophrenia . " Presented at the
Second International Congress in Psychiatry, Zurich,
Switzerland, September 1957 •

Savage, C, 'tProblems of Class ic8.1 Analysis in the
Treatment of Schizophrenia. " Clinical paper for the
Washington Psychoanalytic Institute. To be presented
at the Moiint Sion Hospital in San Stsrancisco in December
1957^ San Francisco, California.

- 26 -

Serial No. M°AP(c)-6

1, Mult Psychiatiy Ba^aaefe

3. Bethesda, Jfesyland

PES=NIH
IDadividual Project Report
Calendar Yeai- 195t"

Part A.

Project Title: Family Relations in Schizophrenia

Principal lanrsstigator : Igrmsm Go "■^Tme, M.D.j Jijliaaa Dsgr, M.D..,
Leslie Schaffer^, M.D,, and Stanley Hirseh, M.S.W.

Other Investigators: Harold Greenbex'-g, M.D., Kursiag Personnel on Ward

3 West, Morris B. Parloff, Ph.D., Joseph H, Haffidlon, Ph.D., Donald S.
Boomer, Ph.D., Marvin Waldasaa, Ha.D., Morris Rosenherg, Ph.D.,
Leonard I. Peaxlin, Ph.D.j I. M. Ryckoff, M.D., Gonsultamt.

Cooperating Units: The methods aad conceptualization of this project acrs
different from those of aay other PHS project. The general subject
matter, family relationshixjs of schizophrenics, is similar to project

M-AP(C)-1, which, howeTsr, solely uses group methods to sttiSy the
families that generally live on the ward. The present project differs
"by its use of dat^ from indi-^iduaJ. faadly members as well as ob serra-
tion of interaction among the family meaibers. As each project develops
further, it is probable that the eliiaisal material and hypotheses frcan
ea^h will ccm^lement one another so that caj!^a5:'atiYe discussion showld
be increasiagly fruitfal.

OBie of the families being st^2.di@d in this project is also involved
in project M=-^)-5l in the present st'ddy, this family has been considered
intensively from the stisadpoiat of the dynseuics of the family os-ganisa-
tion as a whole, partierjd.aa'2^ in relation to the general hypotheses of
this project.

Man Years (calendar yeaj? 1957): Patient D@^b (eeJLendas' year 1957):

Total: 3.0

Professional: 2.25 lk6o

Other: .75

Project Iteseription:

Ob jectJTes ; This project is parfc of a long-range program of which
the central goal is to examine the part that the family setting
has in the genesis, form, and course of schizophrenic illness,
!Riis reseas-ch has progressed from intensive pilot studies of a
small number of fasEilies of schizophrenics to the fommlation

- 27 -

Serial Ko. M-AP(c)-6 page 2

Objectives (continued) ;

of a series of preliminaiv hypabbeses, which, in turn, have stinm-
lated ciirrent planning of further eE^irical research that will
include a critical evaliiation, modification, and esqjansion of these
hypotheses «

Ifethods Employed;

(1) Data collection. Data was collected "by tape-recorded
psychiatric interviews with the patient, pa:rents and other sig-
nificaat relatives and friends. This included intensive psycho-
therapy with the patient, and interviews with parents TAich
centered on their participation in the therapy of the patient
and which sometimes eventuated in psychotherapy. Collated data
was collected frcsn ward administrator and nursing personnel re-
garding interaction of the patient with ward personnel and of the
parents with the ward staff and with the patient.

(2) Analysis of Data. Chief methods of analyzing the data used
ttnis far include the use of the psychoanalytic viewpoint to examine
the dynamics of the individ\ial relationships, and modified role
theory as hasis for analyzisag the family system of interrelationships.

Patient IJaterial;

Patient material has consisted thus far of young recently ill
schizophrenics with both parents available for outpatient interviews.
Five families have been st-adied thus far.

Total to Date

number of Patients 7

(Hospitalized)
Number of parents 9

(Oat-Patiants)

Major Findiags;

The starting point in the series of hypotheses now formulated was
an examination of the qaality of interpersonal relations in the faaiilies
of certain schizophrenics. According to this conceptualization, the
acknowledged relations in these families in the prre-psyehotic phase have
a quality of intense and endurijag pseudo-jjutuality. Pseudo-asutaelity
involves a sense of relation which hiisges upon fitting in with what are
assumed to be the expectations of othersj inversely, the sense of rela-
tion is exE<erieneed as possible only by excluding recognition of azs^
divergence from this fitting together, or coarj^leiasntarity, of reciprocal
expectations .

28 -

Serial No. M-ig(c)°6 page 3

Ma j or Fteaiags ( c ont inued ) ;

Pseudo=inut'a£il conrplemeiitazs'ity is contrasted with mutual and non-
mutual forms of ccmplementa3.'ity. !Eiis differentiation involves a new
extension of role theory which was a 'by-product of this work.

In the families of cer-baln schizophrenics, it is hypothesized
pseudo-mutuality takes an especially intense and enduring form in
which the family memlsera strive for a sense of relation "by trying to
fit into the family role struetare. The social oi'ganization in these
families is shaped by a pervasive familial subeulture of myths, legends,
and iSeologs,'' which stress the dis-e consequences of evenly recognized
divergence frcaa a relatively limited number of fixed, engulfing family
roles.

The shared, familial effox'ts to exclude from open recognition any
evidences of non-ccarplementarity within the pseudo-matoal relation
become group mechanisms that help perpetuate the pseiido-mutuality.
la the families of schisophrenics these mechanisms act at a primitive
level in preventing the articulation and selection of any meanings that
might enable the indixd-dual family member to differentiate himself from
the family role structure.

It is hypothesized that the resultant patteiTis of interpersonal
perception and coairoanicstion, after haviiag become a part of the
offspring's personality structure, ixr^olve a kind of fragmentation
and confusion of esqserience and thought which is a central feature of
schizophrenia .

Furfcher, it is hypothesised that different family members will
occupy diffe2*ent positions or roles within the family social organiza-
tion, le.9ding to differing consequences for the personality development
of the offspring. This hypothesis has been confirmed by a detailed
examination of very extensive material on a family in which the off-
spring are monozygotic quadEorgilet schizophrenics.

Significance to Mental Health Research;

Severely aisturbed family reD^tdons have been coxisistently found
in the background of schisophrenic: x»sacti<Dns, Q]his is a very iiEportant
lead being examined in this project, par-&ieularly in tei'ias of three
major unsettled problSiass (l) the particular characteristics cxf such
familial disturbance in schiscpbreniai (2) the degree of specificity
that various aspects of such distuj^bance may have for schizophrenia,
or varieties of schizophi'enis, cDaipared to the generality of other
aspects of family distur'banee which may also occur normally or in other
disorders J (3) the question of whether the family disturbance is a pri-
mary factor in the iSBvelopmeiit of schizophrenia ox a secondary consequence
of the individual's patholDgj"'.

29 -

Serial No. M"AP(C)-6 page k

Proposed Course of Project;

Having eonrpleted a phase of exploration of the clinical problem and
the formulation of preliminary hypotheses, it is now planned to proceed
with a major shift and e^qoansion of this project, along three main lines:

(1) Coanparisons of the family relations of schizqphreaics with non-
schizophrenics (a) initially in a time-limited (several months) pilot
study with hospitalized neurotic patients and their outpatient families,
(b) later, in studies of normal families, families of medical patients
of other Institutes, and families of various neurotic subgroups, varied
by diagnosis, social class, and faznily constellation.

(2) After an initial pilot congorison study with neurotics, extension
of the range of observations for the families of schizophrenics both in
terms of such variables as social class and family constellation, but also
in terms of the variety of schizophrenia and type of onset. The question
of differential effects upon schizophrenic and non- schizophrenic siblings
is especially important in family studies.

(3) Extension of techniques for specifying meaningful features of
both the individual psychopathology and its family setting, by trying
out a variety of approaches such as group therapy with an entire family,
including the patient; quasi- experimental group situations for the analysis
of inteirpersonal communication patterns within families (see project
M-P-P-(c)-9), analysis of the place of the family in the wider ciilture

and society, and improved techniques for comparing those behavior patterns
found in intra-f amilial interaction with those carried over into psycho-
therapy and the wai'd setting.

These changes necessa:-:ily involve other prospective changes: an
enlarged patient and family sample, at first with hospitalized patients,
later with others as well; a marked incirease in interdisciplinary
collaboration; a reorganization of the wajrd clinical operation.

Part B included Yes £YJ No /~~7

- 30

Serial Wo. M°AP(c)-6 page 5

Part B; Honors, Awax-ds, and Publications

Publications other than abstracts from this project:

V^mne, L.C., Ryckoff, loM., Day, J., and Hii'sch, S.I.,
"Pseudo-Mituality in the Family Relations of Schizophrenics,"
Accepted for publication in Psychiatry .

Eyckoff, I.M,, Day, J., and Vftmne, L.C., 'family Role
Structure and Schizophrenia. " Presented at the Annual
Jfeeting of the Saint Elizabeth's Medical Society,
Washington, D. C, May 1957 and accepted for publication
as a chapter in book reporting proceedings of this ineeting.

Honors and Awards relating to this project:

Wynne, L.C., Day, J,, Hirsch, S.I., and Ryckoff, I.M.,
'family Relations of Schizophrenics: Some Working hypotheses."
Presented in a synrposium on "OSie Family Emrironment of Schizo-
phrenic Patients, " chaired by J. Delay, Second International
Congress for Psychiatry, Zurich, Switzerland, September *»-, 1957-

\^rnne, L.C., Day, J., Hirsch, S,I., and Ryckoff, I.M.,
"The Family Relations of a Set of Schizophrenic Monozygotic
Quadruplets . " Presented at Second International Congress
for Psychiatry, Zurich, Switzerland, September 2, 1957j and
at a Research Seminar, Department of Psychiatry, Yale
University School of Medicine, December 3f 1957 •

„ 31

PHS-NIH
Individizal Project Report
Calendax Year 1957

Serial Ko. M-AF(C)--7

1. Adult Psychiatry Branch
■ 2.

3. Bethesda, Maryland

Part A.

Project Title: Perceptual Impairsnent in Psychogejaic Mental Disorder

Principal Investigator: lyman C. Wynne, M.D.

Other Investigators: Leslie H. Farber, M.D. and Irving M. Eyckoff, M.D.

Cooperating Units: None

Man Years (calendar year 1957): Patient Days (calendar year 1957) i

a?otal: .2

Professional: .1
Other : .1

Project Description:

Objectives ;

(1) To delineate the quality of an imaginative inrpairjment in
certain neurotic and psychotic patients in their ability to perceive
content and create meaning. (Following general usage, perception
includes, in addition to the processes of conduction and sensation,
the process in which a person attributes significance or msaning to
a stimulus situation,)

(2) To examine and evaluate some of the iinplications for
personality functioning and for psychotherapeutic processes arising
frcm this inipairnent . More specifically, to study the details of
the imaginative isrpairment associated with difficulties in reading,
arithmetic, and social skills, especially, hew such difficulties
relate to the development of anxiety, to past learning failiire, and
to the manner or style in which an individual brings about a sense
of relatedness to others.

Methods Employed:

Research interviews were conducted with psychiatric patients
and "normal" subjects, focusing on the measoixigs with these patients
perceived with a variety of subject matter, media, and situations.
Some of these interviews have dealt with the person's interpretation
of particular passages which he has read, of television prograais
and movies and of recorded material which is played over a speaker.

- 32 "

Serial No. M-AP(C)-7 page 2

Methods En^loyed (continued);

Others have dealt with the person's problems in dealing with common
arithmetic problems and the use of maps^ as occxirring both in his
ordinary life and in the interview situation. A session was conducted
of a mother coaching her children with their reading. All of these
interviews have been tape recorded and transcribed. Several have now
been observed through a one-way mirror and partially photographed with
sound film. Subsequently, the movies have been shown to one of the
patients and her interpretation of her own appearance discussed in a
further interview. Four of the patients have been also seen in psycho-
analytic psychotherapy, so that information from this source covild be
added to the research interviews.

Patient Material;

TVo inpatients (continued as outpatients in 1957) sn.6. two private
patients of Drs. Farber and Ryckoff . Tao "normal" mothers and their
children (not patients).

Major Findings;

(1) A description has been derived of the quality of an unex-
pectedly extensive incapacity of these patients to perceive and deal
with content, both in and out of the psychotherapeutic situation.
Such massive difficulties with content may be overlooked vinless
specific inquiry is made in which the patient's stylistic devices

do not succeed in disguising the failure to derive meaning
imaginatively .

(2) In the usual situation of psychotherapy, the extent of the
patient's capacity to perceive content may be obscvire. The therapist
is apt to believe the patient's diffictilty in dealixig with content
arises from anxiety, instead of consi&SPing the aaxiety as ai'ising
from an inability to distinguish content. In this project data are
being examined which strongly suggest that an impaired capacity to
perceive, understand, and communicate commonly exists independent of
the Impairment produced by ongoing defenses against anxiety, and fre-
quently leads to rather than results from, anxiety. One area of
fxinctioning in which this diffictilty is especially prominent is in
reading difficulties of both adults and children.

(3) Wot only does transference and relationship influence per-
ceptiveness, but also, and to a greater degree, perceptiveness
determines what can go into relationships. A narrow or inflexible
perceptual style will markedly interfere with the development of
mutuality in relationships.

33 -

Serial Ko.

tfeijor Findings (continued);

(k) The form whicti the imaginative irngpairment takes depends greatly
upon the characteristics of individual essperiences in learning situations.
The quality of perceptiveness and ccamnunication is markedly impaired in
each psychiatric disorder and will vary in quality depending upon both
the general characteristics of the disorder and the specific character-
istics of the individual personality.

Significance to Mental Health Research;

It is believed that the meehaaisms being studied in detail in this
project plays a signifieaat part in the learning failures widely reported
in schools and by parents today^ especially upon reading. In present-day
psychiatric theory anxiety is widely regarded as the central problem in
psychogenic mental disorders. Any evidence which challenges or calls for
a modification of this viewpoint clesrly is relevant to a great deal of
current thinking about the nature of these disorders and their treatment.
This work is an exploration of neglected dimensions in psychiatric theory.

Proposed Course of Project;

Current activity in this project is b®ing directed toward review of
past research data and writing of the material in a series of short
papers each focused on a particular aspect of the work. One such paper
was presented by Dr. Wynne in discussion at a meeting of the Washington
Psychoanalybic Society, February 1957 • It is expected that this review
and writing process will contintae through at least six months of the
ccaning year. During the discussion of the material for this p'orpose
new ideas have been emerging which it is planned to examine in farther
research after the writing has been done.

Part B included Yes A°~7 No /" '^7

3^ -

Serial No, M-AP(c)-8
1. Adult Psychiatry Branch
2.
3. Bethesda, Maryland

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Linguistic Study of Emotional Expression

Principal Investigator: Allen T. Dittmann, Ph.D.

Other Investigators: lyman C. Vtynne, M.D.

Cooperating Units: Laboratory of Psychology

Man Years (calendar year 1957): Patient Days (calendar year 1957):

Total: .1

Professional: .1
Other:

Project Description:

See Individual Project Report, laboratory of Psychology, Serial No.
M-P-C-(C)-1^.

- 35 -

Serial Uo. M-/\?(c)"9

1. Ad-alt Psychiatry Branch,

3. Bethesda^ tJaryland

PHS-i^HH
Xxidividiial Project Report
Calendar Year 1957

Part A.

Project Title : Social Mobility and the Milieu of the Psychiatric Hospital

Principal Investigator: Leslie Schaffex", M.D. and Leila Calhoun Beasy^ Ph.D.

Other Investigators j ITone

Cooperating Units: Laboratory of Socio-environmental Studies

Lfen Years (calendar year 1957) = Patient Days (calendar year 1957):

KTone

Total:

Professional :

Other :

Project Description:

Objectives :

Tiie study is an atteiJipt to explore the relevance and implica-
tions of some theoretical vrork "by Harold Lasswell concerning social
structure and social mobility - particularly his notion that there
is a significant negative relationship between the e::tent to which
a group achieves solidarity and high morale and the incidence of
mobility siaong its members « It is hoped to clarify in theoretical
terras a ps-rticular perspective concez-ning the value context of the
psychiatric hospital and, in particular ;, some of the r^roblens con-
cerning respect 8,s a value. Among other questions one is whether
tliere is a significant difference between the incidence and intensit;/'
of vertical mobility in a psychiatric setting as coropared with con-
ventional medical and svirgical settings.

Methods Employed:

A preliminary snxvey of professional, and other personnel in
lilMH. and tv?o other Institutes has been followed up by the collec-
tion of additional, data in (a) a private psychoana].j'"fcic hospital
and (b) a university department of psychiatry « In addition, the
superintendents of two other hospitals have agreed to allow us to
gather data in their institutions. Data from a random sejrtple of
1_,0S7 iBsdical students has been secured throtJigh the cooperation of
KORC who have promised us access to the original protocols.

Serial No. M-AP(c)-9 page 2

Major Findings :

Statistical analysis of the preli^nlna.ry date has shown a well-marked
gradient of achieved vei*tlcal mobilii^ across the professions studied.
The highest degree of vertical mohilitv occiirs in the newer professions
adjacent to psychiatry — i.e.j, psychology and the social sciences j the
least mobile popuj,£.tioa is found in physicians in internal, medicine.
Psychiatrists fall midnfay hetrreen these two groups. The further data
referred to above is in the process of being collected, coded and trans-
lated on to IBM cards.

Significance to Mental Health Research;

It is suggested that some staff csiaflicts, both ijx rtssearch and in
clinical psychiatric settings may be explained in terms of vertical
social mobility in the pa:rbieipants . The notion has long been held that
the provision of respect for the patient in a mental hospital is a crucial
ingredient in a therapeutic milieu. It has also repeatedly been suggested
that all Mnds of collaborative efforts may be expected to flourish in an
atmosphere of mutual respect. It has been suggested in this study that in
hvunan groups which are characterised by the pssjriicipatlon of highly upwardly
mobile persons the value of respect is ioipl^.citly conceived as a competitive
valxie and one that is likely to be in decidedly short supply.

Proposed Course of Project;

(1) To continue to code and sneJ^yze additionad data,

(2) Clarification of the theor.'y. Ixl a sense this study may be under-
stood as an effort to explore the utility of a theoretical perspective
elaborated by Lass^^ell and Kapl^in for the s^imdj^ of politica3. events.

(3) An abstract concer-T-ing sorsB aspects of the \-^ark has been sub-
mitted for the 1958 Ann'j£il Meeting of the Americas, Psychiatric Association.

Part B included Yds fXl JIo

37 _

Seri^a NOo M-iff(C)-c

Part B; Honors, Mexds^ and Publications

Publications other than abstracts from this project:

Honors and Awards relating to this project:

Scha£fer, L. and Deasy^ L C.^ "Deference j, Social Mobility
axid Conflict in Psychiatric Settings, " Presented at the
Section on the Sociology of Science, itoericsn Sociological
Society, August 1957^ and also in a lecture given at the
V. A. Hospitaly Salt lalc® City 3, Utah, September 1957. M
esjpanded version of this paper is presently in preparation
for publication.

- 3i

Serial No. M-AP(c)-10

1, Adult Psychiatiy Branch
2.

3. Bethesda, iVfea-yland

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Psychiatric Research in a Clinical Setting: Integrating
Research and TreatiBsnt in the Role of the Clinical Investigator

Principal Investigator: Stewart E. Perry

Other Investigators: I^nnan C. Wynne, M.D.

Coc^rating Units: Laboratory of Socio^environmental Steadies

Msai Years (calendar year 1957 )s Patient Days (calendar year 1957):

Total: .2

Professional: .2 None

Other:

Project Description:

See Individual Project Report^, Laboratory of Socio-environmental
Studies;, Serial No. M-S-T(C)-7.

- 39 =

Serial KOo M~ig(C )-ll

1. Mult Psychiatry Braxtch

3. Bethesda,, Jferyland

PHS-OTH
Individual Project Report
Calendar Yean' 1957

Part A.

Project Titl© ; Selected Aspects of the Social Staract-iir® of a Clinical
Research Program in the Mental Health Field: Pro"bleJBS Posed hy the
Variety of Roles Built into the Social Strueture

Principal Ijwestigator : Stewart E. Perry

Other Investigators: None

Cooperating Units: Child Research Branch

tfatn Years (calendai' year 1957)5 Patient Days (calendar year 1957):

Total: 1/6

Professional: l/6 kO

Other:

Project Description:

Objectives ;

To explore the consequences for a clinical research progrsan
of the variety of roles which characterize itj special en^hasis
win be placed on examining the prohlems of integrating the various

administrative J research;, and clinical roles and statuses.

Methods Bnployed:

Participant observation in a psychiatric research programi
interviews with staff xaembersj recording of group conferences,
search of extant riscords and xHgmoranday rigsearch and clinical;
and review of li^terature in XDsdical sociolo^ and the sociology
of knowledge and science.

Major Findings:

Preliminary iss^ressions include the following probiesas as
consequences of the role variety in psychiatric clinical research
programs: (l) Basre often appears to be a discrepancy between the
hamaa relations techniques earphasised in administrative roles and
those effi^hs^sized in psychotherapeutic roles==for exanrplej, psycho--
therapeutic roles enjshasiz.® techniques of indirection in the

Serial KOo M-AP(c)-ll page 2.

Major Findings (continued) ;

e:q)ression of views to another, while administrative techniques enrphasize
directive expression of viexfs, (2) There seems to be some discrepancy
between the pattern of integration of non-ioedical roles in a conventional
hospital organization and the pattern of integration of such roles in a
research (iteration— for exaagjle, in some instances functions performed by
doctors assy be transferred to non-doctors (e.g.j, nurses, scientists, etc.)
and statuses ordinarily reserved to the doctor may also be occupied by
non-medical personnel. (3) Differences in the definitions of science,
method, and Imowledge in psychiatry appear to be related to role differ-
ences and to engender problems in scientific ccsmmmication— for exaaiple,
soane research techniques are derogated or valued in relation to the staff
member's role, {h) The staff member's interpretation of crises in the
patient's hospitalisation — such as suicidal attezapts, acute onset of
muteness, etc. — tends to vary with his role and function.

Significance to tfental Health Research;

This project explores the operational difficulties which are inherent
in psychiatric research, treatment, aad adiainistration. Insofar as such
difficulties can be isolated and specified, it is possible that steps
be talsen to minimize their interference with organizational goals in
mental health work.

Proposed Course of Project;

Mditioaal exploratory work is planned for the purpose of formu-
lating more explicit hypotheses and theories.

Part B included Yes /~~7 No fTJ

- kl ~

iliifl

Serial No„ M-AP(C)-12
1. Adult Ps;5)'«hiatry Bra^ich
2.
3. Bethesda, Maryland

PHS-HIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: The Natural History of a Hospital Case Presentation

Principal Investigator: Stewart Ea Perry

Other Investigators: Hone

Cooperating Units: None

Man Yesxs (calendar year 1957): Patient Days (calendar year 1957)

Total : 1/6

Professional: I/6 None

Other:

Project Description:

Objectives :

Taking as a starting point a hospital case presentation of a
psychiatric patient^, to describe the social context of the theory
of behavior explicit and implicit in the case presentation; to
note the potential influences of this social context upon the
theoryi to note the social control in^lieations of the theoretical
perspective on patient behavior which is held hj -ward staff j to
explore the influence on patient behavior of this theoretical per-
spective and of the social organization of the ward.

tethods Employed:

Participant observation of the case cojaferences and in the
general psychiatric research program^ interviews with psychiatric
workers who hsA contact with the subject patient j search of extant
records on the patient,,

?fe,jor Findings:

This case stvidy indicated the following general conclusions:
(1) Intellectual products (such as research reports) in a human
behavior research progrsm may be systesaatieally s^budied as items
of social, behavior themselves, (2) A theory of patient behavior,
explained psychodynamically, may offer clues to the hospital

42 -

Serial Wo. M-AP(g)-12 page

Major Findings (continued) :

social organization within which the patient is treated. (3) Responses
of personnel to a research theory may also provide clues to the hospital
organization, (i)-) As a 'by-product of the study, it appeared ths/fc a re-
view of psychiatric theory would indicate a need for explicit development
of propositions about the social control of patient behavior.

Significance to Mental Health Research;

Psychiatric theories^ lUse all theories in social sciencsj, evolve
in a social context which may influence their development and their
applicability; as such the theories may implicitly as well as explicitly
describe the social structure of psychiatric treatment. To explore such
influences and in^lieit descriptions is to add a further dimension to
the explanation of patient behavior.

Proposed Course of Project;

This project has been terminated with the publication of a paper
reporting findings in detail.

Part B included Yes /IT/ Ko /"" /

1^3 -

Serial No, M-ig(c)-12 page 3

Part B; Honors^ Awards, and Publications

Publications other than abstracts from this project:

Perry, Stewart E. and Shea, Gertrude K., "Social Controls
and Psychiatric Theory in a Ward Setting, " Psychiatry, 20 :
221-21^7 (1957). __

Honors and Awards relating to this project:

NATIONAL INSTITUTE OF MENTAL HEAI.TH

Clinical Investigations
Child Research Branch

BUDGET SHEET

?gtipiated oUi^Mti-ong fgr,,FT, 1S'?S

Total: $J^3,863
Direct: $179,939

Reimbur s ement s : $263 , 92^

Projects included: ]y^CR(C) 1 through M-CR(C) 10

PHS-NIH
Individual Project Report
Calendar Year 1957

Serial No. M-CR(C)-1

1. Child Research Branch

3. Bethesda, Maryland

'art A.

Project Title: Milieu Therapy

Principal Investigators: F. Redl, Ph. D., J. Noshpitz, M.D.

Other Investigators: C. Faegre, B.A., S. Crawfort, M.S.W., E. Citrin, M.S.W.
J. Vernick, M.S. W., E. Maeda, O.T.R.

Patient Days (calendar year 1957)
850

Cooperating Units: None

Man Years (calendar year 1957):
Total: 5 1/2

Professional: 3
Other: 2 1/2

Project Description:

Objectives:

Over-all Goal: To subject the various facets of milieu to an intensive
as well as extensive scrutiny as to their properties and nature, and to
arrive at a breakdown of this global concept into manageable and yet clini-
cally relevant subunits. To study the precise impact of the subunits as
well as the structure of the whole on the child patients as well as on the
staff, to arrive at criteria for assessment of the specific psychological
ingredients of milieu parts for the purpose of clinical prescription as
well as prediction of milieu effects.

Sub-Tasks; Concept formation--creation of workable constructs for the
differentiation of clinically relevant variables involved in milieu-effects,
theory formation related to the impact of milieu-findings on the model of
personality.

Pharmacopaea of games and other child-patient activities--so as to
create a useable manual for the prediction of their effects, and describe
the variations of ingredients necessary for their adaptation to a variety
of different pathologies and of different phases in treatment.

Analysis of all other milieu-aspects that can be clearly distinguished
as variables in their own right, so as to make them more accessible to the
process of therapeutic manipulation and to arrive at safer criteria for
prediction of effects.

Methods Employed;

(1) With the aim of preparing for a pharmacopaea of activity ingredients
as well as of other milieu variables, a thorough analysis is being made of the
records of actual in-game behavior of the child patients over an extended

- 45 -

Part A. M-CRCO-l, page 2

period and during different phases of their therapeutic development. En-
vironmental stimuli involved in sub-facets of any given program or activ-
ity unit are being analysed as to their nature and potential effect on the
children;, and this is then compared with the actual events recorded by
staff o On the basis of this analysis materials are being prepared relating
to indications and eounter-indications in the selection of program activ-
ities as well as for the choice of methods and techniques.

(2) The assessment of social structure, institutional atmosphere and
distribution of staff roles as well as impact of staff behavior and atti-
tudes is being pursued by a variety of methods simultaneously. The ac-
cumulation of sharply focused and detail-rich descriptions of actual situa-
tions of interaction of children and staff under varying circumstances,
will still have to constitute the major method employed^ since this field
is as yet so poor in actual naturalistic and well described data. In
isolated areas more rigorous methods are being employed on sub phases which
lend themselves to such techniques, as for instances Critical Incident
technique, controlled observations by trained investigators, Ossorio-Leary
system of behavioral observation^ and others. On isolated hypotheses
systematic analyses of historical materials and records on special inci-
dents are pursued-^such as, for instance, an analysis of the relationship
between incidents reported on the child patients, and staffing patterns

at the time of the incident^ etc.

(3) Data from other studies are being used to define and clarify in-
formation on the impact of various aspects of the milieu on various facets

of behavior. For example, CR-4 deals in part with the effects of school
milieu factors on school performance, CR=5 is concerned in part with
milieu effects (times space^ props, etc.) on the technique, strategy, and

results of Life Space Interviews^ CR-6 studies the effects of various

settings on interpersonal behavior and changes in such behavior.

Findings ;

This is a long range project, and major findings on the nature of the
milieu ©oncept and its clinical facets cannot be expected to emerge as yet.

However s among the part-findings one could trace in the process of on-
going research the following may be listed;

It is possible to isolate about 13-15 distinct and relatively

indepemdently researchable subunits of the milieu which seem to be at work
in the produetiom of behavioral impacts on the children under study.

At least 7 quite distinct meanings are customarily invoked when
the adjective "therapeutic" is attached to the milieu concept, each one
of" them relevant in its own right, but in need of sharp separation for

the utilisation in an organized research approach.

A considerable list of properties of games, materials, props,
tools involved in activities such as arts and crafts, etc., can be well
isolated as of clinically distinct importance, and the therapeutic
variation of these factors can be described to a considerable amount of

^ h6 =

'art A, M-CR(C)-1, page 3

detail o Effects of some techniques of employing such activities and of
handling child behavior during the process can be distinctly seen as dif-
fering in their effect on the children from others, so that the ground-
work for a more organized pharmacopaea mentioned as one of oxuc objectives,
can be seen to emerge „ Such factors isolated by now can be described
in sufficient detail and with sufficient precision to make them teachable
to others and approachable in sharper research design in later studies.

Techniques for the clinically geared observation of surface be-
havior on the spot can be developed and sharpened up so that they avoid
the traditional gap between observable surface data on the one, and depth-
psychological dynamics on the other hand more successfully than has been
possible in the past„

(5) A milieu design which is well adapted to meet the children's
problems in the earlier phases of their pathology, may, by this very fact,
become detrimental or at least non-supportive toward later phases of re-
covery and on the move toward fuller mental health. The differences be-
tween the clinical characteristics of a social structure on a hospital
ward as compared to that of a family style setting can be described with
somewhat more detail though a really thorough analysis of residential
versus institutional versus family style milieu design will have to wait
for further data and explorations. Beginnings of such comparative data be-
came possible with the move of 6 of Our child patients from the Ward into
the newly created Residence building, and through a trial run on a group of
normal controls in that residence before the child patients were moved in.

Patient Material; Nb. Average Stay (Days)

Children 6 365

7 75

10 25

Major Findings ;

This project is exploratory at present.

Significance to NIMH Research;

The worthwhileness of this project lies in the fact that the clinical
techniques of residential therapy for use with hyper aggressive children are
as yet in a developmental phase in the field of child psychiatry. The
current clinical design in a number of respects is unique within the field.

Proposed Course of the Project;

This project will continue indefinitely as part of the program of the
Laboratory with new areas being developed as time permits. The addition
of a "Halfway House" outside the Clinical Center has already broadened the
scope to include less disturbed children and later phases of treatment.

Part B included Yes X No

Serial No M-CR(C)-1, page 4
PHS-NIH
Individual Project Report
Calendar Year 1957

Part B; Honors, Awards, and Publications

Publications other than abstracts from this project:

Bloch, D. A., & Silber, E. The Role of the Administrator in Relation to
Individual Psychotherapy in a Residential Treatment Setting. American
Journal of Orthopsychiatry. Vol. 27, No. 1, 69-74, January, 1957.

Honors and Awards relating to this project:

48 -

Serial No. M"CR(C)-2

1 . Child Research Branch
PHS-NIH 2o

Individual Project Report 3. Bethesda, Maryland
Calendar Year 1957

Part A«

Project Title: Studies in Psychopathology of the Hyperaggressive Child

Principal Investigators: J. Noshpitz^ Mo Dos Bo Sweet, Ph„D.

Other Investigators; Ho Raushg PhoDo, Ho Kitchener, MoSoWo, H. Perry^ AoB=
Po Spielmanj MoD.j So Berman, MoDo, Ro Lourie, Mo Do

Cooperating Units : None

Man Years (calendar year 1957): Patient Days (calendar year 1957):

4 650

Professional: 2 1/2
Oth®r 11/2

Project Description:

Objectives;

To synthesize clinical and research observations made over a long
period in such a way as to formulate hypotheses about the etiology;,
personality assets and psychopath© logy of hyperaggressive children o
Special attention is directed toward the testing of a hypothesis that a
specific group of child patients £,■ currently included under the label of
borderline cases actually constitute a nosological entity in its own
right and differ significantly from patients of the disease entities
which they are usually listed as being borderline tOo

Methods Employed;

lo Historical material from parents, schools^ physicians, courtSj
social agencies J, is being organised systematically toward a full de-
velopmental description,,

2o Material from nursing, psychotherapy, schools social service,
life space interview notes^ and results from special researches are being
organised and collated with each other and with biographical material ^
for each child.

Patient Material :

Children

No^

Average Sta.

365

= k9

Part Ao Serial No, M-CR(C)-2, page;!'

Only tentative findings can be reported at this timej since data collec-
tion on the later phases of the children's individual therapy, their behavior
in the residences as well as in public school, is still in process. However,
temporary summarization has been accomplished on the material available up to
the present on two of the cases, and clinical studies are in process for the
other fouro These studies are directed toward a synthesizing of data gained
in psychotherapy as well as in the other aspects of the research project, such
as previous history, school, ward and residence behavior, and so forth. Among
the tentative findings the following have emerged with eoough clarity to be
reported at this point;

(1) Kyperaggressive children form a pathology which combines aspects
from childhood neuroses and psychoses to constitute a special syndrome. Al-
though individual children differ in aspects of this syndrome, in all cases
there are profound ego disturbances centering around problems of impulse
controls and particularly around the control of aggression. The ego distur-
bances are reflected in conceptual lacks, learning diff iculties, disturbances
in conceptions of space and time, low tolerance for frustration, hyperdis tract'
ibility by environmental props, readiness for contagion, paranoid-like suspi-
ciousness and projections. Despite these features, the children being studied
here differ in many features from psychotic children as described in the literat
ture. In particular, they do not show the autistic behavior and fantasies of
the latter, they are generally in communication with the environments and
under special circumstances they show marked ego-=intactnessc

(2) In all cases oral themes seem to play a major part in the under-
lying fantasies of these children. The children se«m to interpret experi-
ences via orally incorporative or destructive modes. Even material that
seems initially to be predominantly phallic in tone, can be readily seen

as a developmental phenomenon super-imposed on a rfauBsdation of primary oral
concerns . ,

(3) Related to the abovej, one finds in these children intense anxiety over
the possibility of dependency, and intense defenses erected against both
behavioral and fantasy expressions of dependency. With progress these
defenses seem to diminish both in behavior and in fantasy productions.

(4) All of the children show severe problems in the formation of a
sense of identity » These problems seem related to the absence of or
failure of- figures who might serve as transmitters of cultural or subcul-
tural values. In all cases there is absence of a father, failure of the
father to fulfill a role ChaL might provide a source for social identifica-
tion, or inadequacy of the father as communicated to the child through the
mother's perceptions. With all children the opportunity for establishing any
relationship (even an anti=social one) with a social order seemed lacking „

Significance to NIMH Research;

Although a few detailed clinical case studies of individual children
exist in the literature, this Laboratory's facilities permit comparative

- 50 =

Part A. Serial No. M-CR(C)-2,page 3

study o£ six similar children and hopefully may clarify some of the common
elements seen in the personality disturbance of these children.

Proposed Course of the Project;

(1) Continuation of data collection of the present patient group in
the residence setting, and follow up data gathering after their return home
or their placement,

(2) Gathering of similar data-^but with methods improved by our
previous experienee--on the new inpatients on 4 East, and comparison of
findings on a larger number of child patients followed through several
phases of their treatment.

Fart B included Yes X No,

~ 51 -

Serial No,, M=CR(C)-2j page 4

PHS-NIH
Individual Project Report
Calendar Year 1957

Part B: Honors, AwardSj and Publications

Publications other than abstracts from this project:

Siegels L. Case Study of a 13-Year Old Fire-Setter: A Catalyst in the
Growing-Pains of a New Residential Treatment Unit. American Journal
of Orthopsychiatryj, Vol, 27 , No, 2, 396-410, ^ril, 1957,

Honors and Awards relating to this project;

- 52

PHS-NIH
Individual Project Report
Calendar Year 1957

Serial No. M=CRCC)-3

1 c Child Research Branch

3c Bethesda

Part A.

Project Title: Technical Problems in Individual Psychotherapy with
Hyperaggressive Children «

Principal Investigator: B. Sweet, Ph„D.s H. Kitchener, MoS.W.

Investigators: Fo Redl, PhoD. ^ Bansanaj Ph. Do, S. Berman, M.D.
Ro Louries M.D.

erating Units: None

Man Years (calendar year 1957):
Total: 3 1/4

Professional: 1 3/4
Other: 11/2

Patient Days (calendar year 1957)
375

Project Description:

Objectives ;

To define a variety of therapeutic principles and techniques which
seem to be particularly Indicated for hyperaggressive children within
the setting of intensive individual psychotherapy. To explore a variety
of therapeutic issues which arise when psychotherapy is undertaken in
conjunction with intensive residential treatment; these include choice
of play materials at various stages of treatment, handling of trans-
ference and counters-transference problems peculiar to this situation,
the eliciting and utilization of fantasy material, the handling of
¥arious forms of resistance, etc. Problems of locating and identifying
transference phenomena in the life space and communicating them to the
therapist will be explored. The types of transference phenomena
observable at various stages of treatment are being recorded.

Methods Employed;

In the course of seeing six children three to four interviews per
week for two or more years, experiences are recorded around specific
issues. For example, during the past year experience has been gained
in handling various forms of resistance to coming to the therapy play-
room. This has included experimenting with various policies and roles
(for therapist and for life space personnel) set up to deal with this
resistance.

Patient Material;

Children

No,
6

Average Stay (Days)
365

53 -

Part A. M-CR(C)-3ipage 2

Major Findings ;

(1) Foremost among these is the broad observation that, contrary to
beliefs popular in the field, individual psychotherapy with the hyper-
aggressive child is more like than unlike psychotherapy with other cate-
gories of disturbed children. As in all cases where ego development is
weak or distorted, there is, especially in the early phases of treatment,
greater necessity for the therapist to function as an auxiliary ego for
the patient than is true in more classical neurotic cases; this, however,
is no more than a difference in emphasis, since it is well known that
child therapy always requires that the therapist play a partially educa-
tional role more than does adult therapy, by virtue of the fact that no
child's ego is fully formed.

(2) A second impression is that the therapeutic process, while
similar in course, is more prolonged than is the case with other kinds
of children,

(3) Third, while limit setting plays an important role in all child
therapy, it becomes particularly significant in treating children whose
most crucial problems lie in the area of control, fear of loss of control,
and distrust of the adult's dependability and integrity in controlling
both himself and the child. Since fear of seduction (in both the narrow
sexual meaning and the broader sense of seduction to impulsivity of any
kind) plays a major role in the psychodynamics of these children and
seductive experiences often figure prominently in their history, it
becomes a vital problem for the therapist to avoid confusing the wish

to demonstrate his benevolent intent with seduction. Particularly in
the earlier, more disorganized phase of therapy (which may be prolonged
for many months and even a year or more), it may be a disquieting ex-
perience for the therapist to find himself responded to as though he
were a dangerously hostile figure, and it is easy to become unwittingly
seductive in the effort to correct this projection.

(4) Many counter -transference problems also have become apparent
in this project. While the particular content of the counter -trans-
ference will no doubt vary with the personality of each therapist, all
those participating here have had to deal with feelings aroused by the
need to meet such explosive barrages of raw destructiveness and with
those aroused by the underlying oral demandingness of such children,
whose own fantasy certainly seems to be one of eating up the therapist.

(5) Impressions are beginning to emerge as to specific interpre-
tive techniques. In the earliest phases of treatment, when these
children communicate largely through gross motor behavior and acting
out, it seems necessary to accompany the traditional resistance inter-
pretations with fairly concrete behavioral responses to the child; it is
as though actions speak loudly while words at best mean little or, at
worst, signify oral sadistic attack to this kind of child. Later, as
the child moves into a phase of more symbolic communication, the inter-
pretations also seem to need to shift; at this phase communication seems
best to be achieved by corresponding symbolic gestures on the part of

- 5^ -

Part A. M-CR(C)-3, page 3

the therapists much as one answers a schizophrenic child's fantasy communi-
cations within the framework of his own fantasy rather than by interpretive
translation. It seems only to be in the more advanced phases of therapy,
as the child becomes able to verbalize directly about himself, that the
weight of the interpretive effort can be shifted to direct discussion of
the child's problems and their origins and remain effective. While all
three levels of communication are present throughout therapy, there does
seem to be some difference in their relative usefulness at various phases.

While it is premature to state findings about the effectiveness of
therapy before it is completedj it is our impression thus far that psycho-
therapy is possible with such children, at least within the context of
residential treatment. Issues such as the use of the ward milieu
(see CR(C)=1) and the use of the life space interview (see CR(C) -5) in
handling problems of therapy and resistance to therapy within a residential
setting are being investigated. If impressions as to the possibilities of
psychotherapy with such children were to stand up with the passage of time
it would be a most significant finding in view of the widespread doubt
within the field.

Significance to NIMH Research:

Since these children are rather infrequently given prolonged intensive
psychotherapy in the communityj exploratory observations of the type
described above are indicated at this stage of our knowledge. Hopefullyj
such experiences may be helpful to other clinicians who are beginning to
treat delinquents with the recently developed community support.

Proposed Course of the Project;

This area of inquiry is part of the on-going program of the
Laboratory.

Part B included Yes X No.

Serial No. M-CR(C)-3, page 4

PHS-NIH
Individual Project Report
Calendar Year 1957

Part B; Honors, Awards, and Publications

Publications other than abstracts from this project:

Gordon, G., 6e Siegel, L. The Evolution of a Program of Individual
Psychotherapy for Children with Aggressive Acting-Out Disorders in
a New Residential Treatment Unit. American Journal of Ortnopsychiatry.
Vol. 27, Noo 1, 59-68, January, 1957.

Honors and Awards relating to this project;

56 -

PHS-WIH
Individual Project Report
Calendar Year 1957

Serial No. M-CR(C)-4

1. Child Research Branch

3o Bethesda, Maryland

Part A,

Project Title; Studies in Learning Disabilities in Hyperaggressive Children
Principal Investigator: R. Newman, Ph=D,, So Jacobson, M.A.
Other Investigators: Jo Glaser, B.Ao, C. Faegre, B.Ao
Cooperating Units: None

Patient Days (calendar year 1957):
537

Man Years (calendar year 1957):
Totals 2 1/2

Professional: 2
Other: 1/2

Project Description:

Objectives ;

To investigate the nature of the learning disturbances of hyperag-
gressive ehildren and to develop techniques for their assessment as well

as for their cure.

More specifically: To arrive at a sharper differential diagnosis
between those disturbances of learning or school behavior which are
intimately linked with the basic pathology of the children and those
which are a secondary result of learning failure or behavioral learning
resistances or motivational blocks.

To isolate the variables that go into making a specific learning
sit^iation eg© supportive enough so that motivation for learning can
develop and learning process can unfold and to isolate those variables
which can be expected to be toxic or at least non-supportive to the ego

tasks involved in the learning process.

To produce instruments as well as develop techniques which can
be applied beyond the experimental setting and beyond the group of children

on whom the study is being done.

Methods Employed;

One of the studies focused especially on (1) the problems of moti-
vating ehildreti to maintain interest in learning projects, (2) the
type of play equipment and activity choice that is needed in relation to
the degree of regression or developmental lag exhibited by the child,

(3) the relationship of certain specific learning deficits which appear

commonly in' the hyperaggressive childj such as inability or unwillingness

to subtract, the fear of reading, etc., and other aspects of psychopathology.

57 -

Part A. M-CR(C)-4, page 2

such as anxiety laden fantasies, etCo (4) To observe and explore the various
intervention techniques needed in order to deal effectively with the child's
problem in learning as well as with his behavioral manifestations during the
learning process.

Besides the actual experimentation carried on with our child patients in
relation to above named objectives, various sources of records were used in
measurements for school participation. School records, sampled over a period
of 27 monthSj were rated on this measure, rater reliability being checked by
use of judges not connected with NIMH. Changes in the school behavior of the
six children were studied by comparing ratings for two halves of the sample
by time.

A modification of the Critical Incident Technique was used to develop
categories of factors affecting school adjustment. School incidents for
each child were classified into these categories, after rater reliability
was checked.

Clinical analyses were undertaken on the learning problems of each child,
and on special sources of anxiety in both children and teaching staff with
respect to the learning situation.

With the new group of child patients on 4 East, methods utilized focus
around the following:

1„ Planned variations of school program to provide example-^

of behavior in different settings (individual, group; formal, in-
formal); with different materials (verbal, manual -^manipulative, etc.)
and different content.

2. Participant and non-participant observation.

3. Analysis of observations to isolate variables and to develop !
systematic methods of describing the variables.

Patient Material;

No. Average Stay (Days)
Children Male 6 365

Children Male 7 75

Major Findings;

1. A behavior Rating Scale, which can be used reliably in judging
school incidents for adjustive behavior, was developed.

2o Over the period of 27 months the children changed significantly

in the direction of better school adjustment.

3. Categories for describing clinical factors accounting for school
behavior and behavioral change were developed, and it was demonstrated
that they could be used reliably in judging school incidents. The clinical I
factors in the learning situation can be subsumed under three major

categories:

- 58 - !

Part A. M-CR(C)=4, page 3

1. Self (self picture; inner pressures and forces; infantile
needs and frustrations)

2= Relationships (to adults; to peers)

3. School (subject matter, methods^ material; teacher personality)

Patient Material; No. Average Stay (Days)

Children Male 6 365

Significance to NIMH Research;

1, The instruments developed here can be used in other studies of
learning disturbances with other groups of children.

1„ The juxtaposition of a therapeutic school program to intensive
residential treatment and psychotherapy is perhaps unique in the field
and presents unusual opportunities for sifting out those therapeutic
issues which are best dealt with in school and those which are common to

all three settings.

Proposed Course of the Project;

Further investigation^ refinement, and broadening of these methods,
their collation with other data from school and from other sources.

Part B included Yes X No.

59 -

Serial No. M-CR(C)-'!i, page 4

PHS-NIH
Individual Project Report
Calendar Year 1957

Part B; Honors, Awards, and Publications
Publications other than abstracts from this project:

Honors and Awards relating to this project:

Newman, R, G. A Study of the Difficulties of Hyper-aggressive, Emotionally
Disturbed Children in Adjusting to School and in Deriving Satisfying
Learning Experiences from School. Ph.D. Thesis, University of Maryland,
June, 1957.

Serial No. M-CR(C)-5

lo Child Research Branch
PHS-NIH 2,

Individual Project Report 3. Bethesda
Calendar Year 1957

art A.

Project Title: Studies in Life Space Interview Strategy and Techniques

Principal Investigator: F. Redl, Ph.D., H, Kitchenerj MoS.W.

Other Investigators: A.T. DittmanRj Ph.D., J. Noshpitz^ M.D., H.L.Raush, Pi^.D
P.M. Spielman, M.D., J. Vernick, M.S.W,

Cooperating Units: None

Man Years (calendar year 1957): Patient Days (calendar year 1957);

420

Total

Professional

Other

1 3/4

1 1/4

1/2

Project Description:

Ob|ectives:

Psychiatric In-Patient treatment of children necessitates the use of
interview techniques not only during specifically designed Therapy Sessions
of the child with his doctor, it becomes important to add interviews carried
on by other adults in the hospital or residential setting^ in high proximity

to the events of the day.

We designated this type of interview by the term Life Space Interview
and approached our study of this technique with the following objectives
in mind :

(1) To explore the variety of situations that suggest the use of
Life Space Interviewing as a therapeutic measure.

(2) To subject the technical problems that emerge in this type of
work to am orgarsized scrutiny as to the in^>act of the setting^ the issue,
the objectives of a given interventiori, the specific pathology of the

child as well as other factors in the surrounding milieu.

(3) To collect well recorded illustrative samples for all those
aspects from the sum total of life space interviews recordec^ and to

Work toward a well documented technique of Life Space Interview-
ing similar to the rigorous concept of technique that has been developed
over the years in the more well known style of psychiatric interview
therapy in the office setting.

Methods employed;

Over 500 records of Life Space Interviews at varying phases of the

- 61

Part Ao M-CR(C)-5, page 2

therapy of our child patients have been gathered. Some of these have been
recorded post-sltuatlonally by the interviewer, others have been recorded
by means of stimulated recall — the Interviewer reporting to a trained
researcher following the episode.

Through individual exploration and group discussion of these materials
categories have been devised which shall be used as basis for the coding of
Interview materials, and part of the material has been coded.

Using Interview notes, a preliminary empirical analysis was made com-
paring Interviewer techniques In Life Space Interviews with Interviewer
techniques in Play Therapy Interviews. Interviewer techniques were coded
Into 25 categories under seven major headings.

Data collection as well as conceptual exploitation of the data so
far gained for the development of a theory and technique of the Life Space
Interview has been continued in both settings, the Ward as well as the
Residence.

Patient Material: No. Average Stay (Days)

Children Male 7 ^5

6 365

Major Findings;

Miong the preliminary findings, presented at the National Conference
for Orthopsychiatry in 1957 are the following:

(1) The variety of purposes for which treatment staff uses Life
Space Interview techniques can be ordered around the following sub-goals
which seem to emerge most frequently in in-patient treatment of children
with aggressive disturbances:

A) Clinical Exploitation of Life Events, under which categories
distinct from each other are temporarily singled out under the
following labels: (1) reallty-rub-in, (2) symptom estrangement,
(3) revltalizatlon of numb value areas, (4) new tool interpre-
tation, (5) manipulation of the boundaries of the self.

3) Emotional First Aid on the Spot with subcategories ten^orarily
classified under the following code labels: (1) drain-off of
frustration annoyance (2) communication maintenance in moments
of relationship decay, (3) support for the management of panic,
fury and guilt, (4) regulation of behavioral and social traffic,
(5) umpire functions in decision crises and in cases of loaded
transactions .

(2) In terms of exploration of Criteria for the indications or counter-
indications of holding Life Space Interviews in a given situation, and of
the choice of a specific technique, the following 6 sub-categories of areas
of major relevance have emerged: (1) central theme-relevance, (2) ego
proximity and issue clarity, (3) role compatability, (4) mood manageability,

(5) timing (6) iitpact of terrain and props. ...

- 62 -

A. M-CR(C)-5, page 3

(3) On the basis of preliminary work a number of similarities were found
between techniques employed by interviewer in Life Space and in Play Therapy
Interviews. Among the differences in the techniques employed in the two types
of interviews were the following: (I) as expected, play is used less frequently
i)jt Life Space Interviewer r; (2) techniques of control were used more frequently
by Life Space Interviewers; (3) while there were no differences in the amount
or specific techniques of interpretation used in the two types of interviews,
there were differences in the direction of interpretation: In Play Therapy
Interviews interpretations were directed more frequently toward impulse, whereas
in Life Space Interviews interpretatioms aimed relatively more frequently
toward resistance and defense.

All these findings are based on the first few years with our special
group of child patients and in the earlier phases of their individual and
milieu therapy , Expansion of data collection as well as concept-reformula-
tion is of course contemplated bsfore more final conclusions can be drawn «
The abundance of rather untraditional tkEminology for labelling our tempo-
rary findings and categories must be understood out of the fact that this is
quite a new field of exploration, and that more static technical terminology
has not yet been developed o In part, it also constitutes the conviction on
the side of the investigators that a premature forcing of newly emerging
concepts into all too rigidly technical terms might lead into a premature
theory-freeze which we are eager to avoid.

Significance to NIMH Research;

life space interview is a relatively unexplored psychotherapeutic
technique which holds considerable promise for future employment in treat-
ment institutions if it can be further developed.

Proposed Course of the Project:

This is a continued project.

Part B included Yes X No,

63 =

Serial No. M-CR(C)-5, page 4

PHS-NIH
Individual Project Report
Calendar Year 1957

Part 6: Honors, Awards, and Publications

Publications other than abstracts from this project:

Redl, Fo Strategy and Techniques of the Life Space Interview. American
Journal of Orthopsychiatry, (in press), 1957.

Honors and Awards relating to this project:

6k -

Serial NOo M-CR(C)=6

1 . Child Research Branch
PHS-NIH 2,

Individual Project Report 3. Bethesda, Maryland
Calendar Year 1957

Part Ao

Project Title; Studies of Change in Hyperaggressive Children During the
Course of Residential Treatment

Principal Investigator: Ho RaMsh, PhoD

Other Investigators: F, Redl, PhoD.s Bo Sweet, PhoD,, T. Taylor^ MoAo,
Ao Dittmannj, PhcDo

Cooperating Units? None

Man Years (calendar year 1957): Patient Days (calendar Year 1957):
Total: 2 1/2 170

Professionals 1 1/2
Other : 1

Project Descriptions

iectivess

To develop concepts of improvement that are clinically relevant and
sophistieatea, but go beyond the listing of dropped out pathology o We hope
to arrive at descriptions of the functioning of the intact ego and of other
personality characteristics commonly associated with a state of Mental Healtho
We aim at descriptions as specific and as sharply focused as concepts for the
description of pathology o

To develop methods for the assessment of change in behavior
patterns of children in a wide variety of aspects as well as settings and
situations such as children would be expecfeed to be exposed to in in-patient

residential therapy.

To develop critssxa for the differentiation of change in general,
as compared to the assessment of therapeutic movement as a result of exposure
to treatment, and

Assess the actual changes that occurred in these particular child

patients during the various phases of their therapy o

Existing recordings of all phases of the patient's therapy and
life eaq^erieioices were studied and compared in order to find where traceable

patterns of change can be seen to emerge.

(2) A series of studies was undertaken with the special purpose of
foeusing on various aspects of change:

- 65 -

Part Ao M-CRCC)-6s page 2

(a) Systematic observations in a variety of settings and coding

of individual interactive behavior d«iring two treatment phases.

(B) Systematis observations done on a control group of children,
for age, IQs racSs so©io=®e0nomie status c

Categorisation derived from detailed descriptions contained
in clinical secords and case conference materials.,

Periodic interviews and collections of clinical incidents
from Child Care Staff o

(«) Eaqjloratory interviews with child care and therapy staff
directed at staff's concept of ishange and improvement and matched
with their actual statements about observed functioning of their

Patient Material;

No^ Average Stay (Days)

Children Male (patient) 6 365

Children Male (control) 6 6

Major Findings;

5s in behavior interaction patterns. From the investigation
of two series of observations made a year and a half apart, the following
major conclusions can be drawn;

(a) The interpersonal behavior of the children has changed con-
siderably in the course of treaiSmento

(hi Over the period there is a decrease in inappropriate behavior
toward peers » Most children show a trend toward more friendly peer
relati©!

(e) Changes in relations with adults are much more marked than
(gh&nges in relations with peers o Hostility toward adults decreases
considerably o Particularly, there is a decline in hostile^dominant
beh&vior and an increase in friendly^passive behavior toward adultSj
with a major increase in trusting;, dependent expressions., Inappro-
priate behavior also decreases considerably. The distinetion between
behavior toward peers and behavior toward adult® gets sharpened „

behavior that the children evoke from others shows
corresponding changes. Children are less hostile than they were in
response to a particular child. Adults show an increase in the pro-
portion of friendly, giving, supportive behavior with the children.

(e)- Different behavioral settings produce different qualities

of interpersonal behavior o

CI) There is an interaction between person and situation that goes

^ 66 ^

Part A, M"CR(G)-6s, page 3

beyond what either contribute independently to our ability to predict

behavior o That is, although there are generalizations, settings also
operate differentially for different children.

The effects of settings differ in the two phases. Tenta-
tively, it would seem that in the later phase of treatment the situa-
tion comes to play a greater role as a determinant of behavior than
it did previously o

Changes in interpersonal behavior appear more readily in
some settings than in others.

(i) A paper on some of these findings was presented at national
meetings and is in process of publication. Data analysis is near
completion and another paper is being worked on.

(2) Concepts of Improvement »

(a) Formulations of a sharpened up and clinically relevant con-
cept of improvement are undergoing continuous change as our study
proceeds, and temporary findings are as yet too volatile to be
reported this year.

A siilot study for the collection of data on the staff's
concept of improvement as related to our present child patients is
in a state of partial completion. Preliminary impressions from the
data indicated that the children have improved in a number of areas.
Especially, hostile interactions between children have decreased
and acceptance by the children of staff interventions has gone up.
Other details about improvements are too varied from child to child
or require too much background data to be summarized here.

Significance to NIMH Research;

With some modification findings and methods should be applicable to
other settings s Adult psychiatric in-patient settings^ school situationSj
etc„ The area of change and -improvement is critical for psychiatric and
psychological research in generals

Proposed Goairse of Project;

St ion aiad write-up.

(2) Completion of coding and analysis of control data; further

observations of patient grQ)ep in new residence.

(3) Completion of p^er.
Farther work toward development of categorization scheme.

Part B included Yes No X

„ 67 -

Serial No. M-CR(C)-7

1 . Child Research Branch
PHS-NIH 2.

Individual Project Report 3o Bethesda,, Maryland
Calendar Year 1957

Part A.

Project Title: Interaction Patterns of Normal and Hyperaggressive Children

Principal Investigator; Allen T. Dittmann, PhoD. (Psychology),
D«Wo Goodrich, M«Do (Psychology)

Other Investigators: None

Cooperating Units: None

Man Years (calendar year 1957): Patient Days (calendar year 1957):

None None

Project Description:

Objectives;

(a) To develop methods of studying interaction patterns of children in a

treatment wardo (b) to compare interaction patterns of normal and disturbed

children in the same setting.

Methods Employed;

Short sample observations were taken of groups of children in specific
situations on the ward and in the field, situations selected for their con=

duclveness to nurturing and limit-setting adult behavior. Observations
were recorded on tape by intensive interviewing of the observer: the
recordings form the basic data of the research. These protocols were coded
for interactions between children and interactions involving children and

adul ts .

Patient Material ; No. Average Stay (Days)

None this year.

Major Findings ;

Patterns of interaction of the two groups showed differences such as
might be expected; Less inappropriate behaviorj less overt aggression
among the normals, more real leadership; greater dependency based on
trust toward adults. Adult behavior toward the children includes greater
freedom with the normals in expressing affection setting limits, while
with the disturbed children adults are more caution in their expressions.

Significance to NIMH Research:

The method can be used in descriptive studies where group differences

- 68 -

Part A, M-CR(C)-7, page 2

are the focus., The method's disadvantages were clearly shovm by the ex"
perienee of this study: Recalling everything that goes on with six
children in even a very short observation is impossible, even with in-
tensive interviewing of the observer. Since the data for this study were
collected the observational method has been refined to get more complete
information on one child in one observation, so that sequences of inter-
action can be followed. See M-CR(C)-6,

Proposed Course of Project;

A paper is in preparation.

Part B included Yes No X

„ 69 »

Serial No, M-CR(C)-8

1. Child Research Branch

3. Bethesda, Maryland

PHS-NIH
Individual Project Report
Calendar Ydar 1957
Part A,

Project Title; Research on Anger in Interpersonal Situations

Principal Investigator; Do Kaplanj MoS«Wo (resigned 9/21/56)o
DoWo Goodrichj MoDo (Psychology),

Investigators; To Taylor, M,Aos F, Redl, PhoD.

Cooperating Units : None

Man Years (calendar year 1957); Patient Days (calendar year 1957):

Nome None

Project Description;

Objectives ;

To explore descriptive concepts for analysis of anger episodes in inter-
personal situations within this residential treatment center ■ This study
proposed to develop a theoretical model including categories to describe the
various phases of an anger episode.

Approximately 300 anger episodes have been collected by non-partici-
pant and participant observers » A preliminary analysis of these has led
to development of a model for the anger sequence in interpersonal situations.

Patient Material; No, Average Stay (Days)

None this year

Major Fimdiifflgs ;

With the aim of developing a schema for the analysis of provocative
techniques used in anger episodes, some 50 incidents were examined in detail,
and preliminary attempts at codings were made, A total of 15 over-all head"
ings and 53 sufo=sategorie8 of provocative techniques were described, and

examples were given.

Significance to NIMH Research;

One of the major forms which symptomotology takes in hyper aggressive
children is outbursts of aggression against others. By means of this study

- 70 -

Part_A^ M-CR(C)-8, page 2

an important aspect of the psychopathology of many delinquent children may be
clarified.

Proposed Course of the Project;

A paper has been published and the project is discontinued.

Part B included Yes X No.

- 71

Serial No. M-CR(C)-8,page 3

PHS-NIH
Individual Project Report
Calendar Year 1957

Part B; Honors, Awards, and Publications

Publications other than abstracts from this project:

Kaplan, Do, & Goodrich;, GoWo A Formulation £or Interpersonal Anger,
American Journal of Orthopsychiatry, Vol. 27, No. 2, 387-395, April, 1957

Honors and Awards relating to this project;

- ?2 -

Serial No. M-CR(C)-9

1. Child Research Branch
PHS-NIH 2.

Individual Project Report 3. Bethesda, Maryland
Calendar Year 1957

Part A.

Project Title: Staff Values Concerning Therapeutic Interventions with
Hyperaggressive Children.

Principal Investigators: D. S. Boomer, Ph.D. (transferred to Laboratory of
Psychology), D. W. Goodrich, M. D. (Psychology)

Other Investigators: None

Cooperating Units : None

Man Years (calendar year 1957): Patient Days (calendar year 1957):

0 0

Project Description:

Objectives;

To survey the matrix of common assumptions and therapeutic values which
underlie the therapeutic behavior of the staff of Children's Unit, NIMH.
To formulate these generalizations in such a way as to maximize their use-
fulness for research and training.

Methods Employed;

The technique utilized was the so-called "critical incident" method.
Each staff member was regularly interviewed by one of the investigators
over a 3-month period, to elicit accounts of actual therapeutic inter-
ventions with children, engaged in or witnessed by the staff member. The
incidents thus collected were then categorized with regard to natural
dimensions which emerged from the data.

Patient Material: No. Average Stay (Days)

None this year

Major Findings:

^proximately 240 critical incidents were collected and categorized.
The final groupings are 38 in number, distributed among four superordi-
nate headings :

A. Promoting personality change by helping child to learn to view
his own behavior evaluatively .

B= Promoting ego growth.

- 73 -

Part A. M-CR(C)-9, page 2

G. Supporting existing ego controls,

D. Managing one's own conduct as a staff person.

An interim report has been prepared presenting these categories
together with a selection of critical incidents illustrative of each.
A paper was presented at the American Orthopsychiatric Association.

Significance to NIMH Research:

(1) The clinical staff of the Children's Service has been furnished
with our findings to make use of as they see fit, in research, or train-
ing of new personnel .

(2) Our method has been demonstrated, and shared with other NIMH
investigators. This method, adapted from an industrial psychology
tool, seems to be a useful way of formulating concepts concerning a
complicated clinical operation.

Proposed Course of the Project;

Publication of material.

Part B included. Yes No X

74 -

PHS-NIH
Individual Project Report
Calendar Year 1957

Serial No. M-CR(C)-10

1 . Child Research JBzanoh

3. Bethesda, Maryland

at A.

Project Title: A Study of behavior Reporting by Child Care Workers
Principal Investigators: B. Iflund, Ph.D., D. W. Goodrich, M.D. (Psychology)
Other Investigators: None
Cooperating Units: None

Man Years (calendar year 1957)
0

Project Description:

Patient Days (calendar year 1957);
0

Objectives :

To determine (1) the consensus of expectations by the staff concerning
what should be included in the daily descriptive notes made by counselors
on patients" overt behavior; (2) the extent to which such expectations
are met subjectively; and (3) the extent to which these notes in reality

actually achieve these expectations.

Methods Employed:

Eleven child care workers and twelve clinicians ranked seventeen
categories of items whose frequency of occurrence in a large sample of
behavior notes had actually been determined. Rankings were obtained
which revealed the subjective judgment of the child care workers and
clinicians concerning what is contained within the notes as well as
rankings which reflect what would be most desirable to be in the notes. A
comparison between what is expected and what is believed to be present was
used as a measure of satisfaction or dissatisfaction. Since actual fre-
quencies are also available one can determine further the extent of aware-
ness of what is in the notes on the part of those reading them (the clini-
cians) and those writing them (the child care workers).

Patient Material :

None this year

No,

Average Stay (Days)

Tests of concordance within each group showed the ai^ount of agreement
to be significant at better than the .01 level. Thus we are justified in
considering the combined results of each group.

75 -

Part A, M-CR(C)-10, page 2

Correlations were determined between the following variables: Actual
rank order of frequency, the clinician's "Ideal" order, child care workers'
"ideal" order, clinicians' concept of what is in the notes, and child care
workers' concept of what is in the notes. Eight of the ten correlations
carried out were significant.

Factor analysis of the above correlations yielded two factors which
account for the major portion of the variance. One of the factors is
defined by the clinician's ideal; the other factor by both what the
clinicians and child care workers think is actually present. In reality
the notes themselves have equal loadings of both factors.

Significance to NIMH Research:

The statistically significant results obtained seem to suggest that
further studies of the perception of adults in this setting may be
profitably carried out in relation to the behavior reports of the staff.

Proposed Course of the Project:

Publication of the paper

Part B included Yes No X

- 76

NATIONAL INSTITUTE OF MENTjil HEALTH

Clinical Investigations
Laboratory of Psychology— Section of the Chief

BUDGET SHEET

Estimated Ohiigations for Fy 19*^8
Total: $250,971
Direct: $110,9^1

Reimbursements: $li»-0,030

Projects included: M-P-C(C) 1 through M-P-C(C) 13

Serial Wo. M-P-G-(c)-l

1. Laboratory of Psychology

2. Section of the Chief

3 . Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Administration of Laboratory of Psychology

(a Joint Operation of the Clinical Investiga-
tions and Basic Research Programs)

Principal Investigator: David Shakow

Other Investigators: None

Cooperating Units : None

Patient Days : none

Man Years :

Total :

1.70

Professional

: .70

Other :

1.00

Project Description:

Objectives: A. To achieve an administrative structure which
vill provide the optimum of communication with (l) Chief of
the Laboratory;, (2) among members of a section, (3) within the
Laboratory as a whole, (h) and with other investigators and
units in NIMH and other Institutes ; and at the same time result
in the' least interference with the objectives and time for
research of individual investigators.

B. To complete organization of Laboratory.

Methods Employed: A. To achieve optimal administrative
structure: Organization into a 'reasonable number of sections,
conduct individual conferences with investigators, hold the
minimal necessary number of meetings with individual section
chiefs and with the group of Section Chiefs in the Laboratory
as a whole.

B. To complete the organization: Recruitment of
additional personnel.

- 77

Serial JSo. M-P^C-(C)-1
Page 2.
Part A: Project Description (Cont'd)

Major Findings:

1. Personnel by Sections (Professional):

Clinical Investigations Program

Section of the Chief

Shako-w, David (Chief)

*Bergnian; Paul

Dittmann, Allen

Kendig, Isabelle

Rosenthal^ David
■5^ahn; Theodore

Section on Child Development
Bayley, Nancy (Chief)
Bell, Richard Q.
Gewirtz, Jacob L.
Rheingold, Harriet
Schaeferj Earl S.

Section on Personality

Parloff, Morris (Acting Chief)

Boomer. Donald
*Handlon, Joseph
**Kelman, Herbert
^VJaldman, Marvin

Basic Research Program

Section on Aging

Birren;, James (Chief)

Bondareff, William

Botwinick, Jack

Jerome; Edward A.

Streicher, Eugene

Weiss ; Alfred

*Kay, Harry (Visiting Scientist)

Section on Animal Behavior
Rosvold; H. Enger (Chief)
Mishkin, Mortimer
Mirsky, Allen

*B&ttig; Karl (Visiting Scientist)
*Bush, Elinore (WIMH Fellow)

- 78 -

Serial No. M-F-C-(C)-1

Page 3 •

Part A: Project Description (Cont'd)

Major Findings (Cont'd)

2. Program of conferences held by Chief of Laboratory

3. New Section -- Limbic Integration -- jointly with Labora-
tory of Neurophysiology^ iras organized with Dr. Paul MacLean
as Chief.

Proposed Course of the Project:

1. Continuation of attempt to recruit Section Chiefs for
Section on Personality^ and Perception and Learning. Although
for the Section on Perception and Learning serious negotiations
were under V7ay last spring and summer with a very prominent psy-
chologist for this position, his decision was finally in the
negative because of space limitations — we could offer him so
much less than he already had in his university laboratory. ¥e
appear now to be more fortunate in relation to the Chiefship

of the Section on Personality. Negotiations are tinder way with
a very promising person and it seems likely that we shall be
able to make the final arrangements early next year for a
reporting date sometime during the summer of 1958.

2. Because of certain present limitations in our own Clinical
Center facilities , in some areas of our research, notably Child
Development; it has been necessary to attempt to find settings
outside this building. Some arrangements have already been made
and othei's are in process of being made to find satisfactory
settings in the Washington area for carrying out the planned
resea^rches . The hope is that the Clinical Center will eventu-
ally be able to furnish some of these facilities.

3. The coming year should see more involvement of the members
of the Laboratory in collaborative projects with the Adult
Psychiatry Branch, the Laboratory of Clinical Science, and the
Clinical Neuropharmacologlcal Research Center at St. Elizabeth's.

Part B included: No.

Serial No. M-P-C-(C)-2

1. Laboratory of Psychology

2. Section of the Chief

3. Bethesda

PHS-WIH
Individual Project Report
Calendar Year I957

Part A.

Project Title: The Analysis of the Psychotherapeutic Process:

The cumulative information derived from repeated
viewing of complex material.

Principal Investigator: David Shakow

Other Investigators : None

Cooperating Units : None

Man Years : Patient Days : None

Total: 1.0

Professional 1.0

Other: .0

Project Description:

Objectives: To determine what additional relevant information
necessary for the understanding of the therapeutic process is
derived from successive viewings of a film of a psychotherapy
session^ and whether there are major differences between
active and passive analytic approaches to data of this type.
(Such a study is important because a major problem arises as
to how complex data of this kind best lends itself to significant
analysis. )

Methods Employed: The film for one psychotherapeutic session is
divided into four sections. Eeh section is viewed repeatedly
(15 times) under one of four sets of conditions: active attitude/
once per day; active attitudes/all 15 in one day successively;
passive, free-floating attention/once per day; passive free-
floating attention/all 15 in one day successively. This pilot
experiment is being carried out as a preparation for deteirmining
the design of the analytic process to be followed in the major
project on the analysis of the therapeutic process. The
experimenter dictates into a recorder as much as he can

80 -

Serial No. M-P-C-(c)-2, page 2

Part A (Cont'd)

Methods Employed (Cont'd)

both during the running of the film and immediately afterwards
with regard to content process, relationship, cues for all of
these, etc . , and a comparison is subsequently made of the kinds
of material which is added at successive viewings .

Major Findings: No findings as yet. The study is in its
early stages. Apparatus problems developed which limited the a-
mount of data collected.

Significance to the Program of Mental Health Research: This
is one of a series of studies directed at solving certain
methodological problems in earr;ji,ng out research in the field
of psychotherapy. The importance of this general area for
research is considered in Project Description Sheet M-D-(C) 1,
titled, "The Analysis of the Psychotherapeutic Process,
particularly the Psychoanalytic Process."

Proposed Course of Project: Depending upon the results from
tne completion of the first experiment, further experiments
will be set up with additional subjects and with more rigorous
design and categorizations. The acquisition of a new projector
should make possible the prosecution of this project with
greater facility.

Part B included: No

- 81 -

Serial No. M-F-C-(C) 3

1. Laboratory of Psychology

2. Section of the Chief

3. Bethesda

PHS-EEH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Psychology of Schizophrenia

Principal Investigator: David Shakow

Other Investigators: David Rosenthal; Theodora Zahn, Joseph
Handlon, Marvin Waldman

Cooperating Units : None

Man Years:

Total :

1-5

Professional:

Other :

1.0

Patient Days : None

Project Description:

Objectives: To bring together a large body of experiinental
data on schizophrenia collected over many years into a series
of monographs developing a theory of the psychology of schizo-
phrenia. A detailed analysis of the body of experimental data
already available and of new data to be gathered on our wards
here and at St. Elizabeth's (see Project Description M-P-C-(c) ]
will be carried out to test certain hypotheses as to the
importance of difficulties during the period of preparation
for response in schizophrenics.

Methods Employed: In relation to the already accumulated
material; ranging in complexity from studies of the latent
time of the patellar tendon reflex to studies of social
response; the usual methods of sta-oistical analysis will be
utilized. Some new developments deriving fi-om studies of
PhillipS; Rodnick and Garmezy regarding good and poor prognosis^
and certain other studies on "reactive" as opposed to "process"
schizophrenics will be utilized for 'further differentiation of
the material. Several related studies are being carried out
on senescent and brain damaged subjects and they will be used
in this study for control purposes.

Patient Material: For this particular study no patient material
will be required. The data are already collected.

- 82 -

Serial No. M-P-C-(c) 3, page 2

Fart A (Cont'd)

Major Findings: Some of the major findings from this material
have already been reported hy the proponent and his former
colleagues in an extensive series of papers on the psychology
of schizophrenia. The present project is directed at working
up as yet unpublished material and reworking the total
material in the context of a more carefully delineated theory.

Significance to Mental Health Research; Despite the fact
that schizophrenia is the major disease group of mental dis-
orders and accounts for half the occupied beds in mental
hospitals; little advance has been made in dealing with this
problem. A major defect undoubtedly has been in the relatively
unestablished theories proposed to account for this complex
of disorders. It is hoped i:hat the proposed study will con-
tribute to an understanding of the underlying factors.

Proposed Course of Project: Continuation of analysis of
material and tying it in with experimental findings of
current experimental studies.

Part B Included: No.

- 83 -

Serial No. M-P"C-(C)-U

1. Laboratory of Psychology

2. Section of the Chief

3. Bet>iesda

PHS-EIH

Individual Project Report

Calenda.r Year 19.57

Part A.

Project Title : Linguistic Study of Emotional Expression

Principal Investigator: Allen T. Dittmann

Other Investigators : Lyman C. Wynne

Cooperating Units : Adixlt Psychiatry Branch

Man Years (calendar year 1957) ; Patient Days (calendar year

1957) :
Total t A
Professional: .2
Other: ,2

Project Description:

Objectives ; This project is an attempt to find ways of coding
speech in order to identify disturbances which may be used as an
index for psychological di st'orbance .

Mg.thods Employed: Techniques of linguistic analysis developed by
x'i'ager and Smith as applied to psychotherapeutic interviews.

Major Findings: (a) Pitch, stress and junct'^ara patterns. These
can be coded with high reliability^ but do not in themselves re-
late to outside judgments of distiabaace. Judgoients of inappropri-
ateness of juncture patterns could be related to disturbance, but
the relationship was not strong enough, to make this a useful source
for indi-vidual prediction. Subseq,uent attempts to make judgments
of appropriateness of entire phrases based on the configuration
of pitchy stress, junetxire all t&icen together, proved not to be
relstes^ble to disturbance. This finding leads us to believe that
the meager positive resiilts from appropriateness of juncture
patterns alone were the resiilt of capitalization on chance. Our
conclusion is that these inicro].ingaistic phenomena are too closely
related to the sysitax of language to be carriers of emccional com-
munications.

(b) Eesitations and "breaks" in speech. These can be coded
with fairly high reliability, but psychologic^?,! states other
than dist\irbanee or anxiety affect these phe.aomena. It is
impossible to differentiate, for example, betffean anxiety
e;nd meditative reflection using these codings. It. may be
that other systems, based partly on content, will do this job

- Sh -

Serial No. M-P-C- (C)-i)-page 2
Part A. Project Description Sheet (cont'd.)

better. See, for example, the project, "Development of an Ego-
Integration Conceptual Ss^stem for Studying Psychotherapy", of
Goodrich and Boomer in the Section on Personality of this
laboratory.

(c) Dixring the year of this report we have been trying to
develop in a more systematic way the vocal phenomena of speech
other than those mentioned above, the "pexalinguistic" phenomena.
These include changes in duration, loudness, pitch, intensity,
articulation, and vocalization as applied to units of speech
larger than the morpheme. Preliminary trials indicate that the
paralinguistic phenomena can be coded fairly rapidly, and that
a good deal of work is neeessaury to spell out the criteria for
coding completely enough that objective measuremen-cs can be made.

Significance of the program to tfental Health resegjch; This
p^ojec^ is part of the program devoted to determining ways of
measuring non-verbal comm'onication channels. If successful,
it will sharpen our ability to use interview data more com-
pletely in the analysis of psychotherapy.

Proposed course of the project ; To continue the deve3.opment of
these teehniqLues unxil we find that we have objective measure-
ment techniq.ues or that linguistic technig.ue8 ai'e not the way
to get at vocal communicative phenomena.

Part B included Yes £J Wo [Tl

- 85 -

Serial No. M-P-C-(C)-5
1. Laboratory of Psychology
2o Section of the Chief
3. Bethesda

PHS-KIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Judgment of facial expression from short sequences
of motion picture film

Principal Investigator: Allen To Dittmann

Other Investigators : none

Cooperating Units : none

Man Years (calendar year 1957): Patient Days (calendar year

1957):
Total: 1.2
Professional: .6
Other: .6

Project Description:

Objectives ; To develop techniques of judging emotion from motion
pictvires so that these may be used for sequence ajialysis of thera-
peutic interviews. This project is related to Linguistic Study of
Emotional Expression.

Methods Employed; IXiring the year of this report the technique of
showing short series of prints from motion pictures was abandoned
as being artificial, even though it was a far simpler method of
presenting data to judges than the one finally evolved. The pres-
ent technique involves showing short sequences of film through a
motion pictxire projector to judges ;, sequences about three seconds
in length. Judges make their responses by checking a list of 17
categories of emotional tone, and final scores are derived from
this list. Reliability of pooled scores of three independent judges
was .85 for 2k items,

A pilot study was run to test whether these scores could
be related to other variables. Using sequences of film of a
patient following leading responses and confrontations by the
therapist in one interview, judgments of facial expression showed
greater relatedness and calm following leading responses and
greater discomfort and apprehension following confrontations.
Judgments based on speech with meaning filtered out 3uad on content
alone showed trends in the same direction, but the relative un-
reliability of these judgments for these data meant that the
differences were not significant,

- 86 -

Serial No. M-P-C-(C)-5-page 2
Part A. (Project Description Sheet cont'd.)

Major findings ; This technique definitely holds promise as a
method of getting at emotional communication as mediated by-
visual cues. Reliability on a very limited sample is high, and
the judgments can be related to other variables.

Significance of the program to the Institute : Here is a tech-
nique for measuring nonverbal communication which appears to
work. While it is not simple to carry out (motion pictures
must be used as the basis for judgment), this method, or rather
those which are developed from it, may find wide use in analysis
of interviews and other situations where films are available.

Proposed course of the project: The preliminary findings are
based on very limited material, and further work is iznder way
enlarging the scope to Include many patients in many different
stages of psychotherapy. At each stage in the development,
reliability tests will be run, and pilot studies similar to the
one cited above carried out.

Part B included Yes [J No [Tf

- 87

Serial Ko. M-P-C-(C)-6

1. La.boratorjr of Psychology

2. Section of the GMef

3. Bethesda

PHS-NIE
Individual Project Report
Calendar Year 19.57

Part Ao

Project Title : Interaction patterns of Normal and Hyperaggressive
Children

Principal Investigator: All.en T<, Dittraann

Other Investigators ; B. Wells Goodrich

Cooperating Units ; Child Research Brascch

Man Years (calendar year 1957)" Paxient Dsys (calendar year

1957) t
Total : . 3
Professional i .2
Other ; o 1

Project Dasftription :

Objectives: (a) To develop roethodjs of studying intersection
patterns of children in a treataient setting, (b) To compsjre
interaction patterns of normal and disturbed children in the
same setting.

Methods Emp3-oyed; Short sample observations of chi.ldren in
situations selected to represent daily life experiences. Obser-
vations were recorded, and the recordings tormsd the basic data
of the research. Protocols were coded for interactions bet-^reen
children and interactions involving children and adiilts.

Patient Material: None during the year oovered by this report.

Major Findij^s; Patterns of interaction of the nomial ajid h;yT)er-
aggressive children differed as laight be expected: normals showed
less inappropriate behavior, less overt aggression, more real
leadership, greater dependency based on t.rust t-Xj/ard ad^iJits.
Adait behavior was not so clear Ijr e^zpected: more i'reedoai with
normals in exprassing affection, setting limits, while with
the disturbed children they were more cautious in all their ex-
pressions. Extensive studies of reliability of the observa-
tional method itself aiid of the eodj.ng systeiii used here showed
that the methods were repeatabis by the ssme people at dif-
ferent times and by different people a'l; the saas? tims, thiis

=. 88 -

Serial No. M-P-C- (C)-6-page 2
Part A. Project Description Sheet (cont'd.)

lending greater credibility to the findings. During the year
covered by this report the work has been chiefly concerned with
reliability studies.

The initial methodological paper is complete, and the sub-
stantive findings are in the process of being written.

Part B included Yes [J No /xT"

- 89 -

Serie,! Ko., M-P-C-(C)-7

1. Laboratorj"- of Psychology

2. Sect?: on of the Chief

3. Bethesda

TES-KLE
Individual Project Report
Calendar Year 1957

Part A.

Project Title? Studies of diasensionality of psychological
variables

Pi'incipal Investigator: Allen To Dittmann

Other Investigators : Efone

Cooperating Units : None

Man Yeai's (calendar year 1957) = Patient De-ys (calendar year

1957) s
Total ', . 5
Fx'of essionel : . 1
Other: .4

Project Description:

Objectives ; To investigate systems of psychological ^rariables
for their dimensional structure, using no2i-metric tecbBiques,

Methods employed: Methods developed by W. L. Hays and the late
J. E. Benri.ett under the general theory of Co Gooiabs pre usedo
Systems investigated are the Freediaan-Leary-Ossorio system of
Interpersonal Mechanisms and the" Schasfer Circumplex of 2hild-
I'earing attit-ideso Leary has concludad that the Interpersonal
Mechanisms form a ti-ro-dimensions.! schene, and has applied plan
trigonometric manipiJia"i:;ions of indivlduai profiles based en the
sj'-stem to handJ.e group datao Schatfer has said that the beha'/lors
concomzltant with child-rearing attitudes can be cast in t-^ro
dimeasions , and finds similarities with the c'-imsnsions proposed
by Lesry.

Major Findings; Non-metric ansJ-ysis of these two systeias sho\fs
tha'c ar. lea&t three dimensions Eiust be posxted. to accovjit for
the beha\':loi"3 which they piarport tc organa.E« into oxily two
dimei'Osions. The end-points of these dtinenisions have not been
worked out as yet, but the indications of preliminary vork a^'s
that they do not coincide with those s-aggested by the authors
of tne systems o

Sigpificaiice of the program to Mental Health ggsesrchi The
systeai of interpersorisi mech2;nism£ is in iise in tvo studies in

- 90 -

Serial No.M-P-C-(G)-7-page 2
Part A. Project Description Sheet (cont'd.)

the institute (in the Laboratory of Socio-Enviromnental Studies and
the Child Research Branch), and theoretical analysis of its properties
will give information on how it nsay be most profitably used aad on
what are its limitations. The Scha^er cireumplex will be used in
organizing data of a different kind in the Section on Child Develop-
ment, and can also profit fi-om data from a number of different kinds.

Proposed course of the project : To complete the s^alysis in order
to find end-points of the dimensions, and to publish the results.

Parr. B included Yes ^ No /x/

91 -

M~P-C-(C)-8
lo Laboratory/' of Psycholoar

2. Section of the CMef

3. Betkesda

PaS"NIH
lacUvidoal Project Report
Calendar Year 1957

Part A.

Project Title: Tlae Self -concept and Body Image as Related to
Disease Susceptibility and Organ Choice

Px'inoipal Investigators Isabelle V. Ke?idig

Ot-iier Investigators: None

Cooperating Units: National Institute of Arthritis and Mstaboiic

Diseases

Meja Tears (calendar year 1957) : Patient Days (caiendajj' year

1957} s
Total : . 5^' 6

Prof a 8 3 i onsl : .53
Other: .05

Project Description:

Objectives; To explore attit'iidiaal factors affecting health sjQd
lo.agevlty. Mors specifically;, to invss'cigats thcsc attitudes in-
culcated in e:5i'ly childhood -#hich are inj-trtiiaental ia determxiiag
the 2::iat-are of the self-concept and the body injage er-peelaliy in
relation to susceptibility to illness ^ orgarx choica, coi-rse and
OTiticome of disease.

Mgth..ods Employed ; E:rfcensive use of self-concept tests and a
variety of prcjectiva techniques, inolitdiag the Ror^chach^ Di*aw~
a-Persoa and Four Picture tests ;, with patients proved unsatis-
factory, the results reflecting o:aly the j^resent self-coacept exid
boo;/ image as unfavorably modified by yeai-:"3 of il^jsest^. It seeased
necessary J, therefore, to develop a der-ailsd q,uestion??aire or in-
terview schedixle which woald «iisciOi3e the attitudes toward the
self and the body inculcated in early chiWhood, explicitly by
dirac'c instrtiction g=nd Impli-iitl;;/' thi-ou^ ti;,e emotional climate
of the home and faMly reactions to iljjiess, which aigiit bear a
relation to subsequent cdsease susceptibility. Boring the pss's
year such as inatr'ujsisnt has been dsTeloped a;ad pretesr^ed on t¥0
putient gro^i,ps &nd one gi-oup of 'normal' coatrola. Scales are
now being ii^mm sc that tte dtta cpji ba codec', and treated
quantitati'/ely.

- 92 -

Serial Wo. M~P-C-(C)-8~page 2
Part A. Project Description Sheet (cont'd.)

Patient Material; The two patient groups used for pre-testing the
interview schad^JLLe have consisted of a number of rheiijmatoid
arthritics from KIAMD and a smaller niimber of patients from KflKDB
referred for study because of intractable pain. In addition, the
instrument has been administered to 'normal' controls involved
in drug studies.

Major Findings; There are no substantive findings to report at
this time as the emphasis to date has been upon the development
of an appropriate methodology.

Significance of the progrstm to Mental Health research; To the
extent to which the results of this study may thra^jf light on the
part which beliefs and attitudes to the self and to the body
play in relation to subsequent health suad to longevity;, it should
have value in forr^rarding the work of the various Institutes in
which it is carried on. It should also tie in with studies in
progress in the Laboratory of Psychology, specifically in the
fields of child development and gerontology. In these areas it
will be significant to trace the rise, modification and deteri-
oration of the self-concept over time in its effect upon re-
sistance to disease.

Proposed Course of Project ; Before the close of the current year
it is expected that the coding of the Interview Schediole, which
has already passed through a number of forms, will be completed
and a weighted scoring system devised. It will then be used with
groups of patients in NCI, NHI and KLAID as well as in NIAMD and
NINDB. The next step will be to secure matched control groups,
the Peace Church 'normals' being largely imsuitable because of
the age factor.

A subsidiary project has been in the ways since spring, viz.
to compsjT'e the physical status of a group of Princlpia College
students, raised in the Christian Science faith, with a matched
group of students from a deaomins,tional college of similar stand-
ing, to all of whom medical examinations were given by a Sfa-'iy
team during the Second World War. Permission for access to the
reports on these exagu.nations has already bean granted ty the
Navy and the project is now under consideration by the Christian
Science Mother Chtjreh in Boston. This study should afford a
crucial test of the extent to wblch affinmtlvs attit'ades to
hesilth inculcated in childhood contribute to subsequent re-
sistance tc disease.

Part B included Yes f^ No /^

- 93 -

Serial No. M-P-C-(C)-9

1. Laboratory of Psycholo^

2. Section of the CSaief
3» Bethesda

PHS-WIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title : Precocious Puberty and Pseudohermaphroditism

Principal. Investigator: Roy Hertz, M. D.

Other Investigators; Isabelle V. Kendlg

Cooperating Units s National C9,ncer Institute

Man Years (calendar year 1957) s Patient Mys (calendar year

1957) s
Total: .08 3

Professional: .03
Other: .05

Project Descriptions

Objectives : From the standpoint of the second investigator ;, the
objective of this study is to evaluate the psychological effects
of precocious puberty and pseudohermaphroditism on personality
variables^ particularly upon the self concept and the body image.

Methods Employed; Administration and analysis of the stsmdard
intelligence and projective tests.

Patient Material: All present out-patients a-nd all newly ad-
mitted patients to the NCI suffering from precocious puberty and
pseudohermaphroditism^, an estimated 15 a yesir.

Major Findings : The group of patients seen to date (5) is still
too small to waxrant any statement in re findings.

Significance of the progr-am to Mental Health research: Besides
throwing light on general personality variables in such a group
of patients^ the study should contribute significantly to our
understanding of the bearing of such pathology on the self con-
cept and the body image.

9h ~

Serial Wo. M-P-C-(C) -9-page 2
Part A. Project Description Sheet (cont'd.)

Proposed Course of Project ; To continue to see new patients
with these diagnoses and to re -evaluate from tiwe to time those
already seen until an n is built up of sufficient size to
warrant conclusions about the group as a whole.

Part B included Yes /V No /xj

95 -

Serial Wo, M-P-C-(C)-10
lo Laboratory of Psychology
2o Section of the Chief
3. Bethesda

PES-NIE
Individual Project Report
Calendar Year 1957

Part A,

Project Title: Study of Intractable Pain

Principal Investigator: John M« Van Buren, M.D.

Other Investigators; Isabelle V. Kenaig

Cooperating Units : National Institute of Neurological Diseases

and Blindness

Man Years (calendar year 1957) = Patient Days (calendar year

1957) :

Total; .06 2

Prof e s ■5 io^oal ; a Gl
Other: .05

Broject Description:

Objectives ; From the standpoint of the second investigator, the
objectives in this study are to uncover developmental attitudes
to the self and to the boc'y image which may be related to the
patient's present condition and perhaps enable a differentiation
to be s&ade between those suffering orgs^nic- pain and those with
psychological (phantom) pain.

Methods Employed; Data on early attitudes tc the self and the
boi!ly and family attitudes to illness are being obtained through
the use of the Interview Schediiie.

Patient iyte.terial ; Patients included in the study of intractable
pain being carried on by the principal investigator.

Major Findiiigs; As only k persons to date have been seen in
this stuc^Yj, there are no findings to report.

Sigroificance of t.he progran to Mental Health X'eseareh: The
problem of intractable pain is of s;i:'eat interest i.ii medicine.
If attitudixml factors are found to play an important role,
particularly in connection with phantom pain, a new appx-oach
to treatsQsnt may be suggesT.ed.

- 96 -

Serial No. M-P-C-(C) -10-page ?
Part A. Project Description Sheet (Cont'd,)

Proposed Course of Project; To carry it on until a sufficiently-
large group of patients has been seen to Justify drawing con-
clusions re the psychological variables involved.

Part B included Yes [J No jTJ

- 97 -

Serial No. M-P-C-(C)-11

1. Laboratory of Psychology

2. Section of the Chief

3. Bethesda

PHS-NIH
Individxial Project Report
Calendar Year 1957

Part A.

Project Title: Drug Study

Principal Investigator*. Conan Kornetsky

Other Investigators: Isahelle V. Kendig

Cooperating Ifeits: Laboratory of Clinical Science, HIMH

Man Years (calendar year 1957) : Patient Days (calendar year

1957) :
Total: .25 10

Professional: .2
Others .05

Project Description:

See Serial No. .M-CS-P-(C)-2

Part B included Yes [J No [Tf

98 -

Serial Wo. M-P-C-(C)-12

!• Laboratoiy of Psychology

2. Section of the Chief

3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

JtSLl w Ao

Project Title i Schizophrenic illness in a set of identical
qioadruplets

Principal Investigator: David Rosenthal

Other Investigators; Numerous NIMH investigators and personnel

ftom other NIH institutes

Cooperating Units s None

Man Years (calendar year 195?) '• Patient Days (calendar year

1957);
Total; 2.6 ]Li^50

Professional ; . 5
Other; 2.1

Project Description:

Objectives ; To determine factors related to the development of
schizophrenia in a set of identical quadruplets and to evaluate
factors which lead to differences in their psychopathology.

Jfethodg employed; Interviews of the quadraplsts , their relatives,
and members of their home comrau.nity. Ohser-trations of the quads
and their parents. Biochemiealj, physiological, and psychological

tests.

Patient I^feiterial; A set of 27 year old Identical quadruplet
girls.

Major Findings; A large amount of data of different kinds has
been accumsjilated. The integration and evaluation of these data
will begin oa a mors formal basis very shortly.

Significance of the progiram to Mental Health research; It is
hoped that this intensive analysis will ILUminate the process
of sehizophrenJ.c development, especially with regard to genetic
faetors, social iisolation, parental behavior, family life pat-
tern, maturation of self -concept , and other related concepts.

99 -

Serial No, M-P-C-(C)-12-page 8|
Part A. Project Description Sheet (cont'd.)

Proposed Coarse of the Project; Data collection will teraiinate
at the end of this year, and the formal integration and evalua-
tion of findings will follow.

Part B included Yes [J. No /x7

- 100 -

Serial Nc, M-P-C-(C)-13

1. Laboratory of PsycliolOQr

2. Section of the Chief

3. Bethesda

Individiial Project Heport
Calendar Year 1957"

Part _A.

Project Title i Eesponsivity Patterns ia Schiaopferenics

Principal Investigator i I^vid Rosent^l

Otker Investigators; David Simkowj, William G, Lawlor (visiting

scientist);, Tiieodore P. Zahn, Blaacfee Sweet

Cooperating Units ; Clinical Sciences Laboratory (Ward 2-W) and

St. Elizabeths Hospit'al

Man Years (calendar year 1957) : Patient Days (calendar year

1957):
Total: 2.15 ^5

Prof e ssional ; 1.4
Other: ,75

Project Description:

Objectives ; Schizophrenics of various types are toeing studied
with regard to how they respond at both the aiatonomic and molar
behavioral levels when confronted by neutral^, meaningfuJ., and

performance -de.manding stimuli. The concepts &f set and arousal
are central in planning the pro-am of stiidies, both with regard
to the tests and procedures used and the Ejeas^ares taken. In the
endj, it Is hoped to elucidate the respomeivity patterns of
various kinds of schizophreioics insofar as these may be influ-
enced by externally induced psychological factors and by in-=
ternal factors. With regard to internal factors^, we hope in ,•''
time to relate the phenomena here studied to studies of reticu-
lar activating and limbic systems in schizophrenics.

Methods Employed: Tests administered to date include: orienting
(to light stnd tonej under amytalj, an^hetamiae ^ and chlorpromazlne ) |
conditioning j reaction time; intelligence tests (WAIS and Pro-
gressive Matrices); Wisconsin Card Sorting Test^ Rorschach;
adaptation to blocking of alpha; discrimination of size differ-
ences; word-color test; and subjective pr.obability tests. Even-
tually;, when ssuDpling will have become w3.der;, tests will be in-
tercorreiated to examine whether broad coastellations of response
patterns sure present among schlsophreriics .

- 101 -

Serial Nc. M-P-C-(C) -13-page 2
Part A. Project Description Sheet (cont'd.)

Patient Material; One group of 13 saMzcphrenic patients having
high, middle, and low percent time alpha in their electroencepha-
lograms has been under study since Jiily, 1957« A set of identical
quadruplets with varying degrees of severity of schizophrenic
symptomatology is also being studied. Till now, all patients have
been Clinical Center patients, but plans have been in the making
to include St. Elizabeths Hospital patients next year.

Major Findings : Data are now in process of being evaluated.

Significance of the program to Mental Health research; ¥e hope
to study the possibilities that ;

1. Subgroups of schizophrenics can be differentiated
according to their autonomic and molar behavior patterns.

2. These patterns can be related to schizophrenic
symptomatology.

3. The subgroups caxi be differentiated according to
genotypical background and/or family relationship constellations.

k. The pattern differences can be conceptualized as
involving varying kinds of defect in "arousability".

5« Arousability defects are related to disturbances
in the functioning of the reticular activating and/or limbic
systems.

Proposed Course of the Project ; We plan to evaluate the findings
and to follow the best leads. Some tests and experiments may be
modified and new ones will be planned on the basis of oiir initial
findings .

Part B included Yes £J No Jx/

- 102 -

NATIONAL INSTITUTE OF MENTAL HEALTH

Clinical Investigations
Laboratory of Psychology — Child Development Section

BUDGET SHEET

Estimated Obligations for FY 19S8
Total: $121,198
Direct: $89,956

Reimbiirsements : $31 ,2^4-2

Projects included: M-P-D(C) 1 through M-P-D(C) 17

Serial No. M-P-D-(C)-1
lo laboratory of Psychology
PHS-NIH 2. Child Development Section

Individual Project Beport 3« Bethesda
Calendar Year 1957

Part A.

Project Title: The preparation of procedures for observing and record-
ing infant behaviors and mother-child interactions in testing situations
for use in a stxidy of infant development. A pilot study.

Principal Investigator; KEincy Bayley

Other Investigators: Earl S. Schaefer

Cooperating Units: None

Ifen Years: Patient Days:

Total : .82 5

Professional: .40

Other: ck2

Objectives ; In preparing for a developmental study that is oriented
toward finding significant variables in shaping personality structure,
and rates of behavior development^ it is necessary first to devise
methods of observing, recording and evalviating the behavior of infants
and their mothers during short testing -observation periods. The
objective of this project is to devise and test a set of methods and
recording procedures for such use*

Methods employed; Mothers and their young infants are visited in
their homes ■vrtiere developmental and social tests are given the in-
fants. At intervals each mother and child pair is brought into the
Clinical Center for the same tests, at lAiidi time motion picture and
tape recordings are made of the testing sequences. An earlier attempt
to give these tests in a ■well -baby clinic proved tmsatisfactory, and
has now been dropped. A veiriety of methods of recording the procedures
is being experimented with. Eating scales, adjective check lists,
running accounts, coded records of responses made by observers during
tests, and qualitative descriptive notes as veil as the motion pictures
are being tried out and checked for reliability, validity, and adequacy
for purposes of interpretation.

Major Findings; This sttxdy is still in the stage of developing the
•tools of observation and recording, althou^ several fojans now being
tried are promising. None of them is at p3:«sent ready for general vse.

Significance to the program of mental health research; Findings from
other research indicate that the emotional health of infants and young
children are affected by the emotional climate and characteristic

103

Serial No, M-P-D-(c)-l-page 2

Bart A continued;

Significance to the program of mental health research continued : int er -
action patterns between children and significant adults. These emotional
climates appear, furtheimore, to affect significantly the course of behavior
development « Mach more information is needed on the ways in ■^rfiich these
interactions occur, and on the extent of their effectiveness in determin-
ing mental health or disease. Careful observation in natxiral settings, with
later evaluation of the same diildren is one of the best ways to discover the
important variables.

Proposed Course of Project ; Although this project was initiated as part of
a projected developmental stiody of infants^ the direction of interest of
the members of the section is now shifted toward smaller, more intensive
studies of infant behavior. Some of the foims developed here will be used
in the mental test standardization. Others will be utilized as appropriate
study conditions are instituted.

Part B. included Yes l~~J No /X /

- 104 -

Serial No, M-P-D-(C)-2
Laboratory of Psychology
PHS-ETIH Child Development Section

Individual Project Report Bethesda

Calendar Year 1957

Part A.

Pro.ject Title: Standardization of the California Infant Scale of
Mental Development

Principal nixvestigator: Nancy Bayley

Other Investigators: IVbrjorie Po Honzik and Dorothy Ho Eichom,
University of California, Berkeley.

Cooperating Units: None

Man Years : * Patient Days :

Total: .55 None

Prof e s sional : . 25

Other: o30

Project Description: Objectives: To revise and prepare for re-
standardizing the California First Year Ifental Scale to be extended
through two years and re -named the California ^ntaJ. Scale of Infant
Development. T!he normative testing to be done by or under the im-
mediate supervision of Drs. Marjorie P. Honzik and Dorothy H. Eichom.
The revision of the scale should fill a serious gap in the current
status of developonental tests for infants. The infant sceiles now in
use in this coiontry were all standardized on data obtained 20 to 30
years ago on small samples of infants us\ially from a geographically,
culturally and often socioeconomically restricted source. Because
of these inadequacies of sampling, we have no assurance that the age
norms in ajiy of them are representative of infants in the country
generally. The revision should be standardized by testing repre-
sentative samples from a variety of geographical areas.

Aside from the sampling, however, cvirrent theories about the
nature of the developmental processes caH for inclusion in the scale
of a wider range of behaviors in order to render the evaluations of
a child's status more meaningful.

tfethods employed: The original mental scale has been gone over item
by item to make the procedural directions more clear; new items have
been added for trial; new record forms and work sheets are being
developed that wiU both increase the ease of administering and re-
cording and allow for fuller descriptions of the infants' responses.
An additional foim has been devised for recording the child's
emotional^ attitxidinal, energy output and goetl'^directed behaviors.
These wiH be analyzed for age and developmental trends and for the
relation of individual differences to scores of mental functioning.

- 105

Serial No. M-P-D-(C) 2-page 2

Part A, Continued

Methods employed continued: Tentative revisions are tried out on a few
infants and further revisions are then made. When satisfactory forms
have been devised a program of testing will be instituted according to
a statistical design that will insure good noiraative data.

Ma..1or findings; This project is now at the stage of selecting the items
to be observed and developing the test form. A few infants have been
tested for the purpose of discovering ways to improve the testing instru-
ment.

Significance to the program of mental health; There is need for a
really good objectively scorable well -standardized test of mental
functioning in infants that covers the age span between birth and two
years. This is of primary importance to basic research that is
directed toward early detection of such conditions as mental deficiency
and emotional disturbances. A good test would function as a basic tool
in studies of environmental deprivation and the effects of emotional
trauma on the infant's development and personality adjustment.

Proposed course of project: The testing procedures and record forms
are now almost reaxiy for putting into final form. The next step will
be to organize the testing program. This is now in the preliminary
planning stage.

It is probable that such a normative testing program will be tied
into the large study of infant development that is being carried out
in NBTDB. In that program it is planned that 13-15 cooperating institu-
tions will, over a period of eleven years, measure the development of
some 35^000 children, starting vath pregnancies, and continuing with
the children xintil they are 5 years old. In this program well-standard-
ized developmental tests are needed. It appears now that the pro-
cesses of standardizing the two-year mental scale can be integrated
with this program, in such a way that a standardization sub -sample can
be derived from this total population. This in return would furnish
standard test scores to the entire popxilation, vAiich would be tested
less frequently.

i^rt B included Yes / / No TO

106

Serial No. M-P-D-(C)-3
Laboratory of Psychology
PHS-NIH Child Development Section

Individual Project Eeport Bethesda
Calendar Year 1957

Part A.

Project Title ; Long-term experiences with methyltestosterone as a
growth stimulant in short immature boyso

Principal Investigator: Kancy Bayley

Other Investigators: Gilbert S. Gordon and H. Lisser, XJhiversity of
California MsdicaJ. School, San Etrancisco, California

Cooperating Units : None

Man Years; Patient Days:

Total: .30 None

Professional: <.15

Other : .15

Project Description; Objectives : To investigate the effects of oral
administration of methyltestosterone on the growth and pubertal develop-
ment of small iimoature boys.

tfethods eniployed; Accumulated clinical records, including serisil measure-
ments of height, skeletal X-rays and treatment dosages of 100 boys,
patients of Drs. Lisser and Gordon, were studied. Growth curves of
height, and annual increments were plotted on Bayley 's curves. Sseletal
ages were read from the X-rays and pre -treatment height -predictions made
on 62 of the boys, using the Bayley -PLnneau tables. Subsequent height
predictions, after treatment weare possible from later X-rays of 36 of
the boys. It was possible to compaxe the predictions with eventual
ad;xlt stature for 20 boys v*.ose growth was completed. The effect of
methyltestosterone on growth were found to be most effectively evaluated
by grouping the boys according to age at maximum growth.
Major findings: Staall doses (5 to 20 mg. ) of methyltestosterone ware
found to result in immediate spurts of rapid growth in most instances.
Compared with pre -treatment predictions, both post -treatment predictions
and actual adult statures were found to be, with few exceptions, at or
above the expected growth without treatment. Btew disturbing side-effects
were noted.

Significance to the program of mental health research; Staall boys, -iitio
are retarded in puberal development, have been found to have emotional
problems related to their small size, lack of strength, and immaturity.
If growth can be stimulated at the normal age for such growth without
physical damage, these boys may be helped to regain status and thus re-
duce their emotional problems.
Proposed course of project : Qonrpleted and published »

Part B included Yes / 1 / No /"7

107

Serial Ho. M-P-D-(C)-3 page 2
PES-NIH ...

Individual Project Beport
Calendar Year 1957

tB: Biblications

"1""

1 cations other than abstracts from this project:

Bayley^ Nancy^ Gordon, S. G., & Xlsser^ H« Long term experience vlth
Mstbyltestosterone as a growth stimulant in short inonature boys*
Pediatric Clinics of North America, Ihiladelphia, W. B. Saunders Co«,
1957 > pages ai9-tt25.

801

Serial No. M-P-D-(c)-Ii.
Laborato3ry of Psycholoar
PHS-NIH Child Development Section

Individual Project Report Bethesda

Calendar Year 1957

Bart A.

Project Title; Bslationship of maternal behavior to the subsequent
social, emotional, and intellectual development of children*

Principal Investigators: Hancy Bayley and Earl So Schaefer

Other Investigators: None

Cooperating Iftiits: None

Man Years: I^tient Days:

Tcftal: 082 None

Rrofessional : o^l-O

Other: ckS.

Project Description: Objectives : Recent theories of the effects of
maternal behavior upon personality development of children have
shifted from an emphasis upon such variables as age of weaning and
toilet tiraining to variables 'stiich stress social and emotional be-
haviors of the mother with the child. In another project data
collected by Bayley in the Berkeley Growth Study have been utilized
in developing a method for quantifying notes on behavior observation
of mother-child interactions of children under 3 years and of un-
structured interviews of the mothers ^en the children were approxi-
mately 10 years old. The objective of this project is to st-udy the
relationship between these maternal behavior variables and the
intellectual, social, and emotional behavior data on children ^ich
were collected by Ifency Bayley over a period of twenty -one years.
Some of the analyses will test current theories of the influence of
the mother upon the development of the child ^ile other analyses
win escplore the data in an effort to develop new hypotheses ^ich
can be tested in future studies.

Msthods eH^loyed: Mich of the data on the children was recorded in
quantified form, e.g., intelligence scores, ratings of behavior in
the test situation at various ages, tests of interests and attitudes,
and many others which were collected over a period of 21 years.
Other records on the children consist of unstructured notes on test
behavior, notes on interviews, projective test materials, etc. Qae
phase of the project is to develop a method of quantifying personality
concepts from the available data. A rating scale is being developed
to quantify notes on test behavior between the child's age of 11 to
180 It is Qften necessary to group other scores « Appropriate
statistical techniques to analyze reliability consistency through
time, and the relationships of the various variables with one
another and with maternal behavior must be selected and statistical

109

Serial Wo, M-.P-D-(C)-i(- page 2

I^xt Ac continued;

Methods employed continued; analyses of the material must be done. The
data are being organized to permit the application ot IBM techniques in
order to facilitate the analysis of this comprehensive and unique set of
longitudinal data..

Ma.i or Finding s ; All results of these data indicate differences between
the relation of maternal behavior to personality development of boys
and personality development of girls « Jfetemal behavior is consistently
more highly related to intellectual and personality development of boys
than girls <, This finding may be relevant to the process of identifi-
cation in males and females <, Another finding is that upper socio-
economic groups tend to show more positive behavior toward their children.
This may help in interpreting differences in incidence of mental health
problems among socioeconomic groups. Internal behavior is significantly
related to the intellectual development of males but not of females.
Mothers ^o are Cooperative^ Equalitarian , and Escpress Affection for
their children most often have sons ^o consistently improve in intelli-
gence throu^ the first 6 or 8 years ;, and then remain stable, vftiile the
opposite is true for mothers who are FUnitive, Irritable and Ignoring.
Maternal behaviors which are approved by mental health specialists are
related to the happiness, calmness ;, and positive behavior of their
children between 10 months and three years of age. It was found that
behavior ratings of children of this age level largely define two di-
mensions—Happiness vs. Unhappiness and Activity vs. I^ssivity. The
child's activity between 10 months and three years is more consistent
than the child's happiness, though neither characteristic is highly con-
sistent.

Maternal behavior variables are significantly related to the rated
behavior of boys in the test situation between thiree and nine years of
age. The pattern of relationship of maternal behavior with the rated
behavior of girls is less clear. Internal behavior is also signifi-
cantly related to the test behavior of boys between 11 years ajid l8 years.
Analysis of these data on the girls is incomplete. Eeliable ratings of
adolescent behavior in the test situation were obtained from the rating
scale \dilch was developed.

Correlations among the maternal behavior variables ^ich are re-
ported in another project revealed two primary dimensions of Love vs.
Hostility and Autonomy for the Child vs. Control. An Investigation of
the consistency of maternal characteristics between the two age levels
revealed relatively high consistency of the love vs. HDstility dimension
but low consistency of the Autonomy vs. Control dimension. This result
was meaningful in that the child's needs for a'sxt.onomy vary from total
dependence at birth to relatively complete independence as an adiilt
•(rfiile his needs for positive relationships are relatively consistent
through time. The detailed information on Intelligence and person-
ality ^Ich is available on this group over a

- 110 »

Serial No, M-P-D-(C)-4 page 3

Bart A continued;

Major bindings continued; period of 21 years has resulted in other
findings -^ich are relevant to hypotheses of the influence of
environmental variables upon developments Intensive study of these
results and their interpretation is necessary before their signifi-
cance can be determined-

Significance to the program of mental health research; Since most
of the theories of family influence upon personality development have
been developed from clinical and retrospective studies^ the oppor-
ttmity to test them developmentally should assist materially in
eval\iating these theories » The data on social and emotional inter-
actions of mothers with their children from both observations and
interviews are xmique since most data on maternal behavior are from
structured interviews with no opportunity to check their validity.
The results of this study are highly relevant to the theories of
Sullivan, Eraram^ and Homey ^ich are currently influential among
psychiatrists and psychologists and should be valuable in testing
those theories. Data about personality and intellectxial development
^ich are valuable to personality theory and to the mental health
movement may be obtained..

Proposed course of pro.ject ; Rirther investigations on the interre-
lationships of these data will be madeo The data will be prepared
for IBM analysis and the results will be interpreted and reported.

Part B included Yes J^ No /FJ

111

Serial No. M-P-D-(C)-5
1. Laboratoiy of Psychology
PHS-NIH 2. C3aild Developnent Section

Individual Project Report 3» Bethesda
Calendar Year 1957

rt A«

Project Title; Development of a theory of the role of parental
behaviors in the etiology of personsility structure and psycho-
pathology.

Principal Investigator: Ikrl S<, Schaefer

Other Investigators: None

Cooperating Units: Hone

l&n Years: Patient Days:

Total: .37 None

Professional! .20

Other: .17

Project Description: Objectives : The purpose this research is to
develop a systematic theory of the effects of social influences upon
personality development and to develop a theory of the relationship
of the major diagnostic categories to one another and to the healthy
personality. As systematic theory would enable one to integrate
personality research, both clinical and experimental, into a common
conceptual scheme in which the various findings would be relevant to
one another. A theory would guide futiare research designs as well as
assisting in interpreting previous results.

tfethods Bnployed: Through an important advance in statistical theory,
Guttman's circuraplex theory, a new way of investigating the inter-
relationship of personality variables became available. The circum-
plex method, idiich is a seaxch for a law of neighboring and a law of
polar opposites in a set of correlations, permitted a parsimonious
ordering of a set of maternal behavior concepts ^ich had been
developed by Schaefer, Bell, and Bayley in a previous project in this
laboratory. This parsimonious ordering of maternal behavior concepts
was fo\3nd to apply to other published data and to other concepts
\4iich have been used to describe maternal behavior, i^otheses were
developed concerning the types of personality structures \Ailch. might
be developed from the accumulative effective of the different maternal
behaviors. Predictions were made and the predictions were verified
from enrpirical data. Proposed work on the theory is to apply the
theory as it exists to further published data, to amplify or modify
the theory as indicated by these data, and to plan additional studies
;|;\dxich would test the theory^-

- 112 -

Serial Wo, M-P"D-(c)-5~page 2

Fart A« continued:

Ife.Tor Findings; Two major dimensions of maternal behavior have been
isolated --Love vs. Hostility and Autonomy for the Child vs. Control.
A prediction was made that Love and Autonomy wo'old result in a
normal personality adjustment ^ Love and Control in a more inhibited
neurotic personaJLity^ Hostility and Control in a more schzoid person-
ality, and Hostility and Autonomy in a more psychopathic, delinquent
personality. This prediction specified the relationship between the
various diagnostic types and the normal personality. The prediction
was substantially verified by intercorrelations of the scales of the
Minnesota Multiphasic Personality Inventory i^iich were developed to
differentiate the diagnostic categories. Additional verification was
found in published data from the comprehensive assessment data of the
Institute of Personality Assessment Research and in several compre-
hensive behavior rating studies on Nursery school children, pre-
adolescents, and young adults. The findings were related to Freudian
theory, to data on psychotherapeutic success, to learning theory, sind
to the literature on experimental neurosis in ajaimals.

Significance to the program of mental health research : Current
psychiatric theories of Sullivan, Frcram and Homey stress the effect
of environmental factors upon personality development. The develop-
ment of a systematic theory of the nature of these social environmental
factors and of their effect upon personality development Tri.ll organize,
amplify, and clarify these theories. This theory will permit the
integration of available data and the development of improved research
designs for future studies of the effects of the social environment
upon personality development. The conceptual scheme also simplifies
the problem of communication mental health concepts since it organizes
an extremely complex phenomenological field into an ordered and parsi-
monious set of concepts.

Proposed course of project: A paper entitled "A theory of personality
development, personality structure, and psychopathology" is in pre-
paration and will be sent to Behavioral Science . Further data will
be obtained from published studies and further tests of the theory
will be made in new research designs.

I^rt B included Yes l~~J Wo /X /

113

PHS-NIH

Individual Project Report

Calendar Year 1957

Serial Wo. M-P-D-(c)-6

1. Laboratoiy of Psychology

2. Child Development Section
3o Bethesda

I^rt A.

Pro.iect Title: Organization of ]yfe,temal Behavior and Attitudes Within
a Two nimensional Space.

Principal Investigator: Earl S. Schaefer

Other Investigators: None

Cooperating Units: None

Man Years:

Total: .37

Professional: .20

Other: .17

I^tient Days;
None

Pro.iect Description: Cto.iectives: Qae of the major goals of science is
to order an apparently complex phenomenological field into a parsi-
monious, ordered set of concepts. Previous researches in this laboratory
by Schaefer, Bellj, and Bayley have developed a Parental Attitude Research
Instrument and a Maternal Behavior Research Instrument with which to con-
ceptualize and quantify parental attitudes and behaviors. lepers on
these research instruments are now ready for publication. The purpose
of this research is to study the Interrelationships of the concepts
\Aiich are measxired by these research instruments in order to be able to
develop efficient research designs, to assist in interpreting research
results, and in order to be able to develop a comprehensive theoiy of
the effects of maternal behavior upon the personality adjustment of
children .

tfethods Bmployed; Quantified data on maternal attitudes and behavior
were intercorrelated, and the methods of factor analysis and Guttman's
radex analysis were used to discover a simple nomological network within
the concepts.

Major Findings Both methods revealed two major dimensions of both
maternal attitudes and behavior \*iich were labelled Love vs. Hostility
and Autonomy vs. Control. These two dimensions included most of the
common factor variance of maternal behavior with the child. The dis-
covery of this order among the maternal behavior concepts was general-
ized -ahen it was fovmd that other published data on maternal behavior
could also be organized by this two dimensional scheme.
Significance to the program of mental health research: Recent studies
of personality development in psychiatry, sociology, and psychology have
emphasized the great importance of the family and^ of the mother.

11^ »

Serial No. M-P-D-(C)-6-page 2

Part A, continued:

Significance to the program of mental health research continued;
Although there is some concensus about the important variables, due to
different teiminologies and to the apparent complexity of the data, no
organized conceptual scheme vAiich could integrate this research has
been available. It appears this two dimensional organization of
maternal behavior vdiich we are developing would make it possible to
integrate many of these researches.

Proposed Course of Project : Ripers on this organization of maternal,
behavior and attitudes are being prepared. Rirther confimation and
amplification of the conceptual scheme will be attempted in conjttnction
with other projects and from other published data.

P&rfc B included Yes 7 7 No ^J

- 115 -

Serial No. -M-P-D-(C)-7
1. Laboratory of Psychology
PiB-NIH 2* Child Developnent Section

Individiml Project Bsport 3, Bethesda

Calendar Year I957

Fart A.

Project Title: Development of a Maternal Behavior Research ]jastrument .

j Principal niivestigators : Earl S. Schaefer, Richard Q. Bell and

! Nancy Bayley.

Other Investigators: None

Cooperating Units: None

Man Years: Ifeitient Days:

Total: .67 None

Prof e s sional : . kO

Other: .27

Project Description: Objectives; The pui^pose of this research was to
develop a conceptual scheme and a method ofguantifying maternal behavior
I both from behavior observations and interviews. In order to be able to
test theories of the effects of maternal behavior upon personality
development of children it was necessary to organize two sets of data
that had been collected by Dr. Bayley at the Institute of Child Welfare
at Berkeley.

Lfethods Biiployed: The set of concepts vftiich had been developed by
Schaefer and Bell in the project which developed the I^rental Attitude
Research Instrument were revised and attional concepts were added.
Several trait-actions or specific behaviors were specified \daich de-
fined each of the abstract concepts. Each of the trait-actions were
rated on a seven point scale by each of the three judges for each case.
^ combining the several trait actions vftiich defined each abstract
concept and by combining the ratings of the three judges reliable
scores on the maternal behavior concepts were obtained. This method
was applied to sets of ten to twenty observations on each of 56 mothers
on ^ftiom notes had been written from the child's age of one month to
three years and to 3^ sets of one to two interviews with the mothers at
the child's age of approximately ten years.

Major Findings; The method insulted in reliable ratings of maternal
behavior from both behavior observations and from inteiviews. It was
possible to define the abstract general concepts with specific be-
haviors of mothers and to get agreement between judges from un-
structiired written behavior observations and interviews ;diich had not
been collected with this conceptual scheme in mind.

^ 116

Serial No. M-P-D-(c)-7-page 2
Part A. continued:

Significance to the program of mental health research: Clinical re-
ports have emphasized the contribution of the mother to the personality •
development of the child yet few attempts have been made exactly to
define or to quantify the concepts used. Many longitudinal studies of
personality development have collected unstructvired observations and
interviews with mothers but no method has been available with •vrtiich to '
quantify these data in terms of social -interaction concepts. The
development of this rating scale will permit quantification of ton-
structured observations, interviews and clinical descriptions of mother-;
child interaction and will assist in testing theories of maternal influ-i,
ence upon personality development.

Proposed Course of Project : A paper on this project has been prepared
and is being submitted to Child Development . The method will be used
in future research. Project completed.

I^rb B included Yes /""T" No jTJ

- 117

Serial No. M-P-D-(C)-8
Laboratory of Psychology
PHS-WIH Child Developnent Section

Individiial Project Beport Bethesda
Calendar Year 1957

Part A.

Project Title: Origins of Bnotional Dependency in Early Childhood:
An Experimental Program.

Principal Investigator: Jacob L. Gewirtz

Other Investigators: None

Cooperating IMits: None

Man Years: rfe,tient Days

Total: I0O7 None

Professional: .'+5

Other: ,62

Project Description: Objectives; To enauguiate a program of research
in infants and young children on the basic acquisition processes under-
lying 'emotional dependence'. It is intended to focus particularly
upon children's behaviors like those employed to gain such positive
social responses from adults as their attention, affection, approval,
nearness, and caresses, and upon the earliest environmental conditions
under v4iich they develop.

Methods employed: Proceeding both from simple learning and performance
concepts and from such theories as are available for tracing the early
developnent of emotionsil dependence, it is intended to analyze the
apparent complexities of that behavior class into skeletal terms, so
that they may be related in a simple manner to the fundamental mechan-
isms operating in the developing child.

Methods are being explored with very young children vdiich reduce
to relatively simple terms the complexities of the behavior \ftiich
characterize emotional dependence in later childhood and \daich wo\ild
relate those behaviors to critical aspects of myriad environmentsil
conditions to \jhich young children are typically subject. A series of
prototype essperiments with human infants in a highly controlled insti-
tutional setting represents the core of the experimental program.
Initially, these experiments will attempt to relate effects in the
child's pattern of emotional dependence to variations in selected as-
pects of the caretaking process, analyzed in terms of learning con-
tingencies. At first, the reinforcing aspects of caretaking and adult
responsiveness to the child are employed as variablesj and the range of
adult responses which can function as reinforcers for the young child's
beliavior will be explored. Selected stimulus events associated with the
caxetaker are being set into a variety of contingencies with different
responses emitted by the child. In addition, the attempt will be made

- lis -

Serial No. M-P-D-(C)-8 page 2.

Part A. continued:

Methods employed continued : to determine if environmental change or
novel stimuli as, for example, noises or lights, within and without
the caretaking process, can function to reinforce the child's be-
havior.

After soma of the more common reinforcers vAiich are provided by
adult responses are deteimined, selected stimulus events (e.g., the
attention of a caretaker) involved in or attached to the caretaking
person may be set into a variety of contingencies with these rein-
forcing aspects of the cai^taking process; and selected aspects of this
process may be made contingent upon different responses emitted by the
child.

Majog findings: While this project is in its initial phase, some recent
reseaxch (with Dr. H. Eheingold) suggests that a vocal response in
three -month old infants can be conditioned through use of axi adult's
complex social response as reinforcing stimulus.
Significance to the prop;ram of mental health research: While it is
probable that an understanding of the processes underlying emotional
dependence will be critical to the understanding of a substantial
portion of the social behavior both of children and adults, potentially
useful to the theory of child rearing as well as to therapeutics, almost
nothing is known either about the dimensionality or the antecedents of
that behavior class. This research program constitutes a beginning in
the direction of gathering such information under highly controlled con-
ditions.

Proposed course of project; The "tooling -up" phase of the research
program may requii« another six months before it will be fully under
way. At that time equipment should be available to study a single
. infant at any one time. The project will require a population of in-
fants, ajid the search for such a source is now going on. Suitable ex-
perimental techniques ai^ now being devised.

Part B. included: Yes [J No f^

119 -

PHS-NIH
Individual Project Eeport
Calendar Year 1957

Serial No. M-P-D".(C)-9
1. Laboratory of Psychology
2o Child Development Section
3. Bethesda

lirt A.

Project Title;
Beinforcers

The Effects of Deprivation and Satiation on Social

Principal Investigator: Jacob Lo GevriLrtz
Other Investigators: None
Cooperating Units: None

Man Years:

Total: 1.11
Prof e s sional : . U9
Other: .62

Patient Days:
None

Project Description: Objectives : Events ^ich are the "goals" of human
social behavior are termed "social reinforcers," More specifically, a
social reinforcer is defined as a social stimulus event \Aiich, if made
contingent upon behavior, can systematically affect its output. It is
generally assumed that social reinforcers (e.g., attention, approval,
affection) have developed importance for people through a history of
conditioning.

Deprivation inrplies a period of unavailability of a given rein-
forcer \diich re stilts in an increase in behaviors for it; satiation im-
plies a period of availability of a reinforcer sufficient to effect a
decrease in behaviors for it. Thus deprivation and satiation represent
two statements of a single concept, a dimension characterized by the
relative supply of a given reinforcer in the recent histoiy of the
organism which determines the incidence of behaviors for that rein-
forcer. Laws relating long -and short-term social deprivation as an
empirically defined dimension to certain basic characteristics of social
behaviors would have considerable integrative value (d.f. , e.g.. Spitz,
Bowlby, and others )» But first the experimental operations of depri-
vation and its inverse, satiation, must be implemented in social terms.

Social reinforcers may be supplied and deprived in a variety of
ways, and it is important to discover their responsiveness to many of
these ways. It would be especially inrportant, for example, to imple-
ment the deprivation of a single social reinforcer, rather than of all
such reinforcers (as, for example, is acccanplished through social
isolation in these studies). iUrther, it is essential to Jare some
asstirance that social reinforcers are more or less homogeneous in this
regard.

- 120

Serial No. M-P-D-(C) -9-page 2

I^rt A. continued:

^fethods employed and Ma.ior Findings to date : (l) Brief social iso-
lation (equated to a condition of deprivation of all social rein-
forcers) increased reliably the reinforcing power (i.e., the importance)
of adult approval for children (aged 4~0 to 5-6) as a positive function
of the degree to ^ich they typically sought such approval in other
settings; and older children in this age range were affected to a
greater extent than were younger children. (2) In children aged 6-6
to 9-0^ it was found that brief social isolation (deprivation) enhanced
the effectiveness of social reinforcers representing approval and
social contact relative to a control condition (no treatment); and that
a brief condition of satiation for approval and social contact decreased
the effectiveness of those social reinforcers relative to the control
condition.

Significance to the program of mental health research: This project is
a beginning attenrpt to gain an imderstanding of some classes of short -
and long-term conditions constituting social deprivation, a concept of
importance particularly in the child health literature. At the sams
time it would provide additional understanding of the social rein-
forcers (social goals) important for children, and possibly an under-
standing as well of the conditions under -vAiich they develop.

Proposed Course of Project : This is a program of research: a number
of studies axe being published, and as additional studies axe completed,
new ones will be begun. As relevant variables are isolated, it is
intended that they be investigated paretmetrically -rfiere possible.

Bart B. included Yes /xj Ho [ /

- 121 -

Serial No. M-P-D-(C)-9 page 3

PHS-NIH

Individxial Project Report

Calendar Yeeir 1957

Bart B; Honors, Awards, and Publications

Publications other than abstracts from this project :

Q?he effects of deprivation and satiation on behaviors for social
reinforcers. (with D. M. Baer) American Psychologist, 1957^ 12, ^MDl.

The effect of brief social deprivation on behaviors for a social
reinforcer. (With D. M. Baer) Journal of Abnormal and Social
Psychology, in press.

A note on the similar effects of low social availability and depri-
vation on young children's behavior. (With Baer and Roth) Child
Development , in press.

- 122 -

PHS-NIH

ladivldual Project Beport

Calendar Year 1957

Serial Ho. M-P-D-(C)-10

1. Laboratory of Psychology

2. Child Development Section

3. Bethesda

Bart A.

Project Title: A screening test for selecting parents on the basis
of their attitudes toward children: relations between attit\ides
expressed during the lying-in period and later behavior with the one-
month old infant.

Principal Investigator: Richard Q. Bell

Other Investigators: Belinda Straight (Guest Investigator)

Cooperating Units: None

Man Years:

Total : 1 .21

Professional: .57
Other: .64

Patient Days:
3h

Project Description: Objectives ; To test the hypothesis that atti-
tudes toward child i^aring practices expressed by mothers during the
lying-in period are related to behavior with their infants at a later
point in time.

tfethods Employed: Primiparous mothers are assigned to a sub-group
having a characteristic attitude pattern on the beisis of responses to
a self -reporting attitude questionnaire administered during the lying-in
period. The existence of such sub-groups was established by statistical
procedures carried out in project NIMH 114(c) 1955* ^e mother's be-
havior with her infant at the time of a one -month follow-up is rated on
a variety of scales developed in project NIMH 11d(C) 1955* Similarity
of mothers on the basis of such scales should be greater within sub-
groups than between sub-groups if the parental attitude questionnaire
is related to actual interaction with infants in any ccanprehensive
way involving a variety of behavior. It is not necesseay that there
be direct correspondence between ^at the mother says on the attitude
questionnaire and how she behaves with the infant.

Major Findings: The data gathering stage has been completed, but data
Einalysis will require a major portion of the coming year. It is the
impression of the investigators that the one-month follow-up examination
used in this study provides relatively rich data on the natvae of the
mother-infant relationship. It was possible to identify five mother-
infant relationships \diich seemed incipiently pathological. This^ sug-
gested to the investigators that a future stxidy might be designed
specifically to test the adequacy of a first and second line mass^
screening approach, an initial ^screening during the lying-in period.

- 123 -

Serial No. M-P-D-(C) 10 page 2

Part A. continued. ., ^^j^,,,

Ma.ior TWrifi-ti^gs mn-h-i mie>ri ? followed by a more intensive screening in
the follow-vtp examination at one month. This type of sttaiy woxild re-
quire sampling a much more extensive population than the study i
currently underway idiich sanrpled only from specified statistical sub- |
groups.

Significance to the program of mental health research; If psychologicall|
useful suh-groups can Ije identified it will simplify statistical operatic j
involved in screening any population of young parents for those likely to
form pathological relationships with their children. A one month foUov-il)
examination could be \ised as a second-line of screening to reduce the I
margin of error in the initial screening. The present study is an initia
attempt to test out such screening operations on a limited scale with
selected sub-grovtps from a larger population.

Proposed Co\3rse of Project; Calendar year 1958 will be spent in analyz- ,
ing data now collected, and if viseful resvilts emerge sufficiently early
it should be possible to resvme screening and follow-ttp procedures to
focvis on any leads which emerge.

Part B inclTaded Yes £J Ifo ^

- 12ij- -

PHS-NIH
Individual Project Report
Calendar Year 1^7

Serial No. M-P-D-(C)-11
Laboratory of Psychology-
Child DevelopmentSection
Bethesda

Part A.

Project Title: Early Infant Personality Characteristics;
orality, activity, and sensitivity in neonates.

Principal Investigator: Richard Q. Bell

Other Investigatoi-s : None

Cooperating Units : None

Stvidies of

Man Years:

[Dotal: .97

Professional: .33

Other: .6k

Patient Days;
None

Project Description: Objectives : The objective of this project is to
obtain some precise measures of infant characteristics in the immediate
post-natal period. These characteristics will be vised to test the hypo-
thesis that infant types exist prior to exposure to maternal care.
Methods Employed: Ifotion pictvire records have been made of 31 infants
96 hoturs old from Tdiich estimates are being made of cutaneous and kines-
thetic sensitivity, auditory sensitivity, visual sensitivity, depth and
amount of sleep, strength and muscle tone, reaction to fnxstration,
feeding characteristics, nature of crying, and appearance. Measurements
of feeding characteristics are based on an apparatus which when filmed
in -oae reveals i^te, rhythm, and vacuum created in sucking. Other
variables are estimated by rating infant behavior directly. Precision
is achieved by repeated viewing of the films and making direct compari-
sons between babies. Film records have also made it possible to detect
and evalixate the effects of any deviation £rom standard circumstances
or test administration at the time observations are being made.
Major Findings: Although reliable rating of infants at this age has
been diffictilt to achieve in other studies, use of the film technique
has made it possible so far to achieve reliable measures of five of the
variables rated xip to date. No findings will be available vmtil the
remaining ratings are completed.

Significance to the program of mental health research: Research on the
effects of parent behavior on the emotional adjustment of children is
handicapped by the fact that different children provoke different be-
havior from their parents as well as react differently to their parents.
Att^Dpts by other studies to identify congenital patterns in infants
have'led to confusing results since very little consistency on individual
measures has emerged over time. The present study will attempt to
identify congenital infant types, and test the notion that infants will

125 -

Serial No, M-P-D-(C)-11 page 2

Part A. continued*

Significance to the program of mental health research continued; at
later points in time fall into the same generic tjrpes even thou^ Hie
basis of their being grouped has changed due to metamorphic growth
processes* Thus consistency of pattern may be demonstrable in spite
of lack of consistency in individvial measures correlated over different
time periods.

Proposed course of project; The ratings should be completed during
this calendar year and some information on vhether clxisters or types
e:d.st should be ascertainable soon thereafter. During calendar year
1958 these data will be related to observations made on the same in-
fants at one month. This project serves an independent purpose in
studying congenital patterns in infants as well as providing control
data for a related study NIMH— P-3(C) \riiich compares mother-Infant
interaction in mothers grouped into one of five groups based on an
attitude questionnaire. Dils project provides data on vhether the in-
fants bom to the mothers in the jM.ve grovgps differ significantly prior
to leaving the maternity hospital.

Part B included Yes / / Kb /TJ

- 126 -

Serial No. M-P-D-(C)-12

1. Laboratory of Psychology

2. Child Development Section

3. Bethesda

PHS-WIH

Individual Project Report

Calendar Year I957

Fart A«

GOC

Project Title: Further Studies of the Conditioning of Vocal
,.f,~ Behavior in the Human Infant.

Principal Investigator: Harriet L. Rheingold

Other Investigators: None

Cooperating Units : None

Man Years (calendar year 1957) > Patient Days (calendar year

1957) :
Total: .05
Professional: .05
Other :

Project Description:

Objectives : The results of the first study suggest that the
social vocalizations of three -month-old infants were conditioned
(i.e. increased) by means of a social reinforcer. Several ques-
tions were raised and require further study before the results
can be unequivocally attributed to the experimental procedures.
The first of these asks to what extent the stimulating properties
of the reinforcer might have been responsible for the increase
rather than its having been made contingent upon the child's
vocalizing. The second asks whether home babies woxild respond
similarly to the original institutional subjects. The third
asks questions about the effect of different schedules and their
use over longer periods of time.

Methods Employed: Both home and institutional babies will be
used. Intensive studies will be made of a few children, now
that a result has been demonstrated in large groups of infants.
To test the stimulating properties of the reinforcer, the re-
inforcer will be administered at regular intervals (e.g. 10"
apart) but never directly after a vocalization. To further
test the possibility that operant conditioning did occiir in
the original experiment, some work should be done with different

- 127

Serial No. M-P-D-(C)-12, page 2

Part A. Project Description Sheet (cont'd.)

schedules, with both fixed and variable ratios, with recon-
ditioning after extinction, with continuing conditioning until
certain predetermined rates of vocalizing are obtained.

Major Findings; These studies are in the planning stage.

Significance of the program to MenteuL Health research; If con-
ditioning of any behavior can be obtained in the three -month-old
hiunsin infsmt, we have learned an important fact about human
learning. If, further, social behavior proves to be modifiable
by environmental response, specifically a social response, we
are closer to accounting for early differences in sociability.
Finally, since the social behavior here studied is vocal, we
may obtain clues to the later use of speech for social and
perhaps other purposes.

Proposed coiirse of the project; The study will be begun in the
next month or two. ' ■ — '^"

^a^Q-i-i

j.^-::.";-i.v. ^li*z.- 'j'^^.i.-

Part B included Yes £J No /x7

- 128 -

Serial No, M»P-D-(C)-13

1. Laboratory of Psychology

2. CTnild Development Section

3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: The Chick.' b Preference for Some Visvial Properties
of Water.

Principal Investigator: Harriet Lo Rheingcld

Other Investigators; Dr. Eckhard H. HesSj, Department of Psychology,
University of Chi sag: .

Cooperating Unite; None

Man Years : Patient Days :

Total; .20 None

Professional : ,10

Other ; ,10

Project Description: Objectives: The chick discovers and drinks
water ver-y soon after ha-oching, "On tiie ass'osrption that water must
possess some sharacteristie or pattern of characteriscics which
draws the chick to itj, we set out to asalyze t-he "attractiveness"
of water "s visxjal properties. The questions asked were: What are
the visual properties of water which attract the naive chick? To
what extent are these changed as the chick acquires experience with
water?

Methods Employed: Kewly-liatched chicks were presented with an array
of six stimuli;, namely waber and five other siibstaaces,, each of which
possessed some 5 but not aH, of the visual attributes of water. The
subjects were 100 White Rock ehiclcs. Seventy- two of these, having
no experience with food or water, were tested at the age of three
days. Twenty-ei^t ■%rere control chicks also tested at the age of
three daysp but these had been given food and water from the time of
hatching. All animals were t-ested again foijr days 3,ater^ both
experimental and control an.t!Bals having had access to food and water
in the interval, except for 1.2 hoinrs of ^■ratev deprivation just prior
to the tes-So

Major Findings : The distributions of responses given hy experimental
and control euiimals at both ages were sii^ilar. The order of stimuli
for chicks three days old was mercury, plastie_, blue water, water,
metal, and red water. Ejcperience with i^ater did not alter the

- 129 -

Serial No. M-P-D-(C)-13 page 2
Part A. Project Description (cont'd.)

position of mercury as first "choice" and of water as foiorth.
It seems proTjatle that attractiveness to the chick lies in a
comhination of a "bright reflecting surface and the movement of the
stimulus .

Significemce to Mental Health Research: Some investigators "believe
that "behavior may "be released "by stimuli which are prepotent for
the species, i.e., that certain stim\xLi are "innately releasing."
While this principle may "be truer for lower-order species, it may
also account for some of the "behavior of other species, e.g. the
human infant. The present study demonstrates a method "by which
this principle can "be tested.

Proposed Course of Project: This study was executed in I955 at the
University of CJhicago. It was prepared for pu'blication at NIH in
1956, and in 1957 i't was accepted for pu'blication by the Journal of
Comparative and Physiological Psychology.

Part B included Yes /T/ No / :: /

- 130 -

Serial No. M-P-D-(C)-13-page 3
PHS-NIH
IndividueLL Project Report
Calendar Year 1957

Part B; Honors, Awards, and Publications

Publications other than abstracts from this project :

Rheingold, Harriet and Hess, Eckhaiti. The Chick's Preference for Some
Visvial Properties of Water. Accepted for publication by the Journal of
Conrpsirative and HiysiologicaJ. Psychology.

- 131 -

Serial No. M-P-D-(C)-lll-
,.-,-> 1 . Laboratory of Psychology
'"-''"'' "~ 2. Child Development Section

3. Bethesda ,.:,: ^ . ^

p . ... Individual Project Report - -■.:■-,.._.-
,:T..., , -r. Calendar Year 1957

Part A.

Project Title : Increasing Social Vocalizations in the Infant by
Means of an AdixLt's Social Response (formerly: Ttie effect of
social reinforcement upon social behavior in the hvanan infant:
the effects upon vocal behavior.) -^ ^^r-

Principal Investigator: Harriet L. Rheingold ,q r■,e.c,,•^cfo'3:^

Other 3Javestig^tP?§.: Jg,c9b,,ii. Gevirtz -•■-*

Cooperating Units: None

Patient Days:
2

Man Years:

Ibtal:

.90

Professional :

.ko

Other :

.50

Project Description: Objectives : Vocalizations are a prominent
component of the response three-month-old infants give to an adult.
In turn, adults often respond to -Uiese vocalizations. If the
advilt's responses are made contingent upon the infant's vocalizing,
thus functioning as a social reinforcer, will the infant increase
his rate of vocalizing?

Methods Employed: Twenty-two three-month-old infants were studied
in two separate experiments. In one experiment 11 babies were
reinforced by one experimenter; in the other, 11 different babies
were reinforced by another experimenter.

The basic unit of measure was the nimber of discrete vocali-
zations produced by an infant during three-minute periods. Vocal-
izations were coimted for nine three-minute periods distributed
throughout a day.

In the baseline condition, the first two days, E leaned over
the baby and looked at him with an expressionless face. Uilder
conditioning, the next two days, E reinforced vocalizations by
simulteineously smiling cluclcing, and lightly pressing the infant's
abdomen. During the last tx<ro days, extinction, E retvirned to the
expressionless face of the baseline condition, and made no response
to the infant's vocalizations.

Major Findings : By means of the social reinforcer the number of
vocalizations was raised from the baseline mean of 13 to a mean
of 2k.Qf an increase of 86.5^« Removing the reinforcer depressed

- 132 -

Serial No. M-P-D-(C)-lU page 2

Part A. Project Description (cont'd.)

the rate until "by the second day of extinction it was close to the
level of baseline performance. The results suggest that (a) verhal
"behavior produced by three -month-old babies in a^ aocial situation
can be very quickly broii^t under control and ^t) eui everyday
complex of acts, typical of a mother's social behavior can function
as a reinforcer. • "

Significance for Mental Health Research; This is part of a larger
inquiry into how different components of mothering influence the
development of social behavior in the human infeint.

Proposed C!o\irse of Study: The study has been completed sind the
data analyzed. It was reported at the 1957 American Psychological
Association meetings eind now is being prepared for publication.

Part B included Yes £J_ No ^

' 133 -

Serial No. M-P-D-(C)-15

5scr •?I-(5)-fr-^-M .oW Xst-x^v. j.. Laboratory of Psychology

2. C3iild Development Section
3 • Bethesda

PHS-KIH
Individnal Project Report
Calendar Year I957

Project Title: A Follow-Up Study of Social Responsiveness in a
Group of Institutional BaMes.

Principal Investigator: Harriet L. Rheingold

Other Investigators: Nancy Bayley

Cooperating Units : None

Man Years : Patient Days :

Qbtal: A6 None

Professional: .20

Other: .26

Project Description: Objectives: Eight experimental infants, as
a result of special mothering, showed a marked Increase in social
responsiveness with little, if any, significant increase in in-
tellect\3al performance. One year after termination of treatment
both experimental and control babies were tested to discover if
the experimental babies showed any persisting effects of treatment.

Methods Employed; Fifteen children were located and examined
in their own homes by the second investi^tor who did not know
the children's experimental status. All but one of the children
had left the institution for their own or adoptive homes. They
were given the Cattell Infant Intelligence Scale and a specially
constructed test of social responsiveness. Incidental informa-
tion was obtained on the mother and the home.

Major Findings ; The babies were found to be living in a great
variety of different life situations. The "intellectual" per-
formance of both groups was practically identiceil . The experi-
mental subjects, however, were more responsive ("Hhen positive
and "negative" reactions were given equal weights) than the
control subjects (£ at the .1 level). Especially interesting
were the marked ne^tive responses shown by two experimental sub-
jects.

Significance for Mental Health Research; Generally it is assumed
early ejcperience will affect later behavior. This study seeks to

„ 132+ .

Serial No. M-P-D-(0)-15 page 2

Part A. Project Description (cont'd.)

discover the extent to vhich this assxanption may "be accepted in the
case where social behavior vas modified in the sixth, seventh, and
ei^th months of life and then assessed one year later.

Proposed Course of Project: The data have "been analyzed. The study
will be written up for publication.

Part B included Yes £J No ^

' 135 -

Serial Wo. M-P-D-(C)-l6

1. Laboratory of Psychology

2. Child Development Section

3. Bethesda

PHB-MIH

Individiial Project Report

Calendar Year I957

Part A.

Project Title: The Differential Responsiveness of Infants to
Familiar and Unfamiliar Persons.

Principal Investigator: Harriet L. Rheingold

Other Investigators: None

Cooperating Units: None

Man Years : Patient Days :

Total: .38 None

Professional: .I5

Other: .23

Project Description: Objectives : It was predicted that infants
responsive to the social overtures of a person iJith whom they
were familiar, .; . -n though this person had performed fevf, if any,
caretaking acts for them, than they would be to a person totally
strange .

Methods Employed: In order to test the proposition the re-
sponses of '+0 institutionalized infants, k to 10 months of age,
were obtained to three different persons. The first v/as the
person in charge of the floor who had some contact with all the
babies but who did not routinely perform caretalcing services for
them. The second was an unfamiliar person who \Tore the same
distinctive garb as the first person. The third person had never
been seen by any of the babies before the day of testing. In
garb she did not resemble the first person but instead the class
of persons who regularly cared for the babies. The order in
which the three persons presented themselves to the babies was
systematically varied.

Major Findings: The infants appeared to be most responsive to
the third person, the stranger. Tvro possible explanations are
being explored. One is tliat the stranger possessed greatest
novelty value. The -second is that the response to the stranger
represents a response which has generalized from the infants'
experiences with caretakers who, in general, were constantly

- 136 -

Serial No. M-P-D-(C)-l6 page i
Part A. Project Description (cont'd.)

changing persons (volunteers).

A more detailed analysis is now in process. Contemplated are
studies of the contribution each subtest makes to the total score;
of the extent to which subtest scores cast light upon the mechan-
isms responsible for the differences in response to the three
persons; of the ratio of positive to "negative" responses accorded
each person; of number of vocalizations made by the infant in re- ■
sponse to each person; of changes in response with age. Responses :
can be compared with those given a constant caretaker (obtained froit
an earlier study).

Significance for Mental Health Research; This study is part of a
larger program which seeks to explore the development of socia-
bility in the infant. It is assumed that early manifestations of
social behavior influence later behavior and that social behavior
is central to an understanding of personality. i

Proposed Course of Project; The data have been gathered and are
being analyzed.

Part B included

Yes fj_ No ^

- 137 -

Serial No. M-P-D-(C)-1T

1. Laboraix)ry of Psychology

2. C!hild Development Section

3. Bethesda

PHS-NIH
Indlvidioal Project Report
Calendar Year I957

Part A.

Project Title: The Effect of a Strange Environment upon the Behavior
of Infants.

Principal Investigator: Harriet L. Rheingold

Other Investi^tors : None

Cooperating Units : None

Man Years: Patient Days:

Tbtal: .55 I8

Professional: ,30

Other : , 25

Project Description: Objectives : It is predicted that infants,
even in the first few months of life, are sensitive to changes in
both the physical and hi;raan components Of their environment. This
stvidy seeks to discover the kinds of behavior which are affected
by change, the degree to which they are affected by sittiations
reinging from minimal to maximal change, individTial differences in
reactions eind the relationships between these variables and the
infant's age.

Methods Employed: Severeil related studies are planned, using
home and institutional babies, in situations which involve differ-
ent kinds and aaaounts of change. The first pilot study is being
carried out on twins, who are examined at monthly intervals both
in their home and in the Clinical Center, usually on successive
days, the order of place of examination being alternated regularly.

Major Findings : By the fifth month of age the babies began to
give a more restricted performance at the Clinical Center on the
tests used, that is, on tests of social responsiveness to the
mother and to a stranger, and on tests of developmental progress.
At present the twins are eight months of age.

Significance for Ifental Health Research; The general problem is
the charting of the gro-v/ing awareness of, and sensitivity to, the
environment in the human infant. The problem caai be attacked by
measuring his responses to changes in his environment. The term

- 138 -

Serial Kb. M-P-D-(C)-1T page 2

Part A. Project Description (cont'd.)

"environment" is conceived "broadly and includes l)oth people and things.
Some changes may produce an acceleration of growth, some may inhibit
it. In another sense, change may he viewed as frustrating, and the
alternations in "behavior as modes of defense.

Proposed Course of Project; The twins will "be examined monthly
•until they are twelve months old. After the resvilts are analyzed,
a more definitive study will he set vp.

Part B included Yes £J No Jx/

- 139 -

NATIONAL INSTITUTE OF MENTAL HEALTH

Clinical Investigations
Laboratory of Psychology — Section on Personality

BUDGET SHEET

ggtlmated Qbligatigns fpr,n:.,19'?8
Total: $92,675
Direct: $69,597

Reimbursements : $23 , 078

Projects included! M-P-P(C) 1 through ^^.P-P(C) 12

Serial No. m-P-P°(C)°1

lo Laboratory of Psychology
2o Section on Personality
3e Bethesda

PHS-NIH

Individiial Project Report

Calendar Year I957

Part A.

Project Title: Communication of Value Systems Between Therapist and
Schizophrenic Patients

Principal Investigator; Itorris Be Parloff^ Ph^Ds

Other Investigators; Norman Goldstein^ MeDa^ Boris Iflxindj, Ph^D.

Cooperating Ifoits: None

Man Years (calendar year 1957: Patient Days (calendar year 1957):
Total: ..68 None

Professional: *20
Other: .H8

Project Description:

Ob.lectives; To devise techniques for the study of the process by which
the schizophrenic patient learns the therapist's value system re^
garding therapy, and by which the therapist learns the patient's
values..

Methods •p^rrplnypd; Topics introduced by schizophrenic patients in daily
psychotherapy sessions were recorded by observers and presented to
the i)atient and therapist at the end of each session s. Topics were
independently rank ordered by therapist and patient regarding im»
portaace for therapy s. Each participant also predicted the sortings
of the other « Changes in understanding and convergence of values
over time was compared for inrproved and unimproved patient*

Patient Material; The study focusses on two paranoid schizophrenic
cases treated individually by the same therapist over a period of
approximately two years » One patient recovered »

Major Findings:

1* The therapists values regarding the ingrartance of content for
psychotherapy is communicated to the patient*.

2» Acceptance by the patient of the therapist* s values varies

consistently with such factors as day of the week and therapist's
responses and activity level «

l^i-O

Serial No. M-P°P-(c)-l-Page 2

Part A. Project Description (Coat'd)

3. A positive relationship was foimd laetween the therapist's mode
of response to a topic ("approving" or "disapproving") and the
rate at which the patient subsequently introduced the topic.

k» Although the patient's choice of topics appeared to he con-
sistent with the therapist's expressed values, the patient's
own evaluation of these topics in some instances, moved quite
independently .

5. A patient's verbal "behavior may appear to be superficially
compliant to the unconsciously expressed expectations of the
therapist, without the patient having internalized such
therapist-values .

Significance to the Program of Mental Health Research: Basic to the
understanding of psychotherapeutic treatment of schizophrenia is
the tinderstaading of the interrelationships between therapist
and patient. It is this relationship that provides the con-
ditions which permit the patient to learn that it is safe to
give up his defenses and to learn more adaptive ways of re-
lating. The above technique permits the study of the factors
influencing the learning process which occurs in theraiy.

Part B included - No

1. Laboratory of Psychology
2;. Section on Personality
3i. Betliesda

Individual Project Report
Calendar Year 1957

Part A.

Project Title: Nature and Stability of Psychiatric Nurses Concepts of
Their Roles

Principal Investigator; Morris B* Parloff^ Ph*D»

Other Investigators; Charlotte Schwartz, M.A. , TAn* G» Jenkins^ M.-D^

Cooperating Iftiits; Adult Psychiatry Branch, Socio^Environmental Studies,

and Laboratory of Clinical Sciences

Man Years (calendar year 1957)' Patient Days (calendar year 195*/);
Total: *88 None

Professional; =20
Others «68

Project Description:

Objectives ;

1« To develop an instrument for measuring nursing role concepts*
2. To describe the "Ideal Nursing" concepts of psychiatric nvirses
at NIMH and to compare them with (a) "Ideal Nursing" concepts
of varying degrees of psychiatric training and (b) other re= ill

lated professions® views of the '"Ideal Nursing" concept e^g^, ''

administrative psychiatrists # psychotherapists, attendants etc.
3 c. To investigate the relationship between initial nursing^role f

concepts of staff members and (a) professional ident if i cations #

(b) nature and extent of training^ and (c) experience*.

U, To study the relationship between nature and extent of changes '
in nursing role concepts and (a) the initial discrepancy be-
tween the "prescribed" role and the individual's own role
concept^ (b) time of exposxire to prescribed philosophy^

Methods Employed; A 60 item Q^ssatple was devised<» This Q-^deck
consists of statements describing attitMes and behaviors of
psychiatric nursing personnel in dealing with psychotic patients.
These were sorted periodically by all staff members of the Adtalt
Psychiatry Branchj. NIMHo The attitudes of staff members on each
ward were ccmpared with the '"nursing role" concept of the ward
administrator. Data were obtained from 23 psychotherapists^

- 1^1-2 =- I

Serial No. M°P-P-^(C)-2 - Page 2

Part A, Project Description (Cont'd)

5 ward administrators (psychiatrists) an experimental grot^ of 19
psychiatric nvjrses and a control group of 19 psychiatric niirses.
The study covers a period of two years during which each of the
five administrators attempted to establish different treatment
philosophies on wards treating chronic schizophrenic patients.

^fel.1or Findings;

1. Psychiatrists and nurses showed consistently different con-
cepts of the preferred psychiatric nursing role.

2. Nurses initially show small but statistically significant
modification of their nursing concepts in the direction of
the new ward philosophyi however, these changes were unstable
and disappeared in time.

3. The less acceptible a ward administrator's philosophy was to
nurses initially, the less it was finally accepted by them even
after 21 months of exposure to it.

Significsmce to the Program of Ifental Health Research; The ward

administrator who wishes to conduct research regarding the natxire
and effectiveness of a given "ward milieu" philosophy is dependent
on the nursing staff for the faithful implementation of his ideas.
This raised basic questions regarding the processes of accomplishing
the goals of communication and acceptance by the nurses of the ex-
perimental philosophy. Our findings suggest that in selecting a
ward staff, attention should be paid to the fact that (l) Training
differences between psychiatrists and nurses may result in basic
differences in expectation regarding nursing roles, and (2) The
nvirses' concept of her position may effectively limit the kinds
of ward atmosphere that may be established.

ProTX>sed Course of Pro.lect; Project has been completed and paper is
heing prepared for presentation at the Annual Meeting of the
American Psychiatric Association in San Francisco, May 1958.

Part B included = No

Serial No. M°P-P°(C)

1. Laboratory of Psychology

2, Section on Personality
3e Bethesda

PHS-HIH
Individual Project Report
Calendar Year 1957

Part A»

Project Title; Evaluation of the HIH Research Associates Training Program

Principal Investigator; bforris B« Parloff, Ph,D«, Herman Turk, M.A.

Other Investigators; Donald S. Boomer, Ph.Do, Allen To Dittmann, Ph.D.,

Joseph Ho Handlon, Ph.D., James Kincannon and
Marvin Waldman, Ph.D.

Cooperating IMits; laboratory of Socio-Environmental Stvidies

Man Years (calendar year 1957) J Patient Days (calendar year 1957):
Total: .85 None

Professional: .31
Other: .511^

Project Description;

Ob.lectives; To prove data permitting the directors of the Research
Associate Program to evaluate:

a) The extent to which the program meets the goal of communicating
basic research philosophy and techniques to the medically trained
investigator.

b) The reactions and recommendations of trainees currently in the
program.

Methods Enrployed;

1« Open<=end and structured interviews at regular intervals with
the entire Research Associate group on individual career
aspirations and reactions to the Program.

2. Analysis of background data on the Research Associates to pro-
vide a framework for 1. above.

Mft^^n-r TJHwfU^ripfg? Cannot be reported as yet.

Significance to the Program of Mental Health Research: One of the
basic problems of any research organization concerns the question
of selection of personnel and provision of the appropriate setting
to enhance the research capacity of the individual. This study

. m.14. „

Serial No. M~P-F-(C)«3 - Page 2

Part A. Project Description (Cont'd)

may provide some preliminary notions concerning the nature of the
intricate relationships "between l) the capacities of the investi-
gator-trainee, and 2) the attributes of the training setting in
assisting the Investigator to utilize his potentialities creatively.

Proposed Coxnrse of Pro.lect; Periodic data collection will extend over
a period of about two years. A preliminary report will be made on
or about November 13, 1957*

Part B included - No

- 1^5

Serial Ko=

1. Laboratory of Psychology
2« Section oa Personality
3o Bethesda

PHS-ISIH
Individual Project Report
Calendar Year I957

Part A,

Project Title; Attitude Changes in Nurse Trainees Subsequent to
Psychiatric Training

Principal Investigator; Morris B<, Parloff, Ph.D.

Other Investigators; Donald S. Boomer, Ph.D., Marvin Adland, M.D,

Cooperating Ifeits; Chestnut Lodge, Rockville, Maryland

Man Years (calendar year 1957) s Patient Days (calendar year 1957):
Total: ,58 None

Professional; .30
Other;. 28

Project Description;

Objectives;

1. To determine the "nurse-patient" attitude of nurse trainees
prior to and following three months of psychiatric training o

2. To investigate the relationships among personality variable®,
conditions of training and nattore and extent of changes sub-
seijuent to training.

3« To determine the relationship between "suceess" in psychiatric
field work and personality and attitude measures.

Methods Employed; Before and after a 3 month field work placement at
Chestnut Lodge, 62 nurse trainees described their concepts of
"Ideal Nxjrsing" of psychotic patients, con5)leted the Welsh Anxiety
and Repressions Scales, the Fascism Scale, and the Leary Inters
personeQ. Checklist. The staff nurses were similarly tested. The
nature of changes will be related to the personality measures
available. Each student is graded on theory and practice. These
grades will be related to (a) degree to which the students* final
attitude approximates that of the staff nurses' and (b) the degree
of authoritarianism, "Anxiety and Repression",

tfetjor Fiadtogg;

1, Nurses scoring high on the Fascism scale have significantly
less "permissive"' attitudes toward psychotic patients than do
nurses low on the Fascism scale.

» li^6 -

Serial No. M-P-P-(C)-t^ - Page 2
Part A. Project Description (Cont'd)

2» In the course of the training progrMn, students^ personeility
(as measured by the above instruments) show the following
changes: significant decrease in "repression", a tendency to
be less anxious, and significantly less authoritarian in their
general attitudes.

3. Nursing Role Concepts are altered generally in the direction
desired by the training staff with the exception that trainees
reveal a significantly increased emphasis on "Riysical Care".
This latter finding may be interpreted as a response to covert
training or an anxious reaffirmation of basic nursing concepts.

k. Nurses who subsequent to training decided to enter psychiatric
nursing revecJ. a significant increase in emphasis on "Qnotlonal
Care" of the patients. This change is not found in nurses not
desiring a psychiatric nursing placanent.

5» No relationship was found between personality measures and
success as measured by grades received.

Significance to the Program of Mental Health Research; Information
regarding the selection and training of nursing personnel is of
importance to NIMH in view of the heavy emphasis placed on the
establishment of a therapeutic ward milieu to facilitate treat-
ment of schizophrenic patients. Since the nurse is expected to
play a critical role in this program, information which would
facilitate appropriate selection and subsequent training would
be useful.

Proposed Course of Pro.iect; These and other findings have been
prepared for publication. A paper also is to be read at the
American Psychiatric Association Annual Meeting in May 1958 •

Part B included = No

- 1^4-7 -

Serial No. M«»P-P-(C)-3

S.<^ Laboratory of Psychology

2« Section on Personality
3o Bethesda

Part A.

Project Title: The Process of Change and the Conmnmication of Value
^sterns in Psychoasmlyfcie Therapy

Principal Investigator: Morris B, Parloff, PhaD,, Seymour Perlin, M.D,

Other Investigators: None

Cooperating Units: Laboratory of Clinical Sciences

Meua Years (calendar jrear 1957) J l^tient Days (calendar year 1957)5

Total: .US 1 in°patient = 30 patient days

Professional: ,20 3 outpatients = 30 patient days
Other: .28

Project Description:

Ob.lectives: To study the nature and direction of change in:

1) VaQ.ue systems of the analysand, analyst and control analyst.

2) Perceptions of self and each other during the period of
psychoanalysis (approximately 2 years).

3) Psychodynamics of the analysand.

Methods Tgrnployed; Data collection techniques include two Q-sorts that
are administered to all participants periodically during the
treatment period. One Q-sort is descriptive of "Moral Values"
and the other descrihes attitudes and "behavior ranging from
normal to pathological. A "battery of psychological tests are
administered at six month intervals to each of the patients.

Patient Material; Three psychoneurotic outpatients and one ambulatory
schizophrenic patient "began trealanent with Dr. S. Perlin approxi-
mately l8 months ago and have continued to date. Each case is
imder the supervision of a different "control" analyst. These
nine individuals are the subjects of the study.

Ma.ior Findings; No detailed analysis of the data has "been xjndertaken
since material is still "being collected.

Significance to the IFtogram of Mental Health Research; This study is

^■■■■iMIMliwiJiiilB.ii.lwiiiiiLiiluMliiiM.ii>wiiiiw wfiliiiinpiWiiMm"iii 1 IT n Trwrrnfmifiiiiii iii'iiiTnfnnnrTTtnTriin"Ti'-T~iMiiirrTT~~'^~^^--~' *

consistent with the NIMH general interest in psychotherapy for it
attempts to investigate some aspects of the psychotherapeutic
I'process and the natere of changes effected in patients whose
-treatanent is carried through to "eoi^Ietioa'" . One focus of this

I'^S

Serial No. M-P-P-(C)-5 - Page 2
Part A. Project Description (Cont'd)

study takes up the popularly raised question that since effective
therapy is an "attitude change** and "influence" procedure, the
patient in addition to "being assisted to modify his pathological
perceptions may he influenced to take on the moral values of the
therapist. Another area of significance to HIMH is the emphasis
on descrihing the nature of the changes in the patients' personality
over a period of extended intensive therapy.

Proposed Course of the Pro.ject; The final rete sting of patients is
currently underway. The data will be analyzed and presented for
publication.

I^t B included - No

- li^9'

Serial No, M"P-P-»(C)-6

Laboratory of Psychology

Section on Personality
Bethesda

ras-KiH

Individual Project Report
Calendar Year 1957

Part A,

Project Title: Development of an Ego-Integration Conceptual System

for Studying Psychotherapy

Principal Investigators; Donald Se Boomer^ PhoD*^ D» Wells Goodrich, McD,
Other Investigators:

Cooperating Units: Community PsycMatric Clinic in Rockville^ Mi»,

Washington Mental Health Clinic, Laboratory of
Clinical Sciences, and Section on Personality Theory

Man Years (calendar year 1957): Patient Days (calendar year 1957) J
Total: 1.72 Outpatients - 42 patient days

Professional: «80
Other: .92

Project Description:

Ob.lectives : (l) Lomg-term: To develop a theoretical model and observa-
tional tools for the purpose of generating and testing a network
of hypotheses about the conditions of personality change.
(2) Immediate: To organize a loose set of clinical-theoretical
ideas and observations into a coherent model, as indicated above,
and to determine the feasibility of observing certain critical
changes in patient behavior during psychotherapeutic sessions »

We are concerned with the moment->to=moment level of ego°
integration in the patient in his dealings with the therapist*
We have conceptualized and hope to be able to identify in action
■ four pattern® of ego integration smong •atoieh patients are pre°
simied to shift during a therapy session* These have been carefully
spelled out, but for the purpose of this report, brief descriptive
summaries must swffiees

Defended (f.) - The patient is controlling anxiety by his
customary means, and is functioning at his characteristic
level, involuataz'ily revealing frcm time to time, the ego-
distorting aspects of his defensive fusietioning.
Partially defended (^_»)^ - Similar to f «, but less stable
and ccanfortableo Patient displays some readiness to move
toward a suspension of hi® defenses, with eeneciBitant pre°
monitory an3d,aty<,

- 150 -

Serial No, M"P-P-(C)-6 - Page 2

Part A, Project Description (Cont'd)

Self observing (o.) - The widely-described "split ego" state
in which the patient is monitoring his own behavior and
considering simultaneously, or in rapid alternation, hie
feelings, his behavior and his defenses.

Decompensated (co) - The overwhelmed ego: Anxiety is so high
as to submerge defenses, disrupt some or all ego functions, i
and interfere with interpersonal and task-directed functioning. ]
This may be a clear open panic state or a transitory disturbance^!
virtually unnoticeable unless reported by the patient.

Methods Enroloved; The investigators function together as a therapist-
observer team, utilizing a one=way observation screen and a tape
recorder for monitoring and recording the content of the inter-
views. Each investigator functions periodically as observer for
the other's psychotherapy. In addition to the content of the hour,
the observer's amplifying description of non-verbal events is
electrically recorded.

These records provide a basis for regular discussion aimed
at refining our concepts and operations. In addition to the
theoretical work, we are exploring a set of verbal measures which
we hope to use in the context of the ego-state model.

Our effort at present is primarily focused on two such measures:
(l) Speech disruptions, and (2) The interpersonal locus of the
patient's productions, gauged at the manifest level.

The speech disruption measure, adapted from tfahl, is a simple
count of the incidence of a set of specified disruptions in speech,
such as stutter, superfluous repetition, tongue-slip and the like.
We are attempting to determine what effect rate of speech has on
the incidence of these speech disruptions.

The interpersonal measure we are developing consists of a
set of clearly defined categories for characterising what or whom
the patient is talking about, along a scale which ranges from
things and abstractions through Increasingly intense personal
relationships to the relationship with the therapist.

It is our aim to use these measures, together with others
yet to be developed, to define shifts in the patient^s ego state.

Patient Matfirifti i Two female psychoneurotic outpatients are currently
serving as ovcc subjects. One is being seen twice weekly by
Dr. Boomer; the. father four times weekly by Dr. Goodrich. Briefer
courses of therapy have been completed with three other patients.
We conten5)late the addition of from three to five more patients
during the coming year.

- 151 -

Serial lo<, M-P-F°-(C)-6 °> Page 3
Part A. Project Descriptioa

Sigyilficance to the Prograa: of Mental Health Eeseareh; The syste=
matie inyestigation of relevaiet aspects of psyefeotlierapy is a
salient part of the program of KIMH. This project may con-
tribute to this effort directly with suibstantive findings or
indirectly with methodological SEd conceptiual developnents
which caii "be utilized ia other parallel investigations.

Proposed Course of the Pro.lect; This work, as currently envisaged,
will continue throughout this year and well beyond. Some

carefully controlled def iaitive work will be carried out
during this year with regard to the incidence of speech-
disruptions and the correlates of high and low incidence o The
broader conceptual=t&eoretieal work of formxilating a model will
also continue along the lines outlined above o

Part B included - No

152 - ,;

Serial No. M°?-P-(c)-7

lo Laboratory of Psychology
2c Section on Personality
3o Bethesda

PHS=EH

Individual Pl'-oject Seport

Calendar Year 1957

Part A,

Project Title; Patterns of Responses on Psychodiagnostic Tests

Yielded by Patients Suffering from Various .r-;vycho-
somatic Diseases

Principal Investigator; Joseph Ho Handloa^ PhoD.

Other Investigators; Hone

Cooperating IJiits: Hone

Man Yeeor's (cs^ei-'.ds.r year 1937)? Patient Days (calendar year 1957):
Total: .19 None

Professional: «11
Other: .08

Project Description:

ffl?.1ggUYgg;

a. General: To study the rsletionsMps "betvyeen Indiifidoal personality
struct'ore ar^d susceptibility to the various psycl-j.oscEatic diseases.

b. Specific: Prelisnins^rjf to fur-S'ier study of this ■pi^o'blanD.^ a coarplete
survey is to be made of the results of pra\rious studies relating
patterns of responses oii psychodiagi2>ostic tests to specific
psychoscaiatic diseases.

Methods Enmloy^d; It T>rill first be necessaxy to review ojrlta ex-
haxxstively the findiiigs of isrevious ia^-estigators wio fcave
attempted to relate vario'^is issychoscrastic iiJjaesses with specific
responses on psychodiag^ostie tests. Af^feer a OHTetcl. eoiKpiiation
of such resxilts, caaimon p5,ttsms -wilJ. be looked for. If such
cammunE.:Ilties are fo^iad^ an atteiapt will be weAe to relate this
with what is known about personality dj'nsmLcsi and sucli res'olts
will serve as a base for further refineaient of diagnostic work,
partici-Larly in relationship with preventative medicfjie.

Sianificapce to the Il:or^-.as^.oT.¥jsr.:t!s2^JB&&2^Ui..BQS.QSXd^ It is hoped
that the results of tb-is studs'- tirill shed some light on the
etiology, general dyui^a^sdcE of, aad the appropi:'iate therapeutic
interventions necessary for psychosomatic illness. It is also
hoped that more refined diagnostic methods snay be discovered

- 153 -

Serial No. M-P-P-(C)-7 - Page 2

Part A. Project Description (Cont^d)

which vill make for more accuracy in the early discovery of the
disease, as veil as the specifying of personality types vho
wovild be likely to fall victim of such illnesses vith an eye
to preventing such an occurence.

Proposed Coiirse of the Pro.lect: An exhaustive search of previous
studies which have used a variety of techniques upon a variety
of disease entities will precede an analysis of the consistent
patterns fo\md in such stiidies. If such patterns are found and
diagnostic instruments can he refined, further empirical vali-
dation of such findings will he attempted.

Part B. included - No.

- 154 -

Serial UOc M-?-P--{G)~8

1. Laboratory of Psycb.ology
2o Sactioa on Personality
3. Bethesda

PHS-MIH
Individual Project fieport
Calendar Year 1957

art A.

Project Title: Development of Objective Measxires of "Mental Health"*

Principal Investigators; Joseph H.. Handlonj, PfaoDo, Morris Rosenberg^ PkoD,^

Leonard Pearlin^ Ph»D«

Other Investigators: None

Cooperating IMits: laboratory of Socio-EnirirorEaeatal Studies

Man Years (calendar year 1957)? Patient Days (calendar year 1957):
Total: »kO Hone

Professional: .11
Other: .29

Project Description:

Ob.leetives;

1« General: To develop techniques for the economic evalxxation of

"mental health" of large samples of subjects*
2, Specific: To apply the Guttrran Scalogram Technique in the develop-
ment of valid and reliable measvires of "mental health",

^fe-|j^9d Emploved; An analysis will be made of questionnaire items of more
or less loiown validity and reliability. In order to reduce the
manber of items administered to the respondent, the Guttaian method
of scalogram analysis will be employed to evaluate various existing
personality scales of several well laioim questionnaires. Using
those protocols which are at the present time available to us, the
items will be processed to see if they lend themselves to the scalo-
gram analysis. If a variety of items are found to scale, they will
he further validated on selected samples of individuals^ aiid results
compared with other clinical tasts.

Major Findings; No findings to report as yet. Project has just begun.

^^;S3^S^S^m,.^.,:^JS2^^^.2lJ^^^MSi^m^M§^QU^ if -the socio-
environmental ijifluence of a coramuiaity iipoti the mentaJ. health
of individuals living ^rlthin tliat ccfinamnity is to be stuiLied with
any adequacj!-, it will be necessary to develop techniques that lend
themselves to such a study. So far there bave been few attea^ts

- 155 -

Serial No„ M-P-P-(C)-8 - Page 2
Part Ae Project Description (Cont'd)

to develop methods by which large segments or tlie popiolation can
be sampled and eval>J!at6d* If suc'3 siethods can be devised, it
will mean that much important information heretofore not
available to investigstors who are interested in stiadying in an
objective fashion cOTmimity health problems will now be available,

Prppq sed Course ._of .. tl),e„Stafflbr t After a statistical analysis of the
data now available at KIMH, the resialts will determine whether
such previously used meastires lend themselves to scalogram
analysis. If satisfactory scales can be derived^ they will be
checked out on other saatples which, will be made available for
this purpose. It is proposed that other questionnaires having
to do Tri.th psychic health as well as disease will be evaltiated
as well. The advisability of the development of new scales
will also be considered.

Part B included ■= No

- 156 -

Serial No. M-?°?-(c)°9

1, Laboratory of Psychology
2o Sactiom on Personality
3o Bethesda

IHS-KIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: An Analysis of Interpersonal Communication Patterns
Within Faaiilies of ScMzophrenics and Non-Schiso-
phrenics in Quasi -Eacperimental Group Situations

Principal Investigator: Joseph H. Handlon, Ph,D«

Other Investigators: Morris B« Parloff, Ph.D., Donald S. Boomer, Ph.D.,

Marvin Waldman, Ph.D., liyman Wynne, M.D.

Cooperating Units: Adult Psychiatry Branch, Laboratory of Socio-

Environmental Studies

Man Years (calendar year 1957): Patieat Days (calendar year 1957):
Total: .30 None

Professional: .22
Other: .08

Project Description:

Objectives: There is evidence to suggest that there may be inter-
personal coiinaunieation patterns ^hich are \jniquc to fianiliss one
of whose members is a schizophrenic . It will be the ptiirpose of
this study to attenrpt to demonstrate these assumed differences
in structured, quasi^escperimental group situations which lend
themsel^'es readily to objective obser\?atiDnal and measurement
techniques.

Method Emrployed; Making use of previous studies, techniques will be
developed which will permit accurate meas'orss of interpersonal
comfflunication patterns in an observed group situation. At the
present stage of planning se\'eral tec"anij^ues sroggest themselves,
including the use of quasi-groaps where, Tsaknowi to the subjects,
interpersonal cosnmunication caa be maaiptilated systematicallj' by
the experimenter. The advantage of such obsei"/ational methods of
evaluating intra-faaiily behavior is that it lends itself to
objective, reliable measures suitable for coagyarative studies,
while at the same time preserving in large measure the natural
group dynamics. Both faaiilies of schizophrejaics as well as
control groups of various normal and non=i?cliizophraaic psycJiii«»
atric entities will be studied, Belatiojaship® be-fcween the
findings in the cxTperimenial gro;^ sitae. tioa and l) discovered

- 157 -

Serial No. M-P-P-(C)-9 - Page 2

Part A. Project Description (Cont'd)

patterns on diagnostic tests of personality; 2) personality
dynamics as gleaned from individual and/or group psychotherapy;
and 3) vhere appropriate, ward behavior will "be examined,

%P![}f^i''rK*i M' *^r ?*-"gT-«" "^ Mftn+Al TTRftlth Bffaf*ftrf^hi If it is the
case that the intra-family dynamics play a crucial role in the
course of schizophrenia, then a careful study of these dynamics
under controlled conditions would seem to be profitable. It
will be particularly important to determine whether such
consistent intra-family communication patterns as are found
are really unique to families of schizophrenics, or whether
they are to be found in non-schizophrenic families as well.
If found in both schizophrenic and non-schizophrenic, is
there a difference in degree? A correlative question is that
of whether such patterns as may be fovind are a result of having
a mentally disturbed member in the family, or whether they are
an important contributing factor in the actual development of
schizophrenia .

Pro-poged Course of Pro^iect; After an exhaustive review of the various
techniques which have been emplojred in the experimental study of
group processes, appropriate methods will be tried out in pilot
studies with a variety of groups. Once techniques have been
perfected, use will be mside of the families of schizophrenics
and others who are in-patients at NIH as well as normal groups.
Findings will then be correlated with other psychologically
relevant material gleaned frcan diagnostic tests, group and
individual therapy, and ward behavior.

Part B included - No

- 158 -

Serial No. M-P-P«(c)"10

1. Laboratory of Psychology
2» Section on PersoneuLity
3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part__A^

Project Title: Value Ciianges in Psychiatric Nursing Trainees

Principal Investigator: Herbert C. Kelman, Ph,D.

Other Investigators: Donald S. Boomer, Ph.D.

Cooperating Iftiits: None

Man Years (calendar year 1957): Patient Days (calendar year 1957):
Total: ,63 None

Professional: .17
Other: *h6

Project Description:

Objectives ; The purpose of this project is to study some of the
factors that are related to changes in attitudes, values, and
role conceptions on the part of student nurses undergoing
psychiatric trainings Of particular interest are those values
which relate to patient care and sensitivity to the patient's
needs, as well as to sensitivity in interpersonal relations in
general. Specifically, the project will be concerned with the
effects on value change of (l) certain specified personality
predispositions of the student nurses, and (2) variations in
the training method employed. In measuring the effects of the
training, the study will focus not only on amoxmt of change,
but also on level of change: an attempt will be made to measxrre
changes in public attitudes, in behavior, and in general values 4
This study represents an integration and elaboration of two
previous studies reported in 1955: NIMH 118(C) and NIMH 128(C).

Methods Employed: As presently planned, the study will involve
experimental manipulation of one part of the training program^
and informa.1 observation of the training program in generals
In order to measure relevant personality predispositions, a
variety of techniques will probably be used* These may in-
clude standard personality tests, interviews, and special
laboratory sitioations (probably of a guasi-group nature ) . Both
the variations in the training procedure and the personality

- 159 -

Proposed CouTb.- .

the resignation of ur.

Part B included - NO

r:|^^«-^i<-,^'

r*i«

w«-

T^'^^mm

re: a«^^

isfU^- ■■■

?^:ci,

S ■:

>ryp<;XjT!0'Sj' i"'*" '''■"*

;.^,. ^Tts' 'uiQjs^'i

.^."r:rT%;r,

- 160 -

Serial No, M-?-?-(C)-U

1. Laboratory of Psychology

2. Section on Personality

3. Bethesda

PHS-NIH

Individual Project Report

Calendar Year 1957

Part A.

Project Title: Validation of Specificity Theory of Psychosomatic Disease

Principal Investigator: Herbert C. Kelman, Franz Alexander, Morris Stein

Other Investigators: None

Cooperating Iftiits: None

Man Years (calendar year 1957) t Patient Days (calendar year 1957) J
Total: .25 None

Professional: .17
Other: .08

Project Description:

Objectives:

1» To validate hypotheses about specific personality dynamics^
life hi story _, and onset situations related to each of seven
psychosomatic syndromes*

2, To develop methods for such validation and determine the effects
of degree of psychiatric sophistication on results obtained.

Methods Employed: Detailed checklists were filled out after reading
of transcribed ananuiesic interviews with psychosoraatic patients,
from which all medical information had been deleted. From those,
diagnoses will be derived and checked against presenting sjrmptoms.

Subjects Used: Two groups of judges completed the checklist — a
group of secretaries, unacquainted with psychiatric concepts and
the specific hypotheses; and a group of gradi'vate students in
psychology, who in addition were infortTtied of the specific
hypotheses. Diagnoses made by a groiap of psychoanalysts ^ who
read the some case riiaterial but did not use the checklist are
available for comparison..

Major Findings: (l) In general, the study shows that it is possible
to isolate factors in a patien-c^s life history and personality
dynamics which are related to the specific psychosomatic syndrome
which he develops. (2) The data support three of the six personality

- 161 -

Serial IJo, M'P"P-'(C)-11 - Page 2

Part A. Project Description (Cont'd)

and life history patterns which were studied: patients \^o develop
peptic ulcer, "bronchial asthma and thyrotoxicosis tend to be
characterized by the psychological patterns which the investi-
gators hypothesized* The patterns for neurodermatitis and essential
hypertension tended in the hypothesized direction but were not
statistically significant. The hypotheses in the case of tilcerative
colitis were clearly not supported.

Significance to the Program of Mental Health Reseerch; Trea-tanent of

psychosomatic patients depends on an understanding of the personality
and conflicts of the patient. This study aims to get some indication
of the validity of certain hypotheses about specific syndromes. The
methodological part of the study should give some information on
the reliability of various ways of collecting relevant data.

Proposed Coiorse of the Project; This project has been terminated due
to the resignation of Dr, Kelman.

Part B included - No

- 162 -

Serial No. M-»P»P-(C)~12

1. Laboratory of Psychology

2. Section on Personality

3. Bethesda

PHS-NIH

Individual Project Report

Calendar Year 1957

Part A*

Project Title: Processes of Acceptance of Social Influence

Principal Investigator: Herbert C. Kelman

Other Investigators: None

Cooperating llhits: None

Man Years (calendar year 1957): Patient Days (calendar year 1957):
Total: »50 None

Professional: .17
Other: ,33

Project Description:

Objectives: To distinguish three processes wherehy influence is
accepted — con^pliance, identification, and internalization
and to show that these are produced by different motivational
conditions and have different subsequent histories.

Methods Employed: Several different tape recorded communications
were used xo create different perceptions of the comrauni-
cator's power and different motivations for acceptance of
influence. The effects of these on an area of social attitudes
were measured through repeated questionnaires.

Subject Used: College students

Major Findings; Attitudes accepted through compliance (communicator
has means-control) tend to be expressed only under conditions
of surveillance by the communicator. Attitudes accepted throvigh
identification (comnunioator is attractive) tend to be expressed
only under conditions of salience of the communicator. Attitudes
accepted through internalization (communicator is trustworthy)
tend to be expressed regardless of sturveillsuace or salience of
the communicator.

Sipilflcance to the Program of tfental Health Research: The thera-
peutic sitxaation can be regarded as a situation of social inter-
action and the therapeutic process as a product of social influence.

- 163 -

Serial No, M-P-P-(C)-12 - Page 2

Part A. Project Description (Cont'd)

It is through these interpersonal relationships that the patient
is able to modify his values, attitudes, and role expectations.
Therefore, the development of a general theory of social inter-
action and inf Ivience should increase oiur understanding of the
therapeutic process. The present study can contribute to our
understanding of the conditions mxder which therapeutic chwiges
will be lasting and integrated with the patient's values and the
conditions under which they will be superficial and of short
duration. In addition, it can be useful for the development of
programs of public education on mental health.

Proposed Course of the Project; A detailed report of the study and
of the theory underlying it has been written. This report will
be revised and expanded for publication as a monograph. This
project has been terminated due to the resignation of Dr. Kelman.

Part B included - Yes

- 16k -

Serial No. M-P-P-(C)-12 «■ Page 3

Part B: Honors, Awards, and Publications

Publications other than abstracts from this project:

Kelman, Herbert C, Social Influence aad Personal Beliefs; A Theoretical
and Experimental Appi'oach to the Stady of Bet.ayior Chgjage 'fTo be
published by Wiley and Sons, Inc., New i'lbrk

Kelman, Herbert C. "Three Processes of Acceptance of Social Influence:
Compliance, Identification and Internalization" Sociometry (In press)

Honors and Awards relating to this project:

Awarded the $1,000 Socio-Psychological Prize of the American Association
for the Advancement of Science, New York City, December, 195^ for his
essay entitled, "Compliance, Identification, and Internalization: A
Theoretical and Experimental Approach to the Study of Social Influence,"

- 165 -

NATIONAL INSTITUTE OF MENTAL HEALTH

Clinical Investigations
Laboratory of Clinical Science— Office of the Chief

BUDGET SHEET

Estimated Obligations for FY IQ'^S
Total: $151, 8U9
Direct: $107,067

Reimbiirsements : $^4- , 782

Projects included: M-CS-OC(C) 1 through ^^CS-OC(C) k

Serial Wo. M-CS-0C(C)-1

1. Laboratory of Clinical Science

2. Office of the Chief

3. Bethesda; Maryland

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Biological Studies in Schizophrenia

Principal Investigator: Sejinour S. Kety

Other Investigators: See individual projects.

Cooperating Units: See individual projects in the Laboratory
of Clinical Science , NIMH^ as follows: Office of the
Chief, Serial Wos. M-CS-0C(C)-2^ 3, and h; Section on
Medicine, Serial Wos. M-CS-M(C)-1 and h; Section on
Psychiatry, Serial Nos. M-CS-Ps(c)-2 and k; Section on
Cerebral Metabolism, Serial Nos. M-CS-CM-1, 5, 6, and 7;
Section on Drug Evaluation, Serial Wo. M-CS-DE-1; and
Section on Biochemistry, Serial No. M-CS-B-4 and 5-

Man Year (calendar year 1957): Patients Days (calendar year 1957):

Total: 3-5 See individual projects.

Professional: 2-5
Other: 1.0

Project Description:

Objectives: To direct and coordinate a multidisci-
plinary program of biochemical; pharmacological,, and physiological
studies in schizophrenia and their correlation with psychological
and psychiatric aspects of the disease .

a. Studies on amino acid raetaaolism

b. Studies on the fate and effects of epinephrine

c. Evaluation of reported biological abnormalities

Methods Employed: Selected populations of schizophrenics
and normal controls have been esteblished and are maintained
under controlled conditions of normal diet, activity and
management. Three general techniques are employed for studies of
a particular substance in both populations: l) examination of its
blood level or urinary excrL-tion and their correlation with
psychological and psychiatric observations; 2) examination of the
psychological, biochemical, and physiological effects of the

- 16^

o -

Serial No M-CS-0C(C)-1 , page 2

Project Description (continued):

administration of measured amounts of the substance to
permit assessments of differences in the handling or effects of
the substance in the two groups j and 3) the administration of
radioactively tagged substances and examination of blood levels
and ujTinary output of all radioactive products to permit qualita-
tive and roughly quantitative estimates of its various metabolic
pathways .

Major Findings: The program, is relatively recent in
its inception. Criteria for the selection of patients have been
established and the sample drai^m up from an examination of several
thousand state hospital charts. Techniques have been adapted for
the effective fractionation of metabolic products in blood and
urine, and animal experiments are in progress to permit determina-
tion of safe doses of particular radioactive compounds in man.
Specific findings are reported in the component projects.

Significance to Mental Health Research: Many positive
findings relating to biological abnormalities in schizophrenia
have not been subjected to well controlled and critical evalua-
tion. There are num.erous reasons which suggest abnormalities
in the metabolism of amino acids or certain amines as essen-
tial factors in some forms of schizophrenia. This program
offers a means of evaluating such h^.-potheses .

Proposed Course of Project: The program is plan_ned
for several years' duration.

Part B included: Yes

- 167

Serial No,, M-CS-OC(C) -1 , pag.a 3

PliS NIH
Individual Project Report
Calendar Year 1957

Part B: Honors. Awards and Publications

Publications other than abstracts from this project:

Sokoloff, L , Perlin S., Kornetsky. C.^ and Kety, S.S,:
The effects of d-lysergic acid diethylamide on cerebral
circulation and over-all metabolism, Ann. N,Y. Acad.
Sci., 66: 468-477 1957.

Kety, S.S-: The implications of psychopharmacology to
the etiology and treatment of mental illness. Ann.
N.Y. Acad. Sci . 66: 836-840. 1957,,

Kety. 3 S.: Recent studies in psychopharmacology. A.M. A.
Arch. Neurol, and Psychiat . , 77. 278-279. 1957.

Kety. 3.S.: The cerebral circulation in man. Triangle.
3: 47-52, 1957

Kety, 3,S,: The general metabolism of the brain in^ vivo .
The Metabolism of the Nervous System,, edited by D. Richter
Pergamon Press. London IS 57 (In press) .

Kety. S,S . Determinants of tissue oxygen tension.
Fed. Proc . . 16' 666-670. 1?57 .

Honors and awards relating to this project:
Dr Seymour S. Kety

Elected to the Council of the International Collegium

of Psychopharmacology .
Elected to membership in American Psychopathological

Society .
Appointment to Committee on Research in Dementia Praecox.

Supreme Council 33° Scottish Rite. Northern Masonic

Jurisdiction ,
Presented Eastman Memorial Lecture on "Biological Aspects

of Schizophrenia". University of Rochester, Dec, 1957
Address to the Harvey Tercentenary Congress, London.

June 1957.

- 168 -

Serial No. M-CS-0C(C)-2

1. Laboratory of Clinical Science

2. Office of the Chief

3. Bethesda, Maryland

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A,

Project Title Comparison of the Excretion Patterns of

Metabolites of Aromatic Amino Acids by Normal Subects and
Schizophrenic Patients

Principal Investigator: Elwood H» LaBrosse

Other Investigators: Jay D. Mann

Cooperating Units: None

Man Years (calendar year 1957): Patient Days (calendar year 1957):

Total: 0.50 94

Professional: 0.25
Other: 0.25

Project Description:

Objectives: Numerous investigators have described
quantitative differences in the excretion of urinary
phenolic acids between normals and schizophrenic patients.
In many cases these studies have been so incompletely
reported that they could not be repeated in exactly the
same manner or they had insufficient numbers or inadequate
controls. Because of the close biochemical relationship of
the neurohumors, such as epinephrine and norepinephrine and
of such compounds as serotonin; to the aromatic amino acids,
the metabolism of the latter is important in mental function--
this has been clearly shown in phenylpyruvic oligophrenia in
which a disturbance in the hydroxylation of phenylalanine to
tyrosine is consistently associated with mental deficiency.
The objective of this investigation will be to establish
whether there is a significant difference in the metabolism
of aromatic amino acids by normals and by schizophrenic
patients. If a difference actually is found to be present ^
it will then be possible to set up further experiments
which will elucidate the biological relationship between
metabolism and schizophrenia.

169 "

Serial No. M-CS-0C(C)--2 , page 2

Project Description (continued),,:

Methods Employed: The rormal subjects and schizophrenic
patients will be given identical diets in addition, following
a double-blind technique; half of each group will be given
a loading dose of phenylalanine, tyrosine or tryptophane.
Urine specimens will be collected over known time periods
and replicate portions of each urine specimen will be
analyzed using quantitative paper chromatographic methods
to analyze numerous urinary metabolites of the aromatic
amino acids. These data will be analyzed statistically to
determine whether there is a significant difference in the
excretion of these metabolites between the normals and the
schizophrenics .

Major Findings: This project is just getting started
and no major findings have yet been obtained.

Significance to Mental Health Research: If a
significant difference between normals and schizophrenic
patients were found, it would be a major breakthrough in
the understanding of mental illness and would provide a
point of entry for elucidation of the biochemical factors
in mental illness and thereby lead to a more rationa.1 and
effective therapy.

Proposed Course of Project: To begin the loading
experiment as soo«a as equipment , supplies, and technical
assistance can be obtained. To combine with or extend this
study to include administration of C-^ -labeled amino acids.

Part B included: No

170 -

Serial No, M-CS-0C(C)-3

1 . Laboratory of Clinical Science

2. Office of the Chief

3. Bethesda,. Maryland

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A,

Project Title: Study of the Metabolites of Epinephrine and
Norepinephrine in Human Body Fluids

Principal Investigator: Elwood H. LaBrosse

Other Investigators: Seymour S Kety, Julius Axelrod

Cooperating Units: None

Man Years (calendar year 1957) . Patient Days (calendar year 1957)

Total: 0,50 15

Professional: 0.25
Other: 0„25

Project Description:

Objectives: To investigate the metabolites of
epinephrine and norepinephrine in the urine and in the
blood in the approach to studies of the in vivo metabolism
of these important neurohumors in normal~~and mentally ill
subjects.

Methods Employed: Treatment of the urine with
P-glucuronidase j followed by extraction and paper chroma-
tography of the extracts were used in the search for these
metabolites. This study will be greatly facilitated when
the tritium labeled epinephrine becomes available, at which
time the total radioactivity in the urine and the relative
amounts in various constituents will be determined.

Major Findings: This project has just begun and
there are no significant findings to report at this time.

Significance to Mental Health Research: Both
epinephrine and norepinephrine are well known as neuro-
humors and have been found in the brain as well as in the
peripheral nervous system, Because of this fact an under-
standing of their metabolism would facilitate an evaluation
of their role in normal function of the nervous system and
in mental disease.

- 171 -

Serial No. M-CS-0C(C)-3; page 2

Project Description (continued):

Proposed Course of Project: It is planned to
continue this investigation and to study the labeled
metabolites after the intravenous injection of tritium
labeled epinephrine.

Part B included: No

- 172 -

Serial No, M-CS"Of;(C)-U
Iffl Lab,, of Clinical ScieM
2., Office of the Chief
5» Bethesda, Mi*

PHS-KIH
Individual Project Report
Calendar Year 1957

Part A«

Project Title: Studies of the interrelationships of the nervous aad circul=
atory systems.

Principal Investigator; P,V* Csirdon, Jr„, M<.Do

Other Investigators: So Kety^, M*D<,^ L« Sokoloff, M,D*, E* Labrosse, M,D,,

Wc Pollin, MftD», Ri Butler^ M»Dt^ Wa Goodrich, M,D*,
R* Gordon, MaD*, and C» Kometsky, Ph>rD»

Cooperating Units: Clinical Investigations, HIMH; Lab, of Cellular Pjjysiologi

and Metabolism, KHI

Man Years (Calendar year 1957) Patient Days (calendar year 1957)
Total: 2 1/5 70

Professional s 1
Other 1 1/5

Project Description:

Objectives: 1. To clarify the nature of the changes which occur in the

circulatory system in association with changes in various
parameters of central nervous system function such as
attitudes, feeling states, modes of interpersonal reaction,
and psychomotor performance »

2o To develop and standardize reproducible, simple, and non^
traumatic methods for the assessment of such circulatory
changes »

Methods Employed: Circulatory changes are assessed by the following methods:
Pulse rate, blood pressure (ausculatory or direct arterial measurement), .
ballistocardiograph, impedence plethysmography i

More studies this year involved comparison between groins (i.-,e« normf^l
vs, schizophrenic patients) rather thaxi meastirement of changes in the same \
individual. Four preliminary studies of the effects of infusing epin=
ephrine into normal and schizophrenic subjects have been done in collabor"
ation with six other investigators in the laboratory^ One psychoneurotic
out-patient was studied immediately before and after therapeutic interviews
for 17 weeks (Dr« Goodrich)... The number of normal subjects in whom plasma
unesterified fatty acid (UFA) was measured before and after a sham

- 173 -

Serial Noo M''GS-OC(C>APage 2

tramttatic procedure was e3cpanded to 18 (Dr. Gordon) » The circulatory
effects of amphetiffiKiae^ phenobarbital^ and mepro'bamate were studied
in normal subjects (Dr, Kometsky)^ Comparison of the ia^edence plethysmo^
graph and Ha2'+ methods of estiaaatisg leg blood flow was coEpleted (Dro
Sokoloff)c. Induction of circulatory changes with structured interviews
has been abandoned for the time being because of the data-reduction problem
and the resignation of the participating psychiatrist (Dr. J,M. Scher),

Patient Material; Patients oa i^-W and 2-W of the Clinical Center*

Major Finding: (Findings enumerated include results of analyzirag some data
collected in 1956)»

As a group, schizophrenic men tend to have sHjaller brilistocardiographs
than do normal men. Other eiroalatory variables studied are not different.
Within the schizophrenic sasssplep variables studied have not beea foimd
so far to correlate with behavioral ^ EEG, or biochemical sub -groupings <,

In the studies of the acute affects of a variety of centrally acting
drugs, chlorpromazine si^ific^jtly increased pulse rate aad meproTbamate
decreased ballistocardiograph ajaplitude.

On the basis of comparison with the Na^^ clearaace method, the
impedence plethysmograph is not a good method for estimating relative
change in liiab blood flow.

Acute anxiety usDially causes an increase in plasma UFA*

Significance to Jfeatal Health Research; Problems to which these studies may
prove pertinent include; tranquilising drugs, anxiety states^ schizophrenia,
neurocirculatory asthenia, essential hypertension, and coronary heart disease.

Proposed Course of Projects Continue studies of the types reported on the
same relatively" saall aaid flescible scale.

'I*

Part B included; Yes

= 17ij- -

Ml:

Serial No-- M-CS»OC(G)-i^; Bage

Part B»

Publications: Cardon, P*V*j Jr« "Psychic factors in hypertensive heart
disease b" "Psychic factors in coronary heart disease,"
Chapters in Encyclopedia of Cardiology > Ed, A«, A* Luisada,
Philadelphia, Blackiston, (in press) 7 i

- 175 -

NATIONAL INSTITUTE OF MENTAL HEALTH

Clinical Investigations
Laboratory of Clinical Science — Section on Medicine

BUDGET SHEET

Estimated Obla-ggtipng fgr , n 19'??

Total: $172,05^
Direct: $56,31^

Reimbiirsements : $115 . 7^0

Projects included! M»CS-M(C) 1 through M-CS-M(C) 6

II !i

1. 1

Serial No. M-CS-M(C)- 1

1. Lab. of Clinical Science

2. Section on Medicine
5o Bethesda, Md.

PHS-rHH
Individual Project Report
Calendar Year 1957

Part A,

Project Title: Behavioral and biochemical correlates of the electroenceph-
alogram (EEG) in schizophrenic patients*

Principal Investigators; Roger K. McDonald, M,D,^ William Pollin, M,D,

Frederick Snyderj, lUL^^ Robert R, Butler, M»D,
and Edward V, Evarts, M,D.

Other Investigators 2 Bonnie Peacock

Cooperating Units: None

Man Years (calendar year 1957) Patient Days (calendar year 1957):
Total s 5/6 751

Professional: 1/2
Other: l/5

Project Description:

Objectives: A variety of biochemical studies in schizophrenic patients
have yielded data whose mean does not differ significantly from the
mean of a normal population, but vhose variability exceeds that of
the normal population. So far^ few attempts to determine the rela-
tionship between these variable biochemical data and behavioral or
biological processes have been made^ The present project represents
a preliminary effort to determine the degree to which one form of
biological activity (the EEG) may be related to a number of bio-
chemical and behavioral measures.

Methods Employed: (A) Patient Selection: Approximately 150 white male
schizophrenic patients between the ages of 20 and iK) were selected
from the population of the Springfield and Spring Grove State Hospitals.
Care was taken to exclude any patients with organic brain disease or
mental deficiency. Tracings of occipital electrical alpha activity were
obtained in these patients. The EEG records were divided into three
groups according to whether they showed high, low, or intermediate
aasounts of alpha activity, A number of patients in each of these
categories was admitted to the Clinical Center, All patients who were
selected for admission to the Clinical Center were evaluated clinically.
Only those patients with clearly schizophrenic disorders were admitted.
These patients had been hospitalized for one or more years «

176

Serial No. M-CS»M(C)-1 Page 2

EEG Studies; Patients were exanined electroencephalographically
at the time of admission aad at weekly intervals thereaftero Records vrere
analyzed with respect to per cent alpha so that a quantitative score describ-
int amount of alpha would be available for correlation with behavioral and
biochemical variables. Studies of photic activation of the EEG were also
carried out,

(C) Pharmacologic and Electromyographic Studies; The attempt was made to
test the hypothesis that the percentage of alx^ha activity is a reflection of
the degree of arousal of the organism by measuring several physiological
indices which are reputed to be correlated with the level of anxiety j, i.e,
the sedation threshold and surface muscle activity. The sedation threshold
is obtained by determining the amount of intravenous sodium amytal which is
necessary to produce the specific electroencephalographic change associated
with the effect of barbiturates on cortical rhythms, Muscle activity was
measured by siorface electromyographic methods from the various parts of the
body to provide an objective indication of tension in individual subjects.

(D) Behavioral Studies; Patients were seen for recorded, observed evalu-
ation interviews shortly after their admission. Their EEG characteristics
were unknown to the evaluating psychiatrists at that time. Data obtained
were used for final confirmation of the diagnosis of schizophrenia, and

for the purpose of making independent rankings of 19 personality variables
which^ on the basis of prior work, were thought likely to relate to per
cent alpha., These rankings fell into five major categories t Ego
intactness^ reality contact^ reality distortion^ affects and activity. Two
hypothesised profiles using these rankings were constructed. These profiles
were based on work from the literature, and were designed to differentiate
the high from the low alpha. Predictions were made as to which of the two
categories each patient would be in. After coniparison of the EEG character-
istics and psychiatric findings, patients were re-evaluated„ Continuing
ward obseiryations were made by psychiatric and nursing personnel. A modi-
fied version of the Lohr scale, and various additional experimental
techniques were employed for rating ward behavior.

(E) Biochemical Studies « The laboratory methods employed in this study
are described under the project entitled, ^ Evaluation of Certain Reported
Biochemical Differences Between Schisophrenic and I^on -psychotic Subjects.

Major Findings ;

Correlations Between EEG and Behavior. The relationship between
psychiatric rankings and behavioral ratings, on the one hand, and per cent
alpha on the other was not statistically significant. Re-eveduation after
coarparison of EEG and psychological data has led to a reformulation of the
hypothesised clinical picture %>*i,ich may be related to high or low alpha
characteristics ,

177

Serial No. M-CS-M(C)-1 Page 5

No consistent relationship was found between the percentage alpha and the
sedation thresholds of the patient groi^j, nor could the latter measure be
correlated with psychiatric judgments concerning apparent anxiety in the sub-
jects » The results were in keeping with previous provocative reports that in
schizophrenics there is no clear-cut relationship between the sedation
threshold and behaviorally manifest anxiety ^s, as there is in neurotic patients
or normal controls a Neither was there a consistent relationship between a
global measure of muscle tension and the alpha index,, The data suggest^
however, that there may be such a relationship with muscle tension in certain
area^ of the body, notably the forehead and periorbital muscles <, This
possibility is still being escplorede,

(B) Correlations Between EEG and Biochemical Measures » Of the variety of
biochemical measures which was carried out, only red blood cell glutathione (GSH)
was significantly correlated with per cent alpha in the schizophrenic patients.
The mean GSH was 76.6 mgo in patients with high alpha and 65oO mg,^ in patients
with low alphas

Initial observations suggesting differences in blood levels of ascorbic
acid between the high and low alpha groups appeared to be the result of
differences in dietary intake of ascorbic acid. Evidence for this belief
rests on the complete similarity of blood levels of ascorbic acid in the two
groups following an ascorbic acid loaxiing-deprivation experiments

Adrenaline oxidation, which has been shown to be a function of ascorbic
acid and copper levels in the blood, did not differ in the two groups. Like-
wise, serum oxidation of paraphenylenediamine, which is a function of
serum copper, did not differ in the two groups.

Significance to Mental Health Research;

(a) Biochemical Findings. The positive correlations between blood gluta-
thione and per cent alpha is of considerable interest in view of the obser-
vations of some previoxis investigators that blood glutathione is depressed
in certain forms of mental illness » The present study does not demonstrate
such differences between normals and schizophrenics taken as a group, but
does indicate that there is a suggestive relationship between blood glutathione
and at least one measure of central nervous system activity.

(B) Behavicjjjl F indl^gs . Thus far, no significsiit clinical correlates of
' high or low alpha characteristics have been established.

178 -

Serial No. M-CS-M(C)-1 Page
Proposed Coxirse of Project:

(a) Biochemical. The small size of the present sample vould make ■
it mandatory that the observations on blood glutathione and EEG be
extended to more schizophrenic patients. In addition, studies will

be carried out to determine the relation of blood glutathione to the
EEG in a normal population,

(b) Behavioral. High aad low alpha schizophrenic patient groups at
two nearby State Hospitals will be psychiatrically evaluated, without
knowledge of which EEG groxaping each patient belongs to. On the basis
of the study of the present patient groiip, predictions as to EEG
characteristics will be made to test the significance of suggested
clinical correlates of alpha per cent.

Part B included; No

- 179 -

Serial No. M-CS-M(C)-2

1, Lab. of Clinical Science
2o Section on Medicine
rf 5« Bethesda, Md,

»r

PHS-MIH

>X Individual Project Report

Calendar Year 1957

Part A.

Project Title; Qualitative intraspecies variations in human serum
cholinestersise ,

Principal Investigator; Franklin T. Evans, McD*

Other Investigators; Roger K« McDonald and Raymond Wo Patrick

Cooperating Units; Kone

Man Years (calendar year 1957) Patient Days (calendar year 1957)
Total; 1 60

Professional: 5/12
Other; 7/12

' Project Description;

Objectives; To examine the possibility that qualitative differences
in serTmi cholines t erase exist between different human
subjects,

Miethods Employed; The rate of hydrolysis of B-carbonaphthoxycholine and
B^naphthyl acetate by human serum^ and the effect of calcixm and
magnesium ions on this rate have been studied by the colorimetric method
of Ravin, Tsou and Seligmanc The rate of hydrolysis of acetylcholine
by human seron has been studied by the colorimetric method of de la
Huerga^ et al.

Method for studying individual variation in human senmi cholin-
esterase. Various concentrations of calciiim and magnesium, with and
without eserine, were added to the sera of a group of patients, and the
resultant hydrolytic activity of the sera was determined individually*

Patient Material; Normal male and female volunteers and schizophrenic males.

Major Findings; Presently avsiilable data do not justify definite conclusions
regarding intraspecies variations of cholinesterase at this time. The
preliminary findings do suggest that further investigation of the effect
of calcium and magnesium on cholinesteraise is warranted.

- 180 -

Serial No. M-CS-M(C)-2 Page 2

Significance to Jfental Health Research: Although the physiologic substrate
of serum cholinesterase is at present uhknovn, recent evidence has shovn
that inhibition by the serum-type cholinesterase in isolated brain
preparations restilts in a so-called arousal response on electroencephale-ij
gram. In addition^ a nxmber of psychotomimetic drugs are known to j
inhibit this enzyme. These facts suggest that a more careful exploratio!
of the nature of this enzyme may ultimately clarify its possible role ia ;i
central nervous system activity. !

Part B inclxided: No

181

Serial No. M-CS-M(C)-5
■ M .oH iBri:-.: 2.. Lab. of Clinical Science

2a Section on Medicine
3= Bethesda, M.

1 PHS-NIH

Individual Project Report
C-lendar Year 1957
I
frt A.

Project Title: Effect of morphine and nalorphine on plasna hydrocortisone levels.

Principal Investigator; Roger K. McDonald, M»Do

Other Investigators: Franklin To Evans ^ M,D„, Raymond W=, Patrick, and

Virginia K, Weise

Cooperating Units: None

Man Years (calendar year 1957) Patient Days (calendar year 1957)
Total: 1 1/6 128

Professional: 2/5
Other: 1/2

Project Description:

Objectives: To determine whether raoi'phine and nalline suppress ACTH
release in man..

Laboratory Methods; Plasma hydrocortisone concentrations vere determined
by the method of Peterson et al.

Methods Earployed: The hourly plasma hydrocortisone levels from 8 a.m. to
1 p.ffio were determined on a group of normal subjects on one day follow-
ing placebo injections, on another day following morphine injections,
aad on a third day following nalorphine. The second design employed
in this study consisted of determining the effect of morphine on the
large rise in plasma hydrocortisone concentration which characteristically
occurs between k a.m. and 8 a.m. In this design a group of normal
subjects received on one night oral pentobarbital and at 3 a.m. a
subcutaneous injection of morphine sulfate. At 6 a.m., 7 a.m., and 8 a.m.
fasting blood saanples were drawn for a conrparison of plasma hydrocortisone
levels with levels on other mornings when either nembutal or placebos were
given at the scheduled times.

Patient Material: Normal male and female volimteers were used exclusively «

Major Findings: In the first part of the study both morphine and nalorphine
produced a significant depression of the plasma hydrocortisone level
which occurred at 11 a.m. aad continued through 1 p.m. In the second
part of the study morphine blocked the mondng rise in plasma hydrocortisone
concentration .

182

Serial No. M-CS-M(C)-5 Page 2

Significance to Mental Health Research: These observations indicate that
morphine and nalline suppress significantly the release of ACTH by the
anterior pitxiitary gland. Since the c.ction of morphine and nalline
is most likely on the central nervous system it woiild appear that the
normal control of ACTH release in man is under central nervous system
control <.

Proposed Course of Project: The present approach has provided an
answer to the question of the Interrelationship between morphine,
nalorphine administration and ACTH release. The project will not
be continued unless new approaches become apparent.

Part B included: No

- 133 -

Serial No, M-CS-M(C)-iv

1, Lab, of Clinical Science

2. Section on Medicine
5o Bethesda, Mi.

PHS-WIH
Individual Project Report
Calendar Year I957

Part A.

Project Titles An evaluation of certain reported biochemical differences
between schizophrenic and non-psychotic subjects.

Principal Investigator: Roger Ko McDonald, M.D.

Other Investigators; Virginia K^ Weise, Franklin T. Evans, M.D., and Raymond

W. Patrick

Cooperating Units: Springfield State Hospital, Sykesville, Mi,

Stc Elizabeths Hospital, Washington, D.C.

Man Years (calendar year 1957) Patient Days (calendar year 1957)

Total: 1 1/U 255

Professional: 2/5
Other: 7/12

Project Description:

Objectives: To determine the plasma copper and ascorbic acid levels, the
red blood cell reduced glutathione levels and the oxidizing capacity of
serum and plasma for W-W dimethyl para-phenylenediamine (DPP), p-phenyl-
enediamine and adrenaline in schizophrenic and non-psychotic subjects.
These various parameters have been reported to be abnormal in schizophrenic
patients ,

Methods Employed: Laboratory methods included copper analysis by the method
of Cubler et al , , ascorbic acid analysis by the method of Roe, red blood
cell glutathione determination by the method of Grunert and Phillips and
the serum oxidation of DPP by the method of Akerfeldt, of p-phenylenediamine
by the method of Aijood and of adrenaline using the method of Leach et al.

Patient Material: Schizophrenic patients were studied at the Clinical Center,
St, Elizabeths Hospital and Springfield State Hospital, Normal male and
female volunteer subjects were used as controls.

Major Findings: No significant difference was foimd between the serum copper
and red blood cell glutathione values and the serum oxidation rates for
DPP and p-phenylenediamine for schizophrenic and control subjects. The
serum ascorbic acid levels were lower in the schizophrenic group^but this
was shown to be a dietary phenomenon. Adrenaline oxidation was more
rapidly oxidized by plasma from schizophrenic subjects, but this was
shown to correlate highly with the plasma ascorbic acid levels. The
latter observation suggests that abnormally high dye and aidrenaline oxi-
dation rates found in schizophrenics are simply a result of low plasma
ascorbic acid levels resulting from low dietary intake,

~ 13k ~

Serial No. M-CS-M(C)-lt Page 2

Significance to Mental Health Research: This study falls into the over-all
laboratory approach to biological studies in the psychoses. It is hoped
that this approach will be of aid in better understanding the complex
phenomena of mental disease.

Proposed Course of Project: Certain aspects of this project are continu-
ing to provide a more critical evaluation of "peripheral" biochemical
findings and central nervous system function.

Part B included: No

135 -

Serial No. M-CS-M(c)- 5
(, , 1. Lab. of Cliniccu Science

' 2. Section on Medicine

3. Bethesda, M.

ri/^rrv^^ri r-^ ?- -Orel's-

• •" ~ PHS-NIH

Individual Project Report
Calendar Year 1957

Pi-t A.

'reject Title: The relationship betvfeen endogenous antidiuretic hormone
activity and ACTH release in n:.ri.

'rincipal Investigator: Roger K. McDonald^ M.D,

)ther Investigators: Henry N. Wagner, Jr., M,D. and Virginia K» Weise

Jooperating Units: Laboratory of Kidney and Electrolite Metabolism, Ifiil

Ian Years (calendar year 1957) Patient Days (calendar year 1957):
Total: 5 A 150

Professional : 5/12
Other: 1/3

'roject Description:

Objectives: To determine if the endogenous release of antidiuretic hormone
causes ACTH release.

Methods Employed:

Laboratory Methods: 1. Determination of plasma hydrocortisone

concentration by the method of Peterson et al.

2. Urine osmolality determined by freezing point
depression.

Method of studying interrelationship of antidiuretic hormone and ACTH
release.

Stimxili used for production of either antidiuretic hormone or ACTH
release consisted of water deprivation, intravenous injection of hyper-
tonic saline, intravenous injection of insulin and nicotine, intra-
muscTJlar injection of mecholyl and hand immersion in ice water. At
appropriate intervals urine and blood were collected for analysis of
plasma hydrocortisone concentrations and antidiuretic hormone activity.

- 186

Serial No. M-CS-M(C)-5 Page 2
Patient Material: Normal male and female volunteers.

Major Findings: The experiments demonstrate that antidiuretic hormone and
ACTH release can occur independently of each other and therefore
antidiuretic hormone is not the neurohormone causing ACTH release.

Significance to Mental Health Research: The ACTH release associated with
various stress is a study of this problem pertinent to the inter-
relationship between stress and bodily function. This study disproves
one of the current hypotheses employed in explaining the relationship
between the central nervous system and endocrine control.

Proposed Course of Project: This particular project has provided the answer
to the problem examined and is not being studied further.

Part B included: Yes

- 187 -

Serial No. M-CS-M(C)-5 Page 5

Part B.

Piiblications .

McDonald, R.K., Wagner, H. N., and Weise, V.K« The relationship between
endogenous antidiuretic hormone activity and ACTH release in man.
Proc. Soc. Exper. Biol. & Med., 96: 1957^ (in press).

Other Publications.

Ader, R. and Clink, D.W. Effect of chlorpromazine on the acquisition and
extinction of an avoidance response in the rat. J. Pharmacol. & Exper.
Therap, 121: ll^-lU8, I957,

- IE

Serial No. M-CS-M(C)-6

1. Lab. of Clinical Science
2„ Section on l"iedicine
PHS-KIH 3. Bethesda, Md.
Individual Project Report
Calendar Year 1957

:3,rt A.

fj Project Title: Morphine suppression of pitressin-induced ACTS release in man.

Principal Investigator; Roger K^ McDonald, M.D»

Other Investigators: Virginia K. V7eise, Raymond W. Patrick, and Franklin T,

Evans, M,D.

Cooperating Units: None.

fj Man Years (calendar year 1957) Patient Days (calendar year 1957)
Total: 2 110

Professional: 2/5
Other: 1 1/5

Project Description:

Objectives: Pitressin (vasopressin) has been postulated to be the neuro-
hormone responsible for directly stimulating ACTH release from the
anterior pituitary gland. In addition to causing ACTH release the
intravenous administration of pitressin in human subjects is accompanied
by unpleasant subjective symptoms which, in themselves, could be suffi-
ciently stressful to cause ACTH release. This study is designed
to determine whether pitressin-induced ACTH release in man can be
suppressed by morphine, a drug which has knovm central nervous system
action.

Methods Employed: Plasma hydrocortisone concentrations were determined by
the method of Peterson et al. The levels obtained were assumed to be
an indication of ACTH activity.

Patient Material; Normal volunteer subjects were employed in this study.

Major Findings; In normal human subjects the ACJTH release resiolting from
the intravenous injection of pitressin is significantly reduced by
morphine premedication. Morphine has no suppressive effect on adreno-
cortical responsiveness to intravenoxisly administered ACTH.

Significance to Mental Health Research; This study provides further evidence
against the hypothesis that antidiuretic hormone acts directly on the
anterior pitxiitary gland to produce ACTH release. It is part of the over-
all program for evaluating hypothalami co -hypophysial interrelationship
which is concerned with the individual's adaptation to frequently changing
life situations.

- 189 -

Serial No. M-CS-M(C)-6 Page Jj

Proposed Course of Project; No direct continuation of this project is
contemplated at the present time.

Part B included; No

190

NATIONAL INSTITUTE OF MENTAL HEALTH

Clinical Investigations
Laboratory of Clinical Science — Section on Physiology

BUDGET SHEET

gsUtnated oi?lieat3„ong for n 19'?8

Total: $196,226
Direct: $69,^6?

Reimbiirsements : $126 , 759

Projects included: l^CS-P(C) 1 through ]^CS-P(C) 5

Serial No. M-CS-P(C)-1

1. Laboratory of Clinical Science

2. Section on Physiology

3. Bethesda, m.

PES-1«H

Indivldvial Project Report

Calendar Year I957

Prt A.

Project Title: An attempt to differentiate between the thinking disorder found
in schizophrenics and that found in patients vith the diagnosis
of chronic brain syndrome.

Principal Investigator; Irwin Feinber'g, M<,D.

Dther Investigators: Edward V. Evarts, M.D.

Cooperating Units: St. Elizabeths Hospital, Washington, D,C.

to Years (calendar year 1957): Patient Days (calendar year I957):
Total: 2/3 -'^■z

Professionals S/5

Other: None

'reject Description:

Objectives: 1. To characterize more precisely the nature of the think J ng
disorder found in schizophrenia,

2. To devise a test which will distinguish the thinking of
schizophrenics from that of patients with chronic brain
syndroffie.

Methods Employed: Our starting hypothesis is that schizophrenics may have a
selective difficulty in recognizing relationships and that, in a test com-
paring the ability to recognize identities and relationships, organics may
perform equally poorly on both but that schizophrenics will be significantly
worse on the latter. oxts,uxxAcaaT,xy

^^^IT'K^^^^^'^' P^*ien*s hospitalized in the William A, White Building of
St, Elizabeths Hospital with the diagnosis of schizophrenia and those in
other buildings >rith the diagnosis of chronic brain syndrome.

Major Findings: None at present.

Si^iflcance to Mental Health Research: A more accurate description of this

i^n*" T^^J\°^ *^! ^^°^^^ P^^^^^^ '"^^ ^^ ^^ ^^ ^ tl^e Assessment of
induced raodel-psychoses and of the effect of various treatment procedures.

^SlS^ff °K ^^°J^^*V ^^^^*i"g ^11 b« started shortly in an attempt to
evaluate the above hypothesis. The literature in the field is beinTreviewed.

B included: NOo

■191

Serial No, M-CS-P(C)-2

1, Lab, of Clinical Scienii
2e Section on Physiology ;
5= Betbesdaj, Md.

PHS=NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Titles The effects of a variety of centrally acting drugs on intellectual
motor, and perceptual behavior in normal subjects.,

Principal Investigators Conaa Kornetsky^ PhoD«

Other Investigators: Thomas Vates^ Mt.D,, Mary Lee Geisser^ end Edith Karnmen I

Man Years (calendar year 1957)° Patient Days (calendar year 1957)° '
Totals 1 1/3 650

Professional; l/5

Other; 1 i

Project Description;

Objectives; 1, To determine what differences may exist in the psychological

effects of opiates, tranguilizing drugs, barbiturates, psychoto-]j
mimetics, and alcohol »

2 a To study the individxial differences in subject response to drugs

Methods Employed; During the past year we have altered the procedure eniployed
in measuring the psychological effects of dsrugs such that instead of em-
ploying a number of separate pieces of apparatus we now use a single multiple '
stimulus -response apparatiis. This allows the measurement of a variety of ,
types of behavior involving the same motor response on the part of the I
subject* This multiple stimulus-response apparatus was developed by Michael
Davis, formerly of Technical Development, with the collaboration of Dr« James
Birren, Section on Aging, Laboratory of Psychology, and Conaa Kometsky,
Laboratory of Clinical Science, Three measures of behavior have been used
this past year; Simple motor response, choice reaction time, and a simple
learning task.

One eacperiment has been con!i)leted this year and another is in
progress* The completed experiment compared the effects of 800 and 1600
mg=, of meprobamate, 60 and 120 mg. of phenobarbital, and 5 and 15 mg, of {

d-anrphetaraine ,.

The second experiment which is stiH in progress conipared the
effects of chlorpromazine, dextro-amphetamine^ pentobarbital, benactyzine,
and alcohol in normal subjects. The pxirpose of this experiment was primeirily
to test the hypothesis that individuals whose performance was most impaired
by depressant drugs would have the greatest facilitation after stimulant
drugs. In order to obtain facilitation after dextro=amphetamine this drug
was administered after 48 to 72 hours of sleep deprivation^.

- 192 »

Serial No.. M-CS-P(C)-2 Page 2

In both of these studies Dr« Allen Mirsky of the Section on
Animal Behavior^ Laboratory of Psychology, determined the effects of the
drugs on the "continuous performance test,-." (See Dr^ Mirsky* s report for
details )« Dr.. Philippe Garden of the Laboratory of Clinical Science studied
the subjects employed in the first study o, He compared the effects of the
varioiis drugs on a number of physiological indices,, (See Dr, Caxdon's report
for details)= Dr, Virgil Carlson of the Section on Perception and Learning,
Laboratory of Psychology, has been testing all subjects of the second study
on a suggestion test and a variety of perceptual tasks, (See Dr.. Carlson's
report for details), Dr^ Isabella Kendig of the Laboratory of Psychology has
interviewed all subjects prior to the start of the experiment in an attempt
to see if relationships exist between health and health attitudes and
response to drxigs, (See Dr., Kendig' s report for details )« Dr* Darab Dastur
of the Section on Cerebral Metabolism, Laboratory of Clinical Science, has
collected urine during the sleep deprivation part of the experiment to
determine if sleep deprivation changes the constituents of the urine «

Major Findings: In the first study engjloylng meprobamate, phenobaxbital and
dextro-aatphet amine, only I6OO mgm, of meprobamate catused significant impairment
of functioning on all three parameters of the multiple stimulus -response appeiratus*
Eight hundred m@n„ of meprobamate reduced the rate of learning but did not affect
performance on simple motor response or choice reaction timeo Phenobarbital
did not si^ificantly affect performance on ar^r of the procedures 0 Dextro-
anphetaffiine did not facilitate performance j on the contrary, it produced a
slight though statistically insigiificant impairment of performance.

In the second escperimeat, l4 subjects have been studied. The data will
not be analyzed imtil I8 to 20 subjects have been completed,.

Significance to Jfental Health Research; This project will give information on
the relative effects on performance in normal man of a vsiriety of drugs that
are used in the treatment of mental illness =. In the early studies^, it was
found that those subjects who were most affected by one drug were very likely
to be the same subjects who were most affected by other drugs » If this
finding is confirmed, an attempt can be made to relate this to such variables
as personality and the physiology of the individual. Such studies may give us
a basic understanding of the important non-dxug variables in an individual's
response to drugs <.

Proposed Course of the Project;

1. The present study will be completed early in 1958 after which
further studies on individual differences in drug response will
be carried out and the relationship of these responses to the
response of the individual to psychological and physiological
stress will be determined^

2o The effects of smaller doses of the drugs will be studied in an
attempt to siscertain minimal effective dose.

Part B included; Yes, - 193

Serial No. M-CS-P(c)-2 Page 5

Prt B,

Publications :

1. Koraetsky, C. Relation of physiological and psychological effects
UMT-Ifs" 1%^^,^^*^^-^^^* A.M.A. Arch. LLl. I PsycSatf

Honors: Dr. Conen Kometsky was elected to membership in the American
Society for Pharmacology and Experimental Therapeutics.

- 19^ -

Serial Wo. M-CS»P(C)-5

1, Latoo of Clinical Science
2o Section on Physiology
5. Bethesda, M.

PHS-HIH
Individual Project Report
Calendar Year 1957

et A

Project Title; Studies on the effects of various centrally acting drugs
in the rat.

Principal Investigator; Conan Kometsky^ PhoD, and Joseph Cochin, MeD,, :!''.

Other Investigators 2 Michael Malainud*aRd Straty Economon

Cooperating Units; Laboratory of Chemistry, NIAMD

Man Years (calendar year 1957) s Patient Days (calendar year 1957):

Total; 5/6 None

Professional 1/3
Other; 1/2

Project Description;

Objectives; 1» To study the effects of various centrally acting drugs
on siinple motor behavior in the rat.

2, To determine the degree to which individual differences
in the extent of response to drugs may be partially
independent of the drug being studied,

3, To study tolerance to various centrally acting drugs.

Methods Employed: The primary dependent variable used in these experiments
is the time it takes the rat to swim a cireiilar pathway 13 feet in length.
Two experiments comparing the effects of chronic administration of mor-
phine on swimming time to an analgesic measure of morphine effects have
been corapletedc. Two methods of determining analgesic effects have been
used; tail flick response to thermal radiation and the hot plate method.
A third and preliminary experiment has been started to study tolerance of
the rat to LSD.

Major Findings; The morphine stisdies suggest that tolerance to the be-
havioral effects of morphine lasts longer than tolerance to the anal-
gesic effects. The preliminary LSD experiments suggest that tolerance
to LSD in the rat does not develop so rapidly or to so great a degree
as does tolerance to LSD in man. Also, it is not clear at the present
time whether or not complete tolerance to LSD ever appears in the rat,

"Sunmer students

19-5 -

Serial No. M-CS-P(C)-5 page 2

Significance to Mental Healtti Research;

1« These studies will help us understand the course of the development
of tolerance to variovis drugs used in the treatment of the mentally

2, A more basic problem but one that may have far more significance
to the problems of mental disease is that of individual differences
in response to drugs. If animals that are most affected by one drug
are also the same animals that are most affected by other drugs, it
will indicate that there is something present in the animal that
determines the relative effects of drugs independent of the drug. If
physiological mechanisms can be elucidated that contribute to the
extent of drug effect it will contribute to an vsnderstanding of the
important variables in human response to drugs.

Proposed Course of Project; The effects of a variety of drugs on the swimming
procedure will be studied. If it is found that animals who are
relatively most affected by one drug are relatively most affected by
other drugs, an attempt will be made to elucidate the iniportant
variables contributing to individual responsivity to drugs.

Part B included; No

- 196 -

Serial No» M-CS-P(C)-lv

lo Lab, of Clinical Science
2o Section on Physiology
5o Bethesda, Md..

PHS»NIH
Individual Project Report
Calendar Year 1957

]irt A

Project Title; A comparison of the effects of chlorpromazine and secobarbital
on intellectual^ motor and perceptual behavior in schizo-
phrenic patients*

'Principal Investigator; Conan Kometsky^ Ph»D<,

Other Investigators; Ronald Wynne^ MaSe^ Edward Vo Evarts, M«De^ and John

M, Petit ^ M^D^

Cooperating Units s St» Elizabeths Hospital^ Washington j, D«C»

Man Years (calendar year 1957): Patient Days (calendar year 1957) s
Total; 1 1/6 885

Professional; 1/2
Other; 2/5

Project Description;

Objectives; To compare the effects of both acute and chronic administration
of chlorpromazine and secobarbital on a variety of behavioral measures
in schizophrenic patients.

Methods Employed; Acute Study - Twelve schizophrenic patients with a minimum
of one year of hospitalization were selected frcan the population of the
William iU White Building at Sto Elizabeths Hospitals On separate days
each subject received 100 aad 200 mgm, of secobarbital, 100 and 200 mgm.
of chlorpromazine^ and a placebo « Each dose of each drug was repeated
once^ so that each subject had a total of 10 testing days. All drugs
were admnistered in identical capsules and the "double -blind" procedure
weis used throu^out* Ninety minutes after drug administration j, subjects
were tested on a variety of motor, intellectual and perceptual tests.

Chronic Study = A week after the coH^letion of the acute study,
subjects were placed on a two=week regime of chlorpromazine, secobarbital,
or placebo. All subjects received each drug for two weeks *, A balanced
design was used« During the first week on each drug, subjects received
100 mgm. twice a day, while during the second week subjects received
200 mgm. twice a day. Testing was done ©a the fifth day of each week.
The same behavioral measures used in the acute study were used in the
chronic study.

197

Serial Bo^ M-CS-P(C)-it Page 2

Major Findings s Acute StxKly = The restjlts indicate that the effects of
eMLorpromazine aud secobarbital on perfonaance in schi'^ophrenics are
not sigDififfiantly different from the effects of these drugs on per-
formsnce in normal subjects o That is^ both 200 m^^ of secobarbital
aad 20D m@no of chlorpromasine inspair intellectual^ perceptual and
motor functioning in both normal and schizophrenic populations. In
the studies on normal subjects 100 m^« of chlorpromazine also signi-
ficantly affected performance on these same testsj in the schizophrenic
population^ however^ 100 rngm, of chlorpromasine caused a sli^t but
statistically insignificant decrement in performance level.

Chronic Study » In the chronic study neither 100 nor 200 mgm. of
chlorproma:zine caused siggiificant in^airment in performance^ where-
as the 200 mgm<, dose of secobarbital did cause significant impairment
of perl'ormanceo

Research;
SigQifieanee to Mental Health/ Since drugs are one of the primary methods
used in the treatment of the mentally ill^ it is importajat to know to
what degree these drugs do or do not iiopair psychological functioning.
Drugs which lead to amelioration of a patient's psychotic syu^itoms
but catise significant impairment of mental ftmctions may not be the
therapy of choice in certain groups of psychiatric patients.

Proposed Course of the Projects In 1958 this project will make use of
operaat conditioning procedures in the study of the effects of drugs

ia schisophrenic patients. It is hoped that the use of operant con-
ditioMng procedures will allow the studies of learning and perception
in patients ifeo otherwise would not cooperate enough so that meaning-
ful results could be obtained» These techniques may prove useful in
evaluating the efficacy of traaquiliziag drugs in this population.

Part B included; lo

198 ~

Serial No. M-CS-P(C)-5

1. Lab. of Clinical Science

2. Section on Physiology
5d Bethesda, Mi.

PHS-NIH

Individual Project Report

Calendar Year 1957

Prt A.

Project Titles Behaviorally and pharmacologically induced effects on the
electrical activity of the "brain.

Principal Investigators; Edward V. Evarts, M»D, and Corwin Fleming, M.D.

Other Investigators; Mortimer MLshkin, M.D, and Bonnie Peacock

Cooperating Units; Section on Animal Behavior, Lab. of Psychology, NIMH

Man Years (calendar year 1957): Patient Days (calendar year 1957);
Total; 1 5/6
Professional; 5/6
Other; 1

Project Description;

Objectives; In the previous annual report (1956) from this section, two
separate neurophysiological projects were outlined, one dealing with neuro-
pharmacolosr and one dealing with the excitability of primary and diffuse
thalamo-cortical projection systems. These two areas of investigation
have been combined in the present project. The purpose of this project
is to correlate a variety of behavioral and electrophysiological
observations. Studies of the effects of pharmacological agents on
behavioral and electrophysiological events are also in progress.

Methods Employed; MDSt of the studies on this project have been carried
out in cats with chronically implanted electrodes. The loci of place-
ment of the stimulating and recording electrodes depends upon the
particular phase of neural activity ^ander investigation.

Major Findings;

(l) Studies of the characteristics of cortical recruiting responses
in unanesthetized cats were begun in 1955 in collaboration with
Dr. H. W, Magoun. These studies have been completed. It was found
that well -developed cortical recruiting responses could be evoked
in awake cats by stimulation of the intralaminar nuclei. Stimu-
lation of the brain stem reticular formation reduced the amplitude
of the recruiting responses in these preparations! novel auditory
stimuli had a similsir effect. With repeated presentation, a
given auditory stimulus ceased to affect recruiting responses
("habituation")* Repeated stimulation of the brain stem reticular
formation, however, consistently reduced the amplitude of
recruiting responses.

199

Serial No, M-CS-P(C)-5 Page 2

(2) Previous studies carried out in collaboration with Dr. Arnold
Schoolman and Dr, Wade H. Marshall demonstrated that pentobarbital
has marked effects on the excitability cycle of the primary cortical
response to lateral geniculate radiation stimulation. This effect
of pentobarbital consists of a marked increase in the initial sub-
normality of the test response. Further studies have now shown that
ethyl ether has a similar effect. In contrast, chlorpromazine and
reserpine do not exert this depressant effect on the early phase of
the cortical excitability cycle.

(3) A series of observations concerning the electrophysiological effects
of metabolites of epinephrine and norepinephrine has been carried
out. In anesthetized cats, metanephrine and normetanephrine were
tested on

(a) the transcallosal response

(b) the cortical response to retinal photic stimuli

In unanesthetized cats with chronically iniplanted electrodes, obser-
vations were made on the effects of the two substances on

(d) the cortical response to geniculate radiation stimulation

(e) the cortical response to retinal photic stimuli.

Large doses of the two substances were without effect on any of these
forms of electrical activity. ,

{h) Studies aimed at analysis of electrophysiological correlates of condi-
tioning have recently been vindertaken in collaboration with Dr. Mishkin.
In an initial phase of this study, cats with chronically implanted
electrodes were subjected to repeated photic stimuli. In three cats
that were exposed to 3,000 flashes (600/day for 5 days), no decrease
in the aniplitude of the primary cortical response weis observed. On
the contrary, there was a statistically significant increase in the
amplitude of the responses over this period. Subsequent studies
will analyze the effects of a conditioning procedure in which the
light flash will be paired with a painfral shock.

200

Serial No. M-CS-P(C)-5 Page 5

Significance to Mental Health Research: The four general findings which
have been described may be divided into two groups:

1. The electrophysiological studies have shown rapid habituation to the
effect of an auditory stimulus on recruiting responses, but have failed
to show any decrease in the primary cortical response to a repeatedly
presented flashy These observations are related to the problem of
central electrophysiological changes in association with learning, and
may be regarded as generally relevant to basic problems of mental
function.

2, The pharmacological studies have demonstrated a clear end striking
difference between the cortical effects of barbiturates and ether
on the one hand;, and chlorpromazine and reserpine on the other » The
absence of cortical depression by chlorpromazine and reserpine may
in part explain the selective behavioral effects of these drugs «

Proposed Course of Project: The project will continue along the lines indicated
above* During the coming year emphasis will be placed on studies of the
electrophysiological correlates of learning and conditioning.

Part B included: Yes

lOl =

Serial No. M-CS-P(C)-5 Page k

Part B<

Publications

1. Evarts, E.V. and Magovin^ H,W* Some characteristics of cortical
recruiting responses in unanesthetized cats. Science, 12^; 11^7-
111^3, 1957.

2. Evarts, E,V. Neurophysiological correlates of pharmacologically
induced behavioral disturbrnces . Research Publications of the
Association for Research in Nervous and Mental Diseases, 1956,
(in press).

3. Evarts, E»V, Contributions of neuropharmacological studies to
our present concept of a possible chemical basis for psychosis.
Proceedings of the Symposium on Chemical Concepts of Psychosis,
2nd International Congress of Psychiatry, Zurich, Switzerland,
1957> (in press).

2C2

NATIONAL INSTITUTE OF MENTAL HEALTH

Clinical Investigations
Laboratory of Clinical Science — Section on Psychiatry

BUDGET SHEET

Estimated Obligations for FY 19*^8
Total: $220,722
Direct: $83,673

Reimbursements: $137,0^9

Projects included: M-CS-Ps(C) 1 through M-CS-Ps(C) 5

Serial No. M=>CS-Ps(C)-l

1. Laboratory of Clinical Science
FHS-HIH 2o Section on Psychiatry

Individual Project Report 3» Bethesda^ Maryland
Calendar Year 1957

Part A.

Project Title: Correlation of Psychiatric Evaluation with Neurophys-
iological, Psychological and Sociological Evaluation in the Aged»

Principal Investigators: Seymour Ferliaj Mo D. and Robert U. B-itler^ M= D,

Other Investigators: None

Cooperating Units: Section on Cerebral Mstabolism^ Laboratory of Clinical
Science, National Institute of Mental Health. Serial No. M-CS-CM-1

Man Years (calendar year 1957): Patient Days (calendar year 1957) ^
Total: it. 5

Professional: 1 755

Other: 3-5

Project Description:

Objectives ; (a) To select suitable saniples of "noriaal-a,';:ed" vol-
unteers and Chronic Brain Syndrome patients for nultidisci-
plin-ary study, (b) To psychiatrieally evaluate and characterize
ttie selected subjects in terms of: diagnosis, psychopath-
ology and modes of adaptationo (c) To correlate psychiatric
evaluation vith physical status^ neurophyeiologic (including
cerebral ffletabolism and eleetroeneephalograpliic measurements)
status^ and psychological and sociological status o (d) To
define (through a, b aad c) criteria for the subgroups desig-
nated "normal" aged^ "senile factor" aged, and chronic
brain syndrom'; »

Methods ; Each subject will be interviewed for two 2-hour recorded
and observed sessions; the first (Interview A) being an
unstructured psychiatric interview^ the seccad (interview B),
a structured interview which includes a loental status ex-
axaination and inquiry regarding apparent age-relevant
concepts, 53iere is systeraatic rotation in roles of inter-
viewer and obseirver.

In addition., rating methods will be adapted for use by the
interviewer, observer, and other psychiatrists for indepen-
dent assessment.

Independent and concensus ratings, quantified on a seven-point
scale tdierever feasible, will be made in the following ten

categories: (a) Diagnoses, (b) "Age Relevant" SynsptGSJS,

^03

^^« "^^ Serial Number M-CS-Ps(c)"l I

Project Description: (Csntiaued)

(c) Mental Status, (d) Affective State, (a) PsyeMatric Sya^toms,
(f } Separation Respoase, (g) Concept Evaluation (Disordered Tiiae
Sensej Constriction of Future^ Age ChaBge Attitudesj Death
Concern; Disturbed Body Ismge), (h) Maternal Attitude Scale,
(i) Psy^hodyaamic Formaation, and (j) Intei-view Behavior Scale.

Patient Material;

Major Findi23g3; Adaptational modes in the aged have "been derived from !
the psyxshiatric characterisation aiid differentiation of emerging j
subgroups within the fifty- seven aged volunteers studied, j

Investigations of neurophysiological variables; e.go, cerebral :'
metabolism, in ttie conmmiity aged failed to disclose any simple '•
relationships with psychiatric status (ineludiag cognitive defects]
Bie relationship of reduced cerebraa metabolism to the diagnosed
of chromic brain syndrons was confirmed.. I

i
A group which has been designated as the "Senile Factor Group," i
reveals definitive cognitive losses but no alterations is cerebral;'
metabolism. !Siis may be a coisposite syndrome, a consequence of
both organic and psychosocial alterationso and is distinct from i
the Chronic Brain Syndrome, mis syndrome m.j correlate with '
psychological tests for "orgaaicity. " This m.j represent an !
early stage of the Chronic Brain S^-ndrome. '

Investigations of the effects of psychosocial disruptions or
losses demonstrates that the personal meaning or psychological
significance, of such are more important than the incidence or
nature of these stresses per se. In general, the adaptive or^
maladaptive function of personality variables or psych©pathologica'
features varied with the psychological significance of certain
events in the aging experience (e.g., losses; cognitive deficits:
forced retirement and the like).

The adaptive use of psychopathology, -fee use of activity, the
counterphobic attitude, and the function of denial versus
insight into the aging essperience, axe among the adaptatiosaal
modes identified, to the other hand, maladaptation is seen in
depression, paranoid isolation, identity loss and «ie like.

While the representativeness of the saa^sle cannot be claimed a
variety ©f psychiatric, psyeh©s©oial and other aspects of
these populations are escplieitly ehajraeterized and thus available '
for purposes of comparison. ''

Significance to Mental Health Research; Hi® strueturi^ of problems '
for research in geriatric psychiatry receives nuch. ©f its is^tus \
in the s©atext ef iBie evar«=iacreasiag niaaibers ©f aged in -feis
country. Bie ©Ider pers« himself has been aagiected resea^-ch-wis
and there has been miah faulty extrapolation of data from o-^er ag

10^

Page Biree Serial Number M=CS"Ps(c)-l

Significance to Mental Health Research: (Continued)

periods. The study of the normal aged hr.s been especially neglected.
The sesLTch for adequate evaluation in the aged has its historic roots
in the inability to fully understand psychological symptoms on the
basis of neuropathologies! changes. The question as to which are
the important parameters for investigation eiaphasizes the need for
a multidiscipline approach. Psychiatric diagnoses run the gaimat and
may vary from one dealijag with the individual's personality make-up
to defined neurotic syraptomatology to organicity; e.g., chronic
brain syndrome with arteriosclerosis. Thus the possibility of
correlating data with other disciplines is present. A few examples
of the theoretical questions posed by one discipline against the
data provided by another discipline are as follows: (l) Does the
slowing of reaxition time postulated by the psychologist as a sine qua
noa of aging correlate selectively with depression as evaluated by
the psychiatrist? (2) Does the diagnosis of chronic brain syndrome
with arteriosclerosis formulated as a syndrome by the psychiatrist
correlate with evidence of change as measured by the neurophysiologist
and internist? (3) Are assumptions regarding sequence of changes in
cerebral blood flow and metabolism as meastired by the neurophysi-
ologist supported by changes in intelligence, perception, etc., as
measured by the psychologist and psychiatrist? Follow-up studies,
if undertaiien, can deal with the predictive value of such matex'ial.

Proposed Cetirse of Project; The study of the subgroup of hospitalized
Chronic Brain Syndrome patients will be continued.

I Part B included Yes

! - 2G5

Serial I©, M-CS-Ps(C)-l Page k

mS-NIH

ladividual Project Report

Calendar Year 1957

Fstrt B: Honors, Awards, and Publications

Publications other than abstracts from this praject:

Perlin, S. and Butler, Ro Correlation of Psychiatric Evaluation with
Neurophysiolegic, Psychologic, and Sociologic Evaluation in a Group
©f Normal Aged, (in preparation)

Perlin, S. Psychiatric Aspects ©f Senile Nervous Diseases. Summary
of Fourth International Gerontological Congress, Merano, Italy,
July, 1957. (To be published)

Perlin, S., Pollin, W. and Butler, Ro The Experimental Subject: I. The
Psychiatric Evaluation and Selection of a Volunteer Population.
(Submitted for publication)

Honors and Awards relating to this project:

Butler, R. and Perlin, S. Depressive Reactions in the Aged. Presented
at 113th Meeting, American Psychiatric Association, Chicago,
May, 1957.

206 -

Serial No. M-CS-Ps(C)-2

1, Laboratory of Clinical Science
PHS-NIH 2. Section on Psychiatry

IndivicLual Project Report 3« Bethesda, Maryland

Calendar Year 1957

Part A.

Project Title: Psychiatric Evaluation of Nornal Control Volunteers.

Principal Investigators: William Pollin, M. D,, and Seymotir Perlin, M.D.

Other Investigators: None

Cooperating Units: None

Man Years (Calendar year 1957): Patient Days (Calendar year 1957):
Total: 1.20

Professional: »50 85

Other: .70

Project Description:

Objectives; (a) To study the methodology of evaluating normal
control volunteers, (b) By means of psychiatric evaluation^
to describe the psychodynamLcs of all normal control volimteers
admitted to the Laboratory of Clinical Science for participation
in other projects, (c) To provide data for use in
(l) setting up criteria for selection of normal control
volunteers; and (2) interpretation of the resxilts of projects
in which they participate, (d) To indicate in vhat vays
extension of this investigation into the area of correlation
between psychological and physiological variables in normal
controls can be made* (e) To study the motivation of normal
control volunteers to enter a research hospital and the
relationship between motivation and psychopathology.

Methods Employed; Each normal control is routinely seen for a
psychiatric evaluation interview^ Following this interview,
the interviewer as well as the interviewee provide independent
ratings of a variety of categories of affect and psychological
functioning, quantified on a 7-point scale. In addition,
interview behavior is rated by the psychiatrist-. Interviews
are recorded and available for later independent analysis and
evaluation. During their stay on the ward, subjects are seen
before and after certain investigative procedures for brief,
recorded procedure-oriented interviews.

Patient I'laterial: To date, (10/17/57) ^9 subjects have been so
evaluated.

Major Findings;

1. Psychiatric evaluation of a group of 29 volunteer research
subjects demonstrated the presence of significant psycho-
pathology in 15. In 11 of the 29 subjects psychiatric
diagnoses were made.

- 207 -

Page Two Serial NOo M<=CS=Ps(C)"2

There ■^ras an inverse relationship in this volunteer group
between the presence of psycbopatJiology and the extent to
which environissental influenees contributed to servl,ng as a
volunteer o "-- '- -

3o Kie incidence of psychopathclogy in a subgroup whose
volxinteer status was largely due to thair draft status
was 28^j in a second gubgroup whose volunteer status con-
formed with sociO'Oultiiral tr^sdition^ 3^^$ in a third sub-
group where neither of these factors were operative^ 100^,

ko The volunteer group showed considerable differences in the
motivations involved in volunteering^ in the ability of
its members to accommodate to stress, in defense mechanisms i
employed^ and in the tendency to somatieize anxiety,

5o These differences^ and the relationship between volunteering
and psyehopathology have clsxified a number of questions
pertinent to the selection of ^folimteer groups^ and the
interpretation of results obtained from them.

Significance to Mental Health Research; Normal control volunteers
constitute one of the major subject groups used in psychiatric
and psychological resear'Ch= Until very recently^ little
attention has been given to setting up ci'lteria for the
selection of such groups^ other t-hsa att'Smpts at exclusion of
individuals shoTd.rjg gross psyehopathology » SLniilarly^ there
has been little work done en psychiatric evaluation of normal
controls or with the application of data obtained from such
evaluation to the interpretation cf data obtained by other
discipline So Findings thus far msJse possible a more meaning-
ful use of volunteer Sj, and clarify some problems of one of the
basic elements in personslity,-@ad pfychophys5.ological research; !
the subjects employedo . " .. _ i

' ' ' ■ I

Proposed Course of Projects Eva3.Tu,ation of all normal control

volunteers admitted t© the laboratory of Clinical Science wards,

I
will continue »

Part B included^

--^'^^:'%rt

Page Three Serial No. M-CS-Ps(C)-2

PHS-HIH
Individual Project Report
Calendar Year 1957

Part B; Honors, Asrards, and Publications

Publications other than abstracts from this project:

1. Pollin, W, and Perlin S^ Psychiatric evaluation of

"norinal control" ^'olunteers. Am. J, Psychiato (in Press)

Honors and Awards relating to this project:

1« Perlin, S,, Pollin, W. and Butler, Re N. The experimental
subject: I. The psychiatric evaluation and selection of a
volunteer population. Presented at Divisional Coiaference,
American Psychiatric Association, New York, New York,
November, 1957 •

- 209 -

PHS-NIH 1. Laboratory of Clinical Science

Individual Project Report 2. Section on P^ychiatcj!: :
Calendar Year 1957 3. Bethesda, ifeyland- '- -- •-

s, no ii'j'Vjsa niia-s.ti-^. 01 - S x ^ ~ bbZs^^

Project Title; ^ Psychological Variables and Cereljr.i^ .phy§iqi.ogy^ ..;.

/ Principal Investi^al^drs: ' Seymoxir Perliri/ M» D. and^illiam Pollin.M.D.

Other Investigators J Conan Kornetsky/ M.. D,, Louis Sokoloff, M, D«

and Seymoxir S. Kety, M. D.

Cooperating; Units; None , _^

u., ,.^^»^^ ,.'fm ^ «--.^ ?. *-.jt!r o.*

Man Years (calendar year 1957); Patient Days (calendar year 1957)
Total; >66

Professional; .33 26

Other: ,33

Project Description;

Objectives; To determine -vrhether there is a demonstrable relation-
ship between levels of cerebral blood flow and/or oxygen uptake,
on the one hand and basic personality structure and/or
psychological state at time of the procedure, on the other.. To
characterize such a relationship, if one exists.

Methods Employed; Normal Control Volunteer subjects are routinely
seen for psychiatric evaluation on admission. They are also
seen at intervals before and after the CBF procedure, by the
psychiatrist, for a brief procedure-oriented interview.
Psychological measurements, including MMPI, Rorschach and GSR
recording during procedure, are done. Cerebral blood flow and
metsibolism are measured by Nitrous Oxide technique of Kety and
Schmidt. Four participant -observers make independent and con-
sensus ratings of subjects behavior and adaptation during pro-
cedure. When current second series of subjects is completed,
these independently amassed data will be inspected for possible
correlations and to determine if certain relationships between
personality and cerebral metabolism indicated by the study of
first series of subject is further supported.

Patient Material; Males - 5 x 2 - 10

Females - 6 x 2 - 12

Patients served on a variety of projects

Major Findings; In the first group of subjects, studied by similar
techniques, there appeared to be an inverse relationship between
low normal levels of cerebral O2 uptake and the presence of
psychopathology« There was also a direct relationship between
level of CMIO2 and responsivity during the procedxire. The cxirrent
subject population is being investigated to determine if these
previous findings can be verified^

- 210 -

P&ge Two Serial No. M-CS-Ps(C)-3

Patient Material;

Males - ^ X 2 - 10 Patients served on a

Females - 6 x 2 - 12 variety of projects

Significance to Mental Health Research; Results of this study should
help to clarify the relationship between personality factors, the
stress of certain investigative procedures and the results of such
procedures. They may also indicate a relationship between certain
aspects of cerebral metabolism and personality variables.

Proposed Course of Project; The present second series of subjects will
be completed and data then analyzed.

Part B included Yes

r- 211

Serial Ho. M»CS-Ps(C)-3 Page 3

mS-HIH
Individual Project Report
Calendar Year I957

Fart B; Honors, Awards, and Publications
Riblications other than abstracts from this project:

Honors and Awards relating to this project:

Presented at (l) Peripatetic Club, February 1, 1957; and (2) Public
Health Service Clinical Society, April 27, 1957; under title
"Psychological Variables and Cerebral Functions in a Volunteer
Population: Preliminary Report."

212

Serial No. M-CS-Ps(C)A
1. Laboratory of Clinical Science
PHS-NIH 2. Section on Psychiatry

Individiial Project Report 3. Bethesda, Maryland
Calendar Year I957

Part A.

ft"oject Title: Correlation of Psyckiatrie Evaluations and Their Ibysi-
ological Correlates of tlie Effects of 1-Epinepkrine in a Normal
Control and A Schizophrenic Population.

Principal Investigators: Rohert H. Butler, M. D. and William Pollin, M. D.

Other Investigators: None

Cooperating Units: Section on Cerebral Metabolism

Section, General Haysiology

Man Years (calendar year 1957): Patient Days (calendar year 1957):
Total: olO .

Professional: .50 None

Other: ,(iO

Project Description:

Objectives ; (l) To determine if there is any difference in psy-
chiatric response to a high level of circulating epinephrine
between a group of chronic schizophrenics and a group of
control volimteerso (2) To study the effects of a high
level of circulating epiiiephrine upon the schizophrenic dis-
order. (3) To investigate possible correlations between
psychiatric response to high levels of epinephrine and
concurrently obtained metabolic and psychophysiological data.

Methods; Each experimental subject receives 1-Epinephrine, stan-
dardized according to body weight, infused intervenously at
0.30 micrograms per kilogram per minute. An aliquot of
tagged tritiated epinephrine is included in the infusion.
Experimental conditions are standardized and studies of
control and schizophrenic subjects are interdigitated. Two
psychiatrists participate, one as an interviewer and the
other as an observer-auditor. The psychiatric observations
proceed continuously from the time the patient is informed
of the procedure shortly before it begins through a post-
study evaluation period. The procedural period consists of
a randomized sequence of drug and saline infusion concerning
which the peirticlpating psychiatri&ts remain blind. The
subject also is uninformed as to idiat substance is being
infused. During cBjch infusion period an interview of approx-
imately twenty minutes duration is conducted. The interview
includes a portion of the time devoted to xmstructured
productions by the subject, a standardized symptom check list,
brief tests of mental function, and, in the case of the

" 213 -

^^e Two Serial No. M-CS-Ps(C)-l^

schizophrenic popaatioH, specific questions pointed at each |
subject •s most prominent psychotic features of conflict. The
interviews will he recorded for further and independent analyai,

The observer-auditor employs a scale devised for use in rating
subjects with respect to changes in affect, mental organization
and activity in each of the periods, and in assessing their
attitude toward the procedure. In addition, he writes con-
tinuous descriptive notes and includes data concerning the
interaction between the interviewer and the subject. Observa-
tions are made through a one-way mirror.

Physiological, metabolic, psychophysiological and EEG data 1
sure collected simultaneously.

Patient Material; A group of chronic schizophrenic patients

admitted here from a state hospital, as well as a group of j
resident control volunteers. I

Significance to Msntal Health Research; Bie role of epinephrine

in anxiety has been suspected for some time and the possibility;!

that epinephrine ©r one of its metallolites is ©f Importance i

in the pathogenesis of schizophrenia is under current com- 1

sideratlon. Studies of the psychological and physiological i

effects of epinephrine may contribute t© knowledge of the I
physiology of affects and/or the physiology of schizophrenia.

Proposed Course; Trial studies are now being conducted on both I
control and schizophrenic subjects. The series itself will
shortly begin.

Part B included No

- 214 -

PHS-NIH
Individual Project Report
Calendar Year I957

Serial No. M-CS-Ps(C)-.5

1. Laboratory of Clinical Science

2. Section on Psychiatry

3. Bethesda, Maryland

Part A.

Project Title:

Psychiatric Investigations in the Biological Study of
Schizophrenic Subjects.

Principal Investigator: Seymour Berlin, M. D.

Other Investigators: William Pollin, M. D.; Robert Butler, M. D.j

A. Russell Lee. M. D.

Cooperating Units:

Man Years (calendar year 1957):
Total: 1.2
Professional: 2.5
Other: 3.7

Patient Days (calendar year 1957);
735

Project Description: (l) Criteria for the Selection of a Small Group
of Schizophrenic Patients for Biological Studies. (2) Character-
ization (via interview) of a Schizophrenic Population. (3) Ward
Observations of Schizejihrenic Subjects, (k) Organization of a
Ward for Biologic Studies in Schizophrenia. .

Objectives:

(1) a. To critically explore schizophrenic subject selection
criteria coi^atible with the theoretical and methodological approach
of the multidisciplinary team. b. T® present a design for se-
lection, which attempts to increase the probability of the ex-
pression (qualitative and/or quantitative) of a biological defect.

c. To detail the application of the design in a current NIMH project.

(2) To characterize, in detail, relevant personality features and
adaptations of a normal control and a schizophrenic population
admitted for psychophysiological studies in schizophrenia. To this
end, to develop interview techniques, and rating scales, •jdiich
will be applicable to both groups. Within the schizophrenic
group, to determine if there exist certain patterns of disease,

or symptom clusters, ^ich, though possibly independent of
currently accepted diagnostic groupings, show significant
correlations with organic groupings.

(3) a. To observe the behavior of schizophrenic subjects in a re-
search setting for correlation with psychiatric interview pre-
dictions and psychological test findings, b. To characterize the
experimental situation, and investigate the perception and
response of control and schizophrenic subjects to the experimental
situation. This is an attempt to control for situational
variables extrinsic to the schizophrenic disorder.

Bt^

.211

^^« Two Serial Humber M-CS-Ps(C)-5

Project Description: (Continued)

(k) ihc overall objective is to develop a psychiatric ward milieu suited
to the requirements of biological studies. Complicated by this goal,
but in many ways crucial to its achievement, is the more limited ob-
jective of providing a desirable standard of psychiatric care for the
patients participating in such studies.

Methods;

(1) In attempting to establish criteria compatible with the theoretical
and methodological approach of the raultidisciplinary team, the following
issues were delineated: (A) Group horaogeneityj e.g., age, sex, duration
of hospitalization, exclusion of known organic factors, (b) !Qie biasing
of the sample: An atten^t to increase the probability of the expression
(qualitative and/or gxiantitative) of a biological defect. Concepts
utilized: Multiple versus single etiology, "genetic," familial, "process,"
etc. (C) Generalizations and statistics related to the sm^J^sairole.

(D) The "normal control." " ^ —

The following committee was consulted as regards the issues raised;
Dr. Seymour Kety (Biology); Dr. Gordon Allen (Genetics); Dr. Saniael
Greenhouse (Statistics).

(2) Clinical experience and literature search have provided a number of
alternative interview- and rating scale approaches, which are cvirrently
being tested.

(3) Observation by ward personnel and the investigator. Use of several
scales devised to record and quantify particularly changes in affect,
mental orgajiization and activity observed in the ward and in the ex-
perimental situation.

(i^) In the process of administering the ward there are many vinusual
problems related to the research goals. Through such pragmatic and
empirical experience ward policies, modes of interaction with patients,
and distinguishing characteristics of tiie ward milieu are gradually
being shaped and defined.

Patient Material;
Major Findings: None

Significance to Mental Health Research: The selection, evaluation and
ward observations of schizophrenic subjects are essential aspects of
biological studies in schizophrenia. (Such factors are, in themselves,
areas for research.)

Proposed course: At present, plans call for the admission of ll^
schizophrenic subjects and ik "normal control" volunteers for long-term
biological studies.

Part B included No

- 216 -

NATIONAL INSTITUTE OF MENTAL HEALTH

Basic Research
Laboratory of Nevirophysiology
General Neurophysiology

BUDGET SHEET

Estimatgcl Obligations fgr fl 19^g

Total? $li^O,ivOO
Direct: $107,876

Reimbursements: $32, 524'

Projects included! M-NP-GN 1 through Jt-NP-GN 8

Serial No. M-NP-GN-1
1 . Laboratory or Meurophysiology
2.. General Neurophysiology
3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A,

Project Title: Measurement of Local Circulation in the Brain

Principal Investigator: D. Hansen

Other Investigators: L. Sokoloff and W. Freygang

Cooperating Units: Laboratory of Clinical Science, Section on

Cerebral Metabolism, M-CS-CM-3

Man Years :

Total : . 5
Professional: .5
Other:

Project Description: See M-CS-CM-3

- 236 -

Serial No . M--NF-<:'N-2

1 o Laboratory of Neurophysiology

2» General Neurophysiology

3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A

Project Title: Effects of drugs on specific ionic conductance.

Principal Investigator : W« H» Freygang, Jr. I

Other Investigator: None

Cooperating Units: This work is being done with Dr. A. M. Shanes ij

of the Institute of Arthritis and Metabolic
Diseases and Dr. H, Grundfest of the Departmen
of Neurology,, Columbia University, New York

Man Years :

Total: .15
Professional
Other :

Patient Days : None

15"

Project Description: '

Objectives: It is possible to analyze the components of j
membrane permeability into those which are specific for i
different ion species « A new afiderstaading of the mechanism:!
of the nerve impulse has been achieved with this approach.
The effects of many neurologically potent drugs need to be
studied in the light of this new information in order to
define clearly their mode of action.

Methods Employed: The technique employed provides a con-
trolled voltage across the membrane of a squid giant axon.
Changes in the flow of ionic current across the membrane hav<
been measured. The drugs are applied extra-cellularly .
Cocaine and veratrine have been studied.

Major Findings: A prominent effect of cocaine is a reduc-
tion in the influx of sodium ions daring activity of the axo •

i
Significance to Mental Health Research: The study should !
supply information of fundamental neuropharraacological
importance .

Proposed Course of Project: Analysis of data.

Part B included Yes No x

237

Serial No. M-NP-GN-3

1, Laboratory of Neurophysiology

2, General Neurophysiology

3, Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A,

Project Title: Measurement of Soma -Dendritic Membrane Current.

Principal Investigator: W. H. Freygang , Jr.

Other Investigator: H. Wiener

Cooperating Units: None.

Man Years : Patient Days : None ,

Total: 1 80
Professional: .80
Other: 1 .00

Project Description:

Objectives: To determine the role of the dendrites aud cell
bodies in the process of transmitting electrically coded
information in the central nervous system.

Methods Employed: As the dendrites and cell bodies carry
signals, there is a flow of current across their membranes.
It has been proven both by mathematical means and by an
electrical analogue of a neuron that the electric poterjtial
outside the cellj, but very close to it, is directly related
to the flow of membrane current » The extracellular potentials
are recorded from very fine glass pipettes placed close to
a single neuron and the time course of the membrane curresiit
is calculated from the recordings „

Major Findings: It is apparent that the iatracellular
recording technique does not show whether the site of
recording can produce all-or-none electrically induced
activity or not, for the electrical signs of all-or~none
activity can spread in a relatively undistorted form to
the recording site. The time course of the membrane current
from the dendrites and cell bodies, however, shows that these
parts of the neuron do not respond to electrical excitation.
Therefore, they must be activated primarily by chemical
transmitter substances that do not induce all-or-none propa-
gating electrical activity.

Significance to Mental Health Research: This new technical
approach combined with the finding that the dendrites and cell
bodies are not excited electrically makes it possible to in-
vestigate the chemically excitable soma-derjidritic membrane

- 238 -

Serial No. M-NP-GN-3
page 2
PHS-NIH
Individual Project Report
Calendar Year 1957

Part A. (continued)

with a clearer understanding and possibly a powerful new tool.

Proposed Course of Project. Because the anterior horn cells of
the spinal cord are large and can be impaled easily, much intra-
cellular data have been obtained from them. Also, they have the
additional advantage that they respond synaptically to stimula-
tion of several easily accessible pathways. For these reasons
it seems probable that the nature of synaptic excitation can be
studied more profitably with these nerve cells rather than those
of the lateral geniculate nucleus which have been studied in
this project.

Part B included Yes x No

- 239

Serial No. M~NP-GN-3

PHS-NIH
Individual Project Report
Calendar Year 1957

Part B: Honors, Awards, and Publications

Publications other than abstracts from this project:

Freygang, W. Ho, Jr., An analysis of extracellular potentials from
single neurons in the lateral geniculate nucleus of the cat. J,
Gen. Physiol., In press.

Honors and Awards relating to this project
None.

240

Serial No, M-NP-GN-4

1„ Laboratory oi Neurophysiology

2. General Neurophysiology

3. Be the s da

PHS-NIH
Individual Project Report
Calendar Year 1957

5rt A.

Project Title: Studies on Role of Superficial Neurons "Dendritic

Reactions" in Spreading Cortical Depression,

Principal Investigator: Wade H. Marshall

Other Investigators: W. Ho Freygang, Jr.

Cooperating Units: None.

Man Years Patier.t Days: None

Total: o90
Prof ess J-OB^l : =30
Other: .60

Project Description:

Objectives: To determine relation of reactivity of superficial
elements of cortex to spreading cortical depression ±v. cat and
monkey o The reactivity of superficial elements is typically
recorded electrically as a surface negative wave. This reaction
has been rather loosely designated as the dendritic response.
Spreading cortical depression car, be obtained in cat and moBicey
only by pathological manipulation, that is by prolonged exposure
to room air_, cooling the surface of tbe cortex, treating the
surface with tyrodes containing excess potassium, etc. The
latter two methods have been extensively employed in this labora-
tory. The effect of these manipulations oia the "dendritic"
response was determined.

Methods Employed: The "dendritic" reaction was evoked by direct
stimulation and by stiaiulation of the callosal systemo The
surface of the arachnoid membrane was exposed to excess potassium
or cooled to the level at which spreading depression can be
evoked .

Major Findings: It was found that producing conditions under
which spreading depression can be evoked resulted ia severe
reduction in the "dendritic" response. This reaction is re-
versible. These experiments clearly showed that neuron activity
of J at least, the first layer of tb.e cortex is r-ot necessary for
evocation and propagatiorA of sprea.ding depression. This is a
curious result since it is knows that the upper third of the
cortex is dominant in the spreading depression reaction.

„ 241 -

Serial No. M-NP-GN-4

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A. (continued)

Conversely, the rabbit and other smooth brain corticies are very
susceptible to spreading depression and it occurs in these cases
with no specific pathological manipulation and with the "dendritic"
response intact.

Significance to Mental Health Research: Further progress in
fundamental physiology of the brain.

Proposed Course of Project: Various aspects will be continued
indefinitely.

Part B Included: Yes No x

- 242

Serial No. M-NP-GN-5

1 . La,boratory of Neurophysiology

2 General Neurophysiology

3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A,

Project Title: Effect of Curare on the "Dendritic" Reaction

Principal Investigator; Wade H. Marshall

Other Investigators: J. Brinley^ E. Kandel, S. Lerner,

T Bak

Cooperating Units. None

Man Years

Total » 1.70 Patient Days: None

Professional: .60
Other: 1.10

Project Description:

Objectives- To test the published claim that large
doses of curare transiently block the synaptic reactions
allegedly involved in the "dendritic" reaction.

Methods Employed: It was soon found that the great
fall in systemic blood pressure resulting from injections
of large doses of curare (3 to 10 mg/K) led to various
artifacts, depending on type of electrodes employed
and methods of suspending same With spring-loaded
electrodes the fall of capillary pressure may result in
collapse of the capillary wall under pressure of the
electrode, this being followed by reduction or extinction
of the reaction. With fixed electrodes the brain shrinks
away from, them as the blood pressure falls resulting in
less effective stimulation and recording^ thus giving
the appearance of a reduction of response. In any case
with spring loaded or fixed electrodes spreading cortica,l
depression often occurred after the injection of curare.
Hence we developed a new method of stimulation and
recording which eliminates the a,bove and other artifacts
from the direct cortical response (dendritic) and
callosal reactions. This consisted essentially of a
system of reversible pore electrodes mounted ±n a constant
pressure device^ the pressure being enough to secure good
contact without collapsing capillaries even at very low
systemic blood pressure. This system also permitted the

243

Serial No. M-NP~GN-5 f

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A. (continued)

electrodes to follow the surface as the brain
volume increased or decreased This technique is
absolutely essential for reliable results in those
kinds of experiments.

Major Findings. We found that large doses of curare
do not block the direct cortical (dendritic) response
when the above artifacts including spreading cortical
depression are eliminated.

Significance to Mental Health Research: This new
technical approach is a useful advance in techniques for
experimentation on the brain. It is currently of some
value to determine validity of the claim that curare
blocks synaptic conduction in dendritic systems of
the cortex.

Proposed Course of Project: Project Concluded

Part B Included Yes x No

Serial No. M-NP-GN-5

P?£e 3
PHS-NIH

Individual Project Report

Calendar Year 1957

Part B Honors^ Awards^ and Publications

Publications other than abstracts from this project-

Proponents of the above argument have been notified of
our results. We may eventually publish this but since
it is a negative result we wish to give the other
laboratory time to recheck their findings.

Honors and Awards relating to this project!

Lecture at University of Washington Medical School and
University of Wisconsin Medical School dealing with these
kinds of experimental problems.

- Zti5

Serial No. M-NP-GN-6

1. Laboratory of Neurophysiology

2. General Neurophysiology

3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

t A.

Project Title: Tests of Certain Drugs on Specific Electrical

Reactions in the Brains of Animals

Principal Investigator: Wade Ho Marshall

Other Investigators: E. Evarts, E.Kandel, J. Brinley, and S„ Lerner

Cooperating Units: Laboratory of Clinical Sciences

Laboratory of Clinical Biochemistry
Heart Institute

Man Years Patient Days: None

Total: .90
Professional: .40
Other: .50

Project Description:

Objectives: To further analyze neuron activity with the aid
of specific drugs which may have specific roles in synaptic
transmission^ including those which are currently alleged
to be demonstrable.

Methods Employed: Precise electrical technics are employed to
test effects of drugs on the direct cortical and callosal re-
actions (the "dendritic" reactions)^ and on other systems such
as the specific sensory, recruiting and augmenting reactions o

Major Findings: We have failed to see any specific action of
adrenalin or serotonin when injected I„V. or in the carotid
artery in the cat or monkey. Gamma amino butyric acid applied
topically on the surface of the arachnoid membrane very quickly
(order of 1 sec) produces a dramatic reversal of phase of the
surface negative "dendritic" reaction. Isotonic KCl similarly
applied produces a sufficiently similar reversal so we currently
conclude that the drug blocks the superficial elements unmasking
surface positive recorded elements from slightly deeper structures,
Quanido butyric acid topically applied seems to act oppositely
to gamma amino butyric. It enhances the "dendritic" reactions.

Significance to Mental Health Research: Contributes to knowledge
of physiology of the brain.

Proposed Course of Project: Continue indefinitely.

Part B Included: Yes No x

- Zk6 -

Serial No. M-NP-GN-7

1. Laboratory of Neurophysiology

2. General Neurophysiology
3o Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Activity Cycles and Interaction Between Callosal

and Direct Cortical Reactions, and to Determine
Regions of Chief Activity of Each.

Principal Investigator: Wade Ho Marshall

Other Investigators; E. Kandel, J. Brinley, S„ Lerner

Cooperating Units: None

Man Years: Patient Days: None

Total: 1.50
Professional: .50
Other: 1.00

Project Description:

Objectives: To get better data on interaction and activity
cycles in the callosal, direct cortical response and other
systems.

Methods Employed: Cats, monkeys and rabbits are used
employing techniques developed in the course of the curare
experiments and described in Project No. M-NP-GN-5.

Major Findings: This work is now in progress, no major
findings to report at this time,,

Significance to Mental Health Research: None

Proposed Course of Project: Continued indefinitely.

Part B. Included Yes No X

- 2k-7 -

Serial No, M-NP-GN-8

1. Laboratory of Neurophysiology

2= General Neurophysiology

3o Bethesda.

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A,

Project Title: Measurement of pH Changes in the Cortex During

Spreading Cortical Depression

Principal Investigator: Wade H. Marshall

Other Investigators- J„ Brinley, S, Lerner, T. Bak

Cooperating Units: Department of Physiology, University of

California, Los Angeles. National Heart
Institute, Laboratory of Technical
Development

Man Years- Patient Days: None

Total- 1.20
Professional- .20
Other- 1.00

Project Description:

Objectives: To determine if a specific type of glass pH
electrode could be used to estimate changes in pH during
a wave of spreading cortical depression as has been
reported by a laboratory at University of California, Los
Angeles.

Methods Employed: Using electrodes kindly supplied by
Dr Ralph Sonnenschein, University of California, Los
Angeles. We repeated their experiments with our methods
of recording spreading cortical depression.

Major Findings. We found the Los Angeles laboratory to
be in error, the difficulty lies in a very subtle and
ea.sily made error of interpreting the "D.C." shift
accompanying sprea.ding cortical depression.

Significance to Mental Health Research: Improved techniques
for experiments on the brain.

Proposed Course of Project: Will continue with other and
similar types of electrodes in collaboration with Dr ,
Murray Eden of the National Heart Institute.

»art B. Included Yes X No

Serial No, M-NP-GN-8, pege 2

PHS-NIH
Individual Project Report
Calendar Year 1957

Part B; Honors, Awards, and Publications

Publications other than abstracts from this project:

Since this finding is negative, it will not be published at
present. The Los Angeles laboratory has been informed of
our decision.

- 2^9

NATIONAL INSTITDTE OF MENTAL HEALTH

Basic Research
Laboratory of Neurophysiology
Section on Cortical Integration

BUDGET SHEET

Estimated Obligations for FY IQ-^S
Total: $68,893
Direct: $52,933

Reimbxir sement s t $15 , 960

Projects included: M-NP-CI 1 and M-NP-CI 2

4M0ITit4

oae^c-

K.7..

Serial No. M-NP-CI-1

1. Laboratory of NeurophysTology

2. Section on Cortical Integration

3. Location: Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

[irt A.

Pwoject Title: Analysis of the Electrical Activity of the Brain of

Unanesthetized Monkeys.

Principal Investigator: John C. Lilly

Other Investigators: Robert R. Cox

Cooperating Units: Swarthmore College and National Science Foundation

Man Years Patient Days: None ,

Total: 1.08 1/3
Professional: .33 1/3
Other: .75

Project Description:

Objectives: 1. Analyze origins, courses, and relations of
figures in the electrical activity in the brain of unanesthetized
monkeys.

2. To correlate this activity with behavior and physiological
and psychological states.

3. To analyze the electrical activity which occurs concurrently
with locally stimulated "reward" and "punishment" systems within
the brain itself.

Methods Employed: 1. Using implanted electrodes of a new design
(see Project #2) it is intended to pick up the electrical
activity from 256 points simultaneously within the substance of
the brain of the unanesthetized monkey and relate this to the
activities of the monkey. Development of a system for recording
from 256 electrodes simultaneously was initiated 4 years ago
with the electrical engineering department of Swarthmore College.
Two National Science Foundation grants supported the two-year
development which was completed last summer. It has been found
this year that the prototype which was developed under these
auspices is not quite simple enough in terms of ease of control
to be immediately useful in long term studies. These circuits
are being currently revised, a new type of simplified electronic
switch has been developed recently. An 18-channel tape recorder
was developed, delivered,, and modified to record the switched
outputs of 16 times 16 input channels.

-250=.

Serial No

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A. (continued)

Major Findings: 1. Technical: the problem of electronic
switches at low level has been continued to be attacked on
this project. It is extremely difficult to obtain a switch
which will operate rapidly enough and quietly enough in the i
electrical sense to give us the necessary information from
the brain. Several forms of switches have been developed,
tested and found to be inadequate. Currently a new model has
been produced in a 25-channel prototype to be tested on
animals.

2. Physiological: no physiological results have been obtained
on this project during the last year. Previous work on the I
project with a 25-channel instrument showed that the electrica
activity of the brain contains "figures" which start moving
and die away in characteristic fashions which vary with states
of excitement, drowsing, and sleep, with evoked responses, ^
voluntary movements and epileptic seizures. These results |
have shown that 25-channels are not numerous enough and that I
the old recording system was not fast enough to adequately
record the type of figures which occur when the animal is
awake. These figures are very small and extremely rapid;
the new 25-channel switch is presumably fast enough, combined
with the tape recorder, to record and later reproduce these
figures in a slowed down fashion. '

Significance to Mental Health Research: Since the activity oJ
the brain is the basis of all thought, emotion, and action it
is necessary to investigate and understand this activity in as
many ways as possible. Electrical methods have the advantage li
of high speed and local specificity, i.e. are closest to the
very rapid action to the nerve cell groups themselves. Since i
the brain is a three dimensional, extremely complex, inter-
related network of such groups of nerve cells it is necessary
to observe simultaneously many loci at once in order to
appreciate how this extremely complex "computor" operates.
Since this is basic exploratory work it is hard to say what
its significance will be in the future. These new methods
are the first ones with a great enough ability to begin to
record the large amounts of information needed to understand
the complexities of the brain's action.

Proposed Course of Project: To further develop and use the
25-channel prototype of the 256-channel instrument and then
to further develop the 256-channel instrument which is progre
simultaneously .

Part B included Yes No x

- 251 -

Serial No. M-NP-CI-2

1 . Laboratory of Neurophysiology

2. Section on Cortical Integration

3. Location: Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

b A.

Project Title: Mapping the Behavior Elicitable by Electrical

Stimulation of the Brain.

Principal Investigator: John C. Lilly.

Other Investigators: Alice M. Miller, Robert R Cox,

Horace W, Magoun, Felix Strumwasser .

Cooperating Units; Marineland Research Laboratory, Marineland, Florida

Man Years : Patient Days : None

Total: 2.57 1/3
Professional: .57 1/3
Other: 2.00

Project Description:

Objectives: 1. Define and investigate those regions of the
monkey brain which are of importance in terms of eliciting
(1) specific somatic movements; (2) extreme emotional states,
and (3) those which function as powerful motivational sub-
strates: (a) various types of pleasure including sexual
activities, (b) various types of punishment including pain,
fear, etc. These studies are an extension of the previous
work by Hess ; Ranson and Magoun ; Magoun and co-workers ; Jasper ;
Olds and Milner; Delgado. Roberts and Miller; etc.

2. To continue development of the technical methods necessary
to explore such things in the brain, safely and with relatively
minimal injury due to mechanical insertion of electrodes and to
the passage of electrical currents through the brain.

3. To investigate these systems in larger brained animals than
the monkey such as the chimpanzee and the porpoise. The por-
poise is an animal of choice because it is available through
the Marineland Research Laboratories in Marineland, Florida;
its brain is equal to and larger than the human and it has been
demonstrated recently by Rose and Kruger that it contains, in
an enlarged fashion, all of those nuclei which are considered
to be characteristic of the human.

Methods Employed: 1. A simplified method of implantation of
electrodes and electrode arrays into the brain through the skull
and skin of unanesthetized monkeys has been developed on this

252

Serial No. M-NP-CI-2, page 2

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A. (continued)

project within the last year. This method consists of
hammering small guides into the skull in the stereotaxic
instrument. Later these guides can be located through the
intact skin and the electrodes inserted at will in a monkey
or other animal. Such guides have been completed and inserted'
and used in monkeys and another type has been inserted and >
used in porpoises. j

2. Records are taken of observations on the behavior during !
stimulation.

3. Operant testing methods. (B. F. Skinner) by 'animal start"
and "animal stop" stimulation methods of all areas stimulated I;
in order to find (a) those areas which function as "animal !
start" areas, in other words, reward, i.e. pleasure and
compulsivlB activity and (b) those areas which function as
"animal stop" areas, i.e., punishment areas. j

4. Testing interactions between the stimulation and other j
ongoing behavior such as eating, spontaneous muscular activitils,
naturally evoked emotional states, interactions with the
observers, etc.

Major Findings: 1. Our confirmation of the finding of Sch'afer!
von Bechterew, Ferrier, Sanderson, etc. continues, i.e. that eel
and every small area of the unanesthetized macaque cerebral cc-
tex can cause a specific movement of relatively small groups c
muscles and hence all of cortex is sensorimotor. (It v/as j
learned this year that Sch'afer, in eliciting the post central Ij
motor map, was not using anesthesia contrary to implications
in the published account.)

2. A system in the brain has been found which causes a clinics
state which resembles "fright", extreme anxiety, or terror; it
has been demonstrated that this state is unpleasant to the
animal by showing that he can be taught to act to stop the
stimululation and that once learned the reaction to stop the
stimulus is not lost or forgotten as easily as that to stop
a peripheral pain stimulus. This observation has been borne
out in several animals who havve been trained to avoid stimu-
lation in this system at very low levels of current. If the
animal is prevented from shutting the current off and it is
allowed to rise to higher values, it is found that a high-
priority, urgent escape pattern takes place in which the
animal cannot function in the learned pattern but is forced
to function in a violent multiple escape set of actions and
shows extreme defensive reactions if any threatening object 1
is brought near him. During this state vocalization seems to

- 253 -

Serial No. M-NP-CI-2 , page 3

PHS-NIH
Individual Project Report
Calendar Year 1957

(continued)

be impossible; further back in the pain systems vocalization
is easily elicitable and is part of the pattern of responses
to pain 5 both centrally and peripherally. This observation
has been suggestively borne out by work on humans by Wilhelm
Sem-Jacobsen in Oslo, though his localization is not so good
as ours; i.e. he has not been able to recover the brain. From
his x-rays of the position of his electrodes in the midplane
in relation to the base of the skull it is presumed that he
was in the same system. The patient reports extreme terror
which he cannot control and which does not have any of the
aspects of a quasi-emotion or pseudaf fective state or sham
fright that one might expect from results using epinephrine
and norepinephrine. This system apparently does excite a
primary emotion rather than merely the outward expression of
such an emotion.

3. Continuation of the work on reward systems (Olds and Milner) .
We have mapped these systems in several monkeys. Stimulated

in these zones an animal acts so as to start an electrical
stimulus in his own brain. We have continued Olds' demon-
strations that this kind of system operates as a powerful
motive to learning new and difficult tasks, we have found
that once the animal is taught this reaction, the learned
pattern can be shifted from one output to another quite
easily by the animal. He performs 3 times per second by hand,
2 per second by tongue, and 1 per second by foot; however,
he very much prefers to use the hand. We have continued to
try to force the monkey to vocalize to obtain this reward and
find that it is not as pov/erful as the other outputs, in fact
it requires a combined social situation plus the electrical
stimulation so far; we are not sure we will not find some
area which will give vocalization as an adequate output.

4. In two animals we have found a system which causes erection
of the penis. This seems to be an additional part of a system
recently described by MacLean. We have found that erection of
the penis can be caused by stimulation of parts of the fornix
and of the septal nuclei by electrical stim.uli . MacLean demon-
strated that erection can be aroused by chemical stimulation

of the hippocampus from which the fornix originates. This
system is unique in our experience in that it is both positively
and negatively reinforcing, not simultaneously but sequentially
in time. The animal will push a lever to start his own erections
about once per minute and will stay awake 24 hours a day to
continue this kind of activity. On the other hand, if we start
the stimulus every 30 seconds he will shut off approximately

- 25k

Serial No. M-NP-CI-B, page h

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A. (continued)

every other one and will allow them to come through about
once per minute .

5. Another very small system is being investigated in which
the animal appears to have its "battery drained" when ;
stimulated in this region. All of his spontaneous activity
decreases, he becomes relatively unresponsive through not j
comatose or unconscious and if allowed to be alone will |
go to sleep, this apparently is very closely related to
Hess' so-called "sleep area".

6. Technical Developemnt : a new method of implanting
electrodes which consists of hammering guides into the skull ;
has very much simplified these problems. In the older i
system we implanted buttons in the skull which allowed up i
to 44 electrodes to be moved in and out of the brain, mapping
up to 30-40 points along each electrode track; it was found j
that the skin broke down around such buttons after several |
months of use. In the new system each electrode penetrates
the skin independently; intact skin is left between electrode
So far there is some reaction at the point at which the elec-
trode penetrates the skin but it is not nearly so severe as
it was around the button. We now can map about 30-40 points
along each electrode track from the top of the brain to the
base of the skull in a much simpler fashion and yet be able
to restore the animal to a colony or his cage without any
leads showing from the top of the head. This system has
also been developed for use on the porpoise; it was demon- i
strated 2 years ago that it is practically impossible to
anesthetize the porpoise without using a respirator. With
the new technique local anesthesia is introduced into the
head to the skin down to the bone and the guide pounded

in with porpoise suspended in the restraint system in water. ,
The pain was sufficiently small so that the porpoise showed
very little if any reaction to this procedure; he gave a
small startle response at the first hammering apparently due
to the sound and the sense of pressure but after that he
calmed down and allowed us to keep on going without much
trouble .

7. We have found that in two porpoises that (a) the reward
and punishment systems exist and (b) that the urgency of
these systems for the porpoise is comparable to that for the
monkey 5 (c) that the porpoise learns very much more rapidly
than the monkey to either turn the stimulus on or to turn
the stimulus off, (d) that the porpoise in contrast to the i
monkey learns very rapidly with an assist from the observer
on the proper way to push the trigger^ and (e) that during ,

255

Serial, No. M-NP-CI-2 . page

PHS-NIH
Individiial Project Report
Calendar Year 1957

A. (continued)

stimulation of a reward system in the porpoise he becomes
extremely loquacious and covers a vast repertory of sounds
apparently seeking some way of communicating with the
observer in the fashion in which the porpoise will corajnuni-
cate with his own species.

Significance to Mental Health Research: These various regions of
the brain which are so fundamental to behavior and the subjjective
life, are of fundamental importance to an understanding of those
factors which maintain mental health and maintain mental illness.
Studies upon the rat brain by Olds and Milnerj on the cat brain
by Hess, Delgado, Roberts and Miller, and Ranson and Magoun have
finally given us powerful tools for the investigation of that whicb
is urgent and of highest priority when active within the brain ;
substance. These rewards and punishments and emotional elici- \
tations are more powerful than any other way which we and others 1
have been able to employ to change the behavior of animals;
apparently these methods and these states exert more powerful
effects than food, pain, and Sex itself. Means have now been
found for quickly inducing and as quickly removing profound
mental changes in monkeys and in porpoises. In the rat, cat,
monkey (chimapnzee) . human, porpoise series, we have a spectrum
of brain sizes in which we might expect there to be a spectrum
of physiological determinants of behavior which can be elicited
by small areas of intense activity elicited by electrical stimu-
lation; it is important to investigate brains larger than the
human before approaching the human in order to find out if the
urgency and priority of these built-in emotional patterns
exists in the larger brain and whether the larger brain can
exert control over such patterns. Such methods ultimately
should be applied to the human and currently are by several
investigators. These show that the expected urgency of both
the rev/ard and punishment systems is of the order of intensity
which is importaat to mental health research.

Proposed Course of Project: To continue such investigations
of the electrical stimulation of behkvior and of learning and
eventually to relate the results to elici table and spontaneous
electrical activity in the various regions of the brain. To
continue the work on the monkey, to expand the work to the
chimpanzee, and to continue the work on the porpoise. At some
time in the future we lorsee that we will have progressed far
enough in technical matters to apply these methods to the human.

; B included Yes x No

- 256

Serial No. M-NP-CI-2 , page 6

PHS-NIH
Individual Project Report
Calendar Year 1957

Part B: Honors, Awards, and Publications

Publications other than abstracts from this project: None

Honors and Awards relating to this project:

John C. Lilly: Invitation to serve as Secretary of the First
Conference on the Use of Depth Electrodes in the Human.
Georgetown Medical School, 10-13 June 1957.

- 257 -

Report on Conference on the Use of Depth Electrodes

page

in Human Patients

John C. Lilly, Secretary to Conference
Section on Cortical Integration
Laboratory of Neurophysiology
Research Branch
National Institute of Mental Health

Organization of a conference on the use of depth electrodes
in human patients which was supported under the auspices of the
National Institute of Mental Health and the National Institute of
Neurological Diseases and Blindness through Georgetown University
Medical School; Dr, Francis M. Forster kindly consented to arrange
for Georgetown to sponsor such a conference June 10-13, 1957.
Dr. Desmond O'Doherty carried out the technical details of housing,
organization of space, arranging for banquet, meals, etc. The
Conference was attended by these principal investigators:
M. Baldwin, R. G. Bickford, J. V. Brady, M. A. B. Brazier,
W. P. Chapman, G. E. Chatrian, J. M. R. Delgado, H. W. Dodge, Jr.,
R. Galambos, H. Hamlin, R. G. Heath, W. J. H. Nauta, J. Olds,
H. Patton, C. W. Sem-Jacobsen, E. A. Spiegel, A. Torkildsen,
J. M. Van Buren. It was found to be of considerable value in
mutual education among the participants as to (1) technical
results, (2) indications for future research, (3) possible
therapeutic values, (4) the dangers in employing such methods
on the human, (5) improvement of methods in the future, (6) plans
for a future conference, (7) methods of increasing the accuracy
of localization within the human brain of the sites stimulated
and recorded from.

Significance of this conference seems to be that there
are a sufficient number of people working on the human brain with
implanted electrodes and the results are sufficiently important
at the present time to warrant interest on the part of the
National Institute of Mental Health. It looks as though, with
the methods devised up to the present time., that such methods
are going to become relatively popular whether this is warranted
therapeutically at present or not. It looks as if it is important
to encourage publication and discussion and not to allow ethical
judgments to drive people "underground", i.e. to prevent publi-
cations and full exchange between investigators. This field
seems to be acquiring a respectability and a set of ethics which
are acceptable to most of the medical profession and to m_ost
scientific investigators in the field.

It is generally agreed that indications for use of depth
electrodes in a given patient are (1) cases of epilepsy without
obvious lesions in the cortex and who are not am^enable to drug
treatment: for exploratory searching for deep foci of pathological

- 238 -

page 3

activity, (2) meatally ill cases in which there is a threat
of removal of the frontal lobes in order to render them more
amenable to custodial care , (the depth electrodes are very
much less damaging, and exploratory investigation of such
patients may show a more powerful therapeutic intervention
can be brought about by electrical stimulation of local regions
rather than sacrifice of such important areas of the brain) ,
(3) those cases of severe neurological disease in which some
sort of intervention is needed, such as in Parkinsonism, to
prevent an irreversible clinical course by removal of foci
such as those which occur in the globus pallidus; the investi-
gation by electrical stimulation of such cases is warranted
in view of the definite therapeutic advantage of such inter-
vention as has been demonstrated by several neurosurgeons.
These three justifications were brought out intensively at
the conference and discussed at great length. The dangers
of such intervention were brought out very strongly by the
neurosurgeons present and improved methods were emphasized
and the accounts of at least one death due to the employment
of improper technical procedures was reported. The results
on animals which were highlighted at the conference tentatively
suggested to some of those present that eventually extremely
powerful changes presumably can be brought about by electrical
and chemical stimulation within the human brain, not only in
cases of mental illness but presumably in psychosomatic ill-
ness also. These are some of the speculations which were
exchanged at the conference in addition to the solid results
which were presented.

A Steering Committee was set up with Desmond O'Doherty,
Chairman, John C. Lilly, Secretary , and members as follows:
R. G. Bickfordj M. A. B. Brazier, J. D. French, R. G. Heath,
C. W. Sem-Jacobsen and E. A. Spiegel.

Dr. J. D. French suggested a second conference be held
at the new University of California Seminar Site at Lake
Arrowhead, California, near Los Angeles.

259

NATIONAL INSTITUTE OF MENTAL HEALTH

Basic Research
Laboratory of Neurophysiology-
Limbic Integration and Behavior

BUDGET SHEET

Total J $144, 86i^
Directs $111,307

Reimbursements s $335557

Projects includedJ M_nP-LI 1 and M-NP-LI 2

Serial No. M-NP-LI-1

1. Laboratory of Neurophysiology

2. Limbic Integration and

Behavior

3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Studies on Localization of Function in Limbic

System
I . Effects of Biochemically Induced Lesions

Principal Investigator: Paul D. MacLean, M.D.

Other Investigators: Richard E. Coggeshall, M.D.

Cooperating Units* None

Patient Days: None

Man Years

Total: 1.0
Professional: 0.6
Other: 0.4

Project Description:

Objectives: Lesions of the mammillary bodies and other
subcortical structures of the limbic system are known
to occur in association with Vitamin B deficiency. The
administration of acetyl pyridine, an antimetabolite of
nicotinamide, has been reported to result in acute
neuronal degeneration in the archicortex (hippocampus) ,
but not the neocortex; the supraoptic nuclei also undergo
degeneration. The foregoing findings suggest a means
of inducing lesions throughout integral parts of the
limbic system for the purpose of studying behavioral
changes. As selective damage of neurons throughout
discrete cerebral structures is not possible to obtain
by other methods, this investigation is being undertaken
to evaluate the possibilities of this kind of an approach
in studies on functional localization .

Methods Employed: (1) Mice and rats are being used
in the initial studies. The first series of experiments
are concerned with controlling the variety and extent
of lesions induced by Vitamin B, deficiency and the
administration of acetyl pyridine. The brains of
treated animals are being compared histologically with
those of controls. In addition to the conventional
staining of cells and fibers, the Nauta silver stain

- 260

Serial No. M-NP-LI-1

page 2
PHS-NIH
Individual Project Report
Calendar Year 1957

Part A. (continued)

will be used for tracing fibers of degeneration.
(2) If it proves possible to obtain reproducible
lesions, a study will be made of the effects of these
lesions on the behavior of animals in a variety of
psychological tests, including conditioned avoidance
and delayed response tests.

Major Findings- Serial sections have been cut and
stained on brains of control animals, as well as of
a group of mice that were maintained on a Vitamin B
deficient diet for one month. No lesions were found
in the brains of the experimental group. Another
group of animals that is being fed another variety
of Vitamin B deficient diet is awaiting study. The
brains of a number of acetyl pyridine treated rats
is in the process of being sectioned, stained, and
examined.

Significance to Mental Health Research: There already
exists evidence that the structures under investigation
are concerned in emotional and memory processes. Besides
adding to basic knowledge needed in regard to localization
of function in the limbic system, the present investigation
has the potentiality of yielding information that will
be useful to neuropharmacological investigations concerned
with the differential action of drugs on nervous centers.
It also has unique possibilities for contributing to the
knowledge of anatomical connections of the limbic system.

Proposed Course of Project: If the results on mice and
rats prove promising, the investigation will be extended
to include observations on squirrel monkeys.

Part B included Yes No x

- 261 -

Serial No. M-NP-LI-2

1. Laboratory of Neurophysiology

2. Limbic Integration and

Behavior

3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Ftrt A.

Project Title: Studies on the Limbic System

Principal Investigator. Paul D. MacLean, M.D.

Other Investigator: None

Cooperating Units: None

Man Years: Patient Days: None

Total: 0o2
Professional: 0.1
Other: 0.1

Project Description:

Objectives: During the period when the new section on Limbic
Integration and Behavior is waiting to move into its full
complement of space, part of the principal investigator's
time is being devoted to completing six papers for publication.
These papers , which deal with experimental work that was
performed in the Departments of Physiology and Psychiatry at
the Yale University School of Medicine, are as follows:

1. Effects of hippocampal seizures on conditioned
avoidance behavior. (with DrSo J.R. Stevens and C. Kim)

2. Behavioral changes associated with chemical and
electrical stimulation of the caudate nucleus. (with Dr.
J.R. Stevens)

3. EEG and behavioral changes following chemical and
electrical stimulation of posterior cingulate gyrus, (with
Dr.lttLockhart)

4. Effects of neuropharmacological agents on bioelectrical
activity of limbic system. I. Reserpine and drugs of related
interest. (with Dr. C. Kim)

5. Effects of neuropharmacological agents on bioelectrical
activity of limbic system. II. Ether, nitrous oxide, and carbon
dioxide. (with Dr. C. Kim)

262

Serial No. M-NP~-LI"2 ^^..^ -?

Indi vidua,! Project Report
Calendar Year 1957

Part A. (coB-tixiued)

6. Propagation, of hippocampal seizures in unrestrained

aad wa.ki:ag animals, (with Dr. C. Kim)

Major ,FiB.dingS'; (1) Animals trained ±n a. shuttle box to
avoid a shock following the sound of a huzzer fail to resposd
t.o the conditioried stimul-as during propagaT/i::=g hippocaTrpal
seizures,, but in the majority of iastasic-es will quickly direct!
their ©scape upon receiving the unconditioned stim-ulus. (2)
Either chfri^ical or electrical stimulation of the head of the
caudate nucleus interferes with the performa.nce of an an.im_al
trained in conditioned avoidance. i3) Chemical stimulation of
the cortex just above the posterior ciogwlate gyrus may result
in spontaji:!.eous or easily induced penile 'Erections in male cats,
(4) The administration of reserpirve to ca.ts in a dose of one
mg, per kg, results in distinctive electroencephalographic
changes tha.t can be localized to parts of the hippoca.mpiis aad ;
hypothalamus. (5) Except for the extended tiirje course,, the '
elect.roencepha.logra.phic picture associated with reserpine has
many similarities to that observed during the induction and
recovery stages of ether anesthesia. 16) The pattern of
propagation of electrically induced hippocajEpal sei.zures in
unrest,ra..ined a.n.d waking animals conforms to aB.d co.af irms what
has been found in acute prepa.rations.

Signif ica.'jce to Mental Health Research: E.xperiii;eatation duri.j
the past two decades has yielded evidence that allows one to j
infer a dichotomy in the function of the phylogenetically old

(limbic) a.ad new cortex. This dichotomy has important
implicatiojLS for neurology a.?:.d psychiatry because it bears ob
the distinctive attrib-'ites of emotiona.l a,nd intellectual
behavior. The papers in prepa.ration shed further light on
functional _, electroencephalographies and chemical distiactiom
between the "old" and "new" coreex.

Proposed Coxixse of Projects Completio,n within the near fut'Eix^

Part B included Yes X Mo

263

Serial No. M-NP-LI-2 ^ page 3

PHS-NIH
Individual Project Report
Calendar Year 1957

i.rt B; Honors, Awards., and Publications

Publications other than abstracts from this project:

MacLean^ PoD, , Chemical and electrical stimulation of hippoca,mpus
in unrestrained animals. Part I. Methods and EEG findings. Arch.
Neurol, and Psychiat . , 1957, 78, 113-127.

MacLean^ P.D. „ Chemical and electrical stimulation of hippocampus
in unrestrained animals. Part II „ Behavioral findings. Arch. Neurol.
and Psychiat. , 1957, 78, 128-142.

MacLean, P.D.;, Visceral functions of the nervous system. Ann . Rev .
Physiol"., 1957, 1^, 397-416. ~

Flanigan, S. , Gabrieli, E. „ and MacLean, P.D. _, Cerebral changes
revealed by radioautography with S35_iabeled i-Methionine. Arch.
Neurol, and Psychiat . , 1957^ 77, 558-594.

MacLean, P.D.,, Rosner „ B. , and Robinson, F. , Pyriform responses to
electrical stimulation of olfactory fila, bulb, and tract. Am. J.
Physiol o , 1957, 189, 395-400.

Paasonea, M.D. „ MacLean, P.Do , and Giarmin, N.J., 5-Hydroxytryptamine
(serotonin, enteramine) content of structures of the limbic system.
J. Neurochem. , 1957, 1^, 326-333c

MacLean, P.D,, "Psychosomatics", Handbook of Physiology. (in press)

MacLean, P.D,, The limbic system from the standpoint of self-
preservation and the preservation of the species. Transactions of
"La Semaine Neurophysiologique de la Salpetriere - 1956. "(in press)

Flynn, J.P, , Kim, C, and MacLean, PoD., Effects of hippocampal
seizures on conditioned cardiac and respiratory responses. In:
Symposium on Braio Stimulation, University of Texas Press. (in press)

Honors and Awards Relating to this Projects

1. Senior Postdoctoral Fellowship from the National Science
Foundation, (Affiliated with the Physiological Institute, University
of Zurich)

2. Invitation to become Associate Editor of Psychosomatic Medicine.

3. Invitation to speak at the Neurological Clinic, University of
Freiburg, Freiburg, Germany.

4. Invitation to speak to the neurological and neurosurgical groups
at the University of Graz, Graz, Austria.

Serial No, M-NP-LI-2, page ^■

PHS-NIH
Individual Project Report
Calendar Year 1957

Part B (continued)

5. Invitation to be a discussant at the Ciba Conference on
"Neurological Basis of Behavior" (in commemoration of the

birth in 1857 of Sir Charles Sherrington) London^ July 2-4^, 1957.

6. Invitation to write a review on the limbic system for
Physiological Reviews.

7. Invitation to serve as a member of the Selection Commit te of
the National Institute of Mental Health.

265

NATIONAL INSTITUTE OF MENTAL HEALTH

Basic Research
Laboratory of Neurochemistry

BUDGET SHEET

E,?-'--iiDqt,$(^ Ohnrat^w-? for ^ iQ^s
Total! $97 5,008
Directs $74,536

Reimbursements I $22,ii72

Projects includeds M-NC-PC 1 through I4.NC-PC 9

! Serial No, iHN&PCr-l

1, Neurochemistry

2, Physical Chemistry

3, Bethesdaj Md.

PHS-NIH

Individual Project Report

Calendar Year 1957

I'oject Title: Structure of Transition-Metal Complexes

^incipal Investigator: Gary Felsenfeld

)her Investigators: Leslie E. Orgel

;ioperating Units: None

In Years
Total: 1/4
Professional: 1/4
Other:

Poject Description:

' Objectives : To study by theoretical methods the unusual configurations
of certain transition-metal complexes.

Methods Employed: The quantum-mechanical method known as the crystal-
I field theory was employed,

i Major Findings: It has been shown in a previous investigation by

G. Felsenfeld that the unusual flattened tetrahedral configura-
tion of the complex ion CuCl.~ can be explained theoretically.
The present research has extended the study to a consideration of
complexes of nickel, and it has been shown that for a complex
ion of the form NiCl."^ an elongated tetrahedral configuration is
to be expected. The amount of distortion has been predicted,

ij Significance to Mental Health Research: The role of metal ions in
'i biological systems depends upon the directional properties of the

bonds they form. The understanding of the activity of the metal-
containing enzj^esjof ceruloplasmin,and of cerebrocuprein all
depend upon a knowledge of the stereochemistry of the metal ion
involved. Theoretical studies permit us to predict the behavior
of such ions under varying conditions.

Proposed Course of Project: Calculations will be extended and refined
to take into account further energy terms. In collaboration with
D. R. Davies, X-ray diffraction studies of nickel chloride
complexes will be undertaken to verify the predictions of the

theoretical study.

tB Included Yes X No

iU_

- 266 -

Serial No. M-JtuiC-PC-^l
page 2
PHS-NIH
Individual Project Report
Calendar Year 1957

B: Honors, Awards, and Publications

ublications other than abstracts from this project:

Felsenfeld, G. and Orgel, L» E.^ "Jahn- Teller Distortions of
Tetrahedral Transition-Metal Complexes". In preparation.

onors and Awards relating to this project. None.

- 26? -

Serial No. M-NC-PC-2

1. Neurochemistry

2. Physical Chemistry

3. Bethesda, Md.

PHS-NIH
Individual Project Report
Calendar Year 1957

; A.

Project Title: Physical Chemical Studies on Synthetic Polyribo-
nucleotides .

Principal Investigator : Gary Felsenfeld

)ther Investigators: Alexander Rich, David R. Davies

Cooperating Units: None

Ian Years

Total: 1-1/2
Professional: 1-1/4
Other: 1/4

'roject Description:

Objectives : To study behavior of various synthetic polyribonucleo-
tides .

Methods Employed; The synthetic polynucleotides have been examined

spectrophotometricallyp and with the ultracentrifuge. Theoret-
ical techniques have been applied for discussing the statilptics
of interaction of the polymers.

Major Findings: The study of the interaction between polyadenylic

acid (poly A) and polyuridylic acid (poly U) has been continued.
A new three-stranded molecule, involving two strands of poly U
for each strand of poly A has been discovered using techniques
like those which led to the discovery of the two-stranded
molecules. This three-stranded molecule may be related to a
structure (as yet undetected) involving a single ribonucleic
acid (RNA) strand wrapped about a two-stranded desoxyribo-
nucleic acid (DNA) , and is therefore of considerable interest
with relation to problems of nucleic acid synthesis.

The dependence of the formation of multiple-stranded
structures on concentration of small ions has also been studied.
It is found that small amounts of divalent cation (Mg*^ . Mn ,
etc.) are sufficient to cause formation of the two-stranded
complex, whereas large excesses of cation concentration -are
required for addition of the third strand. The dependence of
two-stranded polynucleotide stabilization upon ion concentra-
tion closely resembles that found for DNA.

- 268 -

Serial No. M-NC-PC-2:

page 2

Part A (Continued)

Theoretical studies have also been carried out to
determine whether the observed experimental data for forma
tion of two-stranded complexes can be explained either on
basis of a rapidly reversible or an irreversible process,
has been shown by means of these studies that only a systej
involving highly labile bonds between the two strands can
account for the data. This suggests that two-stranded DM'
also capable of a very rapid dissociation reaction, a consd
eration of great importance for proposed mechanisms of DNA
replication, which involve separation of the two strands s
part of the process.

Significance to Mental Health Research; These synthetic polymei,
are models of RNA and DNA, and provide a means of studyingt
reactions of the nucleic acids under well-defined chemica.'
conditions .

Proposed Course of Project: Continued combined theoretical andj
experimental studies will be undertaken to determine the
mechanism of interaction between poly A and poly U, and
between other polynucleotides.

Part B Included

Yes X

- 269 -

'■ Serial No, M-NC-PC-2

page 3

PHS-NIH
Individual Project Report
Calendar Year 1957

]art_B: Honors, Awards, and Publications

'I Publications other than abstracts from this project:

Felsenfeld, G.j, Davies, D. R. , and Rich A., Formation of a Three-
Stranded Polynucleotide Molecule. J. Am, Chem. Soc . 79; 2023;
1957.

Felsenfeld, G. and Rich, A. j Studies on the Formation and Two- and
Three- Stranded Polyribonucleotides, Biochim. et Biophys. Acta
in press .

Felsenfeld, G. , Theoretical Studies on the Interaction of 'Synthetic
Polyribonucleotides, in preparation.

Honors and Awards relating to this project: None.

- 270 -

Serial No. MilTC-PCSS

1. Neurocheraistry

2. Physical Chemistry

Bethesda, Md.

PHS-NIH

Individual Project Report

Calendar Year 1957

PDject Title: The Formation of a New Helical Complex between
Polyinosinic Acid and Polyadenylic Acid.

PiLncipal Investigator: David R. Davies

J1ier Investigators: Alexander Rich

Uoperating Units: None

Ma Years

Total: 1/2
Professional: 1/2
Other:

Pi) j act Description:

Objectives : To define the conditions under which these synthetic poly-
nucleotides interact, and to discover the nature of the complex
formed.

Methods Employed: Ultra-violet absorption and ultracentrifugation
techniques have been employed to examine the conditions under
which the complex forms. X-ray diffraction methods were used to
investigate the structure of the complex„

Major Findings; It has been discovered that polyinosinic acid and
polycytidylic acid will combine rapidly in solution to form a
helical molecule. X-ray diffraction photographs show that,
contrary to expectation, this molecule is dissimilar to that
formed when polyadenylic acid and polyuridylic acid react together,
The structure, in fact, appears to be very similar to that of
natural ribonucleic acid (RNA) . One implication of this finding
is that the RNA molecule exists in an even-stranded helical
configuration, at least under the conditions used for X-ray
diffraction studies. It is to be expected that the elucidation
of the structure of this molecule will throw considerable light
on the RNA structure which is at present undetermined.

The reaction takes place rapidly in the presence of 0.1 M
sodium chloride o It is inhibited by the absence of sodium
chloride and by the presence of 1.0 M sodium chloride. Ultra-
I centrifuge studies show that the complex sediments much faster
than either of the separate polymers.

- 271

Serial No. ■lfe3SC-l'C-3

page 2

Project Description (Continued):

Significance to Mental Health Research: An understanding of the roll
played by RNA in cellular metabolism is basic to our understandi(
of cell differentiation and function. RNA is involved in protei
synthesis and most current hypotheses about protein synthesis
invoke the use of RNA as the template on which the amino acids n
ordered. Knowledge of the structure of RNA is therefore importai
since this will clarify our understanding of the manner in whicj
it can act as such a template. The structure of natural RNA ±s'
difficult to obtain directly, whereas much clearer information
concerning the configurations of molecules of this type has bee
obtained from studies such as this on the synthetic polyribonucei
tides.

Proposed Course of Project: Further work will be carried out to oblii
better X-ray diffraction patterns of this complex with a view 1;
elucidating its structure. Further investigations will also b«j
undertaken to define the condition under which the complex is ills'
stable. !

Part B Included Yes X No

''' - L

Serial No. H^lJC-PCr^.
pa^e 3

PHS-NIH

Individual Project Report

Calendar Year 1957

t; B: Honors, Awards, and Publications

>ublications other than abstracts from this project:

Davies, D. R. and Rich, A., The Formation of Helical Complex between
Polyinosinic Acid and Polycytidylic Acid. Submitted to J.A.C.S.

lonors and Awards relating to this project: None.

1^22.

Serial No. M-NC-PC-4

1. Neurochemistry

2. Physical Chemistry

3. Bethesda, Md.

PHS-NIH
Individual Project Report
Calendar Year 1957

rt A.

Project Title: Computation of helical Transforms for Synthetic

Polypeptides o

Principal Investigator: David R. Davies

Other Investigators: Alexander Rich

Cooperating Units: None

Man Years

Total : 1/2
Professional: 1/2
Other: None

Project Description:

Objectives: To study various proposed helical polypeptide models by
means of the helical transform computation.

Methods Employed: The helical transform computation yields a theo-
retical X-ray diffraction pattern for proposed molecular
structures. Use of this technique provides a basis for
comparison with the observed diffraction data.

Major Findings: The a-helix is of considerable importance since it
is now generally believed to be the basic structural unit, not
only of the synthetic polypeptides and the fibrous proteins,
but also of many globular proteins. It was therefore consid-
ered interesting to examine the diffraction patterns of other
helices (notably, the 7r-helix) to see whether they were
markedly different from those of the a-helix. A careful
examination shows that for the synthetic polypeptides, a
clear distinction can be made in favor of the ct-helix. How-
ever, this investigation demonstrates that such a clear
distinction cannot be made for the natural fibrous proteins.

Further computing programs have also been developed for
rapid calculation of interatomic distance and angles in
helical molecules.

12^^^

Serial No. M-NC-PC-4 |

page 2

Part A. (Continued)

Significance to Mental Health Research; This investigation has
led to further understanding of the relation between the
configurations assumed by proteins and their X-ray diffrac-
tion patterns.

Proposed Course of Project: This project has been completed.

Part B Included

Yes X

- 275 -

Serial No. M-NC-PC-4

page 3

PHS-NIH

Individual Project Report

Calendar Year 1957

Part B: Honors, Awards, and Publications

Publications other than abstracts from this project:

Davies, D. R. and Rich, A,, Structure Factor Calculations for Some
Helical Polypeptide Models, Submitted to Acta Crystallographica.

Honors and Awards relating to this project: None.

- 276 -

Serial No» M-NC-PC-5

1. Neurochemistry

2. Physical Chemistry

3. Bethesda, Md.

PHS-NIH
Individual Project Report
Calendar Year 1957

t A.

Project Title: Physical Properties of Ribonucleic Acids

Principal Investigator: Dan F. Bradley

Other Investigators: Jean Johnson

Cooperating Units: None

Man Years

Total: 3/4
Professional: 1/2
Other: 1/4

Project Description:

Objectives; Much attention has been focussed in recent years on
ribonucleic acids (RNA) because they seem to be intimately
associated with in vivo protein synthesis. Their function
in this process rests upon the fact that they are linear,
unbranched polymers, presumably varying from one to another
both in polymer length and rigidity. For several years we
have been acciimulating evidence as to how these properties
change spontaneously in samples of RNA during and subsequent
to isolation from organisms. These studies lead to better
understanding of the structure of native RNA and how it can
be isolated for study with a minimum of alteration. This
work is also relevant to the paradox of the apparent J^ vivo
stability and _in vitro lability of nucleic acids and the
problem of stabilizing these genetic materials against radia-
tion damage.

Methods Employed: Ultracentrifugationj, ultraviolet spectrophoto-
metry, column chromatography J, electrophoresis, viscosity.

Major Findings: Two major avenues of approach have been followed.
One has been the careful study of the relative lability of a
particularly promising RNA in aqueous solutions as a function
of ionic environment. The addition of small amounts of
divalent cations to RNA solutions in ion-fi^ee water lowers
the optical absorption of the RNA (an indication of increasing
polymer rigidity) as well as retards the fa.ll of sedimentation
coefficient upon standing at moderately elevated temperatures.
Monovalent cations perform the same stabilizing functions but
I at much higher concentrations suggesting that they interact less
strongly with the RNA because of their lower ionic charge.

- 277 -

Serial No. M-NC-PC-S
page 2

1_A (Continued)

At temperatures approaching 100°, the ion-RNA complexes
begin to dissociate as indicated by increased optical absorp-
tion. Under these conditions j the monomer-monomer linkages
in RNA are ruptured by polycations so that under these condi-
tions RNA is labilized by divalent cations.

Another avenue followed has been the isolation of RNA
from a source (rabbit muscle) which provides unusually
difficult isolation problems » This work was carrieG. out in
collaboration with Dr, E. Mihalyi and Miss Irene Knoller of
the National Heart Institute. As is true will all RNAs
studied to date, the product was heterogeneous,, having a
distribution of chain lengths and flexibilities. Most inter-
estingly, application of normal isolation procedures resulted
in removal of a non-random fraction. Therefore the mean
values of the properties of RNAs isolated by different methods
varied because part of the RNA was discarded, although
normally, this variation would be ascribed to alterations of
the RNA during isolation. Such changes were also observed.
Further, it was discovered that the chromatographic technique
we developed for separating RNA into various chain lengths is
also suitable for separating RNA from protein contaminants.

Significance to Mental Health Research: This study is part of a

long-term group effort to discover the mechanisms of protein
synthesis and genetic transfer.

Proposed Course of Project; There is recent evidence that cerebral

RNA varies with mental state. We intend to isolate ribo-
jiucle6protein particles from animal brain and see whether
they are in any way different from the corresponding protein-
synthesizing particles found in liver.

We are also interested in searching for methods to
separate low molecular weight RNAs to investigate their
optical properties, their binding of cations, and their
binding to other nucleic acids.

tB Included Yes X No

- 278

Serial No. M-NC-PC-5

page 3

PHS-NIH
Individual Project Report
Calendar Year 1957

rt B: Honors, Awards, and Publications

Publications other than abstracts from this project:

Mihalyi, E. , Bradley, D. F. , and Knoller, I. Physical and Chemical
Properties of the RNA Contaminant of Rabbit Muscle Myosin Prepara-
tions." J. Am. Chem. Soc . ^ in press.

Honors and Awards relating to this project: None,

- ^'^Q

Serial No. M-NC-PC-6

1. Neurocheraistry

2. Physical Chemistry

3. Bethesdaj Md.

PHS-NIH
Individual Project Report
Calendar Year 1957

'rt A.

Project Title: Frictional Properties of Desoxyribonucleic Acid in

Solution.

Principal Investigator: Dan F. Bradley

Other Investigators: None

Cooperating Units: None

Man Years:

Total : 1/2
Professional: 1/2
Other :

Project Description:

Objectives: Desoxyribonucleic acid (DNA) has been shown to carry
genetic information. As DNA is a linear j unbranched polymer
consisting of four different monomer units, this genetic infor-
mation is presumably coded along '^h'b polymer chain by varia-
tions in the sequence of monomers. It follows that a longer
polymer chain can code a larger amount of genetic information.
A great deal of effort has been expended to measure the chain
length of DNA m solution either by light scattering or by
frictional methods. The latter methods which measure the
rate at which DNA molecules move through a solution under
different applied forces do not agree with the former
methods. In the present study the relationships between the
frictional properties and the polymer length of DNA are
reexamined.

Methods Employed: A careful survey of the literature on experi-
' mental determinations of the chain length of DNA revealed
that a heretofore unobserved simple relationship existed
between the chainlength (or molecular weight, M) of DNA and
the velocity with which it moves in a centrifugal field
(sedimentation coefficient, S) , i.e. M a S^-'^^. This was
significant because heretofore an additional frictional
measurement (such as viscosity or diffusion) was believed
to be necessary to calculate M from S. data. Upon further
examination of the data, however, it became apparent that
the equations used to extrapolate the observed S data to the

280 -

Serial No. M-NC-PC-6

page 2

Part A= (Continue(

theoretically meaningful state of infinite dilution were
neither theoretically justifiable in themselves nor even
fit the experimental S data in the measured concentration
range. A theory was developed to explain the observed
variation of S at finite concentrations and provide a
satisfactory extrapolation to infinite dilution.

Major Findings; The theory developed accounts for the observed
decrease in sedimentation rate at finite concentrations in;
terms of a reverse flow of solvent, required by conservatid
of volume conditions. The DNA actually flows faster rela-'
tive to solvent than as measured by a stationary observer.
The theory thus includes terms for the volume of DNA, the
amount of solvent which it carries along with it, and the
degree to which it is permeable to the solvent. DNA is a
relatively rigid polymer and wanders through, oi' "occupies
thousands of times its own molecular voluiiie. Hence its
permeability to solvent molecules is unusually high, a fac)
which increases the frictional drag on the molecule and malijs
the relation between chain length and frictional properti;
obscure.

When observed S-concentration data were fitted to th
theoretical expression, a remarkably good fit was ■■achieved

The values of the parameters for volume, hydration, permea
bility, and S at zero concentration (S.) are of reasonable
magnitudes, while the volume "occupied" agree within a few,
percent of the value calculated from viscosity data- The]
values of S„ and volume occupied may be combined with any
the existing theories to calculate molecular chain lengths)
without resort to any additional frictional measurement.

Significance to Mental Health Research; This study is part of a
long-term group effort to discover the mechanisms of proten
synthesis and genetic transfer.

Proposed Course of Project; Molecular sizes may be calculated fioa

S vs. concentration data using existing theories. However'
these theories treat only limiting cases of complete perme-
bility or impermeability, whereas DNA is approximately haJ-
way between these extremes. An effort is toeing made to
develope a theory which will treat this intermediate case.'
One reason why this case has not been treated previously 2\
that prior to the theory discussed above there was no mettfd
for estimating permeability of highly extended polymer i
molecules. The theory applies generally to all such molecll«
and we hope to extend its application to other cases such is
RNA, synthetic polynucleotides, and nucleoproteins ,

Part B Included Yes No X

» 281-

Serial No. M-NC-PC-7

1. Neurochemistry

2. Physical Chemistry

3. Bethesda, Md.

PHS-NIH
Individual Project Report
Calendar Year 1957

art A,

Project Title" Structure of a Complex Formed Between Polyadenylic

Acid and Polyinosinic Acid.

Principal Investigator: Alexander Rich

Other Investigators: None

Cooperating Units: None

Man Years

Total: 1/4
Professional: 1/4
Other:

Project Description:

Objectives : To discover the configuration assumed by the synthetic
polyribonucleotides polyadenylic acid and polyinosinic when
they combine together to form a helical complex.

Methods Employed: Principal methods in this investigation are

those of X-ray diffraction. Ancillary methods include spec-
trophotometric studies, ultracentrifugal studies j and
titration curves.

Major Findings: It has been discovered that in dilute aqueous salt
solutions, polyadenylic acid will combine with polyinosinic
acid to form a two-stranded helical complex. In addition,
it has been found that this two-stranded helical complex will
take on a third polyinosinic acid molecule to form a three-
stranded helical complex. This reaction is controlled by
the ionic conditions of the environment. Thus, in solutions
with a salt concentration less than 10 "^ M, no reaction occurs
at all. In solutions which are 0.1 M in NaCl, the reaction
occurs very rapidly, resulting in the formation of the three-
stranded complex within four minutes. If the salt concentra-
tion is reduced, however, to 0.01 M, then the reaction
proceeds more slowly, and one can clearly differentiate the
initial formation of the 1:1 complex of polyadenylic acid
and polyinosinic acid followed by the subsequent addition of
a polyinosinic acid molecule to form a final complex which is
2:1 with two polyinosinic acid molecules and one polyadenylic
acid molecule.

- 232 -

Serial No,

I-NC-PC-7

page 2

Part A. (Continue(

An X-ray diffraction photograph has been obtained of
of the 1:1 complex which clearly shows that it is a helical
molecule with a pitch of 38.8 A. These molecules are parall
to each other and packed together in a hexagonal array. Won
has been done in the elucidation of the structure of the twc
stranded complex. At the present time, it is believed that
this complex forms by having the two purine bases hydrogen '
bonded together and the base pairs packed together helicallj!
with the ribose phosphate chains on the outside of the t
molecule.

Significance to Mental Health Research: Ribonucleic acid is a
molecule found in all nervous tissues and is currently
believed to be an essential ingredient for the synthesis of
protein. The synthetic polyribonucleotides are molecules
which have the same ribose phosphate backbone as is found
ribonucleic acid itself, and by studying the configuration
potentialities inherent in these synthetic polymers, we ca:
determine the conf igurational possibilities which are opJen
RNA itself. In this way, we hope to elucidate the fundamenij
mechanisms of protein synthesis, a mechanism which will be
applicable to these protein synthetic activities within
nervous tissue as well as in other tissues.

Proposed Course of Project: This work v/ill be continued by

carefully studying the diffraction patterns produced by the]
various models of the type described above. In addition^
the models will be built for the three-stranded helical
complex.

Part B Included

Yes X

- 283 -

Serial No. M-NC-PC-7

i page 3

! PHS-NIH

Individual Project Report
Calendar Year 1957

lirtB: Honors, Awards, and Publications

Publications other than abstracts from this project:

Rich, Alexander, The Formation of Two- and Three- Stranded Helical
Molecules by Polyadenylic Acid and Polyinosinic Acid, Nature,
(In press) .

Honors and Awards relating to this project: None.

284 -

Serial No. M-NC-PC-8

1. Neurochemistry

2. Physical Chemistry

3. Bethesda, Md.

'PHS-NIH
Individual Project Report
Calendar Year 1957

>art A.

Project Title: Determination of the Structure of Collagen

Principal Investigator: Alexander Rich

Other Investigators: F.H.C. Crick

Cooperating Units: None

Man Years

Total : 1/4
Professional: 1/4
Other :

Project Description:

Objectives: To determine the configuration of collagen and
related proteins.

Methods Employed: Principal method used in this investigation is

that of X-ray diffraction. Diffraction patterns are obtained
from stretched samples of collagen or tendon or of elastin.
These diffraction patterns are then analyzed, using a
computer for calculating the diffraction patterns expected
from various helical structures.

Major Findings: Two years ago, these investigators proposed a

model for the structure of collagen. This proposal has been
accepted in the intervening two years by all of the investi-
■"gators working in the collagen field. At the present time,
we are expanding the work on collagen to work out various
fine features in the structure of the molecule. Thus, we
have been spending a great deal of time on the configuration
and position of the various amino acid side chains which are
known to exist in the collagen molecule. In addition, we
have found several hydrogen bonded side chain linkages which
are believed to be of importance in the lateral stabiliza-
tion of the molecules when they are parallel to each other.
Among other things, these investigations proved useful in
understanding the mechanisms of tanning. In the tanning
process, metal ions are introduced between the parallel
collagen molecules and by complexing onto amino acid side
chains from adjoining molecules, the neighboring units are
firmly held together so that they can no longer separate.
This results in a tanned collagen fiber.

- 285 -

Serial No,

M-NC-PC-8

page 2

Part A. (Continued)

In addition, some work has been done on stretched
elastin fibers. Elastin is a protein which has an amino
acid composition somewhat similar to collagen, but has a
structure which has not been determined as yet. For varioi
reasons }, we have felt that the elastin molecule has a
degenerate collagen structure, and attempts have been made
to re-orient elastin so as to demonstrate its close relatic-
ship with collagen. A certain measure of success has been
achieved along these lines.

■ ■ j

Significance to Mental Health Research: Collagen is the major
tensile element which is found in the animal kingdom. In
addition to being spread through all the phylla, it is
equally well distributed through all the tissues of the
body, including the nervous system. There, collagen is
found in the fibrous wrappings around nerves as well as inii
the fibrous covering of blood vessels in the central nervoii
system. Through a fundamental understanding of the config-
uration of collagen molecule, we hope to better understand
the role which it plays in holding tissues together.

Proposed Course of Project: This work will be continued along
lines described above.

Part B Included

Yes X

- 286 -

Serial No. M-NC-PC-8
page 3
PHS-NIH
Individual Project Report
Calendar Year 1957

'art B: Honors, Awards, and Publications

Publications other than abstracts from this project:

^ Rich, Alexander and Crick, FoH.C, The Structure of

I Collagen. A chapter in a book on Advances in Collagen

Research. To be published by Pergamon Press, London, England,

Honors and Awards relating to this project:

An invitation to present the opening paper at an International
Conference on Collagen and Gelatin, held in Cambridge, England
July 1 through 7, 1957.

- 287

Serial No. M-NC-PC-9

1. Neurochemistry

2. Physical Chemistry

3. Bethesda, Md.

PHS-NIH
Individual Project Report
Calendar Year 1957

.rt A.

Project Title: Investigation of the Structure of Steroid Amino Acid

Complexes .

Principal Investigator: Alexander Rich

Other Investigators: David M. Blow

Cooperating Units: None

Man Years

Total : 1/2
Professional: 1/2
Other :

Project Description:

Objectives; To determine the structure of the molecular complexes
which form between desoxycholic acid and various amino acids
and polypeptides.

Methods Employed: The principal tool used in this investigation
is X-ray diffraction. Other subsidiary tools are spectro-
photometric analyses, viscosity studies, freezing point
depression, and pycnometry.

Major Findings: We have discovered that a steroid moleculej

sodium desoxycholatOj will form a series of helical com-
plexes in the presence of a variety of amino acids or poly-
peptides. X-ray diffraction studies of these complexes show
a remarkably detailed and precise organization of the flat
steroid molecule and the amino acid residues o The crystallo-
graphic investigation has shown that these molecules form a
complex with a diameter of approximately 40 A. Thus, it is
quite likely that the flat steroid molecules lie adjacent
to each other with amino acids between themo This state-
ment is supported by the finding that additional amino acids
added to the complex are usually located on the periphery of
the complex.

A series of investigations has been carried out to
determine the stoichiometry of the interaction between the
steroid and amino acid. These have shown that the optimum
j ratio is one steroid molecule to one amino acid. The
I complex will continue to form if there is an excess of amino

- 288 -

Part A (Continued)

Serial No. M-NC-PC-9
page 2

acids, however, as, for example, going up to a mole ratic
of 3 or 4 to 1. In the presence of additional steroids,
however, the complex failed to form. Thus, if there are
more than two steroid molecules per amino acid, no compl(
forms at alio This effect can be shown very markedly in
viscosity study of these complexes in solution.

Eight amino acids and five peptides have been stud:;d
thus far. It has been shown that all of them will interj||
with a steroid, either through a marked increase in the
viscosity of solution or by the production of a character
istic X-ray diffraction photograph.

Significance to Mental Health Research: A large component in ji«
nervous system are the steroid molecules which are found
largely in the myelin. Very little is known regarding tlJ
structural role which these flat molecules play in
organizing the myelin sheath. The purpose of this study le
to show how the closely related steroid molecule, sodium
desoxycholate, interacts with amino acids in the hope tht
it will throw some light on the role which steroids playin
the nervous system.

Proposed Course of Project: Studies will be continued along t3
lines described above until the complete structure analylis
has been worked out . .'

Part B Included

Yes

- 289 -

NATIONAL INSTITUTE OF MENTAL HEALTH

Basic Research
Laboratory of Cellular Pharmacology

BUDGET SHEET

te^imatga o^UgatiPns for n 195B.
Totali $358,362
Directs $2759350

Reimbursements s $83 , 012

Projects included: M-CP 1 through M=CP 15

Serial No. M - CP 1

Laboratory of Cellular Pharma-
cology
Room 2D-14, Building 10

PHS-NIH
Individual Project Report
Calendar Year 1957

ii_A.

Project Title: Methionine Activating Enzyme in Rabbit Liver

Principal Investigator: Giulio L. Cantonij M. D,

Man Years

Total: 1-1/3
Professional: 1/3
Other : 1

Project Description:

Objectives:

Mammals, plants and fungi and presumably other phyla
utilize the methyl group of methionine for biological
methylations o As a result of recent work on the mechanism
of transmethylation reactions, it has been established that
in reality activation of methionine is a prerequisite to
the transfer of its methyl group. Biologically the activa-
tion reaction is catalyzed by an enzyme found in yeast and
in the liver of numerous mammalian species. In this reaction,
adenosine triphosphate plays an essential role; specifically
adenosine triphosphate fulfills a dual function inasmuch as
it serves a) directly or indirectly as a donor source of its
adenosine moiety, which is incorporated in "active methionine",
and b) as an energy source, since it has been calculated that
the methyl-sulf onium bond in "active methionine" is roughly
equivalent to the pyrophosphate bond in adenosine triphosphate.

Major Findings:

Repeated efforts were directed toward the separation
of the activity of the methionine activating enzyme into
two or more protein fractions. All these attempts were
unifoi-mly negative. Furthermore attempts at recombination
of protein fractions from rabbit liver with protein fractions
obtained in the course of purification of the methionine
activating enzyme from yeast (Project M - CP 2) were likewise

- 290

Part A. (Continued)

Serial No. M - CP 1

page 2

negative. While evidence of this kind is not compelling, all
indications suggest that the formation of S-adenosylmethionine
from methionine and ATP is catalyzed by a single protein moiety.

Significance to Mental Health Research:

This project is part of a larger study of biological
methylations. The role of transmethylation reactions of
biogenesis of neuro-hormones such as acetylcholine and
epinephrine, metabolites important in neuro-muscular functions
like creatine and anserine and of pharmacologically active
agents like bufotenine, mescaline and many other alkaloids
clearly indicates that this broad area of research is of
significance to basic research in neurology and mental health.

Part B included

Yes /"7

No /W

- 291 -

Serial No. M - CP 2

Laboratory of Cellular Pharma-
cology
Room 2D-39, Building 10

PHS-NIH
Individual Project Report
Calendar Year 1957

tA_.

Project Title; Studies on Methionine Activating Enzyme of Yeast.

Principal Investigator: S. Harvey Mudd, M. D.

Man Years

Total: 1-2/3
Professional; 2/3
Other: 1

Project Description:

Objectives:

The objectives of the project have been outlined in a previous
annual report. Briefly; these are to further elucidate the detailed
mechanism of the enzymatically catalyzed formation of S-adenosyl-
methionine, the compound which serves as a biological donor of
labile methyl groups and of certain aliphatic carbon chains.

Major Findings:

The methionine activating enzyme has been extracted from
bakers' yeast and purified 250-fold from this extract by one method
and 200-fold by a second method. The properties of the enzyme in
regard to stability, pH effects, substrate specificity for methionine
and adenosine triphosphate, and the effect of various inhibitors
have been studied. Cof actor requirements for both a monovalent and
divalent cation have been demonstrated and the specificity of these
requirements investigated. The stoichiometry of the reaction and
the reaction products have been studied. By use of P labelled
adenosine triphosphate the method of breakdown of this substance has
been clarified. An important negative finding has been the failure
of the enzymatic activity to fractionate into two or more protein
moieties during extensive purification.

Significance to Mental Health Research:

' This project is part of a larger study on biological methylations,
the significance of which to mental health has been discussed else-
where. In addition, the purification of this enzyme from yeast

- 292 -

Part A. (Continued) Serial No. M - CP 2

page 2

allows detailed comparison with the previously purified analogous!
liver enzyme, a comparison which is especially important from thd
viewpoint of comparative biochemistry.

Part B.

Mudd, S. H., and Cantoni, G. L.

"Activation of Methionine for Transmethylation III.

The Methionine Activating Enzyme of Baker's Yeast"

J. Biol. Chem. , in press

Mudd, S. H., and Cantoni, G. L.

"Selenomethionine in Enzymatic Transmethylations"
Nature, in press

- 293 -

Serial No. M - CP 3

Laboratory of Cellular Pharma-
cology
Room 2D-14, Building 10

PHS-NIH
Individual Project Report
Calendar Year 1957

Project Title: Study of methionine synthesis by enzymatic
j transmethylation from betaine or dimethylthetin.

Principal Investigator: Jack Durell, M. D.

Other Investigators; Qiulio L. Cantoni, M. D.

Man Years

Total: 1-1/2
Professional: 5/6
Other : 2/3

Project Description;

Objectives:

To study the mechanism of the enzymatic transfer of alkyl
groups from "onium" poles and the energetics of such reactions;
to investigate whether two enzymes are involved to characterize
their properties and substrate specificities.

Major Findings:

As reported in 1956 homocysteine-thetin-methylpherase,
HTMP, has been purified to the point where it appears to
be almost pure. The purified enzyme undergoes an interesting
and novel polymerization reaction which can be reversed with
[ a variety of sulphydryl compounds. The kinetics and mechanism
' of this reversible polymerization reaction has been investigated
in detail by biochemical and physicochemical means, in part in
collaboration with Dr. R. Steiner of NMRI .

With the purified enzyme it has been possible to measure
by direct calorimetry the enthalpy change in the methyl transfer
reaction from dimethylthetin. The ^H was found to be -12000,
indicating a very large change in the standard free energy of
the reaction. This aspect of the work was carried out in
collaboration with Professor Julian Sturtevant of Yale
University.

- 29-^ -

Part A. (Continued) Serial No. M - CP 3

page 2

Interesting though preliminary results on the relationship
of HTMP to the enzyme catalyzing the synthesis of methionine
from betaine and homocysteine were obtained and will be pursued
further .

Significance to Mental Health Research:

This project is part of a larger study on biological
methylations. As is well known, "onium" compounds have
profound pharmacological effects upon the nervous system
and it has been suggested that they may play a role in the
conduction and transmission of the nervous impulse. Knowledge
of mechanisms of synthesis and degradation of such compounds
as well as the energetics of such reactions might therefore
contribute to our understanding of nervous tissue function.

Part B.

Durell, J., Anderson, D.G., and Cantoni, G.L.

"The Synthesis of Methionine by Enzymic Transmethylation

I. Purification and Properties of Thetin Homocysteine Methylpherasj"
Biochim. and Biophys . Acta, in press !

Durell, J. and Sturtevant, J.M.

"The Synthesis of Methionine by Enzymic Transmethylation

II. Enthalpy Change in the Methyl-Transfer from Dimethylacetotheti
Biochim. and Biophys. Acta, in press

- 295 -

Serial No, M - CP 4

Laboratory of Cellular Pharma-
cology
Room 2D-08, Building 10

PHS-NIH
Individual Project Report
Calendar Year 1957

_A.

Project Title: Metabolism of S-Adenosyl-L-homocysteine (ASR) .

Principal Investigator: Gabriel de la Haba, Ph.D.

Man Years

Total: 1-2/3
Professional: 2/3
Other: 1

Project Description:

Objectives:

This project is a continuation of last year's finding on the
enzymatic synthesis of ASR by way of condensation of L-homocysteine
and adenosine.

Methods Employed:

The enzyme involved has been purified about eighty-fold from
rat liver by conventional methods of protein fractionation. The
product of the reaction has been characterized chemically and
enzymatically .

Major Findings:

It has been found that the enzymatic reaction between adenosine
and L-homocysteine is very specific for both of the above-mentioned
reactants; no other purine or pyrimidine nucleoside will substitute
for adenosine, and no mercaptan other than L-homocysteine will react.
Of interest also is the fact that the equilibrium of this reaction
has been found to lie very far in the direction of condensation; the
hydrolysis of ASR is however readily obtained with the same enzyme
if both the products of the reaction are trapped enzymatically (a)
adenosine with its specific deaminase, and (b) L-homocysteine with
the enzyme homocysteine-thetin methylpherase which has been purified
and studied extensively in this laboratory.

Chemical methylation of ASR to yield S-adenosyl-L-methionine
was performed and enzymatic studies on the product undertaken. It
I has been found that in the chemical methylation only half of the
S-adenosyl-L-methionine formed is active in the enzymatic

- 296 -

Part A. (Continued) Serial No. M - CP 4

page 2

methylation of guanidoacetic acid to yield creatine. It appears
that two stereoisomers of the sulfonium group are obtained upon
methylation oi ASR in agreement with organic chemical methylations
of simpler thioethers. Further study of this finding is con-
templated.

Significance to Mental Health Research:

I
I

This study is a part of the general problem of transmethylation
reactions under investigation in this laboratory. ASR is a product'
of the transfer of methyl groups from active methionine to a number
of acceptors such as guanidoacetic acid, nicotinamide, etc. It
would appear that investigations on its fate — and as here describee
its biosynthesis — may add to our knowledge of the general problem c
sulfur metabolism, sulfonium metabolism, and methyl transfer reactin
metabolic processes which are acquiring increasing significance in ,
neurochemistry .

Proposed Course of Project: j

This project will be continued especially in conjunction with
Project M - CP 12.

Part B included Yes /~7 No /5c7 i

oo^

Serial No, M - CP 5

Laboratory of Cellular Pharma-
cology
Room 2D-39, Building 10

PHS-NIH
Individual Project Report
Calendar Year 1957

]t A.

Project Title: Amino acid analogue studies of protein synthesis.

Principal Investigator: Michael Yarmolinsky

Man Years

Total: 2/3
Professional: 2/3
Other :

Project Description:

Objectives:

(1) Selective inhibition of the capacity of pancreas tissue
slices for the net synthesis of specific proteins by use
of appropriate amino acid analogues „

(2) Investigation of the transfer of activated amino acid to
its first acceptor prior to incorporation into protein
in vitro.

Methods Employed:

(1) Pigeon pancreas slices v/ere incubated in a nutrient
medium. Increases in amylase activity following homogeni-
zation of the tissue slice in its incubation m-edium were in-
vestigated under various conditions. The initial amylase
levels before incubation were determined by a method pre-
viously developed in this laboratory.

(2) Cell-free preparations of rat liver and of yeast were
studied by measuring incorporations of radioactive pyro-
phosphate or adenylic acid into adenosine triphosphates
in the presence and absence of amino acids.

Major Findings:

(1) In contrast to previous reports, but consistent with recent
analyses of amylase composition j, methionine was found to

-■ 293

Part A. (Continued) Serial No. M - CP 5

~ ~ page 2

stimulate slightly the synthesis of amylase by pigeon panre
slices. Ethionine showed a questionable inhibition. Try]-
tazan can to a certain extent replace or spare the utili-
zation of tryptaphan for amylase synthesis.

(2) The report of an alanine-dependant , ribonuclease-inhibite(
adenylic acid incorporation into adenosine triphosphate b;
extracts of rat liver was not confirmed. Nor was it
possible to demonstrate in yeast extracts an amino acid
dependant incorporation of adenylic acid into ATP.

The sulfonic acid analogue of alanine is not activated.
Significance to Mental Health Research:

For growth and regeneration nerve tissue depends on the procesiefs
of protein synthesis which is the subject of these investigations.!

Proposed Course of Research:

Owing to the extreme variability of the pigeon pancreas experii
ments, this aspect of the work has been discontinued. The work i
with cell-free systems will be continued in the coming year.

Part B included Yes /"7" No /x7

- 299 -

Serial No, M - CP 6

Laboratory of Cellular Pharma-
cology
Section on Cellular Regulatory

Mechanisms
Room 2D-04, Building 10

PHS-NIH
Individual Project Report
Calendar Year 1957

Toject Title: The Conversion of Phenylalanine to Tyrosine.

fincipal Investigator: Seymour Kaufman, Ph.D.

they Investigators: Bruce Levenberg, Ph.D.

an Years
Total; 1-2/3
Professional: 2/3
Other : 1

roject Description:

Objectives:

Almost nothing is known about the mechanism of biological hydroxy-
lation reactions. For many compounds, including steroids and some
drugs, hydroxy lation is on the normal pathway of metabolism. For the
essential amino acid, phenylalanine, hydroxylation to tyrosine re-
presents a preliminary step prior to its complete oxidation via
(ultimately) the citric acid cycle.

Methods Employed:

The methods employed in the problem are those of (classical) enzym-
ology. For the separation and purification of the individual enzymes,
such techniques as salt fract^ionation, organic solvent fractionation
and selective adsorption and elution from gels have been employed.
Spectrophotometric and chemical assays have been used to follow the
course of the reaction.

Major Findings:

From kinetic studies previously carried out on this system, indi-
cations were obtained for the participation of another cofactor in this
reaction, in addition to TPNH. This cofactor has now been isolated from

300 -

Part A. (Continued) Serial No. M ^ CP 6

=,- ■ page 2

boiled extracts of rat liver. It has been shown that the lag periocii
the reaction which has previously been reported, can be eliminated
bv a short anaerobic incubation of TPNH with the cofactor in the pr«.e
of the highly purified sheep enzyme. These results suggest that thtfe
is an interaction between TPNH and the cofactor and that this re-
action is catalyzed by the sheep enzyme as shown in the reaction (1,

TPNH + H"^ + X^ ^ TPN"^ + XHg i

In the subsequent reactions in what must obviously be a complex
seauence this reduced cofactor may be oxidized by molecular oxygen i
to form the primary hydroxy lating agent. The rat enzyme probably I
participates in these later reactions involving the actual hydroxy-:
lation of phenylalanine.

Significance to Mental Health Research:

It is known that this reaction, the conversion of phenylalanine,
to tvrosine, is at least partially blocked in the disease oligophreiij
phenylpyruvica. One of the characteristics of this disease is a
severe impairment in mental ability. With an increased understandi^.
of the nature of the reactions catalyzed by the 2 enzymes which are|
involved in this conversion of phenylalanine to tyrosine, it should^
be possible to delineate more precisely the nature of the biochemicjl
abnormality of this disease. I

Proposed Course of Project:

The work on the purification of the enzymes will be continued,
mainly to explore the possibility that more than 2 enzymes are in-
volved The detailed mechanism of the reaction should be more
amenable to study when larger amounts of the purified enzymes and
the new cofactor become available.

Part B included Yes fj No /x7

- 301 -

Serial No. M '■■.. CP 7

Laboratory^o]f~CeTlular Pharma-
cology
Section on Cellular Regulatory

Mechanisms
Room 2D-04, Building 10

PHS-NIH
Individual Project Report
Calendar Year 1957

Project Title: Hormonal Regulation and Protein Synthesis.

Principal Investigator: Seymour Kaufman, Ph<,D.

Other Investigators; Louis Sokoloff, M.. D.

Cooperating Jnits : M - CS - CM ~ 4

Man Yea:'S
T^talT"-
Prof essional: ~

Other : -

Project Descriptioa:

Objectives:

Only recently methods have become available for studying
protein synthesis in_ vitro. Utilizing these methods, it has
been elearl2/ demonstrated that protein synthesis is coupled
to energy-yielding reactions in the cell. The mechanism of
the synthesis and of this coupling are unknown,, The objec-
tives of this study are three-fold „ (a) Investigate in
general the mechanism of protein synthesis, (b) Attempt to
elucidate the nature of the coupling of the energy supply
and the synthetic reaction. More specifically, this system
v/ould seem to offer the possibility of investigating the
question of whether or not different energy-yielding reactions
are geared to specific synthetic reactions. Thus it is now
known that during oxidation of substrates with molecular oxygen,
energy is tapped from the hydrogen carrier system at three
separate sites . It would be of great interest to know if the
energy liberated at these three sites is equally available
for all synthetic reactions. (c) To investigate the possible
hormonal regulation of protein synthesis.

- 302 -

Part A. (Continued) Serial No. M - CP 7

page 2

Major Findings:

During this year, the course of the problem has paralleled
closely the work described in Project M - CS - CM - 4.

Part B included Yes /T No /3c7

303 -

Serial No « M - CP 8

Laboratory of Cellular Pharma-
cology
Section on Cellular Regulatory

Mechanisms
Room 2D-04, Building 10

PHS-NIH
Individual Project Report
Calendar Year 1957

Project Title: Studies on the Cofactor Required for the Enzymatic

Conversion of Phenylalanine to Tyrosine.

Principal Investigator: Seymour Kaufman, Ph.D.

Man Years

Total: 1-2/3
Professional: 2/3
Other: 1

Project Description: )

) See previous project
Objectives: )

I Methods Employed:

The cofactor has been purified from boiled extracts of rat
liver by a combination of procedures including: Organic solvent
fractionation, ion exchange chromatography and partition chroma-
tography on silica gel columns.

Major Findings:

Enzymatic assays for the cofactor have been developed which can
detect ^ quantities of the material in natural materials. Using these
assays, many tissues have been examined as possible starting ma-
terials for large scale isolation attempts. So far, activity has
been detected only in liver and adrenal tissue. Of the livers
tested (beef, sheep, rabbit, monkey, rat) rat liver has the highest
activity. The cofactor has been isolated from this source by a
procedure which leads to about 1000 fold purification. Extensive
tests for specific chemical groups have been carried out and from
the results of these tests, as well as from some of its physical
properties, it can be concluded that the cofactor is an unstable
heterocyclic organic base which contains 20-30 per cent nitrogen.

Significance to Mental Health Research:

There is good evidence that the conversion of phenylalanine

I I to tyrosine is at least partially blocked in the disease,

' oligophrenia phenylpyruvica . With the realization that at least

- 30^4- -

Part A. (Continued) Serial No. M - CP 8

page 2

2 enzymes are involved in this conversion, experiments have been
reported which attempt to specify whether both or only a single
enzyme is missing or blocked in the disease. The finding that a
non-protein cof actor is also involved in this conversion raises
the possibility that it is the cofactor which is missing in the
disease .

Proposed Course of Project:

The purification and the studies of the structure of the
cofactor will be continued. In addition, the possibility that
it is the cofactor which is missing in oligophrenia phenylpyruvica
will be investigated.

Part B.

Kaufman, Seymour

"A New Cofactor Required for the Enzymatic Conversion of

phenylalanine to Tyrosine"

J. Biol. Chem. , in press

« 305 -

Serial No. M - CP 9

Laboratory of Cellular Pharma-
cology
Section on Cellular Regulatory

Mechanisms
Room 2D-04, Building 10

PHS - NIH
Individual Project Report
Calendar Year 1957

tA.
Project Title: Clinical Studies on Phenylketonuria.

,, Principal Investigator: Seymour Kaufman, Ph.D.

1 ~~~ ~

Man Years
Total: 2/3
Professional: 1/3
Other: 1/3

Project Description:

Objectives:

It has been established that in this disease there is at least
a partial block in the conversion of phenylalanine to tyrosine.
In vivo studies have shown that in phenylketonuria only one of
tEe 2 enzymes which are known to participate in this enzymatic
system is missing. The possibility exists, however, that it is
not an enzyme which is missing but rather a coenzyme v/hich is
required for the activity of this enzyme. Experiments will be
carried out to test the possibility that it is the cofactor
which is missing in the disease. If it is actually an enzyme
lack, the studies on the mechanism of the normal enzymatic con-
version of phenylalanine to tyrosine should allow for a better
understanding of the nature of the metabolic lesion.

Methods Employed:

Liver biopsy samples from children with oligophrenia
phenylpyruvica, as well as from normal controls from the same
age group will be tested for the conversion of phenylalanine to
tyrosine (see Project M - CP 6 for details).

Major Findings:

I The assay system previously used for the work on animal tissues
I has been modified so that it is applicable to small (about 1 g.)

306 -

Part A. (Continued) Serial No. M - CP 9

page 2

amounts of liver tissue. High activity has been obtained with '
2 normal human liver samples. It has been possible to show that
the cof actor, isolated from rat liver (see Project M - CP 8) can
stimulate the human liver system 3-6 fold.

Significance to Mental Health Research:

s j

A precise delineation of the metabolic block in this disease jj
may help our understanding of the relationship if the metabolism'
of phenylalanine and tyrosine to normal brain development and
function.

Proposed Coxirse of Project:

Several additional normal samples of human liver will be chei'si
for activity and then the studies on the oligophrenic liver sampai
will be carried out.

Part B included Yes /"^ No /5E7

- 307 -

Serial No. M n. CP 10

Laboratory^^ofi^T^Trular Pharma-
' cology

Room 2D-08, Building 10

PHS-NIH
Individual Project Report
Calendar Year 1957

Project Title: Biosynthesis of Noradrenalin

Principal Investigator: Bruce Levenberg, Ph„D,

Man Years
Total: 1/3
Professional: 1/3
Other: -

Project Description;

Objectives:

This investigation is concerned with the mode of biosynthesis
of the suprarenal hormone, noradrenalin. Evidence from tracer
studies has indicated that a possible pathway of formation of this
substance is from dihydroxyphenylalanine (DOPA) via hydroxytyramine
(DOPA-amine) „ Research will be directed toward obtaining enzymatic
evidence for such a series of reactions in cell free preparations of
adrenal tissue. It will be of particular interest to make a detailed
study of the postulated hydroxylation step between DOPA-amine and
noradrenalin and to ascertain the nature of the enzymatic and cofactor
requirements of such a system.

Methods Employed:

A simple and rapid chemical method has been devised for the
estimation of small quantities of noradrenalin in tissue extracts in
the presence of considerably larger amounts of DOPA-amine. Other
methods are being perfected which will enable one to follow the course
of the conversion of trace amounts of isotopically-labeled DOPA
to noradrenalin in crude as well as in more purified enzyme prepa- ,1: .:
rations.

Major Findings:

Much of the time devoted to this investigation during the past
several weeks has been spent on development of routine and re-
liable methods of assay. Thus, no major biochemical findings can
be reported at this time .

- 308 -

Part A. (Continued) Serial No. M - CP 10

— — page 2

Significance to Mental Health Research:

Adrenalin and noradrenalin, the major suprarenal medullary -
sympathomimetic agents, have been detected in considerable quantitle
in brain as well as in all types of adrenergic nerve tissue. The
Physiological and pharmacological actions of these hormones have
become the subject of an almost overwhelming number of studies,
but surprisingly little has been definitely established regarding
the enzymatic mechanisms which the body employs in the biogenesis
of the catechol amines from tyrosine. Much in the way of mteres-.i
biochemical reactions lies therein, and it is hoped that informal c
gained from this investigation will make a contribution in that
direction.

Proposed Course of Research: |

Since this is a new project, it is difficult to chart its coirs
until specific findings are made. However, should the hydroxylase
step be successfully demonstrated, purification of the enzyme coil-
ponents and a study of the intimate mechanism of the reaction ar
planned.

Part B included Yes fj No /x7

- 309 -

Serial No„ M - CP 11

Laboratory of Cellular Pharma-
cology
Room 2D-41, Building ,10

PHS-NIH
Individual Project Report
Calendar Year 1957

'>roject Title: Sulfate Metabolism in Chlorella

>rincipal Investigator: Graham Ao Jamiesonj Ph.D.

Ian Years

Total: 1/2
' Professional: 1/2

! Other: -

'roject Description:

Objectives:

It has been suggested (Schiffj Thesis, Pennsylvania, 1956) that in
the sulfur metabolism of Chlorella pyrenoidosa active methionine is
formed without the intermediation of methionine. It was necessary to
confirm these results (i) since the activation of methionine is the
only known mechanism for the formation of active methionine, and (ii)
as an attempt to clarify the role of the adenosine-homocysteine con-
denzing enzyme isolated from rat liver since adenosyl homocysteine
was a possible intermediate.

Methods Employed:

After the addition of carrier, active methionine was isolated by
paper electrophoresis and chromatography from Chlorella cells which
had been incubated with S^^-sulfate and methyl-C '^-methionine,
respectively, of equal specific activity and the radioactivity of
the product determined.

Major Findings:

It has been found that methionine is incorporated into active
methionine by Chlorella eight to ten times more effectively than is
sulfate suggesting that the pathway in this species is substantially
similar to that in yeast and in the rat. A possible explanation for
Schiff's erroneous results lies in the fact that the specific activities
of his substrates were not carefully controlled and hence an apparent

- 310

Part A. (Continued) Serial No. M- CP 11

page 2

non-incorporation of methionine as shown by radioautography was
actually a dilution effect when compared with carrier-free sulfate

Significance to Mental Health Research:

The importance of onium compounds and of methyl transfer read o
in the metabolism of nerve tissue is well known. Because of the
unusual mode of active methionine formation postulated by Schiff :;
was imperative to clarify these findings in the hope of revealing
new interrelationships between thioether and sulfonium compounds iid
of understanding the biochemical basis of methyl group transfer. :

Proposed Course of Research: !

In view of our negative findings this project will not be con
tinued.

■ ■ i

Part B included Yes /~7 No /x7 |

- 311 -

Serial No. M - CP 12

Laboratory of Cellular Pharma-
cology
Room 2D-08, Building 10

PHS-NIH
Individual Project Report
Calendar Year 1957

Project Title: The enzymatic mechanism of generation of the meth3?j.
" ~ group of methionine from one carbon compounds such
as formaldehyde o

Principal Investigators: Graham A. Jamieson, Ph.D., and

r— Gabriel de la Haba, Ph.D.

ilan Years
Total: 1/3
Professional: 1/3
Other: -

Project Description:

Objectives:

To investigate the enzymatic mechanism of generation of the
methyl group of methionine from formaldehyde. Recent investi-
I gations by other workers on the enzymatic reactions of formaldehyde
f or the beta carbon of serine, implicate a tetrahydrof olic complex
I such as a hydroxymethyl derivative as a metabolic intermediate.
It is well known that formaldehyde, formate, or the beta carbon,
of serine are converted to the methyl group of methionine (and
i that homocysteine is required for the generation of methionine
I from formate). The intimate details of this pathway, however,
i are unknown .

If a hydroxymethyl derivative of tetrahydrof olic acid Is an
t intermediate, it is proposed that in a condensation with homocysteine —
I analogous to the reaction between adenosine and homocysteine de-
! scribed in Project No, M - CP 4 — would result in a thioetherj,

which upon subsequent reductive cleavage would yield methionine.'

Such a postulated mechanism is under investigation.

Methods Employed:

To facilitate the detection of the above postulated iner-
mediate, radioactive formaldehyde and C-^'* carboxyl labelled
homocysteine will be employed. To determine the extent of
conversion of the formaldehyde to the methyl group of methionine
the latter will be degraded to release specifically the methyl
group as methyl iodide.

- 312 -

Part A, (Continued) Serial No. M - CP 12

page 2

Major Findings:

This project is at the moment being initiated and as yet no |
vpc,ults have been obtained^ As a first step conditions for maximi
reaction between tetrahydrof olic acid and formaldehyde were es-
tablished and the complex isolated virtually free of f ormaldehyde|

Significance to Mental Health:

This oroiect is part of the broad problem of methyl group
transfer under investigation in this laboratory. For discussion n
the significance to neurochemistry refer to a previous report
(M - CP 4).

Part B included Yes fj No /x7 \

- 313 -

Serial No. M - CP 13

Laboratory of Cellular Pharma-
cology
Room 2D-39, Building 10

PHS-NIH
Individual Project Report
Calendar Year 1957

Project Title: Amino acid uptake by Escherichia coli.
>rincipal Investigator: Michael Yarmolinsky

Ian Years ■

Total: 2/3
I Professional: 1/3

Other: 1/3

>roject Description:

Objectives:

Determination of whether carboxyl activation is responsible for
the concentration of amino acids by E. coli.

Methods Employed:

Amino acid uptake is measured by exposing suspensions of bacteria
to radioactive amino acid and measuring the radioactivity of samples
of bacteria separated from the medium by filtration.

Major Findings:

A specific, rapid, and reversible mechanism has been shown to
be capable of concentrating methionine as well as its analogue
ethionine in E. coli, strain W. The kinetics of uptake of the two
amino acids are strikingly different.

Significance to Mental Health Research:

The mechanism transfer of materials across cell membranes is of '
particular importance in nervous transmission as well as in the
nutrition of all cells.

Proposed Course of Research:

It is expected to continue this project in the coming year.

t B included Yes /~7" No /x7

' T 31^+ -

Serial No. M - CP 14

Laboratory of Cellular Pharma-
cology
Room 2D-14, Building 10

PHS-NIH
Individual Project Report
Calendar Year 1957

l-oject Title: Amino acid incorporation and protein synthesis
in liver.

"rincipal Investigator: Giulio L. Cantoni, M. D.

[an Years
Total: 1-1/3
Professional: 1/3
Other : 1

"roject Description:

Objectives:

The mechanism of biosynthesis of a protein de novo from
its constituent amino acid is one of the most exciting problems
presently under attack in biochemical laboratories throughout
the world. While the structural complexity and fragility of
proteins has so far made it impossible to attack the problem
directly in a cell-free system in vitro ^ there are a number
of less direct ways in which the~problem can be approached.
One line of attack which is of particular interest depends
on the study of the uptake and incorporation of radioactive
amino acid into proteins in a cell-free system.

Major Findings:

It has been established earlier that subcellular particles
called microsomes are active in incorporating amino acids into
proteins. It has now been found that different amino acids
are incorporated at different rates with tryptophane being

incorporated best and glycine least effectively. The kinetics,
requirements and characteristics of the system are being
investigated systematically. It is not known for certain
whether amino acid incorporated by this system in fact enter
into a peptide bond and the exact nature of the bond which

i binds the amino acid to the protein must be explored more

' directly.

315 -

Part A„ (Continued) Serial No. M - CP 14

page 2

Significance to Mental Health Research:

This project is of no immediate significance to mental
health. However, inasmuch as the problem is a most basic one
underlying our understanding of some of the most important
facts in biology, it may be assumed that any progress toward
its elucidation will be of potential interest to basic research
in mental health.

Part B included Yes /~7 No /5c7

- 316 -

Serial No. M - CP 15

Laboratory of (!fellular Pharma-
cology
Room 2D-39, Building 10

PHS-NIH
Individual Project Report
Calendar "ifear 1957

>roject Title: Metabolism of "Active Methionine" in Yeast.

Principal Investigator: S. Harvey Mudd, M. D.

Ian Years
Total: 1/3
Professional: 1/3
Other: -

Project Description:

i Objectives;

Yeast is known to synthesize and accumulate large amounts of
I S-adenosylmethionine ("active methionine") under certain nutritional
conditions. Although this compound can serve as a donor of its methyl
group or (after preliminary decarboxylation) of its aliphatic side
chain, its metabolic fate in yeast remains to be elucidated and the
goal of this project is to seek unknown reactions in which this
compound may participate.

Methods and Findings:

Work is still in a preliminary stage. Chromatographic methods
have been developed to enable ready separation and identification
of micro and macro quantities of S-adenosylmethionine and related
compounds. Very preliminary results suggest the possibility of a
hitherto unknown reaction of S-adenosylmethionine catalyzed by a sub-
stance present in crude extracts of bakers' yeast.

Significance to Mental Health Research:

This project is part of a larger study on biological transmethyla-
tions the significance of which to mental health has been discussed
elsewhere. It may be especially noted that the increasing evidence
that a variety of methylated compounds of plant origin have power-
ful psychic effects suggests that any information on the metabolism
of methyl compounds in plants may be of great significance for
understanding both the natural and the therapeutic role of these
substances .

It B included Yes /~7 No /x7

- 317 -

NATIONAL INSTITUTE OF MENTAL HEALTH

Basic Research
Addiction Research Center

BUDGET SHEET

Estimated Obligations for FY IQ-^B
Total: $255,90^
Direct: $2^^5,975

Reirabiir s ement s : $9,929

Projects included: M-AR 1 through M-AR 6

Serial No. Fi-M-l (C)

1. Addiction Research Center

2» Clinical Investigations

3. PHS Hospital, Lexington, Ivy,

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Addictive Liabilities of Nev/ .'Inalgesics .

Principal Investigator: H. F. Fraser
Other Investigators: Harris Isbell

Cooperating Units: Laboratory of Chemistry, Section on
Analgesics, NI/^J^ID. The Office of Naval Research
provided $33,835. in fiscal year 1957 and $33,385.
in fiscal year 1958 to carry on investigations
designed to find a synthetic substitute for codeine,
This fund provided salaries for 5 subprof ess ional
employees working five man years. NIFH Addiction
Research Center provides administrative and
supervisory services amounting to 1-1/3 ii^an years.

Man Years (cal. yr. 1957): Patient Days (cal. yr . 1957)

Total:

6-1/3

Professional :

2/3

Other:

$-2/3

M-773 (not chargeable to
Clinical Center)

318 -

M-AR-1 (C) J Page 2

Project Description:

^^l^^^Y.^* "^^ detsriTiine the addictive properties
of new anafgesic drugs as t2iey are developed and prior
to release for general sale. This is a technological
prograin carried out in collaboration v;ith the Drug
Addiction Coronittee of the National Research Council
and is designed to prevent uncontrolled use of
potentially addicting drugs.

Methods Smploye^d. Drugs are referred to the NINil-I
Addict'ion Re'search Center by the CoiTuaittee on Drug
Addiction and Narcotics of the National Research Council.
The Addiction Research Center, tising foniier addict
volunteers, determines: (1) the psychological and
physiological effects of single doses of the new drugs,
(2) whether the new drugs v;ill relieve or suppress
symptoms of abstinence from morphine, and (3) in some
cases, v,^hether patients v;ho are not tolerant to morphine
can be directly addicted to the new drug.

Patient Material. No. Average Stay (days)

105

Admissions:
Outpatients:
No. of visits:

56
91+7

(Note: This patient material is not

chargeable to the Clinical 'Center).

Major Findings. The following drugs were shown to
have ad*dictive properties:

1 . ^-i J 2-Diphenyl-Ij.-dimethylamino-3-methyl-2-
propionoxybutane ( d-propoxyphene) ,

2. Normorphine,

3. Norcodeine,

Ij.. _d-3-Methoxy-N-phenethyliTiorphinan.

The addictive properties of d-propoxyphene are so
low (less than codeine) that the drug v/ill not be
controlled by the narcotic lav/. Normorphine is a
slowly acting cumulative drug. Following withdra\\fal
of normorphine, symptoms of abstinence are milder than
after withdrawal of morphine.

-319 -

M-AR-1 (C), Page 3

■^-^M^lk^^R^.^^JlJ^ogra^ior^JjUm. Reports rendered
to the National Research Council are the basis for
recommendations concerning appropriate legal action
connected with the control of these drugs at national
and international levels. This prevents introduction
of potentially addictive substance into uncontrolled
use, thereby niininiizing addiction to new drugs. Vie
also hope to find a nonaddict ing, pain-relieving drug,
thus contributing further to the prevention of addiction.
The psychological effects and mechanisKs of action of
these new drugs are frequently of great theoretical
interest in the field of mental health.

Proposed Course of Pro_.iect. Since this is a
technological project operating for the protection of
the public, it will be continued. Druos tested will be
those recomraended by the National Research Council.

Part 3 included Yes /JTJ No /^~/

- 320 -

(Attachraent I)
Serial No. R-/\R-l ( C)
page ^■

PHS-NIK
Individual Project Report
Calendar Year 195?

Part B: Honors, Aviards, and Publications
Publications other than abstracts frora this project:

1. Fraser, H. F., Isbell, H. , and Van Horn, G. D. :
Effects of horphine as Compared with a Kixture of
Morphine and Diaininophenythiazole (Daptazole) .
Anestiiesiol. , _l8: S31-S3S (July-Aug.) 195^7.

2. Fraser, H. F. : Huiaan Pharr;iacology and Clinical
Uses of Nalorphine. Med. Clin. N. .■^lerica,

PP- 393-ij.03 (March) 1957-

3. Fraser, K. F. , and Isbell, H. : Further Studies on
d-l,2-Diphenyl-i}.-Dimet]iylamino-3-Hethyl-2-
Propionoxybutane ( d-Propox^nphene) . Min. loth Meet.
Corraiittee on Drug Addiction & Narcotics, NRC, Acad.
Sci., 1957 (Mimeographed).

ii.. Fraser, H. F. , and Isbell, H. : Addiction Liability
o f New Ana Igesics:

I. l-(2-Morphol inethyl) -l;--Ph2nyi-lL-Carbethoxy-
Piperidine (NTII-72S9) .

II. 1 - ( 2-Hydr oxy- 2-Phene thyl ) -l|.-Phenyl -!l- Ca r be t hoxy-
Piperidine (NIH-7292) .

III. _l-3-Methoxy-N-phenethyliTiorphinan (NIH-7362).

IV. d-2,2-Diphenyl-3-Methyl-i|.-Morphol ino-But^^r 1-
Pyrrolidine (NIH-7ii.22) .

■ Min. loth Meet. Coi:Ti;iittee on Druf; Addiction £,
Narcotics, NRC, Nat'l. .Iciu. Sci^, 1^.7 (r i-' .vcgraphed)

321 -

(Attachraent I) , Pare 5
Serial No. I'i-AR-1 (C)

Part 3; (continued)

Honors and Av/ards relating to this project:
Isbell , H. ;

1. Appointed Lecturer in Pharmacology with the Rank
of Professor, University of Illinois, College of
Medicine .

2. Appointed Member of Editorial Boards Journal of
Pharmacology and Experimental Therapeutics.

- 322 -

Serial No. M-.^R-2 ( C)

1. Addiction Research Center

2. Clinical Investigation

3. PHS Hospital, Lexington, 1'

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Acute and Chronic Intoxication v/ith

Drugs Other Than Analgesics, Barbiturates
or Alcohol.

Principal Investigator: Harris Isbell
Other Investigators: A. -V/ikler

Cooperating Units: None

Man Years (cal. yr . 1957): Patient Days ( ca 1 . yr. 1957)

Total: 7 636

P r of e s s i ona 1 : ~ S/3

Other: C-l/'i

Project Description:

Objectives. To determine the subjective and objective
effects and pathologic physiology of drugs other tlian thos;
in the opiate, barbiturate, and alcoholic classes. The
drugs studied are of importance in that they: (1) may be
abused hy opiate addicts, (2) are reported to be of value
in the treatment of addiction, (3) are reported to be of
value in the treatment of mental disease, and (I].) produce
profound psychological effects. Examples of such agents
are cocaine, mescaline, reserpine, and LSD.

323 -

K-J^\J\-2 (C) , Page 2

Methods Erap^loyed. Appropriate doses of the drugs
are "din i n i s~re r e d .rcutely or clironically to former
raorphine .-..J.dict volunteers. Phys iologica 1 j psycholo-
gicali fciocheinical ; iiid clinical Uieasurements are made
before, during, and after the intoxicet ion.

Patient Material.

No. Average stay___(_day|sj_

Adr.'iissions : Adult I'ales 63

Outpatients

'^6
0

Ha jor _Finding_s. D-2-Erorii-lysergic acid diethylaraide
(BCl7~s'"tlio"u'gh fa*r less potent tb.an LSD, does have psycho-
soraimetic properties v»'iien given in sufficient dose
(k-G mg./70 hg.). Pretreatment of patients with BOL,
BAS, and phenoxybenzamine did not attenuate or accentuate
tlie LSD reaction. Adrriinistrat ion^ of 0.1^.-0.6 ng.
epinephrine at the height of the LSD reaction caused
neither accentuation nor blocLing of the LSD reaction.
The following congeners of LSD all had psychosoraimet ic
properties, but were less potent than LSD: _d~l-Hethyl-
lysergic acid diethylamide (I^iLD) ,. _d- lysergic acid
inorpholide (LSIl) , d--lysergic acid p^/rrolidid (LPD,
d- lysergic acid diniethylarr.ide (D/>ij) , and ji- lysergic acid
oxazolidone (L,LC} . D- 1-acetyl- lysergic acid diethylamide
was as potent as LSD.

S i gn i f i_ca nee t o Prog r a m of_lil]Atl . The p s ycho s ora i rae t i c
drugs provide means of safely inducing psychotic states
in human volunteers. Various metabolic and toxic
theories of the etiology of natural psychoses have been
based on the effects of these drugs. Interactions of the
psychosomimet ic agents v/ith tranquilizers, horraoncs,
sympathoriiimet ic blocking agents, etc., represent one way

of testing tliesc

hypotheses .

proposed Course of P i' o j e c t . This project ivi 1 i be
contThued with emphaTsi's"" on 'interact ions of LSD with neuro-
humoral blocking agents. A number of indole d
will be studied to determine if correlations e
neurophysiological and pharmacological effects
become available, "tor.ins" isolated from blood
of schizophrenics v/i 1 1 be studied.

r ivat ives
ist betv/cen

As they
and u.rine

part

-/
/

- 32^1 -

(Attachrn.ent I)
Serial No. M-M-2 ( C)
page 3

PHS-NIH
Individual Project Report
Calendar Year 1957

Part B: Honors, Av/ards, and Publications

Publications other than abstracts frora this project:

Isbellj H. 5 and Logan, C. R. i Studies on the
Diethylaraide of Lysergic Acid (LSD-25) « H- Effects
of Chlorpromazine, y\zacyclonol and Reserpine on the
Intensity of the LSD-Reaction. A.M. A. Arch. Neurol,
and Psychiat., JX'- 350-358 (April) 1957-

Honors and awards relating to this project:

Isbell, H.:

Presented seminar, "Psychosominiet ic Drugs," at
University of Rochester School of Medicine, Rochester,
Nev; York, 23 October 1957.

325 -

Serial No. ii-.-ui-_;

1. Addiction Research Center

2. Clinical Investigation

3. PHS Hospital, Lexington, I;y =

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Chronic Intoxication v/ith Barbiturates

and Alcohol.

Principal Investigator: K. F. Fraser

Other Investigators: C-^rl F-., ZS'Sig

Cooperating Units: None

Man Years (cal. yr. 1957): Patient Days (cal. yr. 1957):

Total: 2-2/3
Professional: -2/3
Other: 2

Project Description:

£bje ct_ive_s . To deterniine clinical characteristics
of intoxication v/ith alcohol, barbiturates, and equivalent
drugs: to determine lainiraal limits of dosage and time
necessary for development of serious v/ithdrav/al symptoms;
to study pathologic physiology of these intoxications;
to develop more effective miethods of treatment and
prevention.

M-AR-3, Paq?

He t h o d s Z rap_l o;/e d . Patients v/ho have been
chrolTi'cariy intoxicated v/ith these drugs are
stabilized on some predetermined dosage level;
barbiturates or alcohol are then abruptly v/ithdrawn
or a drug presurn.ed to be equivalent is substituted
for the original drug; physiological, psychological,
biochemical, and laboratory observations are made
during both phases. Similar systems are used in

animals .

V >

Patient Hater ial. No. Average Stay (days)

Admissions: 0 0

Outpatients: 0

Hajor Findings. In sufficient dose alcohol
supp"re"sse"s~" ab'st inence from barbiturates in chroni-
cally intoxicated dogs almost completely. Follov/ing
v;i thdrai\fal of alcohol after substitution for barbi-
turates, dogs develop bizarre behavior and occasionally
convulsions. These findings indicate partial
equivalence of alcohol and barbiturates.

Following v^ithdraxval of meprobamate after chronic
intoxication Xv'ith large doses, 3 of L|. dogs developed
m.ultiple convulsions and died in status epilepticus.
The fourth dog survived although he had convulsions.
These experimients definitely prove that meprobamate
can produce physical dependence.

Significance to Program^ of NIHH. Alcohol ism^ is a
major mental health problem. Research in this field
is therefore of great importance. The extensive use
of barbiturates and of "tranquilizers" indicate that
abuse of these drugs m.ay have public health implications,
It is very significant that one of the most widely used
tranquilizers, meprobamiate, has nov/ been shovm to be
capable of producing addiction.

Proposed Course of Project. Equivalence of intoxica-
tions witli barbiturates, alcohol, paraldehyde, chloral,
and "tranquilizers" v/ill be studied in dogs. Because of
widespread use, first priority will be given to the
tranquilizers. Treatments of delirium tremens v/i 1 1 be
studied, using dogs.

Part B included: Yes /yTJ No /^^

- 327 -

(Attachment I)
Serial No. Fl-AR-3
page 3

PKS-NIK
Individual Project Report
Calendar Year 1937

Part B ; Honors, Av;ards and Publications
Publications other than abstracts from this project:

1. Fraser, H. F. : Tolerance and Physical Dependence on
Opiates, Barbiturates and Alcohol. Annua_l _ Rev i e v/_ of
Medicine. Vol. 8, pp I|-27-i|Ij-0. Pal o AlTo, ' C;. iTf':
Annual Reviev/s, Inc. (May) 195?.

2. Essig, C. F., and Ainslie, J. D. : Addiction to
Meprobamatc. J.A.M.A. , iGh,: (2) I382 (July 20) 1957.

3. Fraser, H. F. , 1/ikler, A., Isbell, K. , and Johnson,
N. K.'. Partial Equivalence of Chronic Barbiturate
and Alcoholic Intoxications. Quart. J. Stud, on
Alcohol (In press).

1|. Fraser, H. F., Wikler, A., Isbell, H. , and Essig,
C. F. : Degree of Physical Dependence Induced by
Various Chronic Dosages of Secobarbital and Pento-
barbital. J./v.M.A. (In press).

5. Essig, C. F. : V/ithdravml Convulsions in Dogs
Following Chronic Meprobamate Intoxication. A.M. A.
Arch. Neurol. & Psychiat. (In press).

6. Belleville, R. E., and Fraser, H. F. : Tolerance to
Some Effects of Barbiturates. J. Pharmacol. & Exper.
Therap., 120: [j.69-I^74 (Aug.) 1957-

Honors and av/ards relating to this project:

Fraser, H. F. ;

Invited to participate in a Syraposium on "Problems
Resulting from Use of Habituating Drugs in Industry,"
Meeting of the /unerican Public Health Association,
Cleveland, Ohio, lb. November 1957-

328 -

Serial No. M-Z'^v-ij.

1. Addiction Research Center

2. Clinical Investigations

3. PKS Hospital, Lexington, Ky.

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Biochenaistry of Addiction

Principal Investigator: A. J. Eisenman

Other Investigators: H. F. Fraser

Cooperating Units: None

Han Years (cal. yr . 1957): Patient Days (cal. yr . 1957)

Total: 3-2/3
Professional: 1-1/3
Other: 2-1/3

Project Description:

Objectives. To determine changes in chemistry in
body fluids and organs arising from acute and chronic
administration of drugs; determine rate, means of
conjugation and destruction of drugs in body; study
distribution of drugs in body; ascertain route and rate
of excretion of drugs; and to determine effects of drugs
on enzymatic processes.

- 329 -

M-AR-i.L, Page 2

I ie thod_s_J£mg_l oved . Standard methods of cli-nical/'
bioclTeiiii stry and" cheniical pharmacology are adapted.'
to the special requirements of the individual
experiments. Measurements of concentrations of drugs,
their metabolites, and of various nature 1 compounds
in body fltiids are made before, during, and after
acute or chronic administration of drugs.

Major^ Findings. Chlorpromazine caused a
dimintitlon, and reserpine caused an increase in
excretion of 17-hydroxycort icoids. Morphine and
barbiturate addiction and withdrav/al had inconsistent
effects on the excretion of 5-hydroxy- indoleacetic
acid. Addiction to and withdrav/al of normorphine had
effects on excretion of 17-hydroxycort icoids sim.ilar
to those of morphine. A method for determination of
normorphine was devised. Preliminary results indicate
tliat not as much normorphine is conjugated as is
morphine. This finding may explain the cumulative
effect and mild degree of dependence on normorphine.

Sionificance to Program of NH"3-i. Understandina of

effects of drugs on chemicaTl 'processes in the body is
basic to understanding of the subjective effects
produced by these drugs and, hence, to understanding
of addiction. Dif f cr ':.ices in distribution, metabolism,
and excretion may account for many of the differences
in addict iveness of the various drugs.

Proposed Course of the Project. Studies on distri-
bution, miCtabolism and excretion of normorphine as
compared with morphine will be continued. Specificity
of the normorphine method i/i 1 1 be studied, and, if
possible, an alternative method developed. As time
permits, other demethylated analgesics v/i 1 1 be
examined. In order to study the role of the central
and peripheral autonom.ic systems, studies on production,
tissue levels, and excretion of epinephrine and nor-
epinephrine v/i 1 1 be undertaken during cycles of addiction.

It is also hoped that studies on enzyme activity can
be initiated.

Part B included Yes / / No /X~7

330

Serial No. t-i-AR-5

1. Addiction Research Center

2. Experimental Neuropsychiatry

3. PHS Hospital, Lexingtonj ivy.

PHS-NIH
Individual Project Report
Calendar Year 1957

Part

Project Title:

Neurophysiology and Neuropharmacology
of Addiction.

Principal Investigator: Q.rl F. Essig

Other Investigators: Harold G. Flanary, Abraham V/ikler

Cooperating Units: None

Man Years (cal. yr . 1957): Patient Days (cal. yr. 1957)

Total': 4-1/3
Professional: 1-1/3
Other: 3

Project Description:

Objectives, To determine the effects of acute and
chronic administrationj as v/e 1 1 as abrupt ivithdrawal ,
of addicting drugs upon the functioning of the central
nervous system.

Me tho ds Emp 1 oye d . In one chronic spinal dog,
hindlimb reflexes v;ere measured v/ith standardized
technics during chronic intoxication with 650 mg./day
of sodium barbital for 5-1/2 months and after abrupt
withdrai/al of the drug. In cats, tv/o studies were
conducted: (a) the effects of chronic sodium

- 331

M-P'J{-$, Page 2

barbital intoxication (190 to 580 mg./<^ay total for
180 days) upon the e Ictroconvul s ivc threshold; for
this study, a group of untreated cats v/as used as
the control; and (b) the effects of cerebral elect-
rical stimulation tivice daily for four days prior to
abrupt withdrav/al of sodium barbital, after chronic
intoxication as indicated above and continued
thereafter during the abstinence period; for this
study an unstimulated group of cats treated v/ith
sodium barbital in a similar manner v/as used as the
control .

Kajor Findings. In the chronic spinal dog,
abrupt xvithdrav/al of sodium barbital was follov/ed by
the occurrence of three grand mal seizures, confined
to the portion of the body innervated by the nervous
system rostral to the level of spinal cord transection.
In the lov/er limis, the only definite change was a
transitory disappearance of the extensor thrust reflex.
In the cats, chronic intoxication with sodium barbital
produces an elevation of the electroconvulsive threshold
(for complete seizures); also, prev/ithdrawal and post-
withdrawal cerebral electrical stimulation appears to
reduce the incidence of withdrav/al convulsions, but such
stimulation is less effective if high doses of sodium
barbital are us3d during chronic intoxication.

Significance to Program of NII'-IK. Although, thus far,
only one cTTfonic sp rfTajT dog has been studied, the
available evidence indicates that unlike m.orphine,
physical dependence on barbiturates involves the rostral
portion of the neuraxis more than the caudal. No final
conclusion can yet be draim from the studies in cats,
but the available evidence suggests that seizures
produced by electrical stimulation and those produced by
withdrav;al of barbiturate following a period of chronic
intoxication share some more m.etabolic or physiological
m.echanism.s in common.

- 332 -

M-AR-5, Page 3

Proposed Course of Project. All phases of this
study will be continued along essentially the same
lines, with the addition of c lectroencephalographic
recording in the studies in cats. It is hoped that
studies of biochemical systems responsible for
synthesis and destruction of acetylcholine can be
studied during the corning year. In addition, stu.dies
of effects of acute and chronic drug intoxication on
activity of single neurons will be initiated.

Part B included Yes /X"7 No / /

- 333 -

(Attachment I)
Serial No. M-AR-5
page i!-

PHS-NIH
Individual Project Report
Calendar Year 1957

Part B: Honors, Av/ards and Publications
Publications other than abstracts from this project:

1, V/ikler, A.: The Relation of Psychiatry to
Pharmacology. Pharmacol. Rev. (In press).

2. Essig, C. F., and Flanary, H. G. : An Activity
Method of Recording Generalized Convulsions in
Experimental Animals. ESG and Clin. Neuroohys iol .
9: (2) 3kQ (May) 1957-

Honors and av/ards relating to this project:

V/ikler, A. :

Appointed member of Behavioral Sciences Study Ssction,
Division of Research Grants, NIMH.

Lectured on "Narcotics," Association for Research in
Nervous and Mental Diseases, New Yorlv City,
13 December 1957-

- 33^ -

Serial No . M-AR- 6 ( C)

1. Addiction Research Canter

2. Exper iraental Kfeuropsj/chiatry

3. PHS Hospital, Lexington^ Ivy.

PMS-NIH
Individual Project Report
Calendar Year 1937

Part

Project Title: Psychological Studies of Addiction.
Principal Investigator: Harris Hill

Other Investigators: A. Wikler, R, d. Belleville,

and H. G. Flanary.

Cooperating Units: hone

Man Years (cal. yr . 1937): Patient Days (cal. yr . 1937)

Total: 5-1/6 Uij.

Professional: 2-2/3
Other: 2-1/2

Project De script! Oil:

Objectives. To determine psychological mechanisms
of addiction, including relationships hetveen personality
characteristics and specific drug use; to measure
intellectual, emotional, and psychomotor changes induced
hy acute and' chronic intoxication with addicting drugs;
to elucidate psychological raechanisms underlying pain
relief by analgesic arugs.

M-AR-6 (C) , Page 2

Methods Einployed. Standardized and nei7 raethods
of clinical and~exp3r imsntal psychology are adapted
to the above objectives. Clini^cal methods include
standard psychometric and projective procedures, and
development and use of original inventories.
Experimental techniques involve measurements of
perception, reaction time, contrived anxiety, and
animial methods such as conditioning, experimental
neurosis, etc. These methods are applied before,
during, and after acute and chronic administration.

Patient Material . No . Average Stay (days)

Adiriiss ions: ijij. 3

Ovitpatients: 25
Visits: 120

I^iajor Findings. Physician addicts comiprised the
only subgroup" studied thus far which did not shov/
marked psychopathic tendencies as measured by the
Minnesota Multiphasic Personality Inventory. Although
the average profile suggested neurotic tendencies and
differed from that of normal m^en and medical students,
it also differed very significantly from the profile
of th.e "general" addict. Similar comparisons showed
striking resemblance betv/een Negro addicts and nonaddict
Negro prisoners, and between Uhite addicts, nonaddict
iifhite prisoners, and '.vhite alcoholics. Construction of
questionnaire item.s which differentiated betv/een CA-lOl,
LSD- 25 3 morphine, pentobarbital, and amphetamine in
preliminary tests has com^pleted the comipilation of an
inventory for distinguishing betv/een drug effects.
Continuing v/ork on the proposed analgesic testing
method in rats has increased the reliability of patterns
of actions which differentiate the n.ajor classes of
drugs. The potent analgesics produce nearly identical
patterns of unconditioned bar pressing, "time-action"
rates, and tone-shock conditioned inhibition of feeding
responses.

336

M-.'\R-6 (C), Page 3

Significance of Program to_ NIMH. The comparative
studies on addicts and nonaddicts holds promise of
providing some evidence on the significance of
personality characteristics and availability of drugs
in the addiction process. Efforj'ts to m.easure
"subjective" drug effects may produce techniques v/hich
vjill he differentially sensitive to analgesics,
hypnotics, analeptics, psychotomimetics, and
tranquilizers. The techniques may be useful in study-
ing new addicting and nonaddicting agents, and may aid
in developing a theory of drug actions. The animal
technique may prove to be a reliable psychological
procedure for screening potent analgesics. It may also
provide a behavioral means of classifying drugs, and
may aid in developing a theoretical frame of reference
of drug actions.

Results of studies on mental set indicate that the
LSD-s},mdrome is only indirectly related to the
"natural" psychoses. Studies of effects of drugs on
visual-hand reaction times as influenced by "regular"
or "irregular" presentation of different i/arning
("foreper iods" or "setting periods"), using the
procedure of Huston and Singer, shov/ed the following:
(1) after placebo, former addicts have faster reaction
times than normal subjects, (2) morphine and pento-
barbital slow reaction time but do not impair "mental
set," (3) 1 meg. /kg, of LSD does not impair mental set
in postaddicts (does not decrease the subjects' ability
to profit from regular schedule of change of the
"forewarning period," ([[.) 2-3 micg./kg. of LSD reduces
slightly the extent to which .subjects profit from
regulariza tion of the presentation of the foreperiods,
but the change is not significant despite pronounced
distortions in perception, body image, hallucinations,
etc., and (5) 20-I|.0 mg. of amphetam.ine had little
effect on reaction time or mental set.

337

M-AR-6 (C) , Page [,l

Proposed Course of Project. During 1958, this
section expect's (T) to conplete the study of physician
addicts, and compare other groups of addicts and
nonaddicts to further isolate the significance of
personality characteristics and drug availability in
the addiction process, (2) to further develop the
inventory for measuring "subjective" drug effects by
constructing preliminary scales through testing of
subjects under various drugs, (3) to increase the
reliability and validity of an analgesic screening
technique in animals by investigating the effective-
ness of different conditioned stimuli, (L|.) to
investigate, by psychological methods, the
significance of drug-produced internal changes in
controlling animal behavior, and (5) to begin an
animal study on the effects of drugs on discrimination.

Part B included

^®2 £E7 ^-o ZZ7

- 338 -

(Attc.chv:.ent I)
Sarial I;o. Ii-Z.^-l. ( C)
page 5

PHS-rHH
Indiviaual Project Report
Cnlandar Year 1957

_^ ______ !ionors^ Av/ards and Publications

Publ ic;;.tions other than abstracts fro];i this project:

1. Kill, H. Z., Belleville, R. ]Z., and h'ii.ler. A.:
Motivational Daterminants in the Pharraacol og ical
Modification of Behavior: Morphine and
pentobarbital. /.rcii. Meurol. a Psychiat., 77:
9b-107 (JaiL) lSh7.

2. Hill, M, ''..: I'loi: to Help the Addict. Book
Reviev. Contemporary Psvc'>.ol., 2: (a.) 11"'-11-|
(April) 1937. • "

sic Dru'~jSc

Honors
None

Hill, H. ■., Pescor, F. T. , Belleville, R. E. ,

and V/ihl er, A. ;

Rates of R,j.ts for Screening Analg

1. Techniques and Affects of Morphine. j.

Pharmacol. £. :Aper. Therap. . 120: f ") '!f:?-"97

(July) 1^-57.

; and awards relating to this project:

•39

NATIONAL INSTITUTE OF MENTAL HEALTH

Basic Research
Laboratory of Clinical Science
Section on ^erebral Metabolism

BUDGET SHEET
Estimated Obli;rat1nTi... for Try tq^r

Total! $129, 95^^
Direct: $76,935

Reimbursements : $53 , 019

Projects included: M-CS-CM 1 through M-CS-CM 7

Serial No. M-CS-CM-1

1. Laboratory of Clinical Science

2. Section on Cerebral Metabolism

3. Bethesda, Maryland

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A,

Project Title: Studies on the Circulation and Metabolism of
the Human Brain. I. Age Changes in Cerebral Blood Flow and
Metabolism. II. Effects of Anxiety and Emotional States on
Cerebral Circulation and Metabolism.

Principal Investigator: Darab K. Dastur

Other Investigators: Louis Sokoloff, Seymour S. Kety,
Douglas B. Hansen, Mark H. Lane

Cooperating Units: Section on Psychiatry, Laboratory of

Clinical Science, NIMH, Serial No. M-CS-Ps(C) -1 ; Laboratory
of Socio-Environmental Studies, NIMH, Serial No. M-S-D-4;
Section on Aging, Laboratory of Psychology, NIMH,
Serial No. M-P-A-3 .

Man Years (calendar year 1957) : Patient Days (calendar year 1957)

Total:

2.5

Professional:

1.0

Other:

1.5

Project Description:

Objectives: Numerous previous studies have demonstrated
that with advancing age, cerebral blood flow and metabolic rate
are reduced. Most of these studies, however, have failed to
give evidence of any adequate control of the effects of various
disease states often associated with aging. It is hoped in
these studies to determine whether in the absence of any
significant degree of age-related disease, these alleged
reductions occur so as to ascertain whether they are represent-
ative of the process of aging per se within the central
nervous system or depedent on disease. If they are still
observed in carefully selected, relatively disease-free,
elderly subjects, then it is hoped to determine whether the
depressions of cerebral blood flow and oxygen consumption
are secondary to circulatory deficiency and cerebral anoxia
or a manifestation of primary changes within the central
nervous system with concomitant readjustment of the cerebral

^ 340 -

Serial No. M-CS-CM-1, page 2

Project Description (Continued) :

circulation. It is also hoped to investigate the possibil-
ity of correlations between changes in cerebral blood flow
and metabolism with those occurring in various psychological
and mental functions observed in old age.

Continuing efforts are being made to solve the
question of whether the cerebral circulatory and metabolic
functions are influenced by emotional factors and, if so,
to determine the nature of such influences.

Methods Employed: The basic method employed in all |
these studies is the nitrous oxide method for the estimationij
of cerebral blood flow and metabolism in man. I

I
Major Findings: Studies in over 50 normal elderly
men carefully selected for their relative freedom from the i
common degenerative diseases of old age and who were func-
tioning more or less normally in their homes and communities
suggest that there are no reductions in cerebral blood flow
and metabolic rate as a result of chronological age per se
The presence of hypertension in otherwise normal elderly
men does not alter the picture. Chronic brain syndrome, on i
the other hand, is characterized by a reduction in metabolic
rate of the brain. The results are too preliminary in
this group to state whether there is evidence of primary
circulatory deficit and cerebral anoxia or the reverse.

Concomitantly with the investigations in the aged,
similar studies have been performed in normal young subjects
so as to obtain adequate comparative control values. These
young subjects as well as the aged have also been subjected
to numerous psychological and psychiatric evaluations so as
to determine the relationship, if any, among cerebral
circulatory and metabolic functions on one hand, and
psychological, psychiatric, mental, and personality factors
on the other. Preliminary observations suggest that there
may be such relationships.

Significance to Mental Health Research: All aspects |
of this project involve disturbances in mental or emotional i
functions whether arising from emotional disturbances or
the degenerative processes of aging, or else are directed
at learning more of the basic physiological mechanisms whici:
determine the normal functioning of the cerebral circulation
and metabolism. Since the brain is presumed to be the orgar
most intimately related to mental and emotional functions,
studies of its circulation and metabolism in these conditioi*
or in its normal state are directly pertinent to problems oi
mental health.

- 3^1 -

Serial No, M-CS-CM-1, page 3

Project Description (continued):

Proposed Course of Project: Studies in normal old
people will be expanded to include aged patients suffering
from the psychoses of senility. Observations directed at
uncovering any correlations between changes in cerebral
blood flow and metabolism and alterations in psychological
and mental functions will be made.

Part B included: Yes

-342

Serial No. M-CS-CM-1, page 4

PHS-NIH
Individual Project Report
Calendar Year 1957

Part B: Honors, Awards, and Publications

Publications other than abstracts from this project:

Sokoloff, L.: Circulation and metabolism of brain in
relation to the process of aging. Proc , of Conference
on the Process of Aging in the Nervous System.
Charles C. Thomas, Springfield, 111, (In press).

Other publications from previous work on this project:

Sokoloff, L., Perlins S., Kornetsky, C, and Kety, S.S.
The effects of d-lysergic acid diethylamide on cerebral
circulation and over-all metabolism. Ann. N. Y. Acad.
Sci. 66: 468-477, 1957.

Kennedy, C, and Sokoloff, L.: An adaptation of the
nitrous oxide method to the study of the cerebral
circulation in children; normal values for cerebral
blood flow and cerebral metabolic rate in childhood.
J. Clin. Invest. 36: 1130-1137, 1957.

Honors and awards relating to this project: None

- 3^0

Serial No. M-CS-CM-2

1. Laboratory of Clinical Science

2. Section on Cerebral Metabolism

3. Bethesda, Maryland

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A,

Project Title: Rapid Continuous Measurement of Leg Blood Flow
and Metabolism by Means of Radioactive Sodium

Principal Investigator: Louis Sokoloff

Other Investigators: Mark Lane, Darab K. Dastur, and
Douglas B. Hansen

Cooperating Units: None

Man Years (calendar year 1957) : Patient Days (calendar year 1957)

Total: 0.75 3*5

Professional: 0.50
Other: 0.25

Project Description:

Objectives: The objective of this project is the
development of a method for the rapid, continuous measurement
of blood flow and metabolism in a region of the body of
special interest to neurological research, the leg, and its
application to studies in a variety of conditions in which
these functions may be changing rapidly.

Methods Employed: The method employed is a newly
developed method based upon the Fick Principle utilizing Na^'*
as the tracer material. The quantity of Na24 in the leg and
its concentrations in the arterial and femoral venous blood
are continuously monitored by means of scintillation
counters following a rapid, single injection of Na^'*Cl into
the femoral artery of the experimental leg.

Major Findings: The development of the leg blood flow
method has been satisfactorily completed. It has been
employed in normal subjects at rest and during mild exercise
and has been found to yield results almost identical with
those obtained with other methods for measuring limb blood
flow. It has likewise proved successful in measuring the
leg blood flow continuously over minute-by-minute intervals
for twenty to thirty minutes, and demonstrates the changes

- 3^'+ -

Serial No. M-CS-CM-2, Page 2

Project Description (continued) : '■

produced by mild exercise as well as vasodilator drugs such
as priscolinOj ArlidinWj etc. Studies in muscular dystrophy
have shown that at rest, leg blood flow and oxygen consump-
tion are markedly lower than normal, but they can be raised
to normal levels during mild exercise.

Significance to Mental Health Research: The availa-
bility of a method for measuring leg blood flow and metabolis
is of interest and usefulness for studies in neuromuscular
diseases since by far most of the leg oxygen consumptio:i is
that of the muscles in the leg. Application of this in vivo
method to studies of diseases such as muscular dystropTiy' may,;
therefore, shed light on some of the underlying disturbances
in muscle metabolism presumed to exist in these diseases.

Proposed Course of Project: The initial phases of
this project have been completed « The method for the rapid
continuous measurement of leg blood flow and metabolism has
been developed, and it has been applied to normal subjects
at rest and during exercise, to studies of muscular dystrophy
and to the testing of the efficacy and the determination of
the continuous pattern of action of two reputed vasodilator
drugs, PriscolindS) and Arlidin®, following their intra-
arterial injection. For the time being, no further experi-
mental work is contemplated. The results of the work thus
far will, however, be organized and definitely presented
in three proposed publications. <

Part B included: No

- 3^5 -

Serial No. M-CS-CM-3

1. Laboratory of Clinical Science

2. Section on Cerebral Metabolism

3. Bethesda, Maryland

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A,

Project Title: Measurement of Local Circulation in the Brain

Principal Investigator: Douglas B. Hansen

Other Investigators: Louis Sokoloff, Walter Freygang

Cooperating Units: Section on General Neurophysiology,

Laboratory of Neurophysiology, NIMH, Serial No. M-NP-GN-1.

Man Years (calendar year 1957) : Patient Days (calendar year 1957)

Total" 0.65 None

Professional: 0.40
Other: 0.25

Project Description:

Objectives: The application of a newly developed tech-
nique for the estimation of the blood flow through the various
parts of the brain to physiological and pharmacological
investigations directed at elucidating the various factors
involved in regulating the normal regulation of the local
cerebral blood flow or causing its alteration in pathological
states .

Methods Employed: The method employed is one pre-
vious ly~3eveTope'3~3urTng the course of this project . It is
based upon a theoretically derived mathematical expression
which relates the tissue concentration of a freely diffusible
inert substance to the history of its concentration in
arterial blood, its solubility in the tissue, and the
capillary blood flow per unit weight of tissue. By using
a radioactive inert gas (trif luoroiodomethane) , the arterial
concentration is recorded continuously by means of an
appropriately designed scintillation counter, and by auto-
radiography, the concentration in the tissue is determined.
From these data and the theoretical equation, capillary
blood flow is calculated.

■}k6

Serial No. M-CS-C'M-3, page 2

Project Description (continued) :

Major Findings: Experiments in large numbers of cats
have demonstrated the validity of the method for determining
regional cerebral blood flow in 28 structures of the brain
and spinal cord, and its ability to demonstrate changes in
the local cerebral blood flow attending alterations in
physiological and pharmacological states has similarly been
proved. Normal values in blood flow per unit weight of
brain tissue have been established in 28 structures of the
conscious cat brain, and studies of the effects of pentothal
anesthesia have demonstrated marked reductions in blood flow
in those areas of the cerebral cortex chiefly concerned
with primary sensory functions and which during consciousness,
have, except for the inferior colliculus, the highest rates
of blood flow in the brain. Retinal stimulation in unanes-
thetized cats by means of repetitive, high intensity photo-
flashes has been found to result in increases in blood flow
in those areas of the brain involved in visual functions,
for example, the visual cortex, the lateral geniculate
ganglia, and the superior colliculi, provided the stimulation
was maintained for five minutes. One-minute stimulation
failed to produce any significant effect . These findings
prove the adjustment of the local cerebral blood flow to
local functional activity, and the latency of the adjustment
suggests strongly that the mechanism is a chemical one
probably related to the accumulation of the products of
an increased metabolic rate. The sensitivity of the 28
brain structures to high and low oxygen tensions and high
carbon dioxide tension have been studied o T^ere does not
seem to be differential effects on various structures,
but white matter tends to change its circulatory rate less
than gray matter.

Significance to Mental Health Research: The
circulation of the brain is fundamental to a proper function-
ing of that organ, and distui'bances in the cerebral circula- j
tion are known to be the basis of important neurological ;
disorders and conceivably might play a roll in many neuro-
psychiatric disorders of unknown etiology. Since the brain
is not a homogeneous organ, but is composed of a number of
structures whose circulations might behave differently, ]
measurement of the local cerebral blood flow could lead
to a better understanding of normal and abnormal brain
function and a means for evaluating various drugs and
other types of therapy. Furthermore, the demonstration of
the relationship between local cerebral blood flow and
local functional activity indicates that the technique
can be employed in the very basic purpose of mapping !
functionally related areas within the brain, knowledge of
which could ultimately contribute to neurological diagnosis
and therapy. 1

- J4-

''V?-

Serial No. M-CS-CM-3, page 3

Project Description (continued) :

Proposed Course of Project: In view of the apparent
relationship between local cerebral blood flow and functional
activity as demonstrated in the studies of visual stimulation,
it is planned to evaluate the technique as a possible means
of elucidating functional relationship between various brai.n
structures. To accomplish this, the results of stimulation
of various cerebral structures on other cerebral structures
as regards both local blood flow and evoked potentials will
be determined. In addition the method will be applied to
studies of the nervous control of the cerebral circulation,
the effect of carotid ligation, the question of cerebral
vasospasms and the effect of drugs with important nervous
effects or functions, such as epinephrine and its oxidation
products, LSD-25, and serotonin.

Part B included: Yes

- 32j3 -

Serial No. M-CS-CM-S , page 4

PHS-NIH
Individual Project Report
Calendar Year 1957

Part B: Honors, Awards, and Publications

Publications other than abstracts from this project:

Sokoloff, L.: Local blood flow in neural tissue.
New Techniques of Neuroanatomy . Edited by Wm. F.
Windle. Charles C. Thomas, Springfield, 111., 1957
(pp. 51-61).

Honors and awards relating to this project: None

_ -^49 -

Serial No. M-CS-CM-4

1. Laboratory of Clinical Science

2. Section on Cerebral Metabolism

3. Bethesda, Maryland

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A,

Project Title: The Mechanism of Action of Thyroxine and its
Relation to Cerebral Metabolism

Principal Investigator: Louis Sokoloff

Other Investigators: Seymour Kaufman

Cooperating Units: Laboratory of Cellular Pharmacology, NIMH,
Serial No. M-CP-7 .

Man Years (calendar year 1957) : Patient Days (calendai' year 1957)

Total: 2.0 None

Professional: 0.5
Other: 1.5

Project Description:

Objectives: The ultimate objective of this project
is the det erminat ion of the unique features of cerebral
metabolism which render the mature brain independent of the
circulating blood level of thyroid hormone. An intermediate
objective, and probably a necessary step in order to attain
the ultimate objective, is the determination of the
mechanism of the physiological action of the thyroid hor-
mone. In pursuit of this intermediate objective, the role
of thyroxine in the regulation of protein synthesis and
turnover is under investigation.

Methods Employed: The effect of thyroxine on the
rate of incorporation of a radioactive amino acid
(DL-Leucine-1-C ) into protein is studied in a completely
in vitro system containing an actively phosphorylating
inTtochondrial system and a microsomal enzyme system. The
mitochondrial system supplies the energy and the microsomal
system the enzymes necessary for the in vitro synthesis
of proteins. It is assumed that the rate of incorporation of
the radioactive amino acid into the proteins of the system
is related to the rate of synthesis of new protein molecules.

350 -

Serial No. M-CS-CM°4, page 2

Project Description (continued) :

i
Major Findings: Previous studies in the course of
this pro j eet have demonstrated that" thyroxine does penetrate
the blood-brain barrier so that the failure of the mature '
brain to respond to elevated blood thyroxine levels cannot
be attributed to the blood-brain barrier. Preliminary
results thus far indicate that thyroxine does influence [
the rate of protein synthesis as indicated by an aecelera- I
tive effect on the in vitro iricorpo ratios of radioactive !
amino acids into proxexlis . These results, riowevorj hays i
been variable probably because of a number of uadeteirmined
physiological and biological factors which are involved
in this process but have thus far not been adequately
controlled. During the past year a systematic attempt has |
been made to determine these variables so as to coFatroL
them better. This attempt has met with some success so
that the application of its results combiKed with a i
progressive improvement in techniques has led to a '

considerable increase in the consistency of the occur-
rence of the thyroxine effects and the predictability
of the behavior of the entire system. In other words, as
a by-product of the iBvestigatioii of the actios: thyroxine
has on protein synthesis , comsiderable fundamental infor-
mation is being uncovered as to the various factors and
mechanisms involved in the incorporation of amino acids I
into protein. '

Significance to Mental Health Research: A
unique feature of cerebral metabolism is its apparent
lack of response to high circulating levels of thyroid
hormone. An understanding of the basis of this unique
behavior may reveal information concerning the cerebral
metabolism in both health and disease. These studies may
also throw light on the fundamental mechanisms of action
of the thyroid hormone .

Proposed Course of Project: It is planned to
pursue this project along the following lines: 1) To
learn more concerning the mechanisms of amino acid
incorporation into protein in order to assess its rela-
tionship to protein synthesis in an in vitro system, and
to investigate the possibility of obtaining conditions
more favorable to a thyroxine effect. 2) To investigate
the possibility of utilizing or developing other more
suitable methods for studying protein synthesis in vitro.
3) To study the effects of thyroxine analogues wETcE""^
do not have a latent period of action on the amino acid
incorporation into protein. 4) To perform similar

- 351

Serial No. M-CS-CM-4, page 3

Project Description (Continued) :

studies in less purified systems, such as tissue slices,
or to add additional factors or other hormones as
indicated to the system so as to avoid the possibility
of missing essential co-factors on whose presence the
hypothesized action of thyroxine may be dependent .
5) To study the action of thyroxine on the activation
of amino acids, a process believed to occur prior to
their incorporation into protein.

Part B included: No

352 -

Serial No. M-CS-CM-5

lo Laboratory of Clinical Science

2. Section on Cerebral Metabolism

3. Bethesda, Maryland

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Chromatographic Studies in Intermediatry
Metabolism Related to Diseases of the Nervous System

Principal Investigator: Darab K. Dastur

Other Investigators: None

Cooperating Units: None

Man Years (calendar year 1957) : Patient Days (calendar year 1957)

Total: 0.75 170

Professional: 0.75

Other:

Project Description:

Objectives: The over-all objective of the project
was twofold: Tythe investigation of the patterns of amino
acids and organic acids in conditions of neuropsychiatric
interest wherein metabolic errors are known or suspected
to occur, as in phenylketonuria, Wilson's Disease, and
muscular dystrophy; and 2) the establishment of experimental
situations, in animals or man, whereby pharmacological
or physiological stress is applied and the metabolic
pathways studied, as in administration of phenylacetic
acid to rats or of labeled phenylalanine to rats and
monkeys J and in sleep deprivation in humans.

Methods Employed: For the greater part, paper
chromatographic techniques have been employed for the
delineation of amino acids and organic acids (such as
some of the Krebs' cycle intermediates and some of the
phenolic derivatives) in blood, urine and many of the
tissues. Occasionally, quantification has been attempted
by spot-elution and subsequent titration.

When radioactive isotopes have been used, techniques
employing liquid scintillation counting and radioautography
have been utilized.

- 353 -

Serial No, M-CS-CM-5, page 2

Project Description (continued) :

Major Findings: 1,, Phenylketonuria: Upon a regime j
of special phenylalamine-free diet , the abnormal free
phenolic acids seemed to disappear from the urines in

phenylketonuric children observed for 2-3 months. There i

was concurrent reduction in phenylalanine excretion also. i

The level of phenylacetyl glutamine, more than normal in ,

the pretreatment phase, diminished with the phenylalanine- j
free diet, and then increased a little again as normal

articles of food were added to the diet. Whenever the !

initial hippuric acid level was also raised, it appeared j

to fall after the special diet, j

2o Effects of phenylacetic acid: As this metabolite!
has been suspected to be toxic, it was administered intra-
peritoneally in large doses to rats one-month and six- - j
months old, for periods up to six months. No striking j
change could be discerned in the condition of any of the ;
animals. Regular urine examinations revealed the presence !
of large amounts of free phenylacetic acid, and an increase
in the excretion of hippuric and phenaceturic acids. (All
rats, including control animals who received injections
of distilled H2O, appeared to excrete much more aconitic ;
acid than men or monkeys.) I

In none of the rats have any of the tissues examined:!

(blood, brain, liver, spleen, kidney, intestines, muscle, \

testis) ever shown any phenylacetic or hippuric or phen- i

aceturic acid. Phenylacetic acid appears to be completely I

detoxicated and to be unable to pass the blood-brain |

barrier. Large amounts of acetyl aspartic acid were t
detected in all the brains.

3. Experiments with C-'-'^-phenylalanine: Following
intraperitoneal injections of uniformly labeled phenyl-
alanine into rats, metabolic studies extending over 24 to
48 hours permitted almost complete "recovery" of the
radioactivity, about three-fourths being from the tissues
(especially muscles, intestines and liver) . The rest
was mostly expired as CO2J only 3 per cent being excreted
in the urine .

Following intravenous injection in the monkey,
relatively less came out in the expired air, and about
20 per cent was still retained in the body at the end of
five weeks (most within the liver) .

- 35.^

Serial No, M-CS-CM-5, page 3

Project Description (continued):

In radioautographs of chromatograms, radioactivity
was detected in spots of phenylalanine, tyrosine, urea and
hippuric acid in urines of both monkey and rat, and in
phenylacetic acid, phenylacetyl glutaminej and succinic
acid in the monkey^ (In the course of the first eight
hourSj the monkey showed increased excretion of succinic
and malic acids, together with glutamine and glutamic
acido) Acetyl aspartic acid was again conspicuous in
the brain.

4. Wilson's Disease: Apart from a generalized
aminoaciduria; varying with the severity of the neurological
disorder, the only other feature of interest in the urines
of the four subjects studied is a suggestion of increase

in phenylacetyl glutamine.

5. Sleep deprivation: Urine samples from
volunteers subjected to sleep deprivation for 60 to 70
hours were collected just before they were allowed to
sleep, control samples being obtained from them three
days later. Many of the subjects showed a clear increase
of pyrrolidone carboxylic acid in the urine, while others
did not manifest this feature. This was at times
associated with prominence of glutamic acid also. Some
revealed increased excretion of hippuric acid. Some of
the group who received benzedrine sulphate during a
second period of sleep deprivation; failed to show the
increase in pyrrolidone carboxylic acid noted during

the first study.

6. Lactic acid in muscle dystrophy: Samples of
femoral venous blood from patients with muscular dystrophy
obtained before and after exercise appeared to reveal in
more than one-half the cases more lactic acid in the
resting stage than after mild muscular exercise, this
being most noticeable in the most severely dystrophic
subject. In the other two cases, the picture was
comparable to that obtained in normal subjects in whom
there was no appreciable difference (as detected visually
on the chromatograms) between the pre- and post-exercise
periods.

Significance to Mental Health Research: Studies
of the intermediary metabolism in diseases or abnormal
states of function of the central nervous system may lead
to basic information concerning the fundamental and
specific biochemical processes of the nervous system

- 355 -

Serial No. M-CS-CM-5, page 4

Project Description (continued) :

as well as to the uncovering of possible biochemical
defects in such disorders.

Proposed Course of Project: For the time being,
it is intended to analyze further the data collected,
complete some of the quantitative studies and prepare
some of the data for publication.

Part B included: No

- 356 -

Serial No, M-CS-CM-6

1. Laboratory of Clinical Science

2. Section on Cerebral Metabolism

3. Bethesda, Maryland

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Determination of the Spinal Fluid Levels of
Y-Aminobutyric Acid and the Enzyme Responsible for its
Formation, Glutamic Decarboxylase, in Normal Subjects and
in Patients with Mental and Neurological Disease

Principal Investigator: Thomas Vates

Other Investigators: Louis Sokoloff, Bernard Agranoff

Cooperating Units: Section on Lipid Metabolism, Laboz'atory
of Neurochemistry, NINDB .

Man Years (calendar year 1957) : Patient Days (calendar year 1957)

Total: Ool 70

Professional: 0.1

Other:

Project Description:

Objectives: Recent developments in neurochemistry
and neurophysiology indicate that Y-aminobutyric acid may
be, if not itself, closely related to one of the chemical
mediators of central nervous system inhibition. It is
formed from glutamic acid by an enzyme, glutamic decarboxylase,
which apparently is distributed uniquely only within the
nervous system. It is the purpose of this project to develop
methods for the assay of both the enzyme and its prodact in
the spinal fluid of normal subjects and in diseased patients
in whom alterations in their levels may reasonably be
suspected. The patients will include schizophrenic patients,
particularly of the catatonic type, and patients with
neurological diseases in which there may be active brain
damage. If feasible, it is planned to develop the technique
to a point of clinical usefulness as a test for the presence
of active brain damage in much the same way as serum trans-
aminase levels have been employed for myocardial damage.

- 357 -

Serial No » M-CS-CM-6, page 2

Project Description (continued) :

Methods Employed: Glutamic decarboxylase concentra-
tion will be determined from its influence on the rate of
release of C-'-^Os from saturating amounts of C-'-'*-glutamate
under optimal conditions for the activity of this enzyme.
C^^^Os will be trapped in strong alkali and measured in a
liquid scintillation counter, y-Aminobutyric acid will be
determined by a fluorometric method.

Major Findings: Preliminary studies have demonstratet
that there are measurable amounts of active glutamic
decarboxylase in the cerebrospinal fluid and that the
proposed methods will be adequate to assay them„

Significance to Mental Health Research: In view
of the possibility that Y-aminobutyric acid may be
involved in central nervous inhibition, the determination
of its level in spinal fluid may provide a means of
approaching in human beings the detection of abnormalities ||
in this function. It is conceivable that such abnormalities;
may occur in diseases such as catatonic schizophrenia in
view of the clinical symptomatology. Also, the enzsmie,
glutamic decarboxylase, appears to be specifically located
in the central nervous system, and during active damage of
the nervous tissues, may leak into the spinal fluid in
significant amounts. The assay of its level may then
become a very useful clinical tool in neurology for
diagnosis and prognosis regarding the degree of active
damage of nervous tissues, from which some recovery or
progression may occur, as contrasted with permanent, but
not active or progressive, functional impairment.

Proposed Course of Project: The initial phase of
the project will be directed at refining the techniques to
the point of obtaining trustworthy quantitative results.
Normal values for both the enzyme and the y-aminobutyric
acid will be determined. Simultaneously, comparative
values will be obtained in patients with schizophrenia,
cerebral palsy, cerebrovascular accident, and other
nervous and mental diseases.

Part B included: No

■- 358 -

Serial No. M-CS-CM-7

1. Laboratory of Clinical Science

2. Section on Cerebral Metabolism

3. Bethesda, Maryland

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A,

Project Title: Copper Dynamics in Normal and Schizophrenic
Serum

Principal Investigator: Douglas B, Hansen

Other Investigators: Seymour S. Kety

Cooperating Units: None

Man Years (calendar year 1957) : Patient Days (calendar year 1957) :

Total: 0.25 72

Professional; 0.25

Other:

Project Description:

Objectives: To study the fate of radioactive copper
within the blood serum of normal and schizophrenic man.

Methods Employed: After intravenous injection of
copper-64 into normal volunteers and schizophrenic patients,
blood is removed at varying intervals and the serum protein
analyzed by electrophoresis. The various protein fractions
are separated and the radioactivity determined by appropriate
scintillation counter technique in the different fractions.

Major Findings: Preliminary cat experiments have been
done and the technique worked through, the approximate
quantity of radioactivity needed has been determined, and
the findings that copper is initially bound to albumin and
gradually transfers to the a^ fraction, which contains the
ceruloplasmin, has been confirmed.

Significance to Mental Health Research: One of the
current theories of the etiology of schizophrenia is based
upon the controversial finding of some investigators that
the copper-containing protein (ceruloplasmin) in the blood
of schizophrenics is altered either in quantity or character

359

Serial No. M~CS-CM-7, page 2

Project Description (continued) :

from normal , Such a study as proposed here would study
in vivo the dynamics of the major characteristic of this
protein, i.e. the bound copper.

Proposed Course of Project: To see if the transfer
of copper into and out of the ceruloplasmin molecule is
altered in selected and diet controlled schizophrenic
patients from normal volunteers. A positive result would
be the occasion of further investigation into the charac=
teristics of the protein.

Part B included: No

- 360 -

NATIONAL INSTITUTE OF MENTAL HEALTH

Basic Research

Laboratory of Clinical Science

Section on Drug Valuation

BUDGET SHEET

Estimated Obligations for FY 19*^8
Total: $6iJ-,879
Direct: $49,8'!+9

Reimbursements s $15«030

Project included: M-CS-DE 1

Serial No. M-CS-DE-1

1. Laboratory of Clinical Science

2. Section on Drug Evaluation

3. St. Elizabeths Hospital,
Washington, D. C.

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Determination of Cerebral Blood Flow aiad
Metabolism in Brain Disease by Means of the Inert Gas
Technique Utilizing Krypton 85,

Principal Investigators: Mark H. Lane, Niels A, Lassen

Other Investigators: Irwin Feinberg, Louis Sokoloff,
Seymour S. Kety

Cooperating Units: St. Elizabeths Hospital, Washington, D. C.

Man Years (calendar year 1957) : Patient Days (calendar year 1957) :

Total: 1.75 16

Professional: 1.25
Other: 0.5

Project Description:

Objectives: To make measurements of cerebral blood
flow and metabolism in brain disease by use of the inert
gas technique, utilizing Krypton 85, a radioisotope, as the
inert gas. By this method it is possible to obtain more
accurate definition of the uptake of the gas by the brainj
especially in the early, more rapid uptake phase. By making
bilateral simultaneous determinations, the questions of
side-to-side differences are also being investigated. Thus,
by these techniques it is hoped to answer the following
questions: 1) the age at which a reduction in cerebral
oxygen metabolism is demonstrable in normal man; 2) do
psychological signs of decreased mental function correlate
with reduction in cerebral oxygen metabolism; and 3) are
the curves of cerebral inert gas uptake resolvable into
components which are physiologically meaningful?

Methods Employed: The method of cerebral blood flow
determination employed is essentially that of Kety and
Schmidt that has been used at the NIMH for the last three
years, with two modifications. First, cerebral venous
blood is sampled from both internal jugular veins

lei -

Serial No. M-CS-DE-1, page 2

Project Description (continued) :

simullaneously, and secondly, the radioactive inert gas.
Krypton 85, is used instead of nitrous oxide. As far as
is known this is the first use of Krypton 85 for cerebral
blood flow determinations in this country.

Patient Material; Up to the present time this
technique has been performed on four young normal control
subjects at the NIH and two patients with arteriosclerotic
senile brain disease at St. Elizabeths Hospital. It is
anticipated that many more brain disease patients will be
studied as well as a few normal control subjects to
establish normal values of blood flow and metabolism for
the St, Elizabeths Hospital laboratory.

Major Findings Since this project has just barely
begun, there are no major findings to report as yet. From
the preliminary studies completed the technique appears
promising .

Significance to Mental Health Research: As the
brain is recognized as the organ of the mind, a study of
the physiology of brain metabolism and circulation as
related to mental processes is desirable. Bilateral
determinations of the cerebral blood flow and the metabolic
rate of oxygen are thought to be less variable among indi-
viduals and more reproducible than unilateral studies,
particularly with the use of Krypton 85 as the inert gas.
Strong relationships established between psychological
deficit and whole brain circulation and metabolism i
measured by an accurate, reproducible method would open '
broad avenues of research in diagnosis and in the evalua-
tion of treatment of brain disease.

Proposed Course of Project; This project at
St. Elizabeths Hospital was first proposed in February 1957.'
Over the next months j equipment was ordered, special equip-
ment constructed and surplus material from NIH salvaged
for use in the new laboratory. An extensive application
for the use of Krypton 85 at St . Elizabeths Hospital was
prepared for the Atomic Energy Commission, and the
project submitted to the Radioisotope Committee of NIH
and a newly formed committee at St. Elizabeths Hospital.
The project was submitted to the Research Committees of
both institutions. Temporary laboratory space at St .
Elizabeths Hospital was negotiated for and the area
modified for laboratory use. Equipment was installed,
instruments tested and analytical procedures were
standardized for the new laboratory by November. A

^. r-.t

Serial No „ M-CS-DE-1, page 3

Project Description (continued) :

biophysicist and radiation safety officer was obtained
for the St. Elizabeths Hospital laboratories. Patients
were screened for suitable subjects, psychiatrically and
medically. Final approvals by all committees and agencies
were obtained by the first week in November, Four
preliminary studies were performed at the NIH during the
summer. The first bilateral cerebral blood flow measure-
ment utilizing Krypton 85 at St, Elizabeths Hospital was
performed on November 7, 1957. It is desired that by the
end of June 1958 a group of at least 25 to 30 organic
brain disease patients will have been studied, with at
least one repeat determination on each subject. A similar
group of normal young and old subjects and functionally
psychotic patients are to be studied as controls, as
available.

Part B included: No

:3 -

NATIONAL INSTITUTE OF MEOTAL HEALTH

Basic Research
Laboratory of Clinical Science
Section on Biochemistry

BUDGET SHEET

Estimated Obligations for FT 19^8
Total: $68,li^5
Direct: $52,359

Reimbursement s : $15 , 736

Projects incl-odedJ M-CS-B 1 through M-CS-B 5

Serial No. M-CS-B-1

1. Laboratory of Clinical Science

2. Section on Biochemistry

3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Fractionation of brain constituents.
Isolation and identification of antigen responsible for
production of allergic encephalomyelitis.

Principal Investigator: Marian W. Kies

Other Investigators: Elizabeth Roboz, Ellsworth C. Alvord, Jr.

Cooperating Units: Georgetown University Medical School,
Washington, D. C. and Baylor University Medical School, Houston,
Texas.

Patient Days

(calendar year 1957) : None

Man Years (calendar year 1957) :
Total: 1 1/3
Professional: 1/3
Other : 1

Project Description:

Objectives: The isolation and characterization of the
material iri~br~ain responsible for the allergic demyelinating
processes.

Methods employed: Brain and spinal cord preparations
have been fractionated by classical biochemical procedures
and the various fractions tested by injection in guinea pigs.
The test has been refined so that it can be used as a bioassay
for encephalitogenic activity. Each animal is assigned a
disease index derived from clinical, histologic and serum
lipid ratings, made independently by two observers. The
disease index varies from 0 (no reaction) to 10 (maximum
reaction). The average of 10 animals injected simultaneously
is the disease index for any given weight of material. One
unit of activity is defined as that amount eliciting an
average D. I. of 4 (half maximal effect) in a group of 10
animals. Thus, for any given fraction, the specific activity
(units/mg. ) or total activity can be calculated and compared

36^

Serial No. M-CS-B-1

rage 2

Part A. Project Description (continued)

with the starting material. Data from experiments on about
a thousand animals were iised to develop the disease index,
and we feel that v/e have a valid reproducible method of
assay. The standard error of the mean for each series is
about ± one D.I. unit.

Major findings:. ED5Q values have been established for
lyophilized guinea pig brain and bovine cord. Their activity
is compared with the most active fractions yet obtained in
the table:

ED50*

I. Bovine spinal cord 0.055 mg.

A. Collagen like protein (II-B) 0.025

B. 5% KCl xt. of CAP 0.005

" " whole cord 0. 007

C. Citrate xt., whole cord 0.005

II. Guinea pig brain 0.03

A. pH 3 xt. of defatted brain 0. OOS

* Weight of material eliciting a half-maximal response.

An accurate determination of the ED50 value for a given
fraction requires a minimum of 20 animals. Usually more are
required to determine the range in which the response is
proportional to the dose.

The collagen-like protein (II-B) which was isolated
from, hot solvent extracted cord was found to be a single
homogeneous protein by electrophoresis and ultracentrifugation
It contains hydroxy-proline and hydroxylysine and chemically
is very similar to collagen from bone and skin.

Fractions B and C from whole cord (KCl and citrate
extracts) are unheated, undenatured preparations, and since
they are chemically similar, they may contain the same
active constituent. They are distinctly different from
the collagen-like protein in that they contain no detectable
hydroxyproline or hydroxylysine.

Fraction II-B has been tested, at our request, in rabbits
by Dr. B. Waksman and in mice by Dr. J. Lee. It appears
that in neither species is this fraction active. On the
other hand, the lipid soluble fraction which Folch and Lees
have prepared possesses only minimal activity in guinea pigs.
Its activity in rabbits is also of much lower magnitude than
that of fresh whole cord. Dr. Waksman has already published
these results, even though the experiment was presumably a

3o5

Series No. M-GS-B-1

page 3

Part A. Project Description (continued)

collaborative one, as a proof of species specificity
and multiplicity of antigens. The fact that the rabbit
is so much less sensitive to whole nervous tissue than
is the guinea pig makes vis hesitant about accepting this
explanation.

Significance to Mental Health Research: This investigation
is basic to an understanding of the pathological process
known as demyelination. Any organic brain damage, if
sufficiently extensive, will lead to impaired mental
processes.

Proposed course of project: (a) Further fractionation
of the acid extract 61 deTatted guinea pig brain material.

(b) Dr. Roboz will continue her studies on the KCl extract
of whple bovine cord. If both sources yield pure proteins,
they will be characterized as completely as possible to
see how they differ (if at all) in chemical composition.

Part B included Yes

366

PHS-NIH
Individual Project Report

Calendar Year 1957 Series No. M-CS-B-1

page U-
Part B: Honors, Awards and Publications

Publications other than abstracts from this project:

Roboz, E. , Henderson, N. and Kies, M. W. A collagen-like
compound isolated from bovine spinal cord, I. J. Neurochem.
(in press) .

Kies, M. W. , Alvord, E. C. Jr., and Roboz, E. The allergic
encephalomyelitic activity of a collagen-like compound from
bovine spinal cord, II. J. Neurochem. (in press).

Honors and Awards relating to this project:

One important professional contribution on this project was
our help in arranging a Symposium on Experimental Allergic
Encephalomyelitis and its Relation to other Diseases of Man and
Animals. In June, 1956, Drs. E. C. Alvord, Jr., E. Roboz,
P. Y. Paterson and I approached Dr. Gordon Seger about the
possibility of a grant from the NINDB Advisory Council to
support such a symposium. In November, 1956, they made avail-
able to us the sum of $5000 to hold a conference here at NIH.
Drs. Alvord, Paterson, Roboz and Kies, with Dr. Henry Imus of
NINDB constituted the committee on arrangements.

Subsequently, we were able to obtain an auxiliary grant
from Smith Kline 8i French Research Foundation for $2500, to
help defray the expenses of certain foreign investigators
whom we wished to attend.

A two day conference was held on October 19 and 20, 1957.
About 70 people attended, at least 50 of whom took a very
active part in the discussion. The formal papers and pertinent
discussion will be published in book form by Charles C. Thomas,
Publishers, and will be edited by Drs. Alvord, Paterson and
Kies.

The program was divided into three categories - pathology,
etiology and immunology. Dr. Alvord was responsible for
arranging the pathology program. Dr. Paterson for immunology,
and the session dealing with etiology was my responsibility.

From the enthusiastic response during discussion periods
and from personal comments of participants, both written and
verbal, we are quite sure that the symposium was well received
and served a most useful purpose.

367

Serial No. M^CS-B-2

1. Laboratory of Clinical Science

2. Section on Biochemistry

3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Immunological studies on allergic
encephalomyelitis.

Principal Investigator: Marian W. Kies

Other Investigators: Ellsworth C. Alvord, Jr.

Cooperating Units: Baylor University Medical School,
Houston, Texas.

Man Years (calendar year 1957) Patient Days

Total: 1 1/3 (calendar year 1957)

Professional: 1/3
Other: 1

Project Description:

Objectives: Investigation of the immunological aspects
of allergic encephalomyelitis in an attempt to obtain defi-
nitive evidence, pro or con, on the question of the allergic
nature of the condition.

Methods employed: The standard assay technique des-
cribed in another project report has been utilized to study
the function of the tubercle bacillus in the production of
allergic encephalomyelitis.

Major findings: (a) Protective action of the tubercle
bacillus in mineral oil emulsion. If adult animals are in-
jected with incomplete vaccine (tubercle bacilli and oil)
30 days before a complete vaccine (tubercle bacilli, oil and
brain fraction) they can be completely protected against the
encephalitogenic effect of the latter. This protective effect
is inherent in the tubercle bacilli (oil alone is ineffective)
but the protection afforded by tubercle bacilli is potentiated
when it is given in an oily vehicle rather than saline. The
protective action of 0. 01 mg. tubercle bacilli in oil is
almost as great as 0. 25 mg. tubercle bacilli in saline.

363

Serial No, M-CS-B-2

page 2

Part A. Project Description (cojitinued)

Contrary to the results reported by Dodd and Bigley, the
guinea pigs receiving these low molecular weight carbohydrates
showed no clinical signs of disease, were normal on histologic
examination, and their serum electrophoretic patterns were
completely normal. Total serum proteins, total polysaccharides
and serum hexosamine contents were also within normal limits.

The discrepancy between their results with rabbits and ours
with guinea pigs may be a species difference. However, they
used such massive doses, that their results may have come from
toxicity effects rather than an antigenic reaction, j

!
It was important to check their observation, because of the
(remote) possibility that the encephalitogenic effect of
nerve tissue might be due to these or related carbohydrates.

Pursuing this same line of reasoning, a polysaccharide
fraction isolated from brain by the method of Glegg and Pearcel
was tested in the same manner for encephalitogenic activity j
and for its effects on serum proteins. ,

No clinical, pathological nor biochemical effects were
noted. This material which was obtained in 0.04% yield con-
tained 2.7% of nitrogen, 10.8% hexose, 13.6% hexosamine, and
32.9% uronic acid. Chromatographic analysis of a hydrolyzed
sample showed no detectable amino acids, but indicated the
presence of the monosaccharides usually found in nerve tissue:!
galactose, mannose and fucose, and galacturonic acid. In addi
tion,rhamnose was also found to be present. This methyl pentoie
which is related structurally to mannose, has never been re- j
ported in brain tissue, to our knowledge. I

Two other fractions obtained by Glegg 's procedure were profcb
glycoproteins, since their nitrogen content was much higher
(7.7, 12.7%) and the total hexose lower (6.6 and 0.6%).
Chromatographic analysis of their respective hydrolysates shoud
the animo acids and monosaccharides usually found in brain
materials. These fractions were also inactive biologically.
This protective effect can be elicited in new born guinea pigs
i.e. the preliminary incomplete vaccine is given to day old
guinea pigs and the subsequent complete vaccine at about 3
months (500 gm. ) . Interestingly, the new born guinea pig is
not susceptible to the complete vaccine. No illness results
when a day old guinea pig is injected with brain fraction and
tubercle bacilli in oil. Therefore, different immunoligical
mechanisms must be involved in the development of protection
and the induction of the disease. The early belief that the j
reason the immature animal' does not respond to the injection

- 369 -

Serial No. M-CS-B-2

page 3

Part A. Project Description (continued)

of brain material is that he has not yet formed myelin is in-
correct. The brain of the day old guinea pig is known to contain
myelin and furthermore, brain tissue from day old guinea pigs can
induce the disease in the adult animal.

(b) Degraded fragments of tubercle bacillus prepared by
Dr. Colover of Taplow, England, have been tested in our lab-
oratory and found to be active when combined with a purified
protein fraction from cord. Whether or not their specific activity
is comparable to whole tubercle bacillus cannot be determined
until both the fractions and the whole bacillus have been tested
at several levels. (See proposed course of project.)

Significance to mental health research: Although experimental
encephalomyelitis is assumed to be an allergic manifestation by
many investigators, it has never been definitely proven. The
experiments in progress may not result in unequivocal evidence,
but they should lend weight to one side of the argument.

This project offers a good possibility of determining the
physiological conditions which predispose an individual to the
development of spontaneous brain lesions and subsequent neuro-
logical and psychotic effects.

Proposed course of the project: Brain fractions found to
be active in producing allergic encephalomyelitis will be used
for skin sensitivity tests in guinea pigs. We would like to
investigate the relation of delayed type skin sensitivity in
the guinea pig, to the disease process.

To our knowledge, no attempts to titrate the effectiveness
of tubercle bacillus have been made except for some unpublished
results of Dr. J. Freund, which are not complete. We are at
present attempting to correlate the amount of tubercle bacillus
required for maximum effect with the amount of brain injected.
It may be that marked differences in susceptibility to lipid
and protein antigens exhibited by rabbits, guinea pigs and mice
may be related to varying requirements for tubercle bacillus
with different antigens in different species.

Part B included No

tTQ

Serial No. M-CS-B-3

1. Laboratory of Clinical Science

2. Section on Biochemistry

3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Biochemical studies on brain, bloody and
spinal fluid of encephalomyelitic animals.

Principal Investigator: Marian W. Kies

Other Investigators: Joseph B. Murphy and Ellsworth C.
Alvord, Jr.

Cooperating Units: Baylor University Medical School,
Houston, Texas.

Man Years (calendar Year 1957) Patient Days

Total: 2 1/3 (calendar year 1957): None

Professional: 1/3
Other: 2

Project Description:

Objectives: To ascertain what biochemical changes occur
prior or during the acute stage of allergic encephalomyelitis,
in order to understand the basic mechanisms involved in the
disease.

Methods employed: (a) Electrophoretic analysis of serum
from normal and encephalitic animals. (b) Analysis of serum
for total protein, total polysaccharide and hexosamine.

Major findings: Following a verbal report at the April,
1957 Federation Meetings, that injection (of massive doses)
of a-d-galacturonic acid and glucuronolactone in rabbits
produced typical lesions of encyphalomyelitis, a similar
test was made in guinea pigs, but with more reasonable amounts
of "antigen". Because the authors of this report (Dodd and
Bigley) had noted characteristic blood changes in their experi-
mental animals, serum studies were also carried out.

From these results, we have concluded that the encepha-
litogenic activity found in whole brain tissue is not associated
with carbohydrate per se, but requires a specific protein. It
is interesting that all of the active protein fractions which

- 371 -

Serial No. M-CS-B-3

page 2

Part A. Project Description (continued)

have been prepared in our laboratory or by Dr. Roboz

have contained small amounts of nondialyzable carbohydrate.

(None have been found to contain rhamnose, however.)

Significance to Mental Health Research: Almost nothing
is known regarding the cause of spontaneous demyelinating
diseases in humans. This disease offers the best experi- ,
mental approach to their study at the present time. :

Proposed course of project: (a) Extension of earlier studid
on the lipemia associated with allergic encephalomyelitis.
It is proposed to study the normal and abnormal lipoproteins;
by preparative ultracentrifugation. (b) Electrophoretic ;
studies of brain proteins, especially the encephalitogenic
fractions obtained from chloroform-methanol extracted brain. j
(c) A recent report on changes in a globulin patterns just
prior to the onset of symptoms in experimental allergic
encephalomyelitis has suggested we reinvestigate the serum j
globulin pattern relative to the course of the disease.

Part B included Yes

- 372 -

PKS-NIH
Individual Project Report Serial No. M^CS-B-3
Calendar Year 1957 P^&e 3

Part 3: Honors, Awards, and Publications

Publications other than abstracts from this project:

Kies, M. W. , Goldstein, N. P. , Murphy, J. B. , Roboz, E. and
Alvord, E. C. Jr., Occurrence of lipemia in experimental allergic
encephalomyelitis. Neurology, 7:175-188, 1957.

Honors and Awards relating to this project: None.

- 373 -

I xS-ir

:;*,:. .'>;*

Serial No. M-CS-B-4

i. Laboratory of Clinical Science

2. Section on Biochemistry

3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Antidiuretic effects of LSD in normal and
schizophrenic subjects.

Principal Investigator: Marian W. Kies

Other Investigators: Edward V Evarts

Cooperating Units: None

Man Years (calendar year 1957) : Patient Days

Total: None (Calendar year 1957): None.

Professional : None
Other: None

Project Description:

Objectives: To study the responsiveness of the hypo-
thalamus in normal and schizophrenic subjects under standard
conditions of stress, and to develop methods for determining
the level of antidiuretic substance in blood.

Methods employed: A study of urine output, pH, chlorides,
and specific gravity under standard basal conditions and fol-
lowing the administration of a stress-producing drug such as
lysergic acid diethylamide.

Major findings: No work had been done on this project
this year. See Publications.

Significance to Mental Health Research: Although the
site of action of LSD has not been established, there has been
considerable speculation that some of the psychological effects
are related to hypothalamic stimulation. Since the antidiuresis
observed was similar in certain respects to the effect of in-
creased production of ADH (a well known corollary of hypothalmic
stimulation) , the data are consistent with the notion that

- 37f^ -

Serial No. M-CS-B-4

TDage 2

Part A. Project Description (continued)

hypothalamic stimulation is related to the psychological
effects of LSD. ' ' " ^ -^;-;wi

Proposed course of project: We hope to do a companion experi
ment on mentally disturbed patients.

Part B included Yes

- 375-

PHS-NIH
Individual Project Report Serial No. M-CS-B-4
Calendar Year 1957 page 3

Part B: Honors, Awards, and Publications

Publications other than abstracts from this project:

Kies, M.W , Horst, D , Evarts, E. V and Goldstein, N.P.
Antidiuretic Effect of Lysergic Acid Diethylamide in Humans.
A.M A. Arch. Neuroi. Sz Psychiat. 77:267-269, 1957.

Honors and Awards relating to this laroject: None.

Serial No. M-CS-B-5

1. Laboratory of Clinical Science

2. Section on Biochemistry

3. Bethesda -H - « - i^-*.

NIH-PHS
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Metabolism of radioactive histidine in
Schizophrenics and normal humans.

Principal Investigator: Marian W. Kies

Other Investigators: Donald D. Brown

Cooperating Units: None.

Man Years (calendar year 1957): Patient Days

Total: . (calendar year 1957): None

Professional:

Other: 1/4

Project Description:

Objectives: To study and compare the metabolism of the
amino acid 1-histidine in normal control humans and schizo-
phrenics.

Methods employed: (a) Administration of uniformly
labelled carbon-i4 histidine. (b) Analysis of the urine
for the metabolites using ion-exchange resins, paper chroma-
tography and radioactivity determinations.

Major findings: Preliminary studies with the rat have
been done to establish the biological half life of radioactive
1-histidine. Urine and carbon dioxide were collected for two
days, the animal sacrificed, and a variety of organs analyzed
for carbon-14. About 30% of the injected radioactivity was
excreted in the CO2 and urine; the remainder was found in
the tissues with the highest concentration in the liver.

At present a method is being devised to identify histi-
dine metabolites in the urine. The use of ion-exchange
resins has given encouraging preliminary results. It is
hoped that enough initial information will be available
soon to begin work with patients.

Serial No. M~CS-B-5
page 2

Part A. Project Description (continued)

Significance to mental health research: Studies on schizo-
phrenic twins have indicated that the disease is genetically
controlled. If susceptibility to schizophrenia is a genetic
phenomenon, it should be possible to demonstrate some meta-
bolic abnormality in people suffering from this disease. This
project i^ one phase of a larger study on carefully chosen
schizophrenics with presence or absence of familial incidence
as the criteria of selectipn.

Proposed course of project: The animal studies described
will be used as a guide for similar studies on human urine and I
blood. Metabolic studies on two classes of schizophrenics -
those with a marked familial tendency to schizophrenia and •
those with no known familial tendency- and on normal controls j
of comparable ages will be made. i

Histidine is one of several amino acids which will eventual]/
be studied. It is interesting because it is the precursor of |
histamine, which has been claimed by certain investigators to
be abnormally high in blood from schizophrenics.

Part B included No

378

NATIONAL INSTITUTE OF MENTAL HEALTH

Basic Research

Laboratory of Clinical Science

Section on Pharmacology

BUDGET SHEET

ggtimatgd Obj^jgatigns for FY 19'?8
Total: $53,231
Direct: $i|-0,899

Reimbursements: $12,332

Projects included: M-CS-Ph 1 through M-CS-Ph 3

Serial No. M-CS-Ph-1

1. Laboratory of Clinical Science

2. Section on Pharmacology

3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Biochemical factors involved in the action
of drugs. I. Studies on the development of tolerance to
narcotic drugs and the action of narcotic drug antagonists.

Principal Investigator: Julius Axelrod

Other Investigators: Joseph Cochin

Cooperating Units: Laboratory of Chemistry, Section on
Analgesics, NIAMD, Serial No.

Man Years (calendar year 1957) Patient Days

Total: 1 1/3 (calendar year 1957): None

Professional: 1/3
Other: 1

Project Description:

Objectives: The phenomenon of tolerance to narcotic
drugs has been the subject of numerous investigations, but
no satisfactory explanation has thus far been evolved. For
this reason, a study on the biochemical factors involved
in the development of tolerance and the action of narcotic
drug antagonists was undertaken.

Methods employed: General biochemical and pharmacological
procedures.

Major findings: Previous studies have shown several
striking similarities between receptors for narcotic drugs
and the enzymes that N-demethylate these drugs. The enzymes
and receptors have been found to be alike with respect to
the type of substrates with which they interact, stereo-
specificity and antagonism by N-allylnormorphine.

An examination of the effect of the repeated adminis-
tration of N-allylnormorphine, a narcotic drug antagonist,
and normorphine, a drug with weak analgesic action, on the
enzymatic demethylation of morphine and analgesic response

379

Serial No. M-CS-Ph-1

page 2

Part A. Project Description (continued)

was studied. The repeated administration of N-allylnormorphjE
resulted in the development of tolerance to morphine and a i
concommitent reduction in the enzymatic N-demethylation of
morphine. Similar results were obtained after the repeated '
administration of normorphine. These findings further sub-
stantiate the mechanism of tolerance to narcotic drugs pre- |
viously proposed.

Significance to Mental Health Res«garch- It is hoped that i
information obtained from these rnvesTigations may give some
insight into the phenomenon of tolerance, cross tolerance
and antagonism to narcotic drugs.

Proposed course of project: The effect of sex hormones on
the N-demethylating enzyme and response to morphine in mor-
phine treated animals will be examined. The effect of the j
repeated administration of drugs which produce tolerance ;
(e. g. LSD, barbiturates) on the enzyme systems which metabo-rj
lize these drugs will be studied.

Part B included Yes

- 380

Serial No. M-CS-Ph-1

page 3

PHS-NIH
Individual Project Report
Calendar Year 1957

Part B: Honors, Awards and Publications

Publications other than abstracts from this project:

Axelrod, J. , and Cochin, J. The inhibitory action of
N-Allylnormorphine on the enzymatic N-demethylation of narcotic
drugs. J. Pharmacol, and Exptl. The rap. (in press).

Honors and Awards relating to this project:

Invited to deliver lecture on the mechanism of tolerance
to narcotic drugs, to Lilly Research Laboratories and Howard
University.

- 331 _

Serial No. M-CS-Ph-2

1. Laboratory of Clinical Science

2. Section on Pharmacology

3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: The Physiological Disposition and Metabolic
Fate of Drugs Affecting the Nervous System.

Principal Investigator: Julius Axelrod

Other Investigators: Bernhard Witkop and Bernard Agranoff

Cooperating Units: Laboratory of Chemistry, NIAMD, Serial
No. , Section of Lipid Metabolism, Laboratory of
Neurochemistry, NINDB, Serial No.

Man Years (calendar year 1957) : Patient Days

Total: 5/6 (calendar year 1957): None

Professional : 1/3
Other: 1/2

Project Description:

Objectives: This project is concerned with the absorp-
tion, excretion, plasma levels, rate of biotransformation
tissue distribution, and metabolic pathways of drugs acting
on the nervous system. Drugs under study at present are
epinephrine and norepinephrine, metanephrine and normetanephrine
and meprobamate.

Methods employed: Biochemical and pharmacological pro-
cedures.

Major findings: A method for the estimation of meproba-
mate has been developed. After administering the drug to
humans, about 12 percent of meprobamate is excreted unchanged
and 40 percent as a conjugated compound.

Epinephrine and norepinephrine: A method for the
estimation of metanephrine (3-0-methyl epinephrine) and nor-
metanephrine (3-O-methyl norepinephrine) has been developed.
After the administration of 1-epinephrine to rats, 3 percent
of the compound was excreted as metanephrine glucuronide.
The administration of metanephrine resulted in the excretion
of 5 percent metanephrine and 30 percent metanephrine glucu-
ronide. When rats were pretreated with iproniazid, a monoamine

- 382-

Serial No. M-CS-Ph-2

page 2

Part A. Project Descriptton (continued)

oxidase inhibitor, the excretion of free and conjugated
metanephrine was doubled. Similar results were obtained with
norepinephrine. These observations suggest the following
pathway for the metabolism of catechol amines in the rat:

EpinephrineQ-"^^;^^y^^^^°^ >metanephrine £2nla£ation_>nietanephrine
70% I ^^/o glucuronide

3, methoxy-4-hydroxymandelic acid

Norepinephrine =^5^— >normetanephrine £2aaMlH£S>normetanephrine

707o -^^/o glucuronide

Significance to Mental Health Research: These studies should
provide basic information about the physiological disposition,
metabolic fate, and mechanism of action of drugs affecting the
nervous system.

Proposed course of project: The fate of ergot alkaloids
(ergonovine, ergotamine) , heroin, meprobamate, epinephrine,
norepinephrine and other drugs acting on the nervous system will
be studied.

Part B included Yes

- 3S3

Serial No. M-CS-Ph-2

PHS-NIH
Individual Project Report
Calendar Year 1957

Part 3. Honors^ Awards and Publications

Publications other than abstracts from this project:

Axelrod, J. and Inscoe^ J. K. l-(3 '-methoxy 4' hydroxybenzyl)
6-7 dimethoxy isoquinoline^ a major metabolite of papaverine.
Experentia, 8:319-320, 1957.

Sjoerdsma, A. , Maling, H. , Pratt, H. D. , Axelrod, J. , Kayden,
H.J. and Terry, L.L. The antiarrythmic action of ambonestyl.
New Eng. J. Med., 255:213-216, 1956.

Honors and Awards relating to this project:

Appointed member of Editorial Board, J. Pharmacol. Si Exptl.
The rap.

- 3S^

Serial No. M-CS-Ph-3

1. Laboratory of Clinical Science

2. Section on Pharmacology

3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Cellular Mechanisms in the Metabolism of Drugs

Principal Investigator: Julius Axelrod

Other Investigators Rudi Schmid and Gordon Tomkins

Cooperating Units: Metabolic Diseases Branch, NIAMD, Serial
No.

Man Years (calendar year 1957) : Patient Days

Total: 1 1/3 (calendar year 1957): None

Professional: 1/3
Other: 1

Project Description:

Objectives: This project is concerned with the enzymes
involved in the transformation of drugs and hormones. We
plan to study the metabolic pathways of drugs and hormones
catalyzed by enzymes, and the intracellular localization,
biochemical mechanisms, specificity and species distribution
of these enzymes.

Methods employed: General biochemical and pharmacological
procedures.

Major findings:

Glucuronide synthesis: We have found an enzyme
that can synthesize a new type of glucuronide (N-glucuronides)
as follows: Aniline + uridine diphosphate glucuronic acid
(UDPGA) — ^-> aniline N-glucuronide. Administration of aniline
to guinea pigs resulted in the excretion of aniline N-glucuro-
nide.

Methods for distinguishing ether, ester and N-
glucuronides have been developed.

The enzymatic conversion of indirect reading (free)
bilirubin to direct reading bilirubin (bilirubin glucuronide)
has been demonstrated. This conversion is catalyzed by an
enzyme in the liver microsomes and requires UDPGA.

- 3S5 -

Serial No. M-CS-Ph-3

■ ■ page 2

Part A. Project Description (continued)

A biochemical lesion in non-obstructive, non-hemolytic
jaundice in rat and man has been found. This disease arises
from a marked deficiency in the glucuronide synthesizing
enzyme. As a result, free bilirubin cannot be removed from
the body by glucuronide conjugation.

0-Methylation of catechol amines: An enzyme that can
0-methylate epinephrine and other catechols has been found.
To carry out this reaction, the enzyme requires S-adenosyl-
methionine and a divalent metal. The enzyme is present in
liver, lung, kidney, spleen, brain and intestines.

Significance to Mental Health Research: These studies may
make some contributions to the understanding of metabolic
mechanisms in health and disease.

Proposed course of the project: Enzyme systems involved in
the metabolism of ergot alkaloids, diacetylmorphine and
meprobamate will be studied. Further work will be done on
the 0-methylating enzyme.

Part B included Yes

386

Serial No. M-CS-Ph-3

page 3

PHS-NIH
Individual Project Report
Calendar Year 1957

Part B: Honors^ Awards and Publications

Publications other than abstracts from this project:

Axelrod^ J. , Inseoe, J. K. and Tomkins^ G. M. The enzymatic-
synthesis of N-glucuronic acid conjugates. Nature, 179: 538-539
1957.

Schmid, R. , Hamraaker, L. and Axelrod, J. The enzymatic
formation of bilirubin glucuronide. Arch. Biochem. Biophys.
70:285, 1957.

Strominger, J., Maxwell, E. , Axelrod, J. and Kalckar, H.
Enzymatic formation of uridine diphosphoglucuronic acid. J. Biol.
Chem. , 224:79-90, 1957.

Freter, K. , Axelrod, J. and Witkop, B. Studies on the chemical
and enzymatic oxidation of LSD. J. Am. Chem. Soc. 79:3191-3193,1957.

Axelrod, J. 0-Methylation of epinephrine and other catechols
in vitro and" in vivo. Science, 126:400-401, 1957.

Honors and Awards relating to this project:

Invited to give a paper on physiological significance of
glucuronide conjugation at the Medicinal Chemistry Section, Gordon
Conference, August, 1957.

NATIONAL INSTITUTE OF MENTAL HEALTH

Basic Research

Laboratory of Psycholo^

Section on -^ging

BUDGET SHEET

5-timated Obligations for
Totals $272 5,016
Directs .$173,i)-2i^

Reimbursements s $98,592

Projects included? M-P-A 1 through M-P-A 12

Serial i^lo. H-P-A-1

1. Laboratory of Psychology

2. Section on Aging

3. Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A,

Project Title: Age Differences in the Behavior of the Rat^ Learning
and Transfer, and Psychomotor Behavior

Principal Investigator: Edward A» Jerome

Other Investigators: James E. Birren

Cooperation Units: None

Man Years: Patient Days: None

Total: 2o75
Professional: 1»25
Other: l.^O

Project Description:

Objectives: It is the purpose of this investigation to study those
aspects of adaptability and psychomotor behavior that can be expected
to manifest changes associated with chronological age and, from these
studies, to construct a theoretical interpretation of the process of
aging.

Methods Employed; A choice-escape apparatus utilizing light-aversion
as drive has been employed in a series of ten experiments designed to
study learning and transfer ability in two contrasted age groups of
albino ratSo

liajor Findings:

lo Mddle -aged and senescent rats were found not to differ signifi-
cantly in respect to the relative frequency with which individuals
reacted appropriately in the test situation under the light -avers ion
drive o

2o Functions describing the rate of acquisition of the basic operant
have been inspected and no important qualitative or quantitative age
differences have been found.

Serial No, M~P~A°1, Page 2

Part Ao Project Description Continued

Major Findings Continued?.

3o Observations have been made on the manner in which illumination
regulates behavior in the test situation and no age differences have
been f oundo

lj.0 Two contrasting age groups have been tested with respect to their
reaction to obstruction. Though these data have not yet been completely
analyzedj, inspection has failed to reveal any age difference in this
connection.

$o Eighteen rats, divided among two age groups, have mastered a series
of eight problems, very similar in form but providing ample opportunity
for both positive and negative transfer. Though this constitutes less
than half of the projected group, their data have been partially
analyzed for the first two problems and reported in abstracts There
were no age differences foimd in either learning or transfer.

Significance to the Program of Mental Health Researchs The general
indications of these experiments tend to confirm the c-urrently
growing conviction that if impairraent in learning ability is common
among aged humans it may well be due, not to a biological pre-
destination created by the inevitable deterioration of living tissue
in time, but to the effects of attitudinal or behavioral patterns
adopted by maturing and aged individuals under the coercion of social
conditions, customs and traditions. If such an interpretation is only
partially true, to that extent the prospects for preventive and cor-
rective procedures are more encouraging than they appear under the
currently dominant explanation on the basis of decay of organization.

Proposed Course of the Projects

lo To continue the search for a problem complexity that shows an age
difference in the learning ability of rats.

2. To activate a series of studies designed to indicate the influence of
the time and type of passed experience on apparent age differences in
the ability to learn.

3. To make additional studies of such behavioral factors as speed of
response, fatigue^ and psycho-motor adjustments to drug administration.

U. To initiate a series of studies designed to provide a basis of
evaluating the appropriateness of the hunger drive in studies of aging
(in animals).

Part B included"— No.

389

li Laboratoi'y oi' ru^'CliclotJ

2, occbion on A^^ing

3. 3e the 3 da

PIB-MIK
Individual Pro.^^c^ .isport
Calendar Year 1957

iT'cject Title: A^;e Changes in Time and Intensity Relations in
rUiViian bcnsation, r^rception, and Itasponse

Frincinal Invasti'.,ator: iiLfred D<

315^;

Other Invssti-ators: Janes .ri» 13irren and Hrrry Kay
Cooperating Units : Kons

Patient Jay,'3 :

Inpatient Days : 63
Outpatient Days :

lian ioars :
•lotal: :'.c75
i-r ci essional : 1
Other: .,73'

Project Ucscription:

Objective; The unders tandinij of the psychological and physiolo^ic^^l
mechanisms in the chan^;e of stimu-lus perception and response tine in
h"a,-.ian ajring,

i\iet.hods_ii!£lo233d; A, A click stimulator in vjhich trains of clicks
of varying len^ith a.nd speed were presented to deterraine certain liraits
of auditory perception. B, Simulta-neous dichotic di ;it span prosanv-ations
and conventional digit span presentations at various rates of speed to
deterriiine certain me:.iory orjardsation and interference effects*
Delayed auditory feedback of speech to coraps.re the effects of various
delays on different age f^roups. D. The effects of clilorproraaaine
end secobarbita!!. on delayed speech feedback, ii;= Reaction tLiie with
electroiTiyo;.;raphic measurements in ultra-short preparatory'" intervals -.

Major l''indin,r-s ; Results thus fax indicate that "ij-hile there is no
general decline in the limits of auditory temporal riscri-instion i/ith
age, perceptual loss increases i-jith s.ge with increasing loading of
the perceptual mechanism. Perceptual change v/ith rate of presentation
is less than that due to age, rate changes affecting both age groups
similar l^v. In this situation, where accuracy of response is highly
stressed, response times of the two age groups do not differ signifi-

cantly; while increasing the nurdbjr of clicks

well

the rate of

390 -

Serial Mo. M-P-A-2, Page 2

Part A. Project Description Continued

Major Findings Continued; presentation significantly increase the
response time for both groups.

In the drug study, chlorpromazine shows no effect on speech
disruption, as here measured, while secobarbital shows dose related
increased speech disruption. With practice, the amount of speech
disruption is reduced under non-drug conditions.

Significance to the Program of Ifental Health Research; These experi-
ments indicate certain aspects of perceptual changes v:hich occur with
age in terms of handling various rates of information flow. They also
give some indication as to the nature of sensory feedback control in
speech.

Proposed Course of the Project; On those portions of the project on
which data compilation is complete, statistical analyses Xijill be
undertaken. Certain other portions of this project have been initiated
only recently and vjill be continued. It is proposed to further ex-
plore certain questions which have arisen as a result of these studies,
both in human and in animal subjects.

Part B included — No

391 -

Serial No= M-P-A-3

1« Laboratory of Psychology
2. Section on Aging
3> Bethesda

PHS-KIil
Individual Project Report
Calendar Year 1957

Part Ao

Project Titles Age Changes in Ifental and Perceptual Abilities
and Personality Structure o

Principal Investigators Jack Botwinick

Other Investigators s James E, Birren

Cooperating Units s Home for the Jend-sh Aged, Philadelphia,

Pennsylvania

l^Ian Years s Patient Dayss

Totals 3<>5 Inpatient days: 600

Professionals 1„25 Outpatient dayss

Others 2„25

Project Descriptions

Objectives g The objective of this project is the description
of normal age changes in mental functions and personality, and
tentative interpretations of the antecedents and consequences
of the changes. In addition, data were processed for correlations
with physiological and psychiatric variables «

Methods Employed g Both standard and new procedures are used.
These procedures include the WAIS, tests of problem solving, alter-
nation, card sorting, perception of hidden figiiresj pencil and paper
tasks such as slow and fast iiiriting, connecting boxes by pencil
linej, mirror tracingj apparatus involving time measurements such as
reaction time, with and xfithout shock motvation, tachistoscopic
presentation of perceptual material, and CSR conditioning o This
latter procedure is done in cooperation with Dr, Gonan Kornetsky,
Laboratory of Clinical Science,

Ifejor Findings g The major findings are that with normal aging there
is; lo a decrease in inliibitcry'- processes and control f;inctions that
relate to motor, perceptual and cognitive abilities j 2, a relation
between speed and accuracy of response as a function of stimiilus

392

Serial No. l'i"I'~Ix-3 , Page 2

Part At Project Description Continued

Major Findings Continued; difficulty, such that a factor or variable of
"level of confidence required before making a discriminative response"
is suggested, i.e^, with age, it is possible that there is an increased
tendency to take time to review the alternative choices before responding,
that is relatively free from the necessity to do so from the point of
view of accuracy of response j 3« an increased reaction time to shorter
preparatory intervals in an irregnilar series. The latter suggests that
either more time is required to get ready, or that more time is required
to recover from the faulty expectancy.

Significance to the Program of I4ental Health Research; These studies
contribute to the description of normal aged and thus on vjhat might be
expected. Understanding the antecedent and consequent factors can aid
in dealing with problems of the aged.

Proposed Course of Project; Studies will be enlarged for those variables
that are found to be of significance in these preliminary studies of
the aging process »

Part B included— Yes

" 393

Serial Noo M-F-A-3, Page 3

PHS-MH
IndividuoJ. Project Report
Calendar Year 1957

Fart B; I-Ionors, Awards, and Publications

Publications other than abstracts from this project:

Birren, James lie Sensation, perception, and modification oi" be-
havior in relation to the process of aging. Proceedings, Conference
on the Process of Aging in the Nervous System. In Press,

Birren, J-ames E, Aging comes of age. Contemporary Psychology, 1957*
2, 32,

Birren, James E. The psychological aspects of senile nervous diseases.
Proceedings, International Siaiposiiai on Medical -Social Aspects of
Senile Nervous Diseases, Venice, Italy, In Press,

Botv/inick, Jack, Jerome, lidward, Birren, James and Brinley, J, Light
aversion motivation in psychologic studies of aging in rats. J« Gerontol.,
1957, 12, 296-299 o

BotxiTinick, J., Brinley, J, F., and Robbin, J, iilffects of electric
shock motivation on reaction time and its relation to age. In Press.

Botwinick, J., Brinley, J,, and Robbin, J, The interactions affects
of perceptual difficulty and stimulus exposure time on age ciifferences
in speed and accuracy of response. In Press.

Botwinick, Jo, Brinley, J., and Birren, J. n). Set in relation to age,
J. Gerontol., 1957, 12, 300-305.

Honors and Awards relating to this projects

National Science Foundation Travel Award to Attend the IVth Congress
of the International Association of Gerontology, July lu-19, 1957,
Merano, Italy,

39^

Serial Ko. M-P-A-l;

1, Laboratory of Psychology

2, [ijection on Aging
3e Eethesda

PHS-MH
Individual Project Report
Calendar Year 1957

Paxt

Project Titles Cytological and Gytochemical Changes in the Ifervous
System as a Function of Ages An Investigation of
Submicroscopic Morphology Smploying the Light and
Electron tlicroscopes

Principal Investigator ; William Bondareff

Other Investigators: None

Cooperation Units t None

Han Years % Patient Days ; i-Ione

Totals 2eO
Professionals ^75
Others 1,2 5

Project Descriptions

Objectives The objective is to determine the subiiu.croscopic
morphology of the nervous system employing the electron microscope,
ifith special regard, to chemical constituents including enzymes,
as a function of age^ IntraneixronaJ. pigment, the accumulation of
which is characteristic of advanced age in certain neurons, will be
investigated ra-th regard to its chemical constitution, submicroscopic
morphology, and genesis o

Methods Employed g Employing Sprague-Dawley rats of varying age,
various portions of the nervous system are surgically exposed and
minute tissue samples are taken. Cerebral cortex, and spinal ganglion
have in most cases been invsstigatedo The specimens are fixed either
iJith osmium tetraoxide or by an improved method of freezing and drying,
stained by a variety of electron microscopic "stains," embedded in
plastic and sectioned by means of an ^iltramicrotome „ Other specimens
are prepared for study with the light microscope and serve as controls*

I'lajor Findings g From light and electron microscope study of osmium
fi>:ed specii'aens of spinal ganglion from old rats it has been found
that the intracellular pigment accumulating a function of age, so--
called lipofuscin, does not originate due to mitochondrial degeneration
as was previously thoughto A mechanism of pigment derivation was

395

Serial Noo M-P-A-U, Page 2

Part A. Project Description Continued

Major Findings Continued;

suggested whereby the pigment is thought to arise in association
with the Golgi complex.

Some progress has been made in the application of freezing
and drying to electron microscopic study of aged neurons and a
few heavy metals, such as osmium, platinic tetrabromide, phosphO"
tungstic acid and silver nitra-);e have been studied in relation
to the study of the pigment and the subraicroscopic morphology of
the cytoplasm of aged neurons.

Significance to the Program of Mental Health Research: An
understanding of the submicroscopic morphology of the neurons
of the central nervous system as a function of age will be re-
quired for any definitive explanation of aging in the nervous
system, for the functional activity of the brain is ultimately
related to integration of its cellixlar units <,

Proposed Course of the Projects After fixation and staining
methods have been fui'ther developed certain cytochemical tech-
niques of light microscopy will be applied to the electron
microscope problem in attempt to further understand the chemical
constitution of such age-associated intracytoplasmic inclusions
as pigment and also to explore possible changes in other intra-
cellular substances such as enzymes and glycogen as a function v
of agingo Morphological investigations, employing heavy metal
staining of frozen=-dried material will be directed toward an
investigation of possible age changes in the submicroscopic
morpholos^ of the extracellular components of nervous tissue and their
effect on intracellular processes . Also the change in intra-
cellular water as a function of age will be investigated mor-
phologically with the electron microscope .

The employment of a small, relatively simple nervous system
in a study of submicroscopic morphology would be most desirable.
An attempt will therefore be made to extend these studies so as to
includfi invertebrate materials With such a morphological study of
invertebrate neinrous tissue, an adjuvant investigation of aging in
invertebrate animals is also planned^

Part B included— les !

- 396 -

Serial No. Ii-P-.A-J4, Page 3

Pffi-NIH
Individual Project Report
Calendar Year 1957

Part B; Honors, Awards, and Publications

Publications other than abstracts Irom this project:

Eondareff, iJilliaiiii Cytooenesis of intracellular pi^iiiant in
the spinal ganglia of senile rats.. An electron raicroscope
study, J, Gerontol., 1957, 12, 36it-369c

Bondareff , »-Jilliam» Submicroscopic morphology of connective
tissue groxind substance vrith particular regard to fibrillo-
gcnesis and agin£> Gerontologia, 1957, 1, 222-233.

Bondareff, William » Morphology of particulate glycogen in
guinea pig liver revealed by electron inicroscopy after freezing
and drying and selective staining en bloc. In Press e

Honors and Awards relating to this projects

National Science Foundation Travel Award to Attend the IVth Congress
of the International Association of Gerontology, July 11.1-19, 1957j
Merano, Italy.

397

Serial Wo. M-P-A-5

1, Laboratory of Psychology

2. Section on Aging
3 ' Bethesda

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A.

Project Titles Age Changes in Brain Electrolytes in the Rat

Principal Investigator: Eugene Streicher

Other Investigator; None

Cooperating Units: None

Man Years; Patient Days: None

Total: 1.08
Professional: .33
Other: ,75

Project Description:

Objective: To measiore age changes in the concentration of
sodium, potassium^ calcium, magnesium, chloride, aluminiim,
and silica in rat brain as a function of age.

Methods Employed; Soditjon and potass iiaa are measured by flame
photometry, ma>gnesium, calcium, phosphate, aluminum, silica,
and chloride by suitable colorimetric methods «

Major Findings;

1. In all a^e groups, from 1 month to 2=l/2 years, the
calciraa content is very variable, the two halves of the same
brain often differing from each other by several hundred per-
cent = An elei/ated ca-lcium level is not necessarily related to

the age of the rat.

2, G?he calcium content of the two halves of the same brain are
more closely related to each other in the brain of old rats than
in yoxmg animals regardless of the level observed.

398 »

Serial No. M-P-A-5, Page 2
le Laboratory of Psychology
2. Section on Aging
3 ' Betbesda

Part A. Project Description Continued

Mg.Jor Findings Continued;

3. The calcium content of the brain parenchjmia is approximately
2 mLlliequivalents/kilogram fresh weight. Additional calcium
probably represents deposition in non-neuronal brain structures
such as the blood vessels »

h. The magnesium content of the brain is somewhat diminished in
rats over 2-1/2 years old.

5. Brain mitochondria, isolated from both young end. old animals
possess approximately the same concentrations of calcium and
magnesium. The calcium content of isolated brain mitochondria
is sufficiently high to account for almost all of the calcium

of rat brain a

1. These studies have demonstrated that the intracellular
mag!aesi\jm content is very higji, possibility 30 mllliequivalents/
kilogi'am of neuronal protoplasm, and e3rpla5.n8 the need for the
addition of relatively large amounts of magKiesiim to brain
horaogenates and mitochondria to secure maximal rates of respira-
tion and oxidative phosphoiylatione The magnesium content of
brain structures can be utilised as a measure of cellular proto-
plasmic mass and can possibly be eaijjloyed to evaluate the extent of
deiEyeliniaation in nem'ological disease.,

2. The decreased magnesiium content of brains obtained from
animals over 2-1/2 year's of age indicates the± advanced age in
rats may be accoH^aaied by the loss of neurons and parallels

morphological obser\fa,tions made on human autopsy material.

3. The observe,tions on the variability of calcium in rat
brain explain the divergent results on brain ealciimi levels
reported in the literature over the course of the last fifty
years sad helps to elucidate the purported effects of vitamin
D def ieieaey and law calciim diets on the calciiM content of
rat braitio Also^ it shedg some li^t on the contradictory re-
sults published on the effects of parathyroidectomy on brain
calcium level.

k. This work suggests that the rat may be employed in
studies concerning the relationship of diet and genetic pre-
disposition to calcium deposition in the brain»

399

Serial No. M-F-A-!?, Page 3

1. Laboratory of Psychology

2. Section on Aging

3 . Bethesda

Paxt A. Project Description Continued

Proposed Course of the Project; In addition to the measurement
of age changes in other electrolytes of rat brain, analyses of
calciiom and magnesium will be carried out on several species of
laboratory animals to provide control data for future studies on
aging.

Part B Included— Yes

ij-OO

Serial No. M-P-A-5^ Page k

1. Laboratory of Psychology

2. Section on Aging

3 . Bethesda

PHS-NIH
Indlvidxial Project Report
Calendar Year 1957

Part B; Honors, Awards, and Publications

Publications other thein abstracts from this project;

Strelcher, E., Bondareff, W., and Gorbus, J. The Keuroblologlcal
Research Program of the Section on Aging of the National
Institute of Mental Health. In Press.

Streicher, E. Biochemical investigations of the aging nervous
system. In Press.

Honors and Awards relating to this project: None

ii-01 -

jrial ,:.o. i-I-F-A-6

Ic Laboratoiy of iaycholo^y
2 , Doction on Afiinr-

othesda

PHS-JIIH
individual i^oject Report
Calendar Year 19^7

jrar't

Project Title ; rletabolisin of Nervous Tissue as a Function of Age
Principal Investigator: Joel L;,?jrbus
Other Investii'-ators: None

Gooperatina' Units :

Br, Et, V'Jeinbach of the Laboratory of Tropical
Disease continues to cooi^erate in certain aspects
of this investigation

Man Years :
Total; . j3
P'rofessional;
Other: .^O

Patient Days ;

'lone

.33

Project Description?.

Objectives The objective is to measure alterations in the meta-
bolic characteristics of nervous tissue as a function of agec

Methods ;ii]mployedg i Metabolic activity of rat nervous system pre-^
parations is measured in vitro under a variety of experimental
conditions. The activities of enajnues are measured spectrophotanetrically
or manome trie ally. Tracer equipment has been installed for the
study of relative metabolic rates usint; radioactive isotopes,,

Major Findings t Observations on the respiration and oxidative
phosphorylation of brain homogenates as a function of age have
been extended to include measureiiients employing cellular partic-
ulates. A preparative procedure 'i.'as developed for the isolation
of cellular particulates of high metabolic activity and excep-
tional stability^ Respiration and oxidative phosphorylation
have been studied employing mitochondria prepared bj these methods
from the central nervous system of rats of vajpious ages. Mo de-
cline with age has been foujnd in either respiration or r.hosphate
esterification and no significant changes were found in the ability
to utilize various substrates and in the stability of the mitochondria*.

- i!-02

Serial Mo. M-P-A-6^ Page 2

Part Ao Position Description Continued

Major Findings continueds

These cellular metabolic activities are measured under optimum
conditions, in vitro j an ample source of substrate, necessary co-
factors, inorganic salts and buffers are supplied to the tissues.
Permeability and diffusion barriers are minimisedo Under these
"ideal" conditions, the implication of our findings is that the
ena^Tnatic potential involved in these jjnportant metabolic processes
are unimparied vrith age. Of course, these model conditions, are
■ not directly comparable to those pertaining in vivo.

Significance to the Prograjn of Mental Health Research s The meta-
bolism of neurons provides the energy required for cellular activities
and directly supports functional nervous processes. A study of the
metabolic potential of excised tissue may indicate whether the
functional aspects of aging are related to quantitative or to specific
deficiencies in the energy producing systems of the nerve cell.

Proposed Course of Projects It is proposed to continue these studies
under restricted or less than ideal biochemical conditions^ e.g., low
oxygen tension, absence or diminution of substrate and co-factors
electrical "stiraulation" of brain slices j to reproduce, in vitro, a
deleterious cellular environment as it were, which may be a factor
in senescence. In addition, specific enzymes, ^ihich occupy important
roles in cellular metabolism and neuronal activity, such as hexokinase,
cholinesterase, monamine oxidase, will be meas^ored.

Part B included--Yes

403

Serial No. M-P-A-6, Page 3

PIB-NIH
Individual Project Report
Calendar Year 1957

Part B; Honors , Awards, and Publications

Publications other than abstracts from this projects None

Honors and Awards relating to this projects

National Science Foundation Travel Award to Attend the IVth Congress
of the International Association of Gerontology, July lii-l^^ 1957 j
Merano, Italy,

i-l'Ok

Serial No, M-P-A 7

1, Laooratory of Psychology

2, Section on A^ing

3, Bathes da

PHS-NIH
Individual Project Report
Calendar Year 1957

Part A=

Project Title I The Metabolism of Neuropharmacological Agents as a
Function of Age

Principal Investigator : Joel Garbus

Other Investigators : Kone

Cooperating Units s None

1-Ian Years ; Patient Days : Kone

Total; ,1^8
Professional; ,33
Others ,25

Project Description:

Objectives The objective is to measure the rate of detoxification
of neuropharmacological agents as a function of age and to relate
the intensity and duration of the effects on the central nervous
system with blood levels of the ad-ninistered drug.,

Methods Biaployeds An appropriate dose of a neuropharmacological
agents is administered, and the blood levels measured at various
times thereafter. Concomitantly, the effect on the central
nervous system, i.e., duration of anesthesia or sponataneous
activity is noted. Behavioral criteria are being surveyed and
developed for the purpose of establishing measures of age changes
in reactivity of the nervous system to neuropharmacological agents »

Major Findings; Previous work was concerned with the effects of
age and sex on the duration ox anesthesia induced in rats by two
dissimilar agents 5 hexobarbital, a short acting barbiturate and
hyroxydione (Viadril), a water soluble steriod. In the current
investigation ethchlorvynol (Placidyl), a chlorinated acetylenic
carbinol is being employed. The unique physical properties of the
drug have necessitated the development of a new method for its
preparation for injection. The accuiiiulation of ds.ta is now in progress.

^05

Serial Mo. M-P-A-7, Page 2

Part A. Project Description Continued

Significance to the Prograjn of Mental Health Research; These
studies should demonstrate v;hether alterations in the functional
effects of drugs that occur with advancing age are due to an altered
sensitivity of the brain, or to changes in the detoxification
potential of the body. The fundamental research should provide
a rational basis for future application of neuropharmacology to
aged persons o

Proposed Course of Projects Studies on the effects of age and
sex on the duration of anesthesia are being extended utilizing
various hypnotic drugs that are chemically dissimilar, are de-
toxified through divergent mechanisms, and v-jhich may exert their
effects on different parts of the central nervous system. In
addition the effect of drugs in modifying behavior in physiological
tests such as hearing will be measured.

Part B included—No

- 1^06 -

Serial No. M-P-A-8

1. Laboratory of Psychology

2. Section on Aging

3. Bethesda

PHS-KIH

Individual Project Report

Calendar Year 1957

Part A.

Project Title; The Effects of Bypoglycemia^ Anoxia, and
Drugs on the Phosphocreatine Content of
Rat Brain in Animals of Different Ages

Principal Investigator; Eugene Streicher

Cooperating Units: Hone

Man Years; Patient Days: None

Total: ,58
Professional: .33
Other: ,2^

Project Description:

Objective; To measure the relative rates of utilization
and synthesis of phosphocreatine by rat brain in vivo as
a function of age in vaxious physiological states.

Methods Engtlcyed; Phosphocreatine wHl be measured as acid
labile phosphate at room temperature in the presence of
mclybdate.

Major Findings: Methods are now being developed to measure
phosphocreatine in the presence of inorganic phosphate and
adenosine triphosphate.

These experiments shoiiLd elucidate the possible differential
effects of age on the relative rate of energy utilization and
production by rat brains to vivoo

Proposed Course of Project: After control values for phospho-
creatine have been established for rats of different ages, the
effects of drugs, anoxia, etc., wiU be ascertained.

Part B included—No.

^07

Serial Mo» M~F-^A-9

1. Laboratory of Psychology

2, Section on Aging

3. Bethesda

PIB-NIH
Individual Project Report
Calendar Year 19^7

Part A,

Project Titles The Effect of Age on the Distribution of Glucose
Between Blood and Brain

Principal Investigator; Eugene Streicher

Other Investigators? None

Cooperating Units: None

I'lan Years s Patient Days: None

Totals s^8
Professionals .33
Others o25

Project Description:

Objectives To determine the effects of age on the movement of
glucose from the blood into the brain and the relationship between
the free glucose level in the brain and the concentration of
glucose~6-phosphate in that organ.

Methods Employe ds "True" blood and brain glucose levels will be
measured by means of glucose oxidase and the Kelson-Somogyl glucose
method. Glucose-6-phosphate will be assayed with glucose-6-phosphate
dehydrogenase .

Major Findings g A method for the extraction of glucose from brain
tissue has been devised for the present investigation and optimal
conditions for the measurement of glucose with glucose oxidase have
been established.

Significance to the Program of i^^ental Health Researchs Glucose is^
the"main substrate of brain from which energy is derived for functional
activity. However, the level of free glucose in the brain is ex-
ceptionally low, i.e., about 8 mgra.^ in rats, suggesting that the
metabolism of parts of the brain may be regulated by the ambient
glucose supply. By employing animals of different ages subjected to
various physiological conditions factors governing the transport of
glucose into the brain from the blood may be studied. Also the

408

Serial No. M-F°A-9, Page 2

Fa.rt A. Project Description Continued

Significance to the I^o^rara of Ilen^.^J, Health Research Continued;
relationship between brain glucose and ^ucose-6-phosphate should
yield inforraation on the kinetics of brain hexolcLnase activity
in vivo and on the "permeability" of brain cells to glucose under
different physiological conditions. It has been suggested that
the mild form of diabetes often associated with aging is a
horaeostatic response to a decreased permeability of the brain to
glucose.

Proposed Course of Projects After normal values for blood glucose,
brain glucose and glucose-6-phosphate have been established, the
effects of hypoglycemia and hyperglycemia will be ascertained.

Part B included— Ko.

- ^4-09 -

Serial No» M-P~A^10

1, Laboratory of Psychology

2 . Section on Aging
3» Bethesda

PHS-I\fIH
Individual Project Report
Calendar Year 19^7

Part A»

Project Title; Components of Cellular Structure as a Function
of Age

Principal Investigator: Joel Garbus

Other Investigators ; None

Cooperating Units: None

Man Years: Patient Days: Hone

Total: s58
Professional: ,33
Other: .-25

Project Jescription:

Ob j so cive : To determine if there are quantitative and qualitative
variations with age in certain chemical components of cellular
structure and in their biochemical activity in the nervous system.

Methods r^mpluyed: opectrophotomotric, colorimetric, chromagjraphic
and electrophoretic methods for specific components will be employed.
Tracer equipment, currently installed in the laboratory, utilising
radioactive isotopes may be usedc Nervous tissue will be excised
from rats of the colony of the Section on Aging »

Major Findings: Specific, sensitive colorimetric methods have been
developed for the extraction and estimation of the nucleic acids in
nervous tissues. Modifications have been made in the Kjeldahl
nitrogen method to provide a rapid estimation of nitrogen in small
amount of nervou.s tissue*

Using these methods, values are being established for the
nucleic acid and nitrogen content of viiole brain and cellular par-
ticulate preparation from norraal, adult rats. These values will
be used as a basis for comparison with tissues from senescent animals,

iHO

Serial No. M-P-A-10, Page 2

Part A.- Project Description Continued

Si^i^-nificance to the Program of Mental Health Research? One of the
difficult problems of biological research in gerontology is to determine
whether the changes observed in the functioning of nei^ous tissue are
due to alterations in the quantities or of various components to their
changed biochemical activity* These investigations should provide
some answers to this problem.

Proposed Course of Projects Determinations will be extended to
senescent animals . In addition, methods for other components may
be developed and employed.

Part B included--Ko

411

Serial No. M-P=.A-11

lo Laboratory of Psychology
2o Section on Aging
3« Bethesda

PHS-MH
Individual Project Report
Calendar Year 1957

Part A.

Project Titles Preparation of a Handbook of the Behavioral Aspects
of Aging

Principal Investigators James E. Birren

Other Investigators: Jack Botwinick, William Bondareff, Edward Jerome,

Harry Kay, and Alfred Weiss

Cooperating Units : None

Man Years s Patient Days; None

Totals 2

Professional: 1.50
Others ,50

Project Descriptions

Objective g The purpose of this project is to organize existing
scientific and professional Imowledge about the behavioral aspects
of aging. The material in.ll be published -in the form of a handbook
which would represent an authoritative technical summary siiitable for
use by graduate students and professional persons.

Method Sraployadg The principal investigator vjill edit the volume
and individual members of the Section will prepare selected chapters.
There will be in addition approximately I8 chapters prepared by non-
Federal employees « Organization of this project is done in collaboration
with the University of Michigan (Project 3M-9118),

Major Findings g A suggested chapter outline was prepared by the editor
and circulated to invited authors, who prepared more detailed outlines.
These author outlines v;ere exchanged among the authors to reduce over-
lapping material.,

Significance to the Program of Mental Health Researchs Problems of older
persons are receiving increasing attention. The natirre and scope of these
problems involves basic biological and psychological changes as well as
social circumstances. If rational methods of meeting mental health problems
of older persons are to be advanced, it is necessarj'" to talce initial steps
such as the present one which is to prepare a basic collection of facts

;'-12 =

Serial Noo M-P-A-11, Page 2

Part A« Project Description Continued

Significance to the Prograjn of Mental Health Ressarch Continued;
and interpretations of existing data. It is expected that the
availability of this handbook will have an impact not only on
training but also on current mental health concepts and practices.

Proposed Course of Projects Authors are now in the process of
reviewing the literature and preparing their chapters. The current
deadline for initial chapter drafts is February 1, 1958. Final
manuscripts should be received by June 1958 • The volume should be
finished for submission to the printer by December 1958 o

Part B included— 'No <

^ i^l3

Serial No, M-P-A-12

1. Laboratory of Psychology

2. Section on Aging

3. Bethesda

PH5-NIH
Individual Project Report
Calendar Year 195?

Part A,

Project Titles Electrophysiologic Correlates of Sensation and
Perception

Principal Investigators: Alfred D. Weiss, and Robert Cohn

Other Investigators : None

Cooperating Units: National Kaval Medical Center, Department of

Electroencephalography

Man Tears : Patient Days : None

Total: e75
Professional: ^2$
Others o50

Pro.ject Description:

Objective? To find electrophysiologic correlates of sensation
and perception, using aging as the raajor variable Xirhen feasible.

Methods Employed; Microelectrodes were inserted into the retina
and optic tract of a curarized cat, and white and color-filtered
lights viere flashed into the eye. Records vjere obtained at steady
state (flashes about every 3 seconds over a prolonged period) and
during dark adaptationo

Major Findings; Results are now being analyzed*

Si^.r-ificance to the Program of Mental Health Research; Information
obtained through such experiments will help to elucidate the re-
lationships between certain aspects of behavior and certain functions
of the central nervous systemo

Proposed Course of the Project; Operant conditioning techniques are
now being devised to permit psychophysical and perceptual measurements
on rats of various ageso Chronic microelectrode implantations for the
recording of electrophysiologic correlates of psychologically determined
differences will then be undertalcen«

Part 3 included—No o

- 414 -

NATIONAL INSTITUTE OF MENTAL HEALTH

Basic Research
Laboratory of Psychology-
Section on Animal Behavior

BUDGET SHEET

Totals $184,652
Direct J $108,873

Reimbursements s $759 779

Projects included! M-P-B 1 through M-P-B 9

Serial Wo. M-P-B-1

lo Laboratory of Psychology
2o Section on Animal Behavior
PHS-HIH 3. Location - Bethesda
Individual Project Report
Calendar Year 1957

Part Ao

Project Title: The analysis of the relationship between emotional

behavior and certain cortical and subcortical
structures in the subhuman primate brain.

Principal Investigator; H. Enger Rosvold

Other Investigators: None

Cooperating Units: None

Man Years: Patient Days

Total: 2 Total: None

Professional: l/2
Other: 1 5/8

(1/3 NIMH Fellow in addition

Project Description:

Project: To identify the emotional behavior which is subserved
by various brain structures.

Objectives; To demonstrate in standard behavioral situations

which elicit emotional approach and avoidance
behavior the effects of electrically stimul.ating or ablating
structures in brains of monkeys and chimpanzees.

Methods Employed; Animals are trained in special situations

designed to elicit certain types of emotion-
al behavior, following which various brain structures are elec-
trically stimulated or destroyed. Sexual activity and condi-
tioned fear, exemplifying emotional approach and avoidance
behavior, respectively, will be the principal behaviors ob-
served. The amygdala, hippocaurpus, axsd central gray will be
the principal structures stimulated or ablated.

Major Findings: Funds and personnel have been insufficient to
pursue this aspect of the program as actively
as was anticipated. Consequently, construction of the equip-
ment necessary for conditioned avoidance studies has not been
completed. However, three pairs of animals have been tested
preparatory to a sex-behavior study, the piirpose of which is
to explore the effect on such behavior of psychopharmacologi-
cal dnigs and brain lesions. It is anticipated that the physio-
logical manipulations will start soon.

Significance to Mental Health Research: A careful description

of the relationships
between the brain and emotional behavior is fundamental to an
understanding of ment^ health and disease.

- ^15 =.

Serial Ho. M-P-B-1 Page 2

Fart A. Project Description Continued

Proposed Course of Project; Various brain structures will be

systematically ablated or stimu-
lated and various drugs will be administered in conjunction
with systematic observations of emotional behavior.,

Part B included Yes No _X_

Serial No. M-P-B-2

1. Laboratory of Psychology

2, Section on Animal Behavior
PHS-niH 3. Bethesda

Individual Project Report
Calendar Year 1957

Part A.

Project Title: The analysis of the relationships between problem-
solving behavior as demonstrated in the delayed
response and discrimination tasks and certain cortical and sub-
cortical structures in the subhuman primate brain.

Principal Investigator: H. Enger Rosvold

Other Investigators: None

Cooperating Units: None

Man Years: Patient Days:

Total: 2 Total: None

Professional: l/2
Other: 1 l/2

(1/3 NIMH Fellow 1 Research Associate in addition)

Project Description:

Project: To identify the brain structures that are essential for
delayed- response types of functions and to describe the
changes in this behavior which follow lesions in these structvires.

Objectives: To determine the cerebral organization subserving

problem- solving behavior and to describe the nature
of the behavioral dysfunction which follows damage to this or-
ganization.

Methods Employed: (l) Chimpanzees. Chimpanzees are trained on

a variety of delayed-response tasks, operated
in the prefrontal lobes, retested and sacrificed.

(2) Monkeys. Lesions are placed in those
subcortical structures which have been shown to be important for
delayed-response-type functions. The animal's performance is
compared with that of monkeys and chimpanzees which have lesions
in the prefrontal lobes. The animals are tested on a variety of
tasks intended to specify the nature of the deficit which they in-
cur. Automc.tic testing devices which will enable a much more
thoroioghgoing analysis of this behavior are being developed.

Major Findings: (l) Chimpanzees. In additional animals it has
been confirmed that, as in monkeys, the perform-
ance of the chimpanzees on delayed-response-type problems is

kl •:

Serial No» M-P-B-2 Page 2

Fart A. Major Findings Continued

is Impaired following damage to the prefronteuL lobes » Unlike
monkeys, hovever, they recover from the effects of the damage
and after considerable retraining approach their preoperative
level of performance. These findings provide a possible ex-
plajiation for the apparent differences in the effects of
frontal lesions in monkeys and man, viz; a more highly de-
veloped brain of man or chimp, the effect of damage to a
particular area may be less than in the more primitive brain.

(2) Monkeys o It has been confirmed that
lesions in the head of the caudate nucleus have effects on
delayed- response-type functions similar to those of frontal
lobe lesions o It has been found in addition that damage to
other subcortical structures, specifically those related to
the hippocampal formation, may have a similar effect. Auto-
matic testing devices have now been developed which will
make it possible to coH5)are directly animals with lesions in
one or the other of these apparently related structures £ind
to study in considerably more detail the role that each of
these structiores plays in problem- solving behavior.

Significance to Mental Health Research; A careful descrip-
tion of the rela-
tionships between the brain and problem- solving beliavior is
fundamental to an understanding of those processes which
limit or reduce intellectual capacity, i.e. mental defici-
ency, brain in,jury, brain disease, etc. IThat part of the
study dealing with chimpanzees suggests that rather severe
damage can be inflicted on the frontal lobes without per-
manently Impairing problem- solving behavior. That part of
the study involving monkeys points up the iurportance of
deep-lying subcortical structures in intellectual types of
behavior. This latter point has generally been neglected
in considering the causes of impaired Intelligence.

Proposed Gourse of the Project; (l) To explore In addi-
tional chimpanzees the
effects of frontal lesions on other types of tests. (2)
To specify more exactly the subcortical structiires Involved
in problem- solving tasks, and where possible to specify the
relationships between these structures. (3) To compare the
effects of lesions In these structures on problem- solving
and other types of tasks designed to make explicit the na-
ture of the deficit following such lesions. This will in-
volve primarily the acquiring of automatic testing devices
and adapting them for use In. these problems.

Part B Included Yes X No

418

Serial No. M-P-B-2> Page 3.

PHS-NIH
IndividviaJ. Project Report
Calendar Year 1957

Part B; Honors, Awards, and Publications

Publications other than abstracts from this project:

Rosvold, H. Eo, Mishkin, M., Szwarcbart, M. K. Effects of sub-
cortical lesions in monkeys on visual discrimination and single
alternation performance. J. comp. physiol. Psychol. In press.

Mishkin, M. Effects of small frontal lesions on delayed alterna-
tion in monkeys. J. Ne\irophysiol . In press.

Honors and Awards relating to this project:

- 14-19

Serial No, M-P-B-3

1, laboratory of Psychology
2o Section, on Animal Behavior
PHS-WIE 3o Bethesda
Individiial Project Report
Calendar Year I957

Part A.

Project Title: The effects of brain lesions and immediate post-
operative experience on dominance behavior in
primates.

Principal Investigator; Allan F. Mirsky
Other Investigators; None
Cooperating Unitss None

Man Years: Patient Days;

Total: 5/6 Total: None

Professional: 1/3
Other: I/2

Project Description:

'Project t The effects of brain lesions and ibnmediate postoperative
escperience on dominance behavior in primates.

Objectives; There are two main objectives in this project: (A)

To compare the effects of frontal and temporal lesions
on social behavior in monkeys and chimpansees. (B) To modify in
predicted directions the dominaD.ce behavior of monkeys with temporal
lobe lesions.

Methods Employed; Groups of monkeys anddiisipanzees are studied

carefully before and after selected members of
such groups are subjected to surgical or stereotaxic electrolytic
lesions. In some studies the monkeys are given immediate post-
operative escperience designed to make them either fall or rise in
dominance .

Major Findings; To date, two chimpanzee colonies have been studied.

One member of each, of these three-aniaml colonies
has been subjected to either a bilateral prefrontal lobotomy, a bi-
lateral anterior temporal lesion or a bilateral ventral temporal
lesion. The temporal lesions appear to have had little, if any,
consistent effect on dominance. The frontal lesions, on the other
hand, produced a marked, although temporary, decrease in dominance
in both animals. The findings in the chimpanzee groups stand in
sharp contrast to the results of similar investigations conducted
in monkeys; dominance in chiarpanzee groups, as measured by food-
getting, is considerably more variable than that found in monkey

^^20 -

Serial Koo M-P-B-3 Page 2

Part A. Major Findings Continued

groups; the anterior temporal-lobe lesions that usually produce
marked changes in dominance behavior in monkeys are apparently
without effect in chimpanzees; the frontal, lesions which usiml-
ly produce increased dominance in monkeys appear to have an ef-
fect in the opposite direction in chimpanzees.

With respect to dominance behavior in monkeys with temporal
lobe lesions, the following are the major findings to date:
Nine colonies have been studied, and the behavior of those
animals whose postoperative behavior has been manipulated
conforms fairly well to predictions, i.e., ajiimals with amyg-
dala lesions that are placed in a postoperative environment
designed to maximize their dominance do not fall in dominance
and may even rise in dominance when returned to their original
groups. In a corallary investigation it was found that bi-
lateral stereotaxic ablations in the hippocampus are without
effect on dominance behavior in monkeys. This suggests that
the behavioral consequences of amygdala and hippocauipal abla-
tions may be quite different, despite the fact that anatomi-
cally and physiologically these two structures are closely re-
lated »

Significance to Mental Health Research; This project should

provide more informa-
tion about the relationship between brain function and social
behavior in several primate species. Experimental evidence
has already been provided that the effects of a brain lesion
on social behavior cannot be evaluated independently of the to-
tal social situation of whicJi the subject is a part.

Proposed Course of Project: Another three-animal chimpanzee

group is under study at the present
time. Eventually, two of these animals will receive bilateral
frontal lesions; if the finding of the first chimpanzee study is
reliable, both animals should exhibit some postoperative depres-
sion in dominance. Unfortunately, the monkey dominance studies
must be curtailed until additional funds and personnel are made
available to the Section.

Part B included Yes X Wo

il-21

Serial Ho. M-F-B-3. Page 3

PHS-NIH
Individual Project Report
Calendar Year 1957

Part B: Honors, Awards, and Publications

Publications other than abstracts from this project:

Fuller, J. L., Rosvold, H. E, and Pribram, K. H. The effect on af-
fective and cognitive behavior in the dog of lesions of the pyriform-
amygdala-hippocampal complex. J. comp. physiol. Psychol. , 1957;. 1^
89-96.

Mirsky, A. F., Rosvold, H. E. ajid Pribram, K. H. Effects of cingu-
lectomy on social behavior in monkeys. J. neurophysiol . In press.

Rosvold, H. E. Evalioation of the effects of pharmacological agents on
social behavior. In publication of the Conference on Eveiluation of
Pharmacotherapy in Mental Illness. In press.

i|-22

Serial Noo M-P-B-if

lo Laboratory of Psychology
2. Section on Animal Behavior
PHS-HIH 3 o Bethesds

ladivldual Project Report
Calendar Year 1957

Pari; A.

Project Title; Further analysis of the Continuous-Performance
technique ae a research tool and diagnostic de-
vice in assessing the effects of drugs and brain pathologyo

Principal Investigators Allma F= Mirsky

Other Investigators; None

Cooperating Units; Walter Seed (AKMC), Neurological Surgery NIHDB,

Clinical Science

Man Years; Ratient Days;

Total; 1 1/3 Total; 1^00

Professional; l/3
Other; 1

Project Description;

Project; Further analysis of the Continuous- Performance technique
(CoPoTo) as a research tool and dieignostic device in as-
sessisag the effects of drugs and brain pathology-.

The objectives of this project include three related
areas of investigation; (l) To assess the effects
of various types of brain pathology on functions measiired by the
CoPoTo (2) To investigate the effects of drugs on the CoP.T., so
as to gain information relative to the functions and brain locus
or loci tapped by the CoPof o (3) To explore the usefulness of
the CoPoTo as a diagnostic device.

Individuals with brain pathology and normal and
pathological controls are tested under various

conditions., inclxading drugs, on the GoPoT, and other standard

measures of intellectual functioning o

Major Findings; In the research conducted to date, several groups

of individuals have been studied » These include
approximately 150 patients from the Surgical Neurology Branch,
NINDB (involving 400 patient hours) and approximately 100 normal
volunteer controls (involving 550 subject hours). The major find-
ings may be summarized as follows;

423

Serial No. M-P--:B-1;I- Page
Part A. Ma.jor Findings Continued

C^PoTo apparently can distinguish reliably between pa-
tients with presumed subcortical pathology and those with focal
cortical pathology 0 The 'subcortical' group appears to be im-
paired on this test, even after statistical control of related
variables such as loQ., age, frequency of seizures, duration
of illness, and degree of EpEoG» abnormalityo These findings
were gathered on jS patients selected on the basis of more or
less clear-cut cortical or subcortical pathology.

0. Approx;Lmately 30 patients have been tested with the C.P.T.
before and after unilateral cortical resections » These remov-
als seem to have no effect on CoP.To performance »

Co The effects of a nvmber of centrally- acting drugs on the
CoPoTo have been measured, using normal controls sind a email
group of schizophrenics. These studies have been conducted on
patients made available by the Laboratory of Clinical Science «
Meprobamate (Milt own) as well as elalorpromazine produces im-
pairment on the CoPoTo, although the magnitude of the effect
produced by meprobamate is much less than that produced by
chlorpromazineo Other centrally- acting drugs, including LoS.Do,
meperidine, secobarbital, phenobarbital, and d-amphetejnine are
without effect on the C.P«T. In a group of 1-^ schizophrenic
patients studied at HE, there was a great range in performance
and a curious finding of no significant impaijment produced by
ehlorpromazine o

Do A group of 36 normal-aged patients were tested on the G„PoTo
As was the ease with other psychological tests given to this
population., there was a marked spread in perl'orsnance, from those
who perform as well as yoimg normal patients to those who appear
as ijoipaired as some of the brain-damaged population o Comparison
of CoPoTo scores with the tests given these individuals by other
investigators reveals significant correlation with tests of re-
action time, line difference limen and the Wechsler Adult Intel-
ligence Scale subtests of arithmetic and digit-symbol substitu-
tiono These significant correlations are compatible with the
conception that the test is a measure of 'attention' » The fact
that none of these correlations accounts for ro.ore than 25^ of
the observed variance, however, suggests that the CoPoTo is
measioz-ing something not tapped by the other testso

Significance to Mental Health Research; The information gathered

to date on the effects
of centrally-acting drvigs, brain-damaged patients, and sleep-
deprivation (in studies done at Walter Reed Army Medical Center)

stiggests that the CPoTo^ as might be eacpected in the case of all
tests involving attention^, is particularly sensitive to altera-
tion in the functioning of mid -brain subcortical structures »

k2i^

Serial No. M-P.^B-4 Page 3
^rt_A. Significance to Mental Health Research Continued

Application of this technique to various pathological groups may
help to elucidate the role and/or importance of subcortical inter-
ference in such disease entities as epilepsy and, possibly, various
psychopathological conditions in which the influence of brain dam-
age is not well understood.

Proposed Course of Project; Epileptic and other neurological pa-
tients will be tested with the C.P.To
and other procedures before and after brain surgery, in an attempt
to replicate the findings previously obtained with this population „
A study is currently in progress on the effects of other centrally-
acting drugs including alcohol, benzactyzine and d-amphetainine . A
particular question being investigated concerns whether the stimu-
lant, d- amphetamine, can reverse the deleterious effects on the
CP.T. produced by 72 hours of sleep deprivation. When the facili-
ties and positions at St. Elizabeth's Hospital become available,
effort will be made to investigate systematically in psychotic pa-
tients the effects of the centrally-acting drugs previously studied
in normal individuals. The performance of schizophrenics vmder
chlorpromazine will be of particular interest, in view of the pre-
liminary finding obtained at MIH.

Part B included Yes X Wo

- ^25 -

Serial No. M-P-B-4. page h.

PHS-NIH
Individxial Project Report
Calendar Year 1957

Part B; Honors, Awards, and Publications

Publications other than abstracts from this project:

Primac, D. W., Mirslcy, A. F. and Rosvold, H. E. Effects of centrally-
acting drugs on two tests of brain damage. A.M. A. Arch. Heurol. and
Psychiat., 1957, 77, 328-332.

Mirsky, A. F., Primac, D. and Batep, R« The effect of chlorpromazine
on the continuous performance test. J. Pharmacol, exp. Therapeut.
In press.

Honors and Awards relating to this project:

kz6

Serial Wo. M-P-B-5

lo Laboratory of Psychology
2o Section on Animal Behavior
PHS-NIH 3. Bethesda
Individual Project Report
Calendar Year 1957

Part A.

Project Title: Defining an extrageniculostriate system in vision

Principal Investigator: Mortimer Mishkin

Other Investigator: None

Cooperating Units: None

Man Years: Patient Days:

Total: 11/3 Total: None

Pi-ofessional: I/3
Other: 1

(1/3 NIMH Fellow in addition)

Project Description:

Project: The nexiral components of an extrageniculostriate sys-
tem in vision.

Objectives: Evidence of severe visual impairment following damage

to inferotemporal neocortex in monkeys suggests that
the inferotemporal region and the primary visual system are close-
ly related. How they might be related is not known. The possi-
bility that either the prestriate cortex, the pulvinar^ or the
superior colliculus serves as the essential relay station between
the primary visueil system and inferotemporal cortex has been ten-
tatively eliminated by previous work. Other possibilities, cur-
rently being tested,, are that (l) the three foregoing structures
serve as alternate relay stations such that any one may serve the
relay fimctions of the others or (2) temporal cortex and primary
visual cortex are linked directly by long association tracts.

Methods Employed; Monkeys are subjected to combined destruction

of (1) prestriate cortex, piilvinar and collicu-
lus or (2) ttnilateral temporal cortex, contralateral occipital
cortex, and corpus callosum. The attempt in both experiments is
to isolate intact temporal cortex from intact occipital cortex.
GThe operated animals are then tested on visual tasks known to
measure reliably the effects of bilateral inferotemporal or bi-
lateral lateral occipital (maciilar projection) lesions.

Major Findings: (l) Combined electrolytic destruction of the
pulvinar and colliculis has been accomplished
by directing the electrode into these nuclei at an oblique angle.

kz7

Serial No. M-P-B-5 Page 2

Part A. Major Findings Continued

(Use of the sinrpler vertical approach resulted in severe sub-
cortical vascular lesions from which several animals never ful-
ly recovered.) Thus far the effects of combined pulvinar and
collicular lesions on visvially- guided behavior appear to be neg-
ligible. The next step^ i.e., destruction of these nuclei in
combination with removal of the pre striate cortex, will soon be
attenipted .

(2) Animals with the second combination of lesions
are now being tested and appear to be markedly impaired.

Significance to Mentsil Health Research; Vision is perhaps the

best understood of
the sensory modalities in relation to the functioning of the
nervous system. Yet a major problem remains unsolved in vision
as it does in all sensory modalities: Delineation of the events
which intervene between stimvilus reception at the cortex and the
observed response. The demonstration that damage to the inferi-
or convexity of the temporal lobes in monkeys produces impair-
ment in visixally- guided behavior has opened up the hitherto in-
accessible area of the intracerebral processes in vision, i.e.,
neural activity related to vision but beyond the level of the
striate cortex. Unravelling these mechanisms in vision shotild
aid greatly in the solution of a general problem for psychology,
viz., accounting for the intervening neural, processes (thought
and its breakdown) in normal and abnormal behavior.

Proposed Course of Project; The two experiments outlined above

will be continued to completion.
For the first experiment this involves adding prestriate lesions
to the subcortical damage; for the second, it involves replicat-
ing the original group of experimental animals and their various
operated controls.

Part B included Yes X Wo

i^28

Serial No. M-P-B-^, Page 3

PHS-NIH
Individual Project Report
Calendar Year 1957

Part B: Honors, Awards, and Publications

Publications other than abstracts from this project:

Mishliin, M. and Weiskrantz, W. Effects of delaying reward on visual
discrimination in monlceys with frontal lesions. J. Comp. Physiol.
Psychol . In press.

Honors and Awards relating to this project:

- 429 -

Serial No. M-P-B-6

1. Laboratory of Psychology

2, Section on Animal Behavior
PHS-NIH 3. Bethesda

Individual Project Report
Calendar Year 1957

Part A«

Project Title: A comparative study in primates on the effects of
temporal lobe damage on visually guided behavior »

Principal Investigator: Mortimer Mishkin

Other Investigators: None

Cooperating Units: None

Man Years: Patient Days:

Total: 5/6 Total: 200

Professional: I/3
Other: l/2

Project Description:

Project; Effects of temporal lobe damage on visually guided be-
havior in monkeys, chimpanzees, and man.

Objectives: Damage to the neocortex of the temporal lobes pro-
duces impairment in visually- guided behavior both
in monkeys and baboons. This project attempts to determine
whether similar impairment may be produced by temporal-lobe
damage in the chimpajizee and in man.

Methods Employed: (l) Chimpanzees are trained on a variety of

visvial tasks (similar to those used with monkeys
and baboons) before operation, after unilateral temporal neocorti-
cal damage, and after bilateral damage. Uhoperated chimpanzees
as well as chimpanzees with different cerebral lesions serve as
controls.

(2) Hvmian subjects with focal temporal-lobe
epilepsy are tested on a difficiolt visual discrimination task
(analogous to the simpler tasks used with animals) before opera-
tion and/or after unilateral temporal-lobe surgery for relief
of epilepsy. Patients with non-teniporal-lobe epilepsy and non-
teraporal-lobe surgery serve as controls.

Major Findings: (l) Chimpanzees that were unaffected by uni-
lateral damage have shown visual impairment
following bilateral damage. Since control animals with bi-
lateral damage to allocortlcal structures of the temporal lobes

430

Serial No. M-P-B-6 Page 2

Part Ao Major Findings Continued

have remained relatively unimpaired, it appears that the visual
impairment is selectively related, as it is in monkeys, to
lesions in the neocortical region o

(2) On the basis of data gathered so far, patients
with temporal-lobe epilepsy, with or without unilateral temporal-
lobe surgery, have shown no deficit as compared with controls on
the visual task.

Significance to Mental Health Research: The assumption underly-
ing neuropsychological
experiments conducted on animals, particiilarly rhesus monkeys,
is that any brain-behavior relationship there discovered will
contribute to an understanding of normal and pathological brain
function in man. This assximption has been amply supported by
comparative data on the fvinctions of sensory and motor cortex.
Now, reliable data are becoming available concerning the func-
tions served in monkeys by "association cortex". This project
attempts to apply these recent findings to aid the study of
"association- cortex" functions in man. The chimpanzee, which
may be considered to lie intermediate to man and monkey, both
from an anatomical and a behavioral standpoint, serves as an
experimental bridge in this comparative study.

Proposed Course of Project; (l) Additional operated eind vm-
operated control animals will be added to the chimpanzee study
and additional behavioral data will be gathered on the ejcperi-
mental sinimals in an attempt to define more precisely the ex-
tent and the nature of their visual impairment.

(2) The results of the chimpanzee
study suggests that the difficulty in demonstrating visual dis-
turbance in patients with temporal-lobe damage is due to the
fact that such damage is rarely if ever bilaterail and symmetri-
cal. Recent work with monkeys, however, suggests that visvial
impairment after unilateral temporal lesions might be detected
if vision is confined to the field opposite the injury. On
this hypothesis an experiment has been set up to compare ta-
chistoscopic recognition in the left and right visual fields
in patients with left or right -temporal-lobe removals.

Part B included Yes No X

^31

Serial No. M-P-B-7

1. Le.boratoi-y of Psychology

2. Section on Animal Behavior
PHS-NIH 3. Bethesda

Individual Project Report
Calendar Year 1957

Part A.

Project Title: Histological Analysis of Brain lesions in
Primates

Principal Investigator: Maria K. Szwarcbart

Other Investigators: Kono

Cooperating Unite: None

Man Yc3,rs: Patient Days:

Total: 1 1/2 Total: None

Professional: 1
Other; l/2

Project Descrixrbion:

Project: (l) Analysis of the lesions which had been placed in
monkeys and chimpanzees.

(2) Tracing caudate -frontal connections.

Objectives: The objective of the first part of this project has
been to define the locus and extent of the different
lesions that have produced similar deficits in the behavioral
studies and of the second, to determine whether any anatomical
relationship exists between the head of the caudate nucleus and
cortex of the frontal lobes.

Methods -'anployed: Sixty-nine brains have been fixed in celloidin

" "■""' ■ or paraffin, sectioned, prepared with several
stains, and examined microscopically. Hie results of these ex-
aminations have been translated into graphic representation by
means of cemera lucida drawings. In the second project, the
brains of several monkeys with selective frontal lesions have
been especially prepared to determine whether such lesions pro-
duce anterograde degeneration of fibers leading to the caudate
nucleus and/or loss of cells in this nucleus.

Major Findings: In the first project it has been verified that

lesions restricted to the head of the caudate
nucleus result in deficits similar to those following damage to
frontal cortex, (it is this finding which gave rise to the second

^62

Serial No= M-P-B-7 Page 2

Part A, Major Findings Continued

project,) The anatomical analysis has suggested further^ that
damage to other subcortical structiires, e.go, the Ammonic Tract
of Cajal^ may also produce 'frontal-lobe signs'. On the other
hand^ these structures and others such as the superior collicu-
lus and medial pulvinar have been eliminated in the search for
areas related to temporal- cortex functions. The second project
is not far enough along to have any definitive findings.

Significance to Mental Health Research: Information on the in-
terrelationships among
various brain structixres is essential if normal and abnormal be-
havior are to be understood in terms of brain mechanisms and
their breakdo-vm. A systematic search for the different struc-
tures which serve similar behavioral functions^ and the search
for connections between these structures should help provide
some of the needed information.

Proposed Course of Project: (l) Tlie analysis of lesions which

provide temporal and frontal -lobe
symptoms will continue. Lesions designed to produce emotional
changes similar to those produced by amygdalectomy will be added
to the study.

(2) In addition to the study of
anatomical connections between frontal cortex and the caudate
nucleus (and other structures which appear to be related to
frontal cortical f\inctions), an exploration for possible di-
rect connections between the temporal lobe and the visual system
will soon be initiated.

Part B Included Yes No X

, /J.33

Serial Mo« M-,P-B-8

lo Laboratory of Psychology
2o Section on Animal Behavior
PHS-ima 3o Bethesda
Individual Project Report
Ca3.endar Year 1957

Part A.

Project Title: Electroencephalographic correlates of sustained
attentive behavior in man.,

Principal Investigator; Allan F. Mirsky

Other Investigators; None

Cooperating Units: Neurological Surgery NIITOB

Man Years; Patient Days;

Total: 5/6 Total; 15

Professional; 1/3
Other; l/2

Project Description;

Project; Electroencephalographic correlates of sustained at-
tentive behavior in mano

Objectives; This st-udy is concerned with the relation between the

EoEoGo and behavior on tasks requiring sustained at-
tentiveness or vigilance during periods of time of varying length.
Both brain- damaged and normal inviduals will be studied; in the
brain-damaged popiilationj behavior concomitant with hyper synchron-
ous discharges in the EoEX will be of particular interest; with
the normal subjects, the interest will be rather in behavior at-
tended by alpha suppression or E.EoG» 'activation' »

Methods; Electroencephalograms and behavior of a continuous na-
ture will be recorded simultaneously., Great flexibility
in the nature of the task is afforded by means of a new projection
instrument which permits stimulus duration to be varied almost
continuously between intervals of 10 milliseconds and 10 seconds
and interstimulus duration to be varied from 100 milliseconds to
10 seconds o In addition^ the new device makes possible the pre-
sentation of continuously presented auditory stimuli, and pos-
sesses a number of features which facilitate the study of learn-
ing and motivational f actoi 3 in this performance.

Major Findings; The instrument was delivered in September, 1957°
Th,e work with it to date indicates that it meets
specifications and shoiild prove useful in investigating the prob-
lems for which it was de signed =

Serial Hoo M-P-B~8 Page 2

Part Ac Project Description Continued

Significance to Mental Health Research; This research should

provide Information
about the relationship between brain function, as measured with
the EoEoGo, and vigilant or attentive behavior o All information
relating brain functioning to behavior contributes significantly
to ovir understanding of those diseases which affect the behavior
of mano

Proposed Coxirse of Project; Hormal aaid brain-damaged individuals

will be studied with this technique
and the records that are obtained will be carefully anal.yzed, to
ascertain the relationship between electroencephalographic phen-
omena and sustained attentiono Some subjects with implanted
electrodes being studied by the Surgical Neurology Branch for
other purposes will also be used.

Part B included Yes No

Serial No. M-P-B-9

lo Laboratory of Psychology
2o Section on Animal Behavior
PHS-NIH 3« Eethesda
Individual Project Report
Calendar Year 1957

Part Ao

Frojeet Title: Electrical activity in temporal cortex dijring
visual-discrimination learning and performsmce

Principal Investigators Mortimer Mishkin

Other Investigators: None

Cooperating Units: None

Man Years: Patient Days;

Total: 1/3 Total: Kone

Pr-ofessional: I/3
Other: 0

Project Description:

Project: • Correlation of electrical activity in temporal cortex

mth learning sjad performance on visual discriminations »

Objeetives; Dsmage to Inferoteaiporal neoeorteac in isonkeys impairs

their visual-discrimination learning and retention «
The purpose of this project is to determine whether or not similar
impainrtent can be produced by electrical stimulation of the temporal
cortex and also whether or not visual. -discrimination learning is ac=
coarpanied by changes in the electrical activity of thisJBgiono

Methods Ejbiployed; Siuxface electrodes are permsmently implanted in

the inferotemporal region c Animal, s are then
trained to discrnmins^te vi.s»jaJ. stim,uli that are escposed brief,ly
by a taehistoscopic projector <, Autosiofltic prQgr.ffirmB,ing permits syn-
chronisation of the s'bimxilug e,xposures with electrical stimulation
or reeording thi'ough the implaxited electrode s.

jor Findings: lo escperiment^ai data have been obtained » However
techniques ha.ve been developed for implamting
electrodes and reeording electrical activity dy.ring perfonnance on
a visual tasko In addition^ a tachistoseopic^ single -framing,
strip-film projector has been designed ¥-hich meets all the neces-
sary specifications o Apparatus for automatically programming the
projector^ tr-alnlng the animal and reeording the animal's behavior
has also been designed „

^36

Serial No, M-P-B-9 Page 2

Fart A . Project Description Continued

Significance to Mental Health; Ablation studies in monkeys have

provided evidence that activity
in inferotemporal neocortex may be one link in the chain of in-
tracerebral processes serving vision. A study of the electrical
activity in temporal cortex during performance on visual tasks
should help to delineate the neural events underlying vision »

Proposed Course of Project; The experiments which have been out-
lined must await receipt and assembly
of the equipment which has been de signed o

Part B included Yes No X

^37

NATIONAL INSTITUTE OF MENTAL HEALTH

Basic Research
Laboratory of Psychology-
Section on Perception and Learning

BUDGET SHEET

Esijjaatsi^^ligatj

Totals $104,936
Directs $69 s 895
Reimbursements s

$35,Oifl

Projects included; M-P-L 1 through M-P-L 6

Serial Noo M-P-L-1

lo laboratory of Psychology
2o Section on Perception

and I^eaxning
3 o Bethesda

:' £%c

PBS-KIH
Indlvidiml Project Report
Calendar Year I957

R^-oject Titles Effects of Lysergic Acid Diethylamide (LSD-25) on
Visual Functions-

Principal Investigator; V. R. Carlson

Other Investigators; Eugene Tassone

Cooperatixig Units; Hone

Maa Years Patient Bays

Total; 83 1/3 ^ £00 In-patients

Professional; 33 I/3 ^
Other; Research Assistants 33 l/3^
Secretarial; 16 2/3^

it'oject Descriptions

Objective s LSD-25 produces various temporaiy distortions in vision when
administered to norxaal human subjects c. These distortions are said to be
sindlar in njaay respects to distortions in perceptual processes often
found, in psychotic conditions^ but the effects have been described for the
most part in general subjective terms » The pxjr-pose of this project is to
specify the effects of LSD-25 on visual and perceptual fimctions more pre-
cisely .and quantitatively o During this past year the effort has been to
determine the effects of LSD --25 on pupillary response and to compare them
with effects of ehlorproEazine, secobarbital^ and meperidine »

ifetfaoda Employed; LSD is administered to normal volunteer subjects as
one condition in a relatively long-term schedule of other da°ugs and
pla.cebo without the subject's knowledge of which condition is being ad-
ministered on each particular occasion » The subject performs the same
vi,s\ial -perceptual tasks under control^ placebo, and drug conditions^ and
the results Qxe compared among these three situations »

'US

Serial NOo M-F-L-1^ Fa,ge 2
Part Ao Project Description Sheet Continued

fejor Findings; Studies of the effects of LSD on the absolute visual
threshold have "been conrpletedo The threshold was raised throiighout the
course of dark adaptation by a small but reliable amount^ and the vari-
ability in the threshold values was not increased,, In addition, the
photopic threshold was affected significantly more than the scotopic
threshold^ strongly suggesting a cortical effect of the drug. Halluci-
nogenic effects were not observed in these subjects » Psychotic and
neurotic patients have shown evidence of an elevated visual threshold,
however, so that this effect of LSD may constitute another point of
similarity between the effects of the drug in normal humans and the mani-
festations of more naturally occurring psychological disorder o

Significance to the Program of Mental Health Research; These studies pro-
vide basic data needed to evaluate comjarisons between the effects of LSD-
25 and other psychologically relevant drugs and between the effects of
these drugs and certain psychological manifestations of psychotic con-
ditions o In addition to interest in the psychopharmacological aspects
of LSD itself, however, these studies are oriented toward the more general
problem, of differentiating aspects of perception which may be related to
changes in the general psychological state of the individual frcm those
which may depend jnore directly upon some particular neural function or
structure and are relatively imjervious to diffuse changes in psychological
state o In this context LSD is ■'/iewed as one means of producing experi-
mentJally a change in the general psychological condition of the subject
without causing any specific, circum.scribed neural impairment »

feogosed Course of Project; Data will be obtained on more complex per-
ceptual fianctions involving the integration of contextual cues, such
as occurs in size^-constancy and various visual illusions « yi

included Yes f^ No /"/"

^39

Serial No. M-P-L-1, Page 3

PHS-KIH
Indlvidiial Project Report
Calendar Year 1957

Part B. Honors, Awards, and Publications

Carlson, Virgil Ro Individual pupillary reactions to cert£iin

centrally acting drugs in mano J„ Pharmacol « exptl. Therap» ,
1957 (in press).

Honors and Awards relating to this project; None

440

Serial No., M-P-L-2

1, Laboratory of Psychology
2o Section on Perception

and Learning
So Bethesda

PHS-WIH
Individual Project Report
Calendar Year 1957

Part A.

Project Titles Test of the Satiation Theory of Perception
Principal Investigators Vo Ro Carlson
Other Investigators? Eugene Tassone

Cooperating Units s Hone

Jfen Years Patient Days

Totals 75^ 50 Out-patients

Fi'ofessionals 33 l/3i>
Other; Reseeirch Assistants 33 l/3^
Secretarial s 16 2/3^

Project Descriptions

Objectives The object of this study is to devise a crucial test of
Kohler's Theory of satiation by means of a figural -aftereffect experi-
ment o

Methods Employed s The subject ie first satiated by viewing a "sati-
8 1 fon^ 'stimulus pattern steadily for about one minute = Then he looks
at a test stimuluss and any distortion in the perception of the test
stiniul.us which is induced by the previous satiation is measured as
the "figural, -aftereffect "o

In this study the experimental satiating stimulus
is a moving field of curved lines^ viewed by the subject with ststion-
ary binocular fixation o The control stimulus is a stationary fiedd of

1j1i\

Serial Hoo M-P-L-2> Page 2

Part Ac Bfoject Description Sheet Continued

Methods Employed Continued s curved lines o In both cases the test
stimulus is a single^ stationery line of adjustable cuxvature.
Under these conditions KShler's theory wovild predict a figural-
aftereffect in the control condition but not in the experimental
condition^ whereas a theory such as that of Hebb could account
for figural -aftereffects in both conditions «

Major Findings; Data has been obtained on a number of subjects
but the results have not yet been analyzed ^ The escperiment is a
very difficult one in terms of procedure and in terms of the per-
formance required of the subject o Experience so far,, however,
indicates successful execution of the experiment o

Significance to the Program of Mental Health Research; Two im-
portant psychological theories of normal perception have been
promulgated in recent years ^ that of Kc5hler and of Hebbo In many
respects these two theories sare alternative rather than comple-
mentary, and this experiment provides an in^jortant soxirce of evidence
for deciding between the twoo In order to understand fully the
distortion in perception which is found in mentally deranged patients,
it is necessary to have a sotind theory of the normal processes of
perception..

But aside

from, these general theoretical considerations, the so-called phe-
nomena of "cortical satiation" may prove to be more specifically
important in studying the central nexiral processes underlying
attention ,and short -tena memory <>

Pr'oposed Course of Projects The e2cperiment will be performed with
a. sisfficient niaiiber of subjects for the z'esults to be statistically
reliable o fhen., depending upon the findings, certain additional,
related experiments may be necessa^ in order to develop a clear
intexpretation in terms of perceptual theory »

The findings will be utilized in

designing future experiments oriented toward studying basic
processes of attention and short-term memory in terms of possible
und^erlying neural meehanismso

Part B included s No

ULP _

Serial Noo M-P-L-3

lo laboratory of Psychology
2. Section on Perception

and Learning
3- Bethesda

PHS-WIH
Individvial Project Report
Calendar Year I957

Part A.

Project Titles Electrical Recording of Eyemovements
Principal Investigators V« R» Carlson
Other Investigators s None

Cooperating Units s None

Man Years Patient Days

Totals 33 1/3^ None

Professionals I6 2/3^
Others Secretarial s 16 2/3^

Project Descriptions

Objectives s The aim of this study is to develop a technically
adequate means of recording eyemovements and eye position electri-
callyo

tfethods_ Employed s A corneo -retinal potential of approximately 25
to 500 mjicrovolts is set up by an eyemovement^ the exact value depend-
ing principally upon the magnitude of the eyemovement. This potential
is picked up by electrodes placed on both sides of the eye^ amplified,
and led to a recording unite The recorded values are calibrated with
reference to some zero point in the visual fields and from the cali-
bration one can deteimine where the^e was directed at a given time.

jor Findings s Certain difficulties with the apparatus have not been
resolved^ and thus far it has not been possible to obtain technically
aydequate measvirements.

- li-k^ ^

Serial NOo M-P-L-3> Page 2

Part Ao Project Description Sheet Continued

Significance to the Rrograai of Mental Health Kesearch % Ey emo ve -
ment recording is potentially a valuable tool in measuring perceptixal
variables such as absolute and difference thresholds;, discriminations^
and complex patternings of perceptual response o Research in percep-
tion as it relates to personality maladjustment and mental disorder
is concerned with the interaction between the individual's more or
less unconscious motivations and his perceptions » Hence in majiy ex-
perimental sitioations it is desirable to be able to utilise a per-
ceptual response which is not primarily determined by the subject's
immediate conscious processes « Eyemovement recording may provide a
feasible means of obtaining an indication of what the subject per-
ceives and where and how he directs his attention in aaa appropriate
experimentatl situation^ relatively iminfluenced by his immediate
conscious motivations.

Proposed Course of Projects The problem breaks down logically and
practically into three stages s

lo Work out the technical apparatus problems <> Progress is currently
in this stage o Ta.e necessary items of equipment have been
obtained and integrated into a functional system » The apparatus
is at the present time undergoing a major technical cheeky re-
pair^, and modification in the Instrument Section.

2o Work out the methodology for measuring psychological variables
by means of eyemovement recording »

3o Apply the methodology to specific problems in perceptual-

attentionsul -motivational pro ce s se s »

Part B included s Mo

W4-

Serial Nc U-F-L-k

Ic Ia,boratory of Psychology
2. Section on Perception

and Learning
3o Bethesda

PHS-NIH
Individual Project Report
Calendar Year I957

*£IXw <ft,o

Project Titles Visual Discriminative Processes in the Pigeon,
Principal Investigator: Donald So Blough
Other Investigators; William Jones

Cooperating Units s None

Me.ffl Years Patient Days

Total; 216 2/3io . None

Prof e s sional ; 100^
Others Research Assistants IC
Secretarial? I6 2/3^

Project. DeBcrlptions

Oyecto^ss To continue to develop methods for the study of stimulus
discrlHdnation and generalization in pigeons 1 using these methods to
describe the basic processes involved in stimulus control of behavior.

fethods^_^gmgloyed s Automatic apparatus and procedures developed in
previous years are stiU. in use» Newly developed behavioral techniques
include a method for maintaining a continuous "standing" response,
and a method for the intensive study of stimulus generalization in

single anSamlSo

•^i„i^-— °^^° Freliminaxy results., indicating that a dosage of

"that has no gross behavioral effect on the pigeon raises its

visual ttoeshold substantially,, were confirmedo Curves showing the

'■iU5

Serial Hoo M-P-L-4^ Page 2
Faxt A« I^oject Description Sheet Continued

^jor Findings continued; extent and course of this threshold
elevation were publishedo LSD was again shown to improve perform-
ance in a complex visual discrimination task.

The effects of several drugs on a delayed
discrimination were determinedo There was some indication that chlor-
promazine produced a particular decrement in the birds " ability to
"remember" a discrimination during a delay..

In contrast to the other procedures^
which show decrements following administration of chlorpromazine,
the ability of pigeons to "stand still" for food reward was markedly
increased by this drugo Pentobarbital^ which acts like chlor-
promazine in several other situations^ here produced opposite effects,
reducing the ability to "stand still" <,

Generalization gradients relating response
rate to visual stimulus intensity were determined^ The gradients did
not indicate an effect of stimulus intensity per se, contrary to pre-
valent theoretical notions « Pentobarbital and chlorpromazine had
little or no effect on the gradients,, suggesting that the effects of
these drugs on discrimination is not a result of broadened general-
izationo Other gradients were determined which relate response rate
to visual stimulus wavelength. An analysis of these results is in
progress o

Significance to the Program of tfental Health Research; The overall
aid of the project is to determine in what manner stimuli come to
control "instrnmiental" or "operant" behavior - the sort of behavior
that constitutes most of normal human activity o Maladaptive behavior
may result from (among other things) the loss of certain stimulus
controls, or from the presence of undesirable control » An under-
standing of this topic thus has fundamental importance to the under-
standing of behavior and its disorders.. The project has contributed
to the effort, now undej^ay in many laboratories, to specify the
behai/loraJ. effects of various drugs ^ especially the so-called "tranquil-
izers" o The procedure outlined above in which the pigeon is trained
to "st-and still." may also prove valijable in selecting potential
tranquilizers from among imfaaaillar compounds «

kh6

Serial No. M-P-L-i^-, Page 3

Part A. Project Description Sheet Continued

Proposed Coiurse of Project; During the next year, the broad
exploratory study of drug effects will be curtailed , Drugs will
be used on studies in which the earlier exploration has indicated
that they may have some analytic value- Considerable effort will
be devoted to the problem of relating discrimination and general-
ization.

Part B included; Yes

- m7

Serial Hoo M-P-L-4, Page k

PHS-NIH
Individxoal I^oject Report
Calendar Year I957

Part B, Honors, Awards, and Publications

Blough^ Donald So Effects of drugs on visual discrimination in
the pigeon, Ann. No Yc Acad.. Sclo, 1957, 66, 733-739..

Blough, Donald S, Spectral sensitivity in the pigeon » J, opto
soco Mero, 1957, k-7, 827-853 =

Blough, Donald S. Effect of lysergic acid diethylamide on absolute
visual threshold of the pigeono Science, 1957, 126, 30i<-305o

Blough, Donald So A method for obtaining psychophysical thresholds
from the pigeono Jo exp. analo Behavior (in press) o

Blough, Donald So Effects of drugs on visually controlled behavior
in pigeons o Proco Int., S^;^-. on Psychotropic Drugs (in press )«

Honors and At.?ards relating to the projects None

448 =

Serial No. M-P-L-5

1. Laboratory of Psychology
2« Section on Perception

and Learning
3» Bethesda

PHS-NIH
Individxxal Project Report
Calendar Year I957

Part Ao

Project Title; Individvial Differences in Normal Perceptual Processes.
Principal Investigator: V. R. Carlson
Other Inveatigators ; Eugene Tassone

Cooperating Units: None

Man Years Patient Days

Total: -{% 50 Out-patients

Professionals 2%
Other: Research Assistant: 33 1/3^
Secretarial: I6 2/3^

Project Description:

Objectives : (l) To obtain normal control data for standardizing
procedures and apparatus in the measurement of perceptual variables,
(2) To investigate inter-relationships and consistencies of individxial
differences among basic perceptioal processes and personeility, emotional,
and motivational variables.

Methods Employed; In the various perceptual situations the subject is
required to view a given stimiilus or pattern for a specified amovmt of
time. The stimulus may vary in brightness, orientation, location, con-
figuration, size, shape, or color. He then makes a perceptual judgment

ii^9

Serial Moc M-P-L-^;, Page 2
Part Ao Project Description Sheet Continued

Methods Employed Continued; in one or more of these dimensions with
respect to that or a subsequently presented stimulus « Personality
data is obtained on each subject by means of standardized psycho-
logical tests « Studies in progress at the present time are concerned
primarily with perceptual size -constancy and with several optical
illusions,, In the size -constancy task the subject is required to
match in size a near^ variable stimulus with a far, standard stimulus
under two different instructional setso One instruction (l) requires
a match on the basis of perceptual appearance without regard to act\ial
size^ the other instruction (II.) calls for a match according to actual
size without regard to perceptual appearance <> The optical illusions
require judgments of length or shape in situations where these per-
ceptual dimensions are distorted by the stimulus configurations em-,
ployed o

Major Findings; Arrangements for obtaining normal subjects have
only recently been completedj, and only the most preliminary results
have been obtained,, It is quite clear, however., that Instructions
I and II do tend to produce different behavioral responses in the
size -constancy sit\iation and that Instruction II manifests a strong
component of performance or non -perceptual judgmental activity..
This is not a necessary result by any means., and subjects who show
less difference in the effects of the two instructional sets seem
observationally to be different personality -wise from those who show
a marked difference.

Significance to the Program of Mental Health Research; Each of these
contemplated studies is aimed toward the clarification of the role of
a perceptual function in determining behavior or toward a delineation
of the determinants of a particul.ar perceptual process » In the
present size -constancy problem some evidence would indicate that
rational! zixig indiv1.duals or individual.s wi.th paranoid-like tendencies
shovild manifest a greater discrepancy beti^reen their responses xxnder
instruction I and II <, In addition to determining whether such an
hypothesis is correct^ the present approach is oriented toward the
very much more important, theoretical issue of whether such a finding
should be interpreted as a perceptual phenomenon or as a judgmental
or performance phenomenon « Much of the character of human behavior
is often attributed to perceptual prooessesj, but there exists very
little experimental evidence which really supports this viewpoint
uneq.ui, vocally »

. h50

Serial No. M-P-L-5, Page 3
Part Ao Project Description Sheet Continued

Proposed Coxarse of Project; This project is conceived as an in-
definitely continuing one in which normal control data relevant
to other projects is obtained.

Part B included; No

^ 451

Serial Noo M-P-L-6

1. Laboratory of Psychology
2« Section on Perception

and Learning
3. Bethesda

PUS-KIH
Individual Project Report
Calendar Year 1957

Psurt Ao

Project Title; Environmental. s«d Genetic Modification of Bio-
logical Systems «

Principal Investigator; Jolm b, Ualhoiin

Other Investigators :? William D> Sliiimer

Cooperating Unite : Area 1 of this project includes the census taking
of small roammals in their native habitat. Many of these are potential
reser'/oir hosts of diseases tracsmittable to xmxi. What we are doing
in this progr.am should be of relevance to certain activities of the
Rocky Moimtain Laboratory arid the Coramuni cable Disease Center.

J'lan Years Patient Days

Total; 216 2/.3?» Nor??

Profession.al: 100^^
Qrthe.T: Research Assistants 100'^
Secretarial:; 1 6 2/35^

■t^'oject .Deeeriptions

Objectimn:; 'To gain insight Into the ability of aniiaa3.s to adjust to
conditions over which they have little or no control o Tlie ultimate
aim is to d.evelop jirinciplers of istructurdng the physical and social
eiOTlr'OiMerit enabling optimyaa adjustment with respect to genetically
determined capacities. In the realisation of these objectives
emphasis is given to the use of space through time by socially organized

Serial NOo M-P-L-6, Page 2

Part Ao Project Description Sheet Continued

Objectives continued; groups in complex environments.. Where single
individuals or small groups axe utilized in highly simplified and
controlled experimental conditions j, these experiments are considered
not as ends of themselves 5 but as meaiis toward a fuller appreciation
of the processes characteristic of organized groups in complex situ-
. jationso

Methods Employed; Wild and domesticated straiiB of rodents as sub-
jects« These fall into three areas;

Area lo Population dynamics of vertebrates living under natural
conditions o This is a cooperative endeavour in which the major
investigator coordinates the activities of a nxjmber of investigators
over North itoierica who utilise standardized procedures for sampling
populations of small majranalso

Area 2o Short term experimental studies »

ao Physiological and behavioral consequences of group for-
na,tion in mice. Groups 1^ 2^ k^ Q^ I6 aaad 32 were given
ten 2-ho\3r sessions in a 24 x 27 inch field composed of
seventy-t^o 3-i^ch square com;^trtments with doors on each
side. All mice were maxked and time lapse photography was
conducted on each session » Mice were killed and preserved
for later study at the end of the 10th sessiono

bo Utilization of space through time by rats in the activity
alley o Hie alley is an 3 inch wide 14 foot enclosure with
a nest compartment at one endo Jfeny different groups of
rats have been given 24 to 72 hour sessions individually
in this ap5€sratus diaring the past three years o We are now
in the process of analyzing the results o

Area 3 c. Gonsequenees of long term experience in differentially
structured enviroxments o This area of the project is now being set
up at the Roekville Farm Bamo A 'wild .and a domesticated strain of
rat will, be reared In each of fo'ur env:lronmentSo

ao Miniffiim environment » Isolation of single individuals in
cages of O0I9 cuo fto which permits few perceptions or

activities »

^53

Serial Noo M-P-L-6, Page 3

Part A. Project Description Sheet Continued

Methods Employed Continued s

bo Moderate environment. Life space cage. This 6 cuo ft..
cage is so designed as to permit most basic behaviors.,
One male, two females, and their imweaned young will com-
prise the group,

Co Positive environment., One -thousand two -hundred and sixty
cu. ft. cage structured to foster tolerance and social
integration c Group will be maintained at approximately
60 ratso

do Negative environment » One-thousand two-hundred and sixty
cu. fto cage structured to foster intolerance and lack of
social organization. Groups will be maintained at approxi-
mately 60 ratSo

An observational record will be maintained regarding the behavior and
biology of nxjmbers of each group in situ. Representative of five age
groups will be permanently removed to serve as "clinical" subjects upon
whom an assessment will be prepared of their behavioral capacities,
physiological state, and pathological picture.

Area^l . Pop-ulation dynamics of vertebrates living under natural
conditions . The analysis of two field studies relating to mice and
shrews living in woodlands revealed that the several species forming
the community express a social hierarchy in their utilization of space.
Members of the dominant species have relatively large home ranges and
ma^-ifflize distaxice between centers of home ranges. Members of the next
most dominaat species have smaller home ranges and each of these in-
dlvidu;5J„s nia-xxmizes his distance from members of h;Ls own species as
well as from indiiaduaJ.s of the most dominant species. This process
continues down the hierarchy uiitil the most subordinate species is
hl,gj]ly cryptic in the sense that its members have very small home ranges
ajid es.ch member maximizes its distance not only from its oT-m kind but
from thftt of members of all Mgher ranking species. When such populations
are subjected to removal, trapping the dominant species is removed first
since it ha,s the highest probability of exposure to traps. As it is
removed the members of each of the subordinate species begins to enlarge

- h-'^li „

Serial Nc M-P-L-6, Page k

Part Ao Project Description Sheet Continued

Major Findings continued; its home range such that their

probability of capture increases o As a result of this process

the lower a species stands in the coimaimity hierarchy the later

in time is the maximuin catch per day. This concept is substsmtiated

by the results of a nine -year cooperative study coordinated by Calhoun

in which the data on 20,000 small mammals trapped in the field have

been supplied himo

Area_2o Utilization of space through time by rats in the activity
alley o Analysis of the first study in this area has been completed.
For each of four behaviors their frequency as a function of their
duration is describable by negative exponential curves » Each behavior
is characterized by a specific equation differing from that of the
other behaviors o Furthermore, the duration of any parti cvilar behavior
is independent of the duration of the preceeding or following behavior
of the same or different kindo The frequency with which trips are
terminated from a starting point is described by a K/di stance relation-
ship in which K is approximately 0<.9°

Area S" Consequences of long term experience in differentially
structured^"eDvironments" See 1956 annual report for details of
these environments o Wo studies axe yet in progress in this area.
The end of 1957 will see the completion of the laboratory at the
Rockville Farm Barn which will enable initiation of the studies o

Significance to the Program of Mental Hestlth Research g Most animals,
including man, live in environments over which they actually have
little control with respect to their life spano That is many charac-
teristics of the environment are extremely stable » If this project
is successful in defining principles by which behavior is modified
by the static components of the environment, it should be possible
to extrapolate these principles to other forms so that a more optimum
environment loay be striven for»

Course of Projects

Area_l.o The results of the past several years cooperative field
studies of small fflammal,s have been typed for lithoprinting as an
administrative publication o As soon as these are distributed to
the cooperators., both Calhoun and some of the other cooperators
will then be in the position to analyze and publish results o It is

k55

Serial Hoo M-P-L-6., Page ^

Part Ao Project Description. Sheet Continued

Proposed Cotirse of Project continued g already apparent that these
biological ''particles '^sSail maimn«is, exhibit many characteristics
similar to the behavior of gas i3iolec\£Leso It is our objective to
define the relevant principles of social physics » We do not know
how far up the animal kingdom toward man these principles will apply »
However^ we believe that these studies are not without relevance
since the equations describing the physics of the movement of an
individual within its own home range have been found to adequately
describe the distribution, of members about an institution exemplified
by a church in a recent pilot study by Calhoun »

Area 2o With the result of the first study now analyzed as a guide
we hope during 1957 to make progress in analyzing related studies of
rats in the activity alley in which either the emotional past history
of the rats was varied or in which the alley was structured with various
stimulus situations o Gross inspection of the records reveals that both
of these types of variables alters the utilization of space and time.
With regard to further studies a major change has been made in the
apparatixso fhis concerns doubling the length of the alley to 28 feet
and speeding up the flow of recorder japer by five times o Thus., we will
be able to analyze the time aspects of behavior with ten times the
prior accxjracy. The initial studies with the activity alley have lead
to the hypothesis that the utilization of space and time is a consequence
of the amplitude and frequency of discharges from the reticular activat-
ing system of the brain stem^ We therefore propose to modify the rat's
physiology through the use of certain drugs or emotional conditioning
processes which should affect the function of the brain stem and^ there-
fore^ the, behavior of the rat in the activity alley o

Area 3- The entire year 1958 will be devoted to pilot studies.
Groups of rats will be raised in each of the four experimental environ-
ments. Observmtional procedures will be standardized and the various
behavioral, testing equipment constructed and calibrated.

i^-5S

SeriaJL WOo M-P-L-6, Page 6

EHS-KIH
Individual Project Report
Calendar Year 1957

Part. Bo Honors, Awards, ajxd Publications

Calhoun., Jotui Bo Social welfare as a varialsle in population dynamics.
Symposia in Quantitative Biology, 1957^ Cold Spring Harbor,
New York ^Tn press, circa 20 pages).

Calhoun, John B. Editor, Proceedings of Conferences on Environ-
mental Determinants of Mental Health. Part I, I30 pages;
Part II, 191 pages. These proceedings were prepared as
Colitho reproductions in a limited supply for the use by
the consultants invited to participate by the National
Institute of Mental Health at these two conferences held
in May and October 195^.

Honors and Awards relating to the projects None

^57

NATIONAL INSTITTJTE OF MENTAL HEALTH

Basic Research
Laboratory of Socio-environraental Studies
Office of the Chief

BUDGET SHEET

Estimated Obligations for FY 19^8
Total! $16,571
Directs $12,732

Reimbursements s $3,839

Projects included: M-S-C 1 through Ji-S-C 3

Serial No> M-S-C-l

1, Socio-envirorunental Studies

2, Office of the Chief

3, Bethesda, Maryland
FHS-KlH

Individual Project Report
Calendar lear 1957

Part A.

Project Title: Analysis of Theoretical and Methodological Issues in
the Sociology of Mental Health and Illness

Principal Investigator: John A. Clausen

Other Investigators: None

Cooperating Units: None

Man Years (calendar year 1957) t Patient Days (calendar year 1957) :

Total: 1

Professional: l/3 None

Other: 2/3

Project Description:

Ob,iectiv3s; To examine current research within the Laboratory and within
the larger field, searching for theoretical convergences and
for problematic issues in the empirical findings, especially
bearing upon the relationship between social structure and
personality development.

Methods Effi]:i loved: Collection of theoretical formulations and research

findings on the relationship of social and cultural
factors to aspects or dimensions of mental health in
various coEimunities, population groups or ciiltures, as a
basis for scrutinizing theoretical linkaii,es, convergences
or critical discrepancies and developing more incisive and
more rigorously testable formulations. Specifically,
investigation thus far has involved studies of narcotics
use among adolescents and young adults (bringing together
psychiatric,, psychological and sociological data derived
from several decades of research in a variety of communities
in an effort to develop an integrated frame of reference
for the understanding of narcotics use in the urban slum)
and studies of the early family experience of schizophrenics
(examining especially ecological studies and studies dealing
with the dynamics of interpersonal relationships in the
family of the patient) .

Ma;ior Findings: In both areas of pathology analyzed thus far, it appears
that the social matrix in which the deviant develops and
his expressions of pathology (as viewed by clinicians) tend

- ^53 -

Part A. (cont.) M-S-C-1. Page g.

to interact and to produce correlations which are
frequently but incorrectly interpreted as evidence of
etiological linkage. The contradicting findings of
studies in different communities of the distribution of
schizophrenia by social class and by social mobility
groupings likewise suggest that correlations may repre-
sent sifting processes rather than causal nexuses.

A variety of formulations which attribute to the
mother a "schizophrenogenic" role appear to rest in
large part upon lack of adequate controls and upon
failure to analyze adequately the selective biases
entailed when a limited niinijer of families of long-
chronic schizophrenics participate in therapy.

Significance to Mental Plealth Research; A great many inconclusive

studies have been attempted
in premature efforts to "establish" causal relationships
between social factors, especially family dynamics, and
specific pathologies. An analysis of the reasons for
inconclusiveness and of the implications of studies
v;hich support or contradict each other, including our
our research gives a basis for planning a series of
limited strategic studies to eliiainate some of the
alternative hypotheses which would "explain" observed
correlations,

proposed Course of Fro.iect; This program of research surveillance

will be more or less continuous. During
the coming months a major formulation on the status of
research on family relations and schizophrenia will be
prepared for publication and several research
possibilities investigated.

Part B included Yes /x /. No I 7

- h53 -

Serial No. M-S--C-1 t page J

PHS-NIH

Individual Project Report

Calendar Year 1957

Part B ; Honors, Awards, and Publications

Publications other than abstracts from this project:

Clausen, John A.^ "The EcolOi^ of Mental Illness," Presented at the
Synirosium on Social and Preventive Psychiatry,
Walter Reed Anay Medical Center, and to be
published in the report of the Syiijposium.

Clausen, John a«, "Social Factors, Personality and Adolescent

Narcotics Use," in Esjp'lorations in Social Psychiatry,
edited h'^ Alexander Leij^hton,, John Ao Clausen and
Robert N. Wilson, Basic Books, Inc, 1957,,

Honors and Awards relating to this project:

~ i+60 -

Serial No M-S-C-2

1. Socio-envircnmental Studies

2. Office of the Chief
; 3. Bethesda, I'iaryland

PHS-NIH

Individual Project Report

Calendar Year 1957

Part A>

Project Titles The Impact cf Mental Illness Upon the Family

Principal Investigators; John A„ Clausen and Leila C„ Daasy

Otiier Investigators; Harriet S. My^phy and Eleanor Carroll

Cooperating Units s Saint Elizabeths Hospitalji, Washington^ D. C. and

Springfield State Hospital, Sykesvillej Maryland

Man Years (calendar year 1957) s Patient Days (calendar year 1957);
Total; 3

Professionals 1-17/30 None

Other: 1-13/30

Project Descriptions

Ob.iegtiyes; To study the effects upon the family of the father'' s or
mother's mental illness „ by focusing on a limited number
of hypotheses and questions raised by an earlier study,
within the following areas; (l) the effects of mental
illness upon the personal relationships within the family
and the family organization^ (2) the family's ijmderstand-
ing and perspectives of the illness, ard (3) the social
Inplications of the illness » Families under study are to
include both parental and conjugal families of schizo-
phrenic patients s

Methods Employed; The data are obtained through two structured inter-
views sehedioled shortly after the patient^ s
admission to the hospital and a third interview after
several months of hospitalization. The respondents are
spouses or parents of stshizophrenic patients who are
first admissions to the mental hospital. A san5)le of
families of appro3d.mately 50 female patients and 50 male
patients is planned,

I^ia.ior Findings; No new substantive findings are ready for reporting,

Sianificance to Menjtal_Healj^h_Res6archs This study provides data

relating to needs in public
education regarding mental illness, to the kinds of help
needed by the families of patients and to the kinds of
social and psychological problems for patient and family
attendant to hospital,ization of a mental patient,

„ ii6l =

Part A. (cont.) M-S-C-2, Page 2,

Proposed Course of Fro.iect; Development of data-gathering instruments

and of codes for the analysis of data has
been conpleted, and data-collection on new cases has been
resiomed. At present 60 of the anticipated 100 cases are
in the series. Field work probably will run another year.

Part B included les ITl No [ZJ

- h62 -

Serial No M-S-C-2 , page 3

PHS-NIH

Individioal troject Report

Calendar Year 1957

Part Bs Honors, Awards, and Publications

Publications other than abstracts from this project;

Schwartz, Charlotte Green, "Perspectives on Deviance — Wives' Definitions

of Their Husband's Mental Illness," Psychiatry,
Vol. 20, No. 3, Aug. 1957.

Honors and Awards relating to this project:

^63 -

Serial No.

Ic Socio-envii-onmental Studies
2. Office of the Chief
3« Bethesda^ Maryland
fHS-NIH
Individual Fr-cject Report
Calendar lear 1957

Part A.

Project Titles The Adaptation of the Mental patient to his Family
Upon Return from Hospitalization '

Principal Investigators; John A.» Clausen and Leila G. Deasy

Other Investigators 2 Harriet S^ IbxrpYij

Cooperating Units; Saint Elizabeths Hospital, Washington, D„ G. and

Springfield State. Hospital, Sykesville, Maryland

Man Years (calendar year 1957) s latient Days (calendar year 1957)

Total: —

Professional; =-=- None

Other:

Project Descriptions

Ob^iectivess To study the rehabilitation process following the

patient's discharge frora a mental hospital, in terms of
two interdependent sets of dimensions; (a) the patient's
progress toward mental health, and (b) the changing
structure and funstioni.ng of the family of the patient.

Pie-thods Employed; Patients and families are the same as those studied

in project I"i-S-C~2 and certain of the data secured
for that project vill be basic to the present project.
Data are obba.lned through interviews with the patient and
the patient's spouse or parents and \vfith selected signifi-
cant others in the patient's social envirorjnent. The
period of follcw-up varies, though for all patients there
wj.ll be assessments cr status reports as of one month,
six months and one year after leaving the hospital » Some
patients studied in the early phase of data collection
will have three to four years of follow--ip,| patients
obtained in the late phase will have one year of follow-
vpo Additional data, come from hospital case reports,
psychiatric evaluations of patient' s condition at dis-
charge a.nd the investigator's observational ratings of
fsjai.ly and patient.

Plaigr^ Findings s Mc analyses ha.Y~. bee^n undertaken beyond those
reported in l'^55e

- k6k ~

Fart A. (cont.) M-S-C-3, Page 2.

Significance to Mental Health Research; The high readmission rate

of patients to mental
hospitals points to the need for research into the
factors influencing the discharged patient's adjust-
ment to the family and the community. The present
study will add knowledge concerning the kinds of
stresses and problems encountered in the process of
rehabilitation, and the relationships between condi-
tions in the patiant-family-community situation and
successful and unsuccessful rehabilitation.

Proposed Course of I-ro,iects Field work on this project has awaited

the progression of cases in Project
l-i_S_C-2 to the point of discharge of patients from the
hospital. In addition to cases currently being
carried in Project M-S-C-2, interviews with families
who were seen in the initial phase of the project
{a ~ 5 years ago) will be interviewed in order to
explore the long-range effects of the patient's first
hospitalization and the subsequent course of family
experiences. Field work will probably run another
two years.

Part B included Yes /~7 No ^/

- k65 -

NATIONAL INSTITUTE OF MENTAL HEALTH

Basic Research

Laboratory of Socio-envirorunerxtal Studies

Social Developmental and Family Studies

BUDGET SHEET

Estimat^g Obliga^^JrOns Xqjt FY 1959

Total! $102,108
Direct: $65,307

Reimbursements J $36,801

Projects includeds 24-3-0 1 through K-S-D 7

Serial No. M-S-D-1

lo Socio-environmental Studies

2. Social Developmental and
Family Studies

3. Bethesda, Maryland
FHS-NIH

Individual Project Report
Calendar Year 1957

Fart A,

Project Title! The Formation of Children's Peer Relationships

Principal Investigators s Marian Radke Yarrow and John D. Cainpbell

Other Investigatorss None

Cooperating Units? Family and Child Services j, Washington, D. C^

Man Years (calendar year 1957) s Patient Days (calendar year 1957)

Total; 2-lA

Professional: 3A None

Other: 1-1/2

Project Descriptions

To investigate the process by which children form
inpressions of each other and develop patterns of
interactions in social situations. To study the effects
of developmental, personality and social factors i this
process^

Two hundred sixty-seven white an.d Negro children,
8 to 13 years of age, were interviewed and observed
in summer canpss, in initial interactions with one another
and over a two-week periods Using open-=endeds socionetric,
and projective questdons, interviewers obtained children's
injjressions and judgments regarding their peers^ their adult
leaders^ and their images of self. Detailed observations of
behavior were recorded at selected time periods.

(1) A marked degree of sensitivity and reality concern-
ing the characteristics and potentialities of their

peers is reflected in the iD5)ressions and evaluations
reported by children about their peers. Their reports
show pronounced agreement with adult assessments and with
behavioral re cords »

(2) Children's initial and almost immediate predictions
of the degree of interpersonal attraction which each of
their peers will have for them show high agreement with the
attraction and rejection developed over a continued period
of acquaintance o

Part A. (cont.) M-S-D-1, Page 2„

(3) In group situations involving increased
uncertainties and ambiguities as to interpersonal
relations, children' s perceptions of one another reflect
increased alertness to the "threatening" aspects of
interaction and of group roles, i.e.j increased sensitivity
to aggressive, disruptive and dominative conponents of
others ' behavior .

(/+) Comparisons of interpersonal perceptions and
behavior in racially segregated children's grov^js with
racially integrated groups show that the psychological
environment is altered by integration for children with-
out prior experience in mixed groups, but that overt ,
behavior conforms overwhelraingly to the requirements of
the equal-status situation.

(5) Negro children respond to integrated groups by
increased concern about control of behavior in themselves
and peers of their own racee Continued successful inter-
action in the mixed groiips brings some decrease in self-
rejection and anxious self-control in the Negro children.
Girls' integrated gro\;5)S appear to have greater diffi-
culties (more tensions and cleavages) than boys' groins,
the Negro girl having the lowest status and most negative
self-appraisal. These sex differences may be related to
differences in adult racial roles of each sex group.

Si:,-nificance to Mental Health Research; A primary concern of parents

and professionals working
i.'ith children is how children's behavior and values are
affected by various inteipersonal influences of peers and
adults and how desired patterns of behavior can be
developed. Answers to these questions rest in part "on
fuller knowledge of the child's interpersonal relation-
ships as he experiences them, ice,, his awareness of
others and his sensltitivy regarding the behavior and
motives of those vrith whom he interacts.

Proposed Course of Pro.iects One aspect of this project's progress

during 1957 has been methodological.
Techniques for analyzing behavioral and cognitive data
within the same conceptual framework have been devised
and used in interpreting research results.

Publication of research findings has begun, A
report on interpersonal dyn.amies in racial integration
has been conjjleted and is in press, A more conprehensive
analysis and intexpretation of the data on integration is
continui.ng and has been scheduled for publication as a
monograph next spring,

- i^67 -

Part A. (cont.) M-S-D-lf Page 3.

Another report is in preparation on factors in inter-
personal attraction and rejection in children's groups.

It is estimated that the above reports will be
coBfileted and additional research papers will be prepared
during the next calendar year.

Part B included Yes /xT No I 7

- i^68

Serial No. M-S-D-1. Page ^

JrHS-NIH

Individual ]:roject Report

Calendar Year 1957

Part B; Honors, Awards, and iublicationa

Publications other than abstracts from this project:

Yarrow, l-iarian Radke, John D. CaB$;bell and Leon J, Yarrow,
"Interpersonal Dynamics in Racial Integration," in Readings
in Social Psychology. Editor, Eleanor tiaccoby. New York,
Henry Holt, in press.

Honors and Awards relating to this project:

^■69

)

Serial No,

M-S-D-2

lo Socio-environmental Studiesg-
2o Social Developmental and

Family Studies
3« Bethesda, Maryland

Part A.

Project Title;

PHS-NIH
Individual Project Report
Calendar Year 1957

Adult Leadership in Children's Groi:ps: A Study of
Leader's Sensitivity and Functioning in Relation to
the Social-cultural Coiaposition of the Group

Principal Investigators; i-iarian Radke Yarrow and John D, Caapbell
Other Investigators: Leon Yarrow and John Theban (Not NIH employees)

Cooperating Units;

Family and Child Services, Washington;, D, C.

Patient Days (calendar year 1957) i

Man Years (calendar year 1957) s
Total; 1
Professional; 1/2
Other; 1/2

Project Description;

Ob.iectivess To study the adiil.t leader's role in children's groins,

assessing? (a) congruencies and discrepancies in leaders'
and children's perceptions of interpersonal processes in
the gro'C^jj (b) bases and consequences of discrepancies
between leaders' and children's perceptions, and (c)
leaders' behavior and sensitivities regarding the
individual child and the group in relation to the social
class and racial conposition of the gx'oupo

Data were obtained on 30 leaders of children's
groups and the children in their groiJfiSc Each adult
led foux groups of children (8 per group) in four successive,
two-week summer canp sessions. Eight counselors and their
cabin groups were studied intensively « Interviews with the
counselor, ratings of the children by the counselor, observa-
tional records on children and counselor and interviews
with the children were obtained. These provided data on
leaders' functioning in groups, leaders' perceptions of the
attitudes toward the children and children's responses
toward each other and toward their leaders »

Analysis has net been sonpletedo Some preliminary

findings are as follows 8

Adult leaders' appraisals of chj.ldren tend to be in

i^70

^art A. (cont.)

agreement with those made by the children themselves.
Children rated high in popularity 5 leadership, etc., by
the counselors are in general similarly evaluated by their
peers.

2. The leader's personal values and motivations do, however,
shape his appraisal of the children, Fbr exanple, leaders
of racially integrated children's groups show a systematic
tendency to rate children racially different from themselves
higher than children of their own race on socially valued
characteristics. Some awareness of this^tendency is shown
by the children,

3. Adult leaders functioning for the first time in
racially integrated children's groups exert tighter control
over these groups than they did in segregation. This has
been interpreted as stemming in part from their motivation
for integration to succeed and in part from their anxiety
about the nature of the situation*

Significance to Mental Health Research; Research and theory in person-

ality, developmental and social
psychology emphasize the in^jortance of adult influences in
shaping children's attitudes and patterns of behavior.
With the exception of his parents, a child's teachers are
the adults most liJcely to play a significant role in his
development. Application of the data of this project can
be made in the field of education,

(a) A recognized problem in many educational settings
concerns difficulties arising from differences between
teacher and children in cultural and racial backgrounds.
Data from this study should identify some of the conse-'
quences of these differences in leader-shild interactions,

(b) Teachers are faced with the problem of coping
with the deviant or the emotionally disturbed child.
This study should provide data on the ways in which the
adult leader defines deviant behavior to himself and to
the children in his groT:^), and on the adequacy of alterna-
tive methods used by adult leaders in dealing with the
deviant child,

(c) Also J data comparing adult and child perspectives
have direct bearing on questions of research methodology
in the field of child developmenti namely, what kind of
data source is the adult informant on children's inter-
personal relationship So

Proposed Course of Pro;iect; Progress on this study is closely linked

to the related research project on
children's peer relationships. Some of the research
findings on the role of the adult leader have been
included in the paper on inteirpersonal dynamics in

- if-71 -

Part A. (cont.) M-S-D-2o Page 3.

racial integration (in press)., and these data will be
more fully dealt vith in a chapter of a report to be
published in the Journal,_of , Social Issues in 1958.

During the coming year coiijjarison of adult leaders'
and children' s perceptions of the personality and
social interaction characteristics will continue »
Differences in patterns of adult-child relationships
and their relations to social and psychological
characteristics of the participants will also be
explored. It is estimated that data analysis will
be coii5)leted in the coining year, and final research
reports should be ready for publication shortly
thereafter.

Part B Included Yes HJ No ^'

*■

Serial No. M-S-D-3

1. Socio-environniental Studies

2. Social Developmental and
Family Studies

3. Bethesda, ^laryland
irHS-NIH

Individual Project Report
Calendar Year 1957

iartA,

iroject Title: The Validity of Retrospective Data on Parent-Child
Relationships

Principal Investigators; Marian Radke Yarrov; and John D^, Can^jbell

Other Investigators: None

Cooperating Units; National Child Research Center, WasMngton, D,. C„

Han Years (calendar year 1957): Patient Days (calendar year 1957)

Total: VU

Professional: l/4 None

Other: l/2

Project Description:

Ob.iectives; To study the extent to which valid information about

early aspects of a child's development and parent-child
relationships can be obtained from parents' retrospective
reports. Specifically: (l) To assess the nature of
differences between earlier events and parents'' recollec-
tion of such eventss, (2) To determine how retrospection
is influenced by such factors as the time interval between
events and recall, intervening events, and the current
social-psychological situation.

Methods Buy loved; Parents of children on whom data were obtained from

one to 20 years ago will be interviewed. The base-
line data consist of direct observations, interviews and
ratings of the child and of parent-child relationships
gathered at an earlier time concerning the same time
period. Parents' retrospective reports will be conpared
with these baseline data„

I'4a;ior Findings: Work on this project has not progressed to the stage
of data analysis,

SiR-nificance to Mental Health Research: This study is basically a

methodological one further-
ing imder standing of the process of recall. Research on
child development and the etiology of personality dis-
turbances relies heavily on retrospectively reported
life-history data. Systematic survey of the accixracy

- -'173 -

Part A. (cont.) M-S-D-3. Page 2.

of such information is necessary to buttress data inter-
pretation and formulation of theory. Thus, study of the
nature and extent of systematic errors or biases in
retrospective reports on earlier life periods can
contribute to the understanding of social developmental
factors in the genesis of schizophrenia, delinquent
behavior, etc.

Proposed Course of Pro.iect; A principal soiirce of baseline data has

been located and the major task of
abstracting such case-record data has just gotten under-
way. Development of an interview schedule is proceeding.
Interviewing to obtain retrospective reports will begin
early in the next calendar year. Two possible extensions
of this study are being explored;

(1) Locating and utilizing other existing sources of
case-record data to provide baseline information in areas
not covered by our present data soiirces,

(2) Obtaining on-the-spot observational records of
nursery school children's interaction with their peers,
teachers, and parents, sigjplementing these observations
with interview data, and using the information thus
obtained as the baseline for conjjarison of subsequent
retrospective accounts.

Part B included Yes fl No fTl

Serial No. /M-S-D-A

1. Socio-environiuental Studies

2. Social Developmental and
Family Studies

3. Bethesda, Marj''land

PHS-KIH

Individual Project Report

Calendar Year 1957

l-art A.

troject Title: Life-styles in Aging

Principal Investigators; Marian Radke Yarrow and Olive VJestbrooke Quinn

Other Investigators: E. Grant Youiaans

Cooperating Units: Laboratory of Clinical Sciences, Laboratory of

Psychology, and Social Service Department, I'lIM,

Man Years (calendar year 19t)7) s Patient Days (calendar year 1957):
Total: 1-1/2

irofessional: 1-1/4 55

Other: l/4

Project Description:

Ob .i actives; This project is part of a larger research on the function-
ing of physically healthy aged persons, which brings the
perspectives and measiirements of physiology, psychiatry,
psychology and sociology, both singly and in combination,
to the examination of the problems and factors in agingo
The primary objective of this part of the total research
is to examine relationships between the demands and
supports of the aged person's social environment and his
functioning— as it is defined in terms of the organization
of his daily behavior, his planning for the future, his
attitudes toward himself and his relationships with others.
Environment is assessed in terms of (l) the social e3{pecta-
tions and stereotypes irijjosed xtpon old age, and (2) the
inifact of common changes or crises of old age, such as
retirement from en^loyment, family losses, and social
isolations.

A second research objective is the investigation of
interrelationships between the social psychological
variables described above and physiological, psychiatric,
perceptual and cognitive data.

Methods Employed; Physically healthy male subjects were brought to

the Clinical Center for two weeks of intensive
study by investigators from several cooperating Labora-
tories. For the social psychological study within the

- i^75 -

i-'art A. (cont.) M-S-D-4-. page 2

larger interdisciplinary project, data are obtained
through a series of interviev/s, two of which are
conducted while the subject is living at the Clinical
Center, a third with the subject in his home about a
month later and a fourth with a person chosen by the
subject who has known him over a long period of time.
In addition, systematic observations of the subjects
are made by the nursing staff on the Ward and by a
sample of the investigators.

Major Findings; Preliminary analyses suggests:

(1) A stable structure of interpersonal relationships

is important for adequate functioning in old age. Extensive
losses suffered by the aging individual, ■•'iihx-ough death of
or abandonments by persons significant to Kim, are
associated with (a) daily behavior which is less organized,
more routine-bound and lacking in goal character, (b) a
lack of goals and emotional investments beyond the self, and
(c) an inability to use or to enjoy leisure time on the
part of the aging individual.

(2) Elderly persons in our society are measured by others
by the yardstick of youth. The respect accorded them is
related to the extent to which they depart from the stereo-
type of the aged person, a stereotype deriving from the
characteristics of sick elderly persons. Many common
social expectations as to what elderly persons can or
should be allowed to do are based on this stereotype,
which to some degree does not fit the physically healthy
group of aged studied herec

(3) Our data do not support the popular belief that
problems of retirement are most ably handled by persons
of higher educational or professional training. Occupa-
tional background, per se, shows no systematic relation-
ship to ability to cope with problems of old age.

(4-) Relationships between physiological measures and
social functioning are being explored. One such relation-
ship appears in preliminary analysis. Persons who have
suffered the greatest personal losses (see 1 above) and
who are at the low extreme in measures of O2 consumption
show the greatest impoverisiiments in daily behavior and
goal striving, and the inverse of the case holds equally.
Causal inferences cannot be drawn from present data of
co-variation.

Significance to Mental Health- Research;"' Ours is a population in which

the proportion of elde-'"'v
people is steadily increasing. Many groups (medicine.,
social work, and other community services) which deal with
problems of old age and which seek to make old age a more
satisfying and productive time of life need the kind of

- k7e -

iMli-A* (cont.) M-S-D-A. Page 3.

information this project seeks, in order that they may
plan their services to meet needs of the aged. In this
respect it is especially iuportant that research data
be obtained on a non-institutionalized population. We
expect this research to contribute to the understanding
of the following qioestions:

(a) What demands and/or. pressures relate to adequate
functioning of the aged person in the community?

(b) What relationships are there between social-
psychological factors and physiological factors in

aging?

V;hat elements of difference between the concepts of
aging for older and yoimger people are conducive to
strain?

(d) What social factors in the individual's daily living
are associated with his adjustment to aging?

Proposed Course of Fro.iect: Data gatherirg was conpleted in the summer

of 1957. Anaxysis of the data is underway,
A paper will be ready for pioblication during the next year.

Fart B included Yes £Z/ No /x7

- ^77 -

PHS-NIH

Individual Project Report

Calendar Year 1957

Serial No„ M-S-D-5

Ic, Socio-environmental Studies
2« Social Developmental and

Family Studies
3« Bethesda, Maryland

Part. A.

Project Titles The Identification of Self in Identical Qus.dri:5)lets:
A Special Case of the Problems of Sibling Rivalry
and of Multiple Status

Principal Investigators? Olive Westbrooke Quinn

Other Investigators? None

Cooperating Units s None

Man Years (calendar year 1957) s Patient Days (calendar year 1957) s
Totals 2/3

Professionals l/3 190

Other: 1/3

Project Descriptions .

Ob.iectivess To analyze (l) interactibnal patterns, .and (2) inconpatible
statuses in a groijp of mentally ill identical quadrijplets,
in an effort to understand the individual's struggle to
establish a definition of self in relation to the group o
This problem is seen within the framework of stresses
arising from or exaggerated by the fact of multiple birth,

I4ethods Eiim loved; The subjects are schizophrenic identical quadruplets

under the care of the Clinical Investigations Branch
of NIMH, Within the clinical setting data have been
collected by means of observations of the patients,
informal interviews with the patients ajad'wi'th nuTses
and attendants^ and observations of and informal inter-
views with the parents i^ion the occasions of their visits
hereo From the home community there are Inter'/iews with
friends, neighbors, teachersj sjid oxhers in a position to
tell how these patients and their family are perceived by
the community in which they lived. In addition, the
personal and public documents concerning the subjects have
been used. ,

ingss Problems of self-identification apparently ^inique to
or exaggerated by the fact of multiple bir"fch seem to
arise from a conflict of two opposing kinds of pressures?
(l) pressures xspon the persons of the multiple sat to

- q-78 -

Part A. (cont.) h-S-D-5, Jraa'e 2

occv5)y a single position and (2) pressiores vtpon the
members of a set defined as "identical" to exhibit
distinctive differences^ The interplay of these
pressures is such that individuality is defined in
reference to the other members of the seto There is
an intermediate zone between seeing oneself as an
indistinguishable part of a whole and seeing oneself
as a unique individual (or being seen in either of these
ways by others) . Sub-groi;{)ings and coalitions within
the set occurj i.ecj a pair or trio distinguishes itself
from another pair or singleton with respect to a given
traitc These sub-groupings change as the trait under
consideration changes «

The process by which others have kept the quad-
ruplets "identical" in their own thinking is one in
which some very obvious and large early differences
were ignored or explained away as ten^joraryj, something
the individual woiJ-d outgrow. On the other hand, the
necessity for distinguishing individual members of the
set gave rise to an opposing process » Initially small
or negligible differences have been slezed upon and
exaggerated, and in their exaggerated form have become
the basis for evaluation of the individual and for
interaction v/ith hers

Sii.<nificance to Mental Health Researchs Certain problems of child

development and child rearing
which arise in the family group are exaggerated by the
fact of multiple birth and are therefore more readily
accessible to study and to analysis., The central problem
of this projectj that of the development of identification
of self, is here placed in the special setting of multiple
birth »

Proposed Course of Projects A report is in preparation, directed toward

answering the following questions; When
two or more persons are defined as "identical," how do they
and those who must Interact with them establish the identi-
ties of each? How is the individual's identity determined
by his similarities to others in the multiple set, and
how does it rest on perceived differences?

Part B included Yes / / No

- i^79 -

Jr'HS-NIH

Individual Iroject Report

Calendar Year 1957

Serial No,

la Socio-environmental Studies

2, Social Developmental and
Family Studies

3. Bethesda, feryland

i-art A.

Project Titles The "X" Family as Seen by the Community
Principal Investigators Olive Westbrooke Quinn
Other Investigators; Leila Calhoun Deasy

Cooperating Units? None

l^ian Years (calendar year 1957)
Totals 1

Professionals 2/3
Other; l/3

Project Description:

Patient Days (calendar year 1957)

none

Methods

This is one part of a larger study of tb_e "X" family from
the points of view of various di s sip line s^ with the intent
of deriving or exenplifying hypotheses regarding nature-
nurture contributions to the development of schiizophrenia.
In this regard, the influences of the family on the
community and of the community on the family C0E$)rise an
area of information essential to a fvtll understanding of
how mental illness in the "X" qua-dri^jlets developed.

Interviews were conducted with the friendSj, relativeSj
teachers, doctorsj, eirployersj work associates,
neighborsj and certain individuals who had ass'jmed some
sponsorship of the subjects. Data include observations
of parental interaction in their homsj hospital and clinic
records, and interviews with 76 informants. Information
was obtained on (a) patterns of behavior within the family
and (b) comraunity attitudes toward the family.

Findings! Analysis is in progress,
at this times

No findings can be reported

Significance to Mental Health Research; Much mental disorder is

believed to stem from unhealthy
family relationships « Any effective program of prevention
of mental illness would have to take into accoujit the
circumstances which contribute to the autonomy of parents
in rearing their children,

- -4-80 -

Part A, (contj M-S-D-6. Page 2.

Proposed Course of Project; Analysis in progress focusses on family

autonomy in child-rearing practices,
with special reference to the problem of access to
pathogenic families. How early and by what means is
such a faxaily detected in the community? Under what
circumstances and through what avenues can community
members influence the parents to alter their conduct
toward their children?

Part B included Yes /~7 No /x~7

- ^81 -

Serial No. K-S-D-']

1. Socio-environmental Studies
2« Social Developmental and

Faraily Studies
3, Bethesda, Maryland
PHS-NIH
Individual Project Report
Calendar Year 1957

Fart A.

Project Title: Exploratory Study of Methodology for Assessing
Interpersonal Relationships Within the Family

Principal Investigators: Marian Radke Yarrow and Thomas Gillette

Other Investigators: None

Cooperating Units: None

Man Years (calendar year 1957) : patient Days (calendar year 1957)
Total: 1/2

Professional: l/2 None

Other:

Project Description:

Ob.iectives; To dpv^io-.. techniaues of investigating interpersonal re-
lationships within the famly, in the natural family
setting.

Methods Enployed; This research is primarily methodological. It

proposes to develop methods of studying the family
in its natural setting, as coBjjared with laboratory,
testing or interviewing settings. It will be necessary
to work through problems deriving from the nature of this
setting, problems of observation and recorclingp problems
of conceptualiaation and ethical problems.

Ma.ior Findings; Not applicable. Project in planning stage.

Significance to Mental Health Research; The fundamental in^jortance

of the family in influencing
development is well recognized. Most research on the
family, however, uses data derived from second-hand
sources. The orthodox techniques have been case
histories, personal interviews and questionnaires^
Rarely are data obtained from direct observations of
intra-familial interaction. It is assumed that new
sensitivities and insights regarding family character-
istics and interactions may be developed if methods of
obtaining first hand data can be worked out. Such
findings woiald be significant for many areas of child
development and family research.

Part A. (cont.) m-S-D-7. Page 2.

Proposed Course of Pro,iect; The past several months have been spent

in assembling methodological leads from
the research litera.ture and in drawing up tentative
■,-;vf plans for testing a number of observational approaches.
■•;■''.-■,;.'■• This work will continue » During the next year a more
'-. definite project formulation will be developed. It

will be regarded as exploratory research, methodologically,
but will attenpt at the same time to obtain substantive
data on the problem of multiple-mothering.

Part B included Yes fTJ No / 7

- 483 -

Serial Ho. M-S-D-7 . page 3

PHS-NIH
Individual Project Report
Calendar Year 1957

Fart B ; Honors, Awards, and Publications

Publications other than abstracts from this project:

Yarrow, Viarxan Radke, "Some Next Steps in Research," in Four Basic

Aspects of Preventive Psychiatry. Report of
the First Institute on Preventive Psychj.atryj
' State University of Iowa, 1957, in press „

Honors and Awards relating to this projects

NATIONAL INSTITUTE OF MENTAL HEALTH

Basic Research

Laboratory of Socio-environraental Studies

Cororaunity and Population Studies

BUDGET SHEET

K.c,ti mated Obligations for FY 1958.
Totals $96,575
Direct! $7^»222

Reimbursements! $22,353

Projects included! >I-S.P 1 through I4-S-P 5

Serial Mo. M^-S-P-l

PHS-NIH
Individual Project Report
Calendar Year 195"

1, Socdo-enviroiainental Studies

2, Coaimunity & Population Studies
3o Bethesda, Maryland

Part A,

Project Titles A Gosi^iarison of the Social Relationships of Children
in the Middle and Lower Soeio=eeonoHd.c Strata

Principal Investigators s Melvin L„ Koim and John Ao Clausen

Other Investigators 8 Eleanor Carroll

Cooperating Units? None

Man Years (calenda" y^r- 1957); Patient Bays (ealendar year 1957)

Total 3-9/10

Professional 1-3/5 None

Other 2-3,'l0

Project Descriptions

To ascertain whether or not there are consistent and
patterned differences between the social relationships
of children from the jniddle and lower so<3io=eeonQniic
strata of urban societya

Structured interviews with a ssjiople of aiiddle

and lower soeio-eeonomic status parents ef 9=10
year old children^ together with interviews with a
sub=-saai)le of the children thesnselveso The interview
schedule for parents has been designed to illi3mix!.e
the several dimensions of the parent=(sfe.iM relatio^n^
ships J the values of the parents most relevant to
their behavior as parents j, their evaluations of their
children'! s behavior, and their knowledge and strustur-
ing of their children '■'s relations with other children.
The interview schedule for the children has b&es
designed to elicit their perceptions of their relations
with their parentSj, as well as a more coa5)lete picture
of their relationships with other children.

Findings s The first portion of data-analysis has been a
coa5)arison of the values of ndddle and working
class parents. It was found that parents in the two
classes share a common value-system with respect to
what characteristics they consider most desirable in a
child of this ages they ascribe predominant in^sortanse
to items connoting character and to happiness? they are

- ij-85 -

Part A. (cont.) M-S-?-l. page 2

not likely to value ],.hy£ical iTowess, t,eriou3ne3,:-; ,
ability to i-lay by oneseJi" or affective responsiveness
very hiciily for children of this age. But happiness
is no. h.'jhiy valued by nearly as large a proportion
of vorking olass as of middle class parents. And,
altiioufjh items connoting character are of primary
importance to parents of both classes, middle class
parents are more likely to value both self-control
and consideration, working class parents to value
obedience. Jtirthermore, middle class mothers are
considerably more likely to regard curiosity as a
prime virtue, whereas working class mothers value
neatness and cleanliness.

The study also demonstrates that the values parents
hold are closely related to the ways that they raise
their children.

Significance to Mencal Health.. Ilesearch; One plausible interpre-
tation of the dispro-
portionately high rates of schizophrenia in the
lower socio-economic strata is that the childhood
social experiences of persons from these strata have
predisposed them to illness. Though plausible, this
interpretation does not get us very far in our under-
standing of schizophrenic personality development
until we are able to specify in detail the respects
in which the childhood social relations of these
persons differ from those of other groups in the
society. This knowledge we seek to secure in the
present research. We hope that the results of the
study will make possible the formulation of more pene-
trating hypotheses about the role of social experience
in the development of schizophrenia than those that
have been produced to date.

Iroposed Course of hro.iect; By the beginning of 1957, the inter-
views with the sample of 300 mothers
had been completed, as were nearly one-half of those
in families where mother, father, and child were to be
interviewed. During 1957 the remaining interviews, the
processing of interview materials for IBM punching and
the first stage of data analysis — a ::omparison of the
values of lower and middle socio-economic status parents
— were completed. During 195S data analysis will be
continued; the emphasis will now shift to a direct
examination of the ;-ieveral aimensions of farrdly inter-
action.

Part B included Yes £J No J^

- ii86 -

Serial Mo„ M=^-P-2

le SociO'-en'Fironm.ental Studies
2o Cosmunity & Population Studies
3« Bethesdaj Maiyland
PHS-NIH
Individual Project Report
Calendar Year 1957

Exploratory S'tudy of the Use of Local Gommmiity Reso'urces
for Handling Mental Health Problems

Principal Investigators Stephen To Boggs

Other Investigators! Ncne

Cooperating Units s Program Development Branchy Bureau of State Services,

Public Heal'th Service

Man Years (calendar year 1957) s Patient Days (calendar year 1957)
Total 1

Professional 1 None

Other =

Project Descriptions

Obiectivess To evolve and test hypo+iieses about the utilisation ©f
formal agencies and anfoiTnal resoiircses (family^ friendSj,
associates, and si.rangers) by people with personal problems|
the social factors in the community affecting this litiliaa-
tioni and the consequences of various ways of handling
problems for the siibaequent career of the individual,

Mflthnda Employed a In the eacploratory phase pr&vious studies of social

class differences in individual relationships with
social and psyehiatr-ie service agencieSj, popular conceptions
of mental illness^ and of the places people take ■fcheir
troi±)les have been reviewed, 'twenty-four trial interviews
were conducted in a rural community on th,e Great Plains as
part of a collaborative study imdertaken with the Program,
Development Branchj, Bureau of State Services^ Public Health
Services The development of a systematic design for test^
ing the hypotheses is now underwayo

A number of hypotheses have been evolved and revised.
These stress the iiifsortance of informal reso'orceSp
social class and rural=-iarban differences in readiness to
utilize these resources effectively, and the in^jact this
may have on the career of the troubled individual and those
abound him*

- 487 -

Part_A., (cont.) i->-'S~P-2^ page 2

Significance to , Mental,. Health Research; It may prove possible

to elucidate individual
social reactions to normal stress and, eventualljj
to differentiate these from the careers which pre-
dispose to hospitalization within certain social
settings ,

Jrroposed Course of Projects V/ith exploratory work complete ^ the

project will be ready for systematic
collection of data and testing of hypotheses during
the calendar year 1958.

rart 3 included Yes /'/ No ^^

~ 488 -

Serial Mo. M=S^P°3

1„ Socio^envirormiental Studies
2o Commimity & Popuiation Studies
3« Bethesda^ Maryland
PHS-NIH
Individual Project Report
Calendar Year 1957

i^Ei_A.

Project Titles Pre-^hospital Social Factors ^ Treatment with the

Tranquillizing Drugs j, and Behavior- as Prognostieators
of Successfiol Release from a Mental Hospital

Principal Investigators Erwin Lo Linn

Other Investigators s Hone

Cooperating Units s The staff of Saint Elisabeths Hospital has cooperated

in this projeet by making available hospital records »

Man Years (calendar year 1957)8 patient Days (calendar year 1957)?
Total 1-1/4

Professional 1 None

Other lA

Project Descriptions

To determine the relationship between (a) the patient's pre-
hospital social baekgro-onds (b) his course of treatment in
the hospital (with partic-olar interest in reserpine and
chlorpromajsine) and (e) his behavior while in the hospital
and the duration of hospitalisation and probability O'f
rea.dffllssicnj, for f-onctionally psyeliotie patients « Among
the questions to be asked are the follow* ings

lo Are patients treaited with ehlorproamzi-ne or reserpine
more likely to be released dxiring t^he firs'ic yeaa." of
hospit^iaation and more likely to remain out of the
hospital one year af^^r release than a isomparable group
of patients admitt^ed to the hospital before the use of
tranquilizing dirags?

2e Have the tranquilizing drugs increased the probability
of release of patients not treated witii dr-^igs because of
the generally "oalmer" a-tmosphere of the hospital dioring
the current period of dT'iog therapy?

3. To what extent do patients of varying social back^-
grounds react differentially to the dr^-igs?

3 s traction of relevant data from the hospital
medical chartSj, including nurses notes and medication
sheetSj of all functional psychoticsj, age 20 through 49j,

- ^^-39 -

Part A. (cont,) M-S-P-3, Page 2

residents of the District of Columbia for one year or
more, who -were admitted to Saint Elizabeths Hospital
for the first time during l/l/53 through 8/3l/56»
These aata have been coded for IBM card preparation
and tabulations .

Ma.i'or Findings; Analysis of dalta not yet begun.

Significance to Mental Health Research: The questions enumerated

above are central to
current interest in factors infliencing admission and
release from mental hospitals.

Proposed Course of Pro.ject: During 1957 the project was formulated

and the data collected and coded for
IBM tabulation. Analysis of data will be carried out
during 19 5S.

Part B included Yes (J iio /x7

- h^Q, -

Serial No. M-S-F-^

1. Socio-enviroruuental Studies

2. Community and Population Studies

3. Bethesda, Maryland
1-HS-NIH

Individual Project Report
Caler-dar Year 1957
Part A.

rroject Title: A Twin Family Study of Mental Deficiency

Principal Investigators: Dr. Franz J. Kallmann (non-PHS) and

Dr. Gordon Allen

Other Investigators: (Those previously listed have not participated

this year.)

Cooperating Units: New York State Psychiatric Institute

Man Years (calendar year 1957): Patient Days (calendar year 1957):
Total: 1

Professional; 1 None

Other:

Project Description:

Objectives; To assess the frequency with Xvhich mental subnormality can
clearly be ascribed to nongenetic factors and to elucidate
the interaction of genetic constitution '-dth environmental
causes of subnormality. Alsc to develop better methods for
the collection and interpretation of twin data in medical
research.

Methods Employed; A reporting system set up in 1937 by Dr. Kallmann

provided index information on a large number of
• mentally subnormal twins in Ke\j York State, mainly in the
State Schools for Mental Defectives. During the four year
period, July 1952 to June 1956, additional information vjas
abstracted from institutional records and obtained on visits
to hpmes and hospitals. Accessible twins v/ere examined,
many of them with the aid of x-rays, electroencephalograms,
and psychological tests.

Pairs studied in detail were classified as to zygosity.
Clinical diagnoses were reviewed in the light of all informa-
tion obtained. Case studies have been summarized and all
essential information is punched on McBee cards for statisti-
cal analysis.

Patient Material; The material consists of 585 multiple

b. rths represented by 725 index cases.
Over 150 pairs have Leer, studied in detail.

- 491 -

rart A., (cont.) M-3-i--4-, page 2

I'-Ia.ior Findings-; The work this year has consisted of reviewing cases
and coding data.

Significance to Mental Health. Research: The slu.dy provides leads for

further genetic research in
mental defect, and in some instances, like nonogolismj it
may provide decisive Inforiuation relevant to e:d.3tinp'
etiological theories.

iro:-osed OcdT^e of Project; Suin.narization of cases and coding of

data took longer than expected and may
continue into 1958. Analysis should be completed during
1958, and publications the following year.

lart 3 included Yes /x/ Wo /~7

- il-92

Serial No. M-S-i:-^ , page 3

rHS-NIK

Individual rroject Report

Calendar Year 1957

rart B; Honors, Awards, and i-ublications

Publications other than abstracts from this projects

Allen, Goraon and G. Baroff, "Mongoloid T\-ixns and Their Siblings,"

Acta Genet.. Basel, Vol. V, p. 294-326,
1956.

Allen, Gordon and F. Kallmann, "Mongolism in Twin Sibsb'ps," Acta

Genet.. Basel, Vol. VII, ^. 385-393,'
1957.

Other publications:

Alien, Gordon and I. Firschein, "The Mathematical Relations /uTiong

Plural Births," Ainer. J. Human Genet.,
Vol. IX, September 1957, p. I8l-9t.

Allen, Gordo. "iratterns of Discovery in the Genetics of

Mental Deficiency," Pis. Kerv. System.
1957, (In press).

Honors and Awards relating to this project:
I\ione

'+93

Serial No. M-S-P-5

1. Socio-environmental Studies

2. Commuaity & Population Studies

3. Bethesda, Maryland
PHS-NIH

Individual Project Report
Calendar Year 1957

Part A.

Project Title: Social Mobility and the Milieu of the Psychiatric Hospital

Principal Investigators; Leslie Schaffer and Leila Calhoun Deasy

Other Investigators? None

Cooperating Units; Adult Psychiatry Branch, M-Ap(C)-9.

Man lears (calendar year 1957); patient Days (calendar year 1957) s
Totals 1/3

Professional: 1/3 Rone

Other:

Project Descriptions

Described in full by Adult Psychiatry, Project Serial No« M"-Ap(C)-9.

Part B included Yes / 7 No J^

DATE DUE

Library, Acquisitions Unit
National in;.t.u::,. of
Building 10
Betiiesda, Maryland 28914

10 Center Drive

Bethesda, MD 20892-1150

301-496-1080

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