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

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ANNUAL REPORT 



F^ROGIRAMI ACTIVITIES 



[^ATIOMAL IMSTITOTE OF MEMTAL HEALTH 




FISCAL YEAR 1972 
PARTS l-ll 



us. DEPARTMFNT OF:M[ALTI-t RDUCATIGM; A^ 
UBIIC; HEALTH SERVICE NATiOIML mSlTfUT! 



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ANNUAL REPORT 



OF 
PROGRAM ACTIVITIES 



(J^ ^ . NATIONAL INSTIUJTE OF MENTAL HEALTH , /^2r/>/^»/ Mf^'^^ 
Fiscal Year 1972 



PARTS I-II 



ANNUAL REPORT 

MENTAL HEALTH INTRAMURAL RESEARCH PROGRAM - 
Division of Clinical and Behavioral Research, and 
Division of Biological and Biochemical Research 



NATIONAL INSTITUTE OF MENTAL HEALTH 
July 1, 1971 - June 30, 1972 



VOLUME I 
Summary Statements 



i 



ANNUAL REPORT 

MENTAL HEALTH INTRAMUR?lL RESEARCH PROGRAM - 

Division of Clinical and Behavioral Research, and 

Division of Biological and Biochemical Research 

NATIONAL INSTITUTE OF MENTAL HEALTH 

July 1, 1971 - Jime 30, 1972 



TABLE OF CONTENTS 

Volume I - Summary Statements 

Page 

Director , Mental Health Intramural Research Program 1 

Director , Division of Clinical and Behavioral Research 5 

DIVISION OF CLINICAL AND BEHAVIORAL RESEARCH 

Adult Psychiatry Branch 9 

Child Research Branch 27 

Laboratory of Clinical Psychobiology 35 

Laboratory of Clinical Science 41 

Laboratory of Psychology 49 

Laboratory of Socio-environmental Studies 6 3 

DIVISION OF BIOLOGICAL AND BIOCHEMICAL RESEARCH 

Laboratory of Brain Evolution and Behavior 73 

Laboratory of Cerebral Metabolism 83 

Laboratory of General and Comparative Biochemistry 91 

Laboratory of Neurobiology 95 

Laboratory of Neurochemistry 97 

Laboratory of Neurophysiology 101 

Office of the Director - Intramural Research Program 

Section on Technical Development 109 

I 



ANNUAL REPORT 
of the 
DIRECTOR, MENTAL HEALTH INTRAMURAL RESEARCH PROGRAM 
NATIONAL INSTITUTE OF MENTAL HEALTH 
July 1, 1971 - June 30, 1972 

John C. Eberhart, Ph.D. 



Perhaps the year just past can best be epitomized for the NIMH Intramural 
Research Program as the year when the total NIMH appropriation went up from 
approximately $400 million dollars to $600 million, while the strength of 
the Intramural Program, which has lost 20 percent of its manpower during the 
past five years, was slightly decreased. One could explain this in several 
ways, but it is clear that non-targeted research (the Division of Extramural 
Research Programs did not fare any better) was not seen in 1972 as the 
answer to the problems of mental illness. (The only budget increases for 
research were for drug abuse and alcoholism, which were the focus of much 
legislative and political action in 1972.) The pressure for widening the 
availability of such mental health services as can be provided on the basis 
of present knowledge seems considerably greater than pressure for new 
knowledge to provide more effective answers. The wisdom of this is yet to 
be tested. 

The pressures of a static budget along with increasing costs of research 
have continued this year, and all laboratories have felt the constraints. 
Adding to them have been Government-wide requirements that the number of 
persons employed be decreased by 5 percent, and that the average grade of 
full-time General Schedule staff members be reduced by .15 grades in fiscal 
'72 and by another .15 grades in fiscal '73. These requirements have been 
difficult to meet, and have made it necessary to treat the whole Intramural 
Program as a unit, utilizing vacancies where they meet the most urgent needs 
of the program and pooling "promotion points" to achieve an occasional 
crucial appointment as well as to make a few highly deserved promotions. 
Another effect of these constraints is an increase in the burden of adminis- 
tration, especially personnel and financial management, and costs for this 
have had to come from the IRP budget, thus further reducing the funds and 
positions available for research. 

A final effect of this support situation is the diversion of management 
effort and attention from the substantive aspects of science and the larger 
issues of management to the minutiae of administration. Though there is 
some question whether this fact diminishes the research output in any 
significant way, or lowers its quality, the possibility exists that it does. 
It is appropriate to point out here how much the program owes to the 
outstanding work of the IRP Administrative Officer, Mrs. Hazel Rea, who with 
the able help of her staff, has very competently handled regular adminis- 
tration along with the recurring crises and unusual expedients that have 
become almost routine. Her work has been a major contribution to the IRP 
as a whole since 1969, and to the Clinical Investigations portion since 
1954. 



Despite the personnel and dollar stringencies of the past year, the 
scientific work of the 15 Laboratories has continued at a high level, as 
the Lab Chiefs' summaries to follow indicate. It is always gratifying to 
report that others also have recognized the merit of many of the projects 
by the award of prizes and medals to scientists on our staff. Among the 
awards during the past year have been the following: Drs . William Bunney, 
Dennis Murphy, and Frederick Goodwin were co-winners (with Dr. Sjoqvist 
of Sweden) of the Anna-Monika Foundation Prize of $10,000, awarded in 
August 1971, in Basel, Switzerland, for their work on the switch process 
from depression to mania. Drs. Floyd Bloom, B. J. Hoffer, and A. P. Oliver 
received the $1,000 A. Cressy Morrison Award from the New York Academy of 
Sciences in December 1971, for their work in "Cyclic AMP Mediation of 
Norepinephrine Inhibition in Rat Cerebellar Cortex: A Unique Class of 
Synaptic Responses." Dr. Paul D. MacLean was awarded the Karl Spencer 
Lashley Prize of $2,000 by the American Philosophical Society in Philadelphia 
in April 1972, for "sustained leadership in research on evolution of the 
brain and nervous system, particularly the brain centers which he identified 
in 1952 as the limbic system." Dr. Michael Goldberg was given the S. Weir 
Mitchell Award by the American Academy of Neurology in May 1972, for his 
work on "The role of ttie primate superior colliculus in usually evoked eye 
movements." Dr. David Shakow was awarded the Distinguished Service Award 
by Division 12 at the American Psychological Association meeting in 
Washington, D.C. , in September 1971. Drs. Burr S. Eichelman and Lorenz K. 
Ng shared the A.E. Bennett Award of $750 in Dallas, Texas, April 1972; 
Dr. Eichelman for his work on "The Aggressive Monoamines," and Dr. Ng for 
his work on "the effects of L-dopa on the disposition of certain chemical 
substances in the brain." Dr. Ichiji Tasaki was awarded an honorary Doctor 
of Medicine degree by the Medical Faculty of the University of Uppsala in 
June 1972. 

Before leaving the recognition of our staff members, it is a pleasure to 
report the award by the Health Services and Mental Health Administration 
of the Superior Service Award to Dr. Floyd E. Bloom, Dr. Erminio Costa, 
and Dr. Marian R. Yarrow, and of the Public Health Service's Meritorious 
Service Medal to Dr. Harvey Mudd , in May 1972. 

To all these outstanding members of our staff, and to the many others who 
have done distinguished work, I take great pleasure in extending 
congratulations and thanks for a job superbly well done. 

During the year, work was begun on a major effort to review the research 
programs of the NIMH and to make recommendations for the future. 
Dr. Bertram S. Brown, in September 1971, appointed a Research Task Force 
to be chaired by Mr. James Isbister to examine all intramural and 
extramural research in order to "provide an overview of the scope and 
national role of the NIMH research programs; an assessment by a variety 
of relevant criteria of the benefits achieved and of the strengths and 
weaknesses of the effort to date; an analysis and projection of a hierarchy 
of priorities for mental health research and of administrative mechanisms 
for implementing them; and recommendations for organizational changes that 
may be necessary to strengthen the Institute's research arm." The remainder 
of the year was occupied in choosing and assembling a staff and in selecting 



members of the subject-matter working committees in the three areas of 
(a) basic research, (b) clinical research, and (c) research on services 
and methods of treatment. We are grateful to the Intramural staff members 
who accepted Dr.- Brown's invitation to join the staff or one of the 
working committees. The following will be staff members: Drs . Donald 
Boomer, Patricia Goldman, William Pollin, and Philippe Cardon. About two 
dozen others are members of committees . The first meeting of the total 
task force was held May 24, 1972. The report of the group is expected to 
be completed by June 30, 1973. 

A year ago I reported the beginnings of an Equal Employment Opportunity 
Program for the Intramural Program, and I want now to bring that account 
up to date. The Affirmative Action Plan has continued to guide our actions, 
and the EEO Council, as a unit and through its committees, continues to 
make recommendations, to raise questions, to inform and stimulate the 
interest of staff, and to exert pressure. At the beginning of the year, 
Mr. John Land replaced Mr. Garrett Bagley as Coordinator of the Council, 
and in September 1971, Dr. Allen T. Dittmann replaced Dr. Winfield Scott 
as Deputy EEO Officer. Dr. Scott, at his request, returned to the research 
which too often had had to take a lower priority. He did a fine job as 
Deputy EEO Officer, for which we are all grateful. 

As during the first year of the program, an important contribution has been 
made by the EEO Counselors. Serving in this post this year have been 
Mrs. Arliene M. Aikens and Mr. James Boone, for the second year, and 
Mrs. Gwendolyn K. Bookman. We have continued to have the valuable counsel 
of Dr. Marian R. Yarrow as Coordinator of the Federal Women's Program. A 
new appointee is Mrs. Doris Droke as EEO Investigator. 

In October 1971, a progress report for the first year of the EEO program 
was distributed to all hands. It revealed some gains and some problems. 
My own one-line summary of the report was that it showed reasonable progress 
under the rather difficult circumstances of that year. During the current 
year we have developed, at the recommendation of the EEO Council, a nev? 
procedure for recruiting minority candidates for vacant positions. It looks 
promising, but we will examine its usefulness at the end of the year. 

While on the subject of personnel, I would like to note with pleasure the 
establishment of a personnel office in Building 36 to serve the Intramural 
Program. It is actually a satellite of the Parklawn Personnel Office, made 
possible by authority and one budgeted position from tliat office, and by 
3 additional positions contributed from the diminished store of the NIMH 
Intramural Research Program. I regret the necessity for using almost 
irreplaceable research resources to staff the personnel office, but the 
function is so important to our operation that I saw no other recourse, 
given the unfortunate decision on assignments of personnel staff. We are 
greatly indebted to Mrs. Margaret Braymer, Personnel Officer for the 
satellite office, for her strenuous and successful efforts to provide good 
personnel seirvice under difficult conditions and with woefully inadequate 
staff support. 



Two members of our senior staff were on foreign work assignments in Italy 
this year. Dr. Howard Moss, Chief of the Section on Parent-Infant Behavior 
of the Child Research Branch, was stationed in Florence at the Harvard- 
Florence longitudinal development project, continuing his studies of 
behavior. Dr. Giulio Cantoni, Chief of the Laboratory of General and 
Comparative Biochemistry, divided his time between Rome and Milan, carrying 
out research on gene action and differentiation in eukaryotic cells. 

The Board of Scientific Counselors met twice this year, on October 29-30, 

1971, and on March 24-25, 1972. The fall meeting was devoted to a review 
of the research program of the Adult Psychiatry Branch, in part because 
the Branch had not been reviewed for several years, and in part because 
Dr. Lyman Wynne, Chief of the Branch, had resigned effective June 30, 1972. 
In making plans for the future of the Branch we wanted the advice of the 
Board, based on a comprehensive review and evaluation of the current 
program. Present for the fall meeting were all members of the Board — 
Drs. Eugene Bliss, Melvin Calvin, Walle Nauta, Robert Stubblefield, and 
Richard Solomon, Chairman, plus Dr. Douglas Bond, former Chairman of the 
Board, as a specially invited guest. At the spring meeting, the two days 
were spent reviewing three laboratories in the Division of Biological and 
Biochemical Research: the Laboratories of Neurophysiology, Neurobiology, 
and Cerebral Metabolism. Because of competing obligations, Drs. Calvin 
and Stubblefield were unable to attend that meeting. 

I would like to express my own thanks and appreciation, and that of the 
rest of the Intramural staff, to Dr. Bond and Dr. Theodore Ruch , whose terms 
on the Board expired June 30, 1971, and to Dr. Melvin Calvin, whose term 
expired June 30, 1972. They have been of major help in a sometimes difficult 
role, and we are much indebted to them. 

I have mentioned that Dr. Wynne will soon be leaving for the University of 
Rochester to become Chairman of the Department of Psychiatry. Also going 
to Rochester will be Dr. John Strauss. They will both be very much missed. 
Dr. Wynne's distinguished contributions have been commented on by Dr. Cohen. 
Early this year. Dr. William Bunney was appointed Director of the Division 
of Narcotic Addiction and Drug Abuse, and has had to give up most of his 
research in the Laboratory of Clinical Science. It is hoped that in due 
course he will rejoin the Intramural Program. Dr. Morris Parloff has spent 
the year in the Division of Extramural Research Programs as Acting Chief, 
Psychotherapy and Behavioral Intervention Section, Clinical Research Branch, 
and will become a permanent part of that staff on July 1, 1972. Our loss 
is clearly the extramural program's gain in this transfer. Finally, we 
were all saddened by the untimely death of Dr. William Caudill on March 24, 

1972. He had been a valuable member of the Laboratory of Socio-environmental 
Studies since 1960, and cannot really be replaced. 



Annual Report of the 

Director, Division of Clinical and Behavioral Research 

National Institute of Mental Health 

July 1, 1971 - June 30, 1972 
Robert A. Cohen, M.D. , Ph.D. 

As I write this report it is 19% years since I assumed my present duties 
and began the recruitment of our professional staff, and almost 19 years 
since we admitted our first patients to the Clinical Center. The date of 
my own retirement is approaching; perhaps it is not unnatural to find one's 
thoughts turning back to early program decisions and reflecting upon them 
in the light of current developments and of the problems we face today. 

Of the original group of six laboratory chiefs who finally assembled fifteen 
years ago, only one remains in Bethesda--David Shakow--who, although offi- 
cially retired, continues as creative and highly productive as ever. The 
other five--Drs. John Clausen, Joel Elkes, David Hamburg, Seymour Kety and 
Fritz Redl--have greatly influenced developments in the behavioral and life 
sciences, and hold distinguished chairs in their respective fields. In 
July, the first of our second generation of laboratory chiefs. Dr. Lyman 
Wynne, will be leaving to become Professor and Chairman of the Department 
of Psychiatry at the University of Rochester. In naming his successor, we 
are faced with the responsibility of deciding whether to maintain current 
studies essentially unchanged or to shift emphases somewhat in accordance 
with our best judgment as to possible seminal developments in behavioral 
research. 

From the standpoint of the Intramural Research Program, the recent decision 
of the Director of the National Institute of Mental Health to set up a task 
force to review the Institute's entire research program, to evaluate its 
achievements to date, and to make recommendations for the future is both 
timely and welcome. The present program of this Division was conceived in 
general outline when the budget of the entire Institute was 12 million dol- 
lars. We have long since gone far beyond the horizon which 19 years ago 
was dimly perceived and seemed light years away. There are more psychia- 
trists in residency training today than were members of the American 
Psychiatric Association then, and each year sees literally thousands of 
trained mental health workers joining our ranks. Although we were aware 
in those days of many of the problems which are of vital concern to the 
Institute today, there was no expectation that we would live long enough to 
be given the responsibility and some of the resources required to cope with 
them. 

In the early days of the program, we decided that intramural research funds 
could be most productively employed in the development of a basic research 
program which would attempt to define the nature and timing of the exper- 
iences which shaped behavior, and the biological processes which mediated 
it. Such knowledge is obviously indispensible for the development of a 
rational therapy, and hopefully might have implications as well for pro- 
grams designed to promote the optimal growth and development of the person. 



Even though the greatest strength of the Clinical Center lay in its re- 
sources for the study of biological processes in which each of the seven 
original institutes proposed to engage, we included in our program a com- 
mitment to the study of the social and behavioral sciences as well. These 
have obvious relevance for the study and treatment of mental disorders, 
and even though the groups concerned in such studies would be relatively 
more isolated in this hotbed of biology, there were still certain freedoms 
and supports built into the setting which afforded them a unique opportunity 
to engage in studies which could not be carried out in the average 
psychiatric hospital or university department. 



I 



As one looks back one sees that, as was to be expected, some of our investi- 
gations have been outstandingly successful in that they have added signifi- 
cant new knowledge and have opened important areas for further study; others 
are distributed along a scale at the end of which lie the negative results 
which constitute the necessary and important but nevertheless frustrating 
and disappointing burden of everyone who undertakes a career in research. 
Each of the laboratories and branches has made contributions which have 
brought it distinction, and have cast a reflected glow on the Institute as 
a whole. As measured by the honors conferred by their scientific colleagues, 
our staff members can justifiably consider that they have made good use of 
the resources placed at their disposal and can take great pride in their 
achievements. Even though these honors and awards have been distributed 
throughout the program, it does seem to me that the most dramatic progress 
has been made in the biological area. The growth of knowledge in physiology, 
biochemistry, pharmacology and molecular biology has been literally spectac- 
ular. That degree of control over human behavior which Huxley depicted in 
Brave New World though still distant can no longer be considered only a 
horror story created by a brilliant, imaginative novelist. Hopefully we 
shall be able to make more constructive use of our increasing knowledge. 
We must seriously consider the advisability of rechanneling our limited 
resources to augment our studies in those areas where progress is so rapid 
and the probable payoff appears relatively imminent. 

In a sense, the present dilemma was to be expected. Science does not 
advance equally rapidly on all fronts, nor are the problems facing each 
discipline of equal complexity. Biology in general was far enough along 
both conceptually and in terms of sophisticated methodologies that the 
really impressive progress which has been made might have been predicted. 
Nevertheless if, as we think, there is merit to providing optimal condi- 
tions for research for a critical mass of dedicated investigators, then 
we must conclude that the Clinical Center was so organized as to support 
very strongly the biological studies while offering comparatively less 
ideal resources for investigating the socio-psychological aspects of 
behavior. In my opinion, the Institute's research task force should con- 
sider the possible advantages of providing another research setting which 
would offer the social and behavioral sciences the remarkable and still 
unique assets the Clinical Center affords biology. Until we can develop 
a truly comprehensive knowledge of both the psychology and physiology of 
behavior we shall not achieve our goal. In another connection I quoted a 
statement by David Stafford-Clark which is appropriate here. In his 1959 



Mental Health Research Fund Lecture he described several exciting biological 
advances and then went on to say: 

"We must never forget that communication remains the ultimate 
key to the treatment of schizophrenia. .. .However skillful 
and appropriate our physical treatment. . .may become as a 
result of refinement in our knowledge and understanding both 
of the biochemical processes which may underlie it and the 
electrophysical processes whose secondary disturbance ultim- 
ately brings about the illness, it remains true that we can 
treat patients successfully and restore them to true health 
and happiness only if we can gain contact with them at a 
human and personal level, and give them thereby the bridge 
over which they may cross back to normal harmony and under- 
standing with their fellows." 



s4^ 



I 



ANNUAL REPORT OF THE ADULT PSYCHIATRY BRANCH 

National Institute of Mental Health 

July 1, 1971 - June 30, 1972 

Helm Stierlin, M.D., Ph.D., Acting Chief 

In the preceding fiscal year, Dr. Lyman C. Wynne, the long-time chief of the 
Adult Psychiatry Branch, had decided to leave NIMH in order to become Chair- 
man of the Department of Psychiatry at the University of Rochester, New York. 
Although he planned to continue his research work in the Office of the Chief 
until July 1, 1972 - the date set for the beginning of his work in Rochester - 
he resigned as Branch Chief. Dr. Helm Stierlin was subsequently appointed 
Acting Chief of the Branch. 

Dr. Wynne's decision affected the Branch on many levels: The Branch lost the 
leadership and stimulation he has given it for many years and, its bearings 
suddenly loosened, veered toward an uncertain future. Unfortunately, this 
happened at a time when resources were shrinking and government agencies had 
to achieve a grade roll-back and reduction in work force. The existing un- 
certainties and concerns about the Branch's future were thus magnified. More- 
over, the impending departure of two of the Branch's outstanding researchers, 
Drs. John Strauss and William Pollin, was recently announced. Dr. Strauss is 
scheduled to follow Dr. Wynne to Rochester in August, and Dr. Pollin will move 
to the Parklawn Building as newly-appointed Area Chief in the NIMH Task Force. 
(However, at this point it appears that Dr. Pollin will keep his section within 
the Intramural Research Programs and, hopefully, will return to the Adult Psy- 
chiatry Branch after a period of twelve to eighteen months.) 

It attests the vitality of the Branch that, despite these pending losses and 
uncertainties, a vigorous research program could be continued and expanded. 
A great variety of - mostly cooperative - research projects were carried out 
and substantial findings made, which have been published or accepted for pub- 
lication in numerous journals and books. 

Three major features have characterized the research in the Adult Psychiatry 
Branch during the last year: 

First, an ongoing, special effort to integrate clinical and experimental re- 
search on various levels. This integrated research drew on the patient popula- 
tion of two wards, an outpatient service and various community resources, 
including normal volunteers. Complementing its research efforts, the Branch 
offered several therapeutic programs that provided a needed community service 
and served as models for therapeutic efforts elsewhere. 

Second, while wide-ranging clinical and experimental research was carried out, 
conceptual frames of reference were employed and developed that increasingly 
allowed to link crucial bio-physiological to behavioral and sociocultural view- 
points and variables. Psychodynamic perspectives continued to hold here a 
central place. 



Finally, the research at the Branch attempted to reconcile a dispassioned 
empxrical stance toward facts with a sensitivity to the truly relevant social 
and mental health issues of our times. 

The organizational structure of the Branch, presently blurred by the above- 
mentioned changes and uncertainties, reflects three major, overlapping re- 
search foci: 

First, studies in schizophrenia, conducted chiefly by Dr. Wynne, by Drs. Strauss 
and Carpenter (Psychiatric Assessment Section), and by Dr. Pollin (Section on 
Twin and Siblxng Studies) and their associates. 

Second, clinical and experimental studies which primarily involve the family 
They are carried out by Dr. Stierlin (Unit on Longitudinal Studies, Office of 
the Chief), Drs. Roger Shapiro and John Zinner (Section on Adolescence and the 
Family), Dr. David Reiss (Section on Experimental Group and Family Studies) 
and Dr. Winfield Scott (Section on Clinical Psychology), and their associates. 

Third, cognitive and perceptual studies, as carried out by Dr. Monte Buchsbaum 
and hxs associates (Section on Perceptual and Cognitive Studies) . 

A brief description of the major research projects follows. 

OFFICE OF THE CHIEF 

Unit on Longitudinal Studies 

Dr. Helm Stierlin 

Dr. Stierlin's Longitudinal Project on Separation in Adolescence, carried out 
in cooperation with Drs. Robert Savard, Kent Ravenscroft, Jr., and others, has 
reached its crucial follow-up stage. Increasing numbers of adolescents and 
their families have participated in this project over the last five years. The 
adolescents - high risks for schizophrenia and other serious psychopathology - 
were referred to as "underachievers" and, together with their families, were 
seen for a minimum of three months in conjoint therapy. During the last two 
years most of these adolescents were hospitalized on 3-West while their families 
were seen in outpatient family and couple therapy. In addition to participat- 
ing m therapy, the family members were individually interviewed and compre- 
hensively tested Detailed predictions were made after the initial screening 
session and at the end of the therapy. These predictions are to be checked out 
by tollow-up interviews which have been or are taking place. 

Although many crucial observations and data from this project have not yet been 
obtained or analyzed, some interesting findings have emerged. Perhaps most im- t 
portantly, the project has already yielded a conceptual framework which promises " 
a much more detailed, as well as more comprehensive, understanding of the adoles- 
cent separation process than seemed possible before. Within this framework 
parents and adolescent children are viewed as contributing to dynamic and complex 
transactions that reflect their interweaving developmental tasks and life crises. 
Depending on how these tasks and crises shape up, are resolved, or remain aborted, 
certain typical separation patterns develop which have been called centripetal, ' 
centrifugal, and intermediate. Where a centripetal pattern prevails, a charac- ( 
teristic binding transactional mode is found to operate. Where a centrifugal 

10 



pattern doFxinates, an expelling mode is usually observed. Intermediate pat- 
terns tend to reflect a predominately delegating mode. Here we find parents 
who - overtly or covertly - send their children out and simultaneously hold 
them back. (The Latin word "delegare" contains these two meanings.) While 
delegating their children, the parents expect them to execute certain mis- 
sions - such as the mission to vicariously live out the parents' own unlived 
adolescence or the mission to launch protests against the Establishment. In- 
evitably, such parents burden their adolescents with their own unrealized 
expectations and their (the parents') disowned conflicts and ambivalences. 

The various theoretical and clinical implications of this point of view were 
developed in six papers which have either been published or accepted for pub- 
lication. The family dynamics of different types of adolescent runaways and 
parental perceptions of separating children, among other topics, were elabo- 
rated. In addition, typical constellations of adolescent separation conflicts, 
the interconnections between peer relations and the above transactional modes, 
the interpersonal dynamics of internalizations (such as incorporation, intro- 
jection and identification), the interweaving life crises of fathers and sons, 
and the family dynamics and separation patterns of preschizophrenic adoles- 
cents were newly conceptualized and clinically illustrated. Also, the con- 
cepts of psychological exploitation and liberation, the main themes of one of 
Dr. Stierlin's forthcoming books, were further developed. 

UNIT ON ART THERAPY 



The Systematic Study of Family Art Evaluations was conducted by Dr. James Dent 
and Mrs. Hana Y. Kwiatkowska. Utilizing factor analyses, the investigators 
have now defined the chief dimensions of the art productions and their rela- 
tions to such characteristics of the subject as his intelligence and his 
artistic talent. 

Family Art Evaluations were conducted with adolescents and their families on 
the 3-West Unit. Last year the focus of the study had shifted from schizo- 
phrenic subjects to patients with nonpsychotic problems such as delinquency, 
drug abuse, and truancy. This year the separation issue became the central 
point of observation. The adolescents and their parents revealed their ambi- 
valence over separation in the realistic and abstract family portraits they 
were required to draw. The adolescents either pictured themselves outside of 
the family group but still somehow clinging to it, or sought escape in fanta- 
sies. The opposite was observed in the parents: Their pictures showed a 
tendency to keep the family world encircled in a pretended happiness, and only 
hinted at a scapegoating of the index patient. 

As a result of this Unit's work, the interest in family art techniques has 
spread in the United States and abroad and a graduate course in Family Art 
Techniques, leading to a Master's Degree, is being offered at the Graduate 
School of Arts and Sciences of the George Washington University in conjunction 
with the Washington School of Psychiatry and is taught by Mrs. Kwiatkowska. 
Two exhibits of Family Art Therapy and Individual Art Therapy were presented 
by invitation at the Fifth World Congress of Psychiatry in Mexico City in 
December 1971. 



11 



PSYCHIATRIC ASSESSMENT SECTION 

The Psychiatric Assessment Section under Dr. John Strauss, Chief, with 
Dr. William Carpenter, Chief, Clinical Research Unit has continued to develop 
diagnostic concepts and categories that will more meaningfully relate to 
etiology, course of illness, and response to treatment, than diagnostic 
systems currently in use. It has employed standardized clinical assessment 
techniques, alternative diagnostic models, cross-cultural comparisons of 
psychiatric syndromes, and measures of course of illness. The following 
were major foci of research: 

I. International Pilot Study of Schizophrenia ; 

The Section has served as the United States Field Center in the International 
Pilot Study of Schizophrenia (IPSS) sponsored by the World Health Organiza- 
tion to develop cross-culturally applicable interview schedules for the 
evaluation of psychiatric patients in different countries. These schedules 
were intended to facilitate future studies of the comparative epidemiology 
and the interplay of cultural and biological factors in psychiatric disorders. 
The schedules were written, pretested, revised and retested until they were 
suitable for use in all nine participating countries. 

So far, 1,202 patients in the participating countries have been interviewed 
and have been followed up after two years. The information thus obtained 
will permit to compare the course of illness of patients with different S3nnp- 
toms and different forms of treatment in culturally diverse countries. 

The data from the initial evaluations have been incorporated into the final 
draft of Volume I of the report of the IPSS soon to be published. Data 
analyses of the follow-up interviews has been started and Volume II of the 
report is being drafted. 

II. Methodology for Analyzing Data for Psychiatric Diagnosis ; 

Together with Dr. John Bartko of the Theoretical Statistics and Mathematics 
Group, Drs. Strauss and Carpenter have evaluated and adapted clustering 
techniques for defining types of psychiatric patients. Such clustering 
techniques are only minimally subject to theoretical bias, and let the data 
itself define the "natural groups" that constitute a patient population. 
When applied to the IPSS patients cluster analytic techniques have revealed 
interesting groupings. In particular they suggest alternative subgroupings 
of schizophrenic patients. Affective psychoses are readily identified by 
cluster analysis and this approach supports therefore the diagnostic concept 
of a schizo-affective schizophrenia category. 

III. Comparative Study of Diagnostic Systems ; 

Different diagnostic systems have been evaluated using past psychiatric 
history and follow-up status as criteria for the validity of diagnostic types. 
At first, four diagnostic systems were investigated; (1) clinical diagnoses 
using the APA Diagnostic Manual; (2) computer derived clinical diagnoses 

12 



developed by J. K. Wing in London; (3) Lorr's Psychotic Types based on the 
In-patient Multidimensional Psychiatric Scale; and (4) clusters of psychiatric 
patients developed from the cluster techniques described in the preceding 
paragraph. Results indicated that none of the four diagnostic systems were 
able to predict significantly two-year follow-up status or to postdict earlier 
psychiatric history. On the other hand, multiple regression techniques 
demonstrated that prognostic items correlate highly with follow-up status. 

To further evaluate other diagnostic systems, the criteria of schizophrenia 
by Kurt Schneider were used to classify American IPSS patients and NIMH 
manic-depressive patients. This first empirical test of Schneider's diagnos- 
tic system, which is accepted throughout most of the world, refuted his claim 
for pathognomonic symptoms in schizophrenia. This finding has now been 
replicated using data from each of the eight other countries participating 
in the IPSS. Similarly, the value of Langfeldt's widely used concept of 
schizophrenia has been challenged through the use of IPSS data. 

These and other findings suggest that new concepts of schizophrenia must be 
considered. A dimensional concept of schizophrenia appears to be more valid 
than a typological notion. 

IV. Miscellaneous Studies ; 

In July 1971 the Psychiatric Assessment Section assumed administration of a 
clinical ward for acute psychotic patients. Standardized clinical instruments 
were developed to provide a coordinated system for evaluating patient symp- 
tomatology and behavior. A shortened form of the Present State Examination 
originally used for the IPSS, a daily nurses rating scale, and a modification 
of the Katz Adjustment Scale were used to provide comparable data on patients 
from three different sources of information. Scales were also developed to 
evaluate more global aspects of psychopathology. These scales collectively 
provided a reliable and comprehensive source of information about clinical 
characteristics of patients. As part of these evaluations. Dr. Michael Sacks 
compared the one-hour evaluation interviews with the entire data collection 
of the first three weeks of the admission period to determine the strength 
and weaknesses of the single research interview which is now being so widely 
used. Initial findings suggest that, while information from both the research 
interview and the larger source of data often result in the same diagnosis 
being given to a patient, certain aspects of the evaluation interview appear 
to be inadequate for indepth clinical studies. The reliability study of the 
nurses rating scale, variability in different nursing shifts, and contrasts 
in nurses' and doctors' observations have been evaluated by Dr. Bernard Frankel. 

In a continuing attempt to validate different snydromes and diagnostic types, 
the clinical characteristics of the patients on the research ward were com- 
pared to several biological, psychophysiological, and psychological variables. 
Leukocyte abnormalities, claimed to discriminate between normal, neurotic and 
psychotic patients by investigators from Prague, were evaluated in an attempt 
to replicate this work, and to determine more precisely what symptom patterns 
relate to leukocyte abnormalities. Steroid assays were conducted by 



13 



Dr. Laurence Drell, to understand the relationship between patient symptoma- 
tology, classification, steroid changes, and patient outcome. 

Harriet Wadeson, an art therapist in the Section, evaluated the relationship 
between art productions, symptom types and course of illness. Dr. Michael 
Sacks devised a creative method for evaluating a patient's course of illness 
in terms of his ability to participate in research. 

Collaborative studies were carried out with other investigators in the Intra- 
mural Program. Relationships between clinical characteristics and psycho- 
physiologica]. function were studied in conjunction with Dr. Buchsbaum in the 
Perceptual and Cognitive Section, Dr. Zahn in the Laboratory of Psychology, 
Dr. Redford Williams of the Laboratory of Psychobiology , and Dr. Carmi 
Schooler in the Socio-environmental Laboratory. The relationships between 
clinical characteristics and psychological test data were studied in conjunc- 
tion with Dr. Winfield Scott of the Section on Psychology, APB. In a collab- 
orative study with Dr. Herbert Meltzer of the Illinois State Psychiatric 
Institute, the relationship between abnormal enzyme levels and clinical 
states was investigated by using both the evaluation procedure developed in 
the Psychiatric Assessment Section, and serum enzyme levels to be evaluated 
by Dr. Meltzer at ISPI. Similarly, the PAS collaborated with Dr. Harold 
Himwich in investigating the transmethylation hypothesis in carefully evalu- 
ated clinical groups. 

SECTION ON TWIN & SIBLING STUDIES 



Despite unprecedented administrative and staff problems, which imposed con- 
siderable obstacles on research activities, the Section's work has proceeded 
in two major areas of continuing study - a) pathogenesis of schizophrenia, 
and b) personality development. 

A stress model of schizophrenia pathogenesis has been conceptualized, and 
after presentation at a number of meetings, is now in press. Unlike the 
weak ego boundary construct, which has been the most widely-used concept in 
clinical and dynamic schizophrenia research, in recent decades, but was 
found by us to be unsupported by empiric findings, this new model is consistent 
with and able to integrate a wide body of data ranging from the genetic, 
through the biochem.ical and experiential, to sociological levels of organiza- 
tion. For each step in the following sequence, hypotheses based on empiri- 
cally-obtained data have been defined, describing what change or deviation 
predisposes to schizophrenia. The sequence encompasses a) an external event, 
the potential stressor; b) the stressor's psychological meaning and signal 
(which is based on (1) previous experience, (2) role within the family and 
psychological characteristics of the family unit, and (3) role within the 
social structure) ; and c) the resultant biochemical and physiologic response 
on the cellular and organ level, (their extent, and possible qualitative 
abnormality determined by (1) genetically controlled levels of enzyme 
activity, and by (2) changes in enzyme levels induced by previous experience.) 



14 



Planning for a replication of previous work, using a new co-twin comparison 
study design, is far advanced, and extensive nationwide screening for 
specialized subject groups has been carried out. Arrangements have been 
made for collaboration with Dr. Harold Himwich at Galesburg to determine 
the presence or absence of psychotomimetic dimethylated indolamine deriva- 
tives; with Dr. Richard Wyatt, to determine the presence or absence, and 
possible genetic control, of the enzjrme (NN-nonspecif ic methyl transferase) 
which is capable of forming DMT, the most significant of these psychotomimetic 
amines; and with Dr. Axelrod and a number of his collaborators, to measure 
other enzymes involved in catecholamine metalolism. 

An extensive review of methionine studies, beginning with the initial one 
reported from here ten years ago by Pollin, Cardon and Kety, has been completed 
by Drs. S. Cohen, Pollin, Wyatt and Mrs. A. Nichols. The administration of 
very high doses of methionine, usually with MAO inhibitor, to chronic schizo- 
phrenic patinets, are attempts to test the hypotheses that disorders in 
biogenic amine metabolism, specifically disturbances in methylation, with the 
possible production of psychotomimetic di-methylated compounds, are involved 
in the pathogenesis of schizophrenia. The clinical phenomenon of exacerba- 
tion of psychosis in schizophrenic patients on large doses of methionine has 
been confirmed by nine subsequent investigators and as pointed out by 
Matthysse and Baldessarini in their just-published study, "is unique among 
biochemical findings in schizophrenia in that it has been confirmed by several 
groups and to date has been disproven by none." Our review analyzes the var- 
iations in treatment and response in the 107 patients thus far reported on, 
and evaluates the possible determinants and significance of these findings. 
The repeated confirmations of the original observation; plus new findings 
and techniques, such as Wyatt 's and Axelrod 's enzyme method in platelets, may 
signal major findings in this area in the near future. 

Mrs. Mae Leisinger, working on her Ph.D. dissertation under my supervision, 
tested a series of hypotheses relating the schizophrenic to family interaction 
and pathology. The conceptual frame of reference was that shared unconscious 
pathology of the family system generates interlocking tensions which are 
reduced and projected onto a particular member. TAT and Leary techniques, 
and data from the discordant-for-schizophrenia twin series, supplemented by 
additional matched normal control families, were used to quantitatively test 
self, ideal and other perception at three different levels of conscious aware- 
ness. It was found that individuals in the schizophrenic families unconscious- 
ly perceive themselves as very similar, whereas normal family members, instead, 
portray themselves as different one from the other within the families, with 
the father particularly being perceived as exhibiting a well differentiated 
role identity (the "undifferentiated ego mass" previously described by Bowen.) 
Further, there is substantial evidence, consistent with Laing's formulations, 
that the parents perceive the schizophrenic in terms that mis-define him to 
himself. In particular, the parental message for the schizophrenic is that 
he is passive and instrumentally unable to master his environment. These 
observations are consistent with our earlier clinical observations, in the 
discordant MZ pairs, that the index was rigidly imprinted with a role expecta- 
tion of incompetence and dependence. A significant relationship between such 



15 



disconfirmation of the index, and repression in the parents, strongly 
suggests that this disconfirmation is not primarily a process secondary to 
the illness. The higher the degree of parental repression, the greater the 
degree of parental disconfirmation of the index twin. This finding presents 
an interesting parallelism to the formulation of defensive delineations 
previously proposed by Roger Shapiro's group, and suggests that the discon- 
firmation is in part a process that is meeting unconscious psychological 
needs of the parent. 

Two major activities use the twin intrapair comparative technique to study 
the determinants of early personality development. Dr. D. Cohen, Mrs. Eleanor 
Dibble, and Mrs. Anna Nichols have been the major workers in this area. One 
is the longitudinal study in which 10 families, with sets of twins ranging 
between four and six years of age, have been followed since before birth by 
a series of home visits, and neurological, psychiatric and psychological 
evaluations. It has defined a set of interactions between constitution, 
family perception and behavior, and how these fit into a developmental 
sequence. The more competent newborn, physiologically and behaviorally, has 
bean found to develop into the more articulate and socially competent pre- 
schooler. A key component to such development is the better endowed child's 
ability to be both highly attentive to external stimulation and at the same 
time relatively calm, based both on endowment and intrafamilial relationship. 
Based on this intensive study, and on prior adult work, a new epidemiologic 
study has been initiated. Particular variables have been operationally 
defined, which emerged from the clinical observations, and 9 newly devised 
psychological questionnaries developed for this purpose. The first 100 of 
an eventual N of 600 twin families are now receiving their questionnaires. 

Though I will be transferred from the Section for the coming year, I hope 
these programs will be able to continue under alternative supervisory arrange- 
ments. 



16 



SECTION ON ADOLESCENCE AND THE FAMILY 

The research activities of this section, under the direction of Dr. Roger 
Shapiro and John Zinner, evolved around five major foci: (1) The Influence 
of Family Interaction on Adolescent Identity Formation, (2) The Relationship 
of Family Interaction to Adolescent Drug Abuse, (3) The Longitudinal Assess- 
ment of Cognition and Identity Formation in Early and Late Adolescents, 

(4) The Interrelationship of Behavioral and Physiological Events in the Family, 

(5) The Follow-up Study of Families Treated in the Study of Adolescent Identity. 
These investigations included observations made on the individual normal or 
disturbed adolescent and on his family, peer group, treatment milieu or class- 
room and community of families of which his is a member. 

Emotionally disturbed adolescents were admitted as in-patients to a residen- 
tial treatment center in the Clinical Center where they and their families 
participated in individual, marital, conjoint family and multiple family 
group therapy. Normal adolescents and their families, in the main, were 
studied in the Clinical Center, at the Sidwell Friends School in Washington, 
D.C. and in their homes. A brief description of these invetigations follows. 

1. The Influence of Family Interaction on Adolescent Identity Formation 

Many of the investigations carried out in this section were based on the 
intensive study of emotionally disturbed adolescents admitted to a long term 
intensive and comprehensive treatment program on the 3-West Nursing Unit in 
the Clinical Center. The range of symptoms and problems experienced by these 
teenagers is representative of the array of difficulties found among adoles- 
cents around the country, such as drug abuse, truancy, failure at school, 
impulsive behavior, running away and depression with suicidal attempts. This 
year the treatment and research program has been augmented by the initiation 
of a multiple family therapy meeting held each week. In this meeting, 
therapeutic work is done at the interface between the community of families 
and the treatment staff on 3 West, and on the boundaries between the families 
themselves. The multiple family meeting provides a major source of data for 
a predictive study of factors that influence the outcome of psychiatric treat- 
ment. This investigation is being carried out by Dr. David Reiss, Chief of 
the Section on Experimental Group and Family Studies, and is an application 
of his theory of consensual variety derived from the problem-solving behavior 
of families in the laboratory. 

A major aim of Drs. Roger Shapiro and John Zinner is to understand the ways 
in which family interaction facilitates or impairs the development of a sound 
adolescent identity. They have found that adolescents may be diverted from 
their own maturational course by a need to protect their parents from 
anxieties arising from unresolved parental intra-psychic conflicts. Papers 
reporting on these findings have been accepted for publication. 

2. The relationshiop of Family Interaction to Adolescent Drug Use 

Dr. Robert Winer has begun to investigate the use of "mind-altering" drugs 
by youth, employing intensive semi-structured interviewing of adolescents 

17 



with and without their families. Two-thirds of the in-patients on 3 West 
have made extensive use of "street drugs" prior to their admission. In 
exploring the motivations for their drug use with these patients, Dr. Winer 
has found that taking drugs represents the troubled adolescents' attempt to 
resolve potent internal psychological conflicts. This finding contradicts 
ones that view heavy drug usage as primarily socially determined, as for 
example, by the peer group. 

In the conjoint family interviews Dr. Winer has found that conflict over 
drug use becomes a focal point in the playing out of deep emotional conflicts 
within the family, such that the substantive issues regarding drugs become 
subordinated. Some families, in an effort to avoid conflict, which they see 
as a threat to family integrity, ignore the drug issue altogether and thereby 
perpetuate the problem. 

3. Longitudinal Assessment of Cognition and Identity Formation in Early and 
Late Adolescents 

The overall thrust of the studies by Dr. Stuart Hauser in the Section on 
Personality Development was to broaden and deepen previously developed tools 
for the measurements of identity formation described in his book Black and 
White Identity Formation. 

To broaden the studies, new populations have been sampled. The previous work 
concentrated on black and white lower socioeconomic class adolescent boys, 
following them in their course through high school. The current investiga- 
tion concentrates on middle socioeconomic class early and late adolescents 
of both sexes who are of patient and nonpatient status. Thus several con- 
trasts of interest are built into the design: patients-versus-non-patients; 
early-versus-late adolescents; male-versus-female adolescents; and each of 
the main groupings (Patients and non-patients) can be subdivided in terms of 
sex and age for intra-group comparisons as well. All of these subjects will 
be studied over a two-year period. 

The instruments for studying the subjects include a self-image interview, a 
Q-sort, and a battery of cognitive tests. The Q-sort is a major technique 
of the study as it focuses on self-images. Modifications of the Q-sort 
Technique developed for this project make it possible to focus on dimensions 
of each self-image as well as overall integration and changes in self-images 
for a subject. Both structural and content aspects of self-images are being 
analyzed at single points in time, and over spans of time. 

The cognitive tests focus on processes of categorization, differentiation, 
conceptualization, and problem solving. The cognitive data are being analyzed 
in terms of sub-sample differences at single points in time and change over 
time. 

4. The Interrelating of Behavioral and Physiological Events in the Family 

Clinical studies of family interaction carried out by this section have 
revealed the important role of anxiety as a subjective experience which 



18 



mobilizes and determines behavior within the family group. Customarily our 
behavioral observations are of the moment to moment verbal and non-verbal 
transactions within the family. On this time scale, anxiety is an elusive 
variable. Dr. Zinner, with the assistance of Mrs. Deborah Runkle, sought to 
gain access to this area of private subjective experience by monitoring the 
galvanic skin responses (GSR) of family members during family therapy sessions. 
The GSR is a peripheral reflection of more central states of arousal, and is 
a good measure of anxiety occurring durr'ng interactions among people. This 
year a quantitative analysis has been completed of verbal and physiological 
events in a pilot study of a group of families monitored at different times 
during their treatment. These data are being examined and meaningful 
physiologic variables are being selected for a study of family behaviors 
which govern the locus and intensity of anxiety within the family group. 

5. Follow-up Study of Families Treated in the Study of Adolescent Identity 

Approximately half of the families treated in the study of adolescent identity 
have been re-interviewed after varying periods of time following termination. 
Special attention has been directed this year to evaluating and interpreting 
the long-term meaning of the program for the parents who were in couples 
treatment. In reports prepared on this study Mrs. Carmen Cabrera and 
Dr. Sheldon Roth demonstrated that parents, precipitated into couples therapy 
by the adolescent turmoil of their children, have important capacities for 
intrapsychic and marital change. These changes are realized through sequen- 
tial processes of regression and progression in couples therapy described by 
the investigators as 1) loosening of ties to the original family, 2) renewed 
adolescence and early marriage, 3) return to parenting. A correlation 
between improvement in the emotional life of the adolescent and in the marriage 
relationship of the parents was observed. Mrs. Cabrera, in collaboration with 
Dr. Carl Feinstein, has been interviewing the remainder of the sample, to 
continue and expand upon earlier findings. 

SECTION ON EXPERIMENTAL GROUP AND FAMILY STUDIES 



This Section, headed by Dr. David Reiss, focuses its work on two interrelated 
objectives. The first, is the continued development of methods and theory 
for studying the relationship of the family to its larger social context. 
The second objective is theoretical: the development and extension of systema- 
tic principles for validating experimental studies of expressive and intimate 
behavior. These principles of validation serve to clarify and extend the 
empirical investigations of families and are designed for more general use 
in experimental social psychiatry and social psychology. 

1. The Relationship of the Family to its Social Context 

During the past year, with the assistance of a new member of the Section 
staff — Dr. Ronald Costell — the work of the Section has become focussed on 
the study of the family's interaction with its larger social context. This 
work takes advantage of previous experiments on family problem-solving con- 
ducted by this Section. These previous studies have strongly suggested that 
the family's capacity to solve problems presented to them depends on a 



19 



shared awareness and evaluation of its immediate social environment. If the 
family trusts its relationship with this environment and believes it has 
been given a soluble problem, it will perform effectively. If a family feels 
threatened by its environment and feels it is being given perverse and 
insoluble puzzles, it will huddle together protectively and its problem- 
solving will be ineffective. Shared perceptions of this kind seem to dominate 
the character of a family's interaction with its social environment. 

In order to extend these observations and determine their role in psychiatric 
treatment programs, Drs. Reiss and Costell have spent the past year complet- 
ing the first phase of a study of families of psychiatric in-patients. This 
study is being conducted at two institutions, the Psychiatric Institute of 
Washington, D.C. and Nursing Unit 3 West at NIMH. Both institutions use 
psychiatric treatment of the whole family as a central part of their program. 
The study is designed to determine the role of the family's shared evaluation 
of the ward social community — doctors, nurses and patients — in the treatment 
process. First, the family's typical affective response to a novel social 
environment is determined in the laboratory. Then, these laboratory data are 
used to predict their adjustment to the early phases of family treatment. 
Results of this study should substantiate the generality of our earlier lab- 
oratory findings and provide new insight into the detailed social mechanisms 
regulating interaction between families and their social community. In this 
sense, the psychiatric ward, though unique in several respects, will be 
considered a model of a large social community in which families operate. 
Since the Psychiatric Institute and Unit 3 West at NIMH differ in many 
respects, the study will also permit an assessment of how differences 
between social communities affect family-community interaction. 

This large-scale project has several subprojects for investigating smaller, 
more manageable questions. For example. Dr. Costell is perfecting a ward 
value questionnaire — used previously by this Section — for making precise 
comparisons between the two institutions. Dr. Reiss is completing an experi- 
mental study of psychiatrist-nurse-patient interaction to determine some of 
the effects of ward values on interaction in small groups. Drs. Reiss and 
Costell are completing additional experimental studies of family problem- 
solving to explore the detailed social mechanisms by which families evaluate 
their immediate social community. 

2. Extending Principles for Validating Experiments 

From its inception, the Section has attempted to design thoroughly objective 
and precise laboratory measures for studying subtle, intimate and expressive 
behavior in families. This is an unusual and difficult task for an experi- 
mental social psychology and Dr. Reiss has found that existing principles of , 
experimental design and validation are inadequate. During the past year he 
has nearly completed a monograph, entitled Validation in a New Key , in which 
existing concepts of validation are critically reviewed and revisions of 
these principles are presented. This project has two parts. First several 
recent developments in the logic of studying expressive behavior are reviewed. 
This review focuses particularly on the work of Langer and Devereux. Then 
the basic principles of content validity, convergent and discriminant 



20 



validity are extended into new principles termed, respectively, portrayal, 
analysis of configuration, and interpretative dialogue. All three attempt 
to show how experiments can be designed and their results interpreted to 
illuminate the expressive intent of experimental subjects. The continuity 
between clinical and experimental investigations is stressed. 

SECTION ON CLINICAL PSYCHOLOGY 

There were two main foci of research activities in the Section on Clinical 
Psychology. The first involved the study of small groups, particularly the 
family as a small group. The second involved individual psychodiagnosis. 
All research activities were rooted in clinical involvements with individual 
patients and families. In collaboration with investigators from other units, 
data were derived from various sources, ranging from laboratory measures of 
perceptual and cognitive functions, through standard and experimental psycho- 
logical tests, to psychotherapeutic encounters with individual patients and 
families. Families studied were those of psychiatrically impaired adoles- 
cents hospitalized on the Unit 3-West. Individual subjects studied ranged 
from normal volunteers to a large variety of psychiatric and neurological 
patients hospitalized for study by the Section on Psychiatric Assessment and 
by units of the Laboratory of Clinical Science. 

1. Family Studies 

In the study of the family as a small group, the major research activity 
involved administration of the Consensus Rorschach to families of psychia- 
trically impaired adolescents, followed by playback of video or audio 
recordings of the session to the families, and subsequently by retesting to 
assess the effects of the procedure on task performance and self-image. 

The family members are met in series of three sessions. During the first, 
the "Consensus Rorschach" is administrered. This is a procedure in which 
family members are asked to see how many agreements they can reach about 
what an inkblot looks like. The procedure is tape recorded and audio 
recorded. During the second session, depending upon the assignment of the 
family to one of several different experimental conditions, family members 
view or listen to themselves going through the first session, studying the 
relationship between interactional process and test product. During the 
third session, they are retested both with the Consensus Rorschach and with 
a paper and pencil psychological test. In some families a serious internal 
competition precluded their accepting the task of reaching agreements, or of 
finding a way to bring together their individual views without its necessarily 
meaning a victory or defeat for each of the individual members. Other 
families were unable to differentiate views sufficiently to permit the defini- 
tion of percepts. Yet other families were unable to organize around the task 
because of their inability to develop task-related role relationships in the 
test situation, or because of preoccupation with their discomfort in the 
test situation. The project thus provided the opportunity to study the 
family as a small group and is likely to result in a technique useful to 
apply as a part of the clinical evaluation of families prior to their 
beginning in family therapy. 



21 



II. Individual Diagnosis 

In the area of individual diagnosis, research activities included projects 
to study the relationship between performances on laboratory measures of 
perceptual and cognitive variables and styles of responding to the Rorschach; 
studies of patients who were acutely psychotic, including not only schizo- 
phrenics but patients with affective disturbances; and studies comparing 
patterns of deficit in intellectual functioning among patients with a variety 
of psychiatric and neurological impairments. Additional work was carried 
out on studies of the relationships between contrasting approaches to 
Rorschach responding and performances on laboratory measures of perceptual 
and cognitive variables. In the first efforts in this study, two contrasting 
approaches to Rorschach responses were identified. The first, the "Recogni- 
tory" approach is one in which subjects tend to respond to qualities of blots 
with associations to things previously seen. In the "Interpretive" approach, 
on the other hand, subjects attribute qualities to the blots which are not 
intrinsic in them, qualities such as movement and depth, and these become 
Important determinants of responses. It appears that the thinking and per- 
ception of subjects who have high scores on the "Recognitory" factor are 
largely stimulus-determined, and at times even stimulus-bound. Among normal 
subjects, relationships were established between Interpretive tendencies 
and scores on such laboratory measures of cognitive variables as the Embedded 
Figures test, a size estimation test and the Category Width test. It appears 
that there is a relationship between Interpretive tendencies and field 
independence. Further studies will be carried out with data on twins in an 
effort to establish other relationships with perceptual and cognitive variables. 

Research continues on studies of deficits in intellectual, personality and 
central nervous system functioning in contrasting groups of patients, includ- 
ing some with established central nervous system pathology, patients with 
acute affective disturbances and schizophrenics. Work has been extended to 
include some studies of the effects of a variety of drugs, including L-dopa, 
on patterns of deficit in intellectual functioning. As a result of work 
carried on during the past year, a challenge is presented to prior claims 
that intellectual functioning is improved by the administration of L-dopa 
to patients with Parkinsonism. Further studies in this area are being con- 
tinued. 



SECTION ON PERCEPTUAL AND COGNITIVE STUDIES 

Research in this section focused on disturbances in perceptual and cognitive 
behavior in psychiatric patients. Its work was closely coordinated with basic 
electrophysiological and perceptual research in the Unit on Psychophysiology, 
DCBR, NIMH. The finding of perceptual and attentional deficits in a variety 
of psychiatric patient groups encouraged the development of theories of psychi- 
atric illness and personality structure based on perceptual style. Special 
problems arise, however, in the study of perceptual behavior in those psychiatric 
patients whose perceptual behavior may reflect poor motivation, poor coopera- 
tion, failure to attend to instructions, or inability to communicate with the 
examiner rather than a perceptual difference. For this reason, this section 
has emphasized electrophysiological correlates of perceptual behavior using 
average evoked response techniques. 

In addition to methodological problems, the question of trait versus state has 
become important: Do the perceptual differences observed in psychiatric pa- 
tients reflect an underlying and relatively fixed biological characteristic, 
or are they related to the attentional, affective, or autonomic arousal state 
of the individual at the moment of the perceptual behavior? At a clinical 
level, the approach to this problem has been to compare two patient groups, 
those with affective disorders and those with schizophrenia. At different 
points in the psychiatric course comparisons were made between, on the one hand, 
correlations between perceptual behavior and day-to-day clinical ratings and, 
on the other hand, correlations between perceptual behavior and historical, demo- 
graphic, and genetic features. In comparisons of perceptual behavior in periods 
of mania or depression in cyclic patients with periods of depression in uni- 
polar depressed patients, diagnostic category as determined by patient history 
appeared to be more closely related to the perceptual behavior than was current 
patient mood as measured by nurse or physician ratings. Data on a large (83) 
population of patients with affective disorders are being analyzed. A group 
of drug-free schizophrenic patients is also being studied. 

In order to assess the relative importance of genetic and environmental factors, 
monozygotic and dizygotic normal twins have been studied using measures of 
autonomic and psychomotor functioning, average evoked response procedures, a 
battery of perceptual tasks, questionnaires, and interviews. Thus far, ap- 
proximately 60 twin pairs have been tested and the project is currently enter- 
ing the data-analysis phase. Family groups, both noimal and psychiatric, have 
also been evaluated. 

The effects of "state" variables such as attention and arousal have also been 
studied in normal populations. Comparison of the effects of muscle tension, 
painful stimulation, and shifts in attention toward or away from evoked re- 
sponse and stimuli have demonstrated the importance of each of these factors 
but have highlighted the importance of underlying individual differences in 
the habitual deployment of attention or the channeling of arousal. 

Three major perceptual dimensions have been investigated. The first, termed 
"stimulus intensity control," is based on recent studies of individual dif- 
ferences in responsiveness to sensory stimulation. Two different ways of 

23 



accepting sensory input have been hypothesized: The "augmenter" who tends to 
increase the perceived intensity of stimuli, and the "reducer" who tends to 
decrease it. Reducing, like habituation, may represent attempts to cope with 
sensory overload. Stimulus intensity control is being inferred from measure- 
ments of the average evoked response to varying intensities of auditory and 
visual stimulation. The second perceptual dimension, field articulation, 
describes the subject's ability to separate elements in a perceptual field. 
The Rod and Frame test, optical illusions, size estimation and the Gestalt 
figures are used to assess this dimension as well as an average evoked response 
measure of anchoring or contrast effects. The third perceptual dimension is 
that of perceptual variability. This is being studied with mathematical anal- 
ysis of average evoked response variability as well as error analysis on the 
perceptual procedures. 

Most previous clinical research in the perceptual area has utilized a cross 
sectional approach. This section has exploited the facilities of the 
Clinical Center in a variety of longitudinal studies where the physiological, 
perceptual, behavioral, autonomic, and biochemical measures can be followed 
in the same patient as the course of his psychiatric illness evolves. 



24 



PROJECTS OF DR. LYMAN C. WYNNE AMD DR. MARGARET T. SINGER 



The research programs of Dr. Lyman C, V^nne and Dr. Margaret Thaler Singer on 
schizophrenics and their families have been described at length in previous 
reports. In anticipation of Dr. Wynne's retirement from the Public Health 
Service on July 1, 1972, this year they have analyzed these accumulated data 
and prepared material for publication. Although a very substantial body of 
new findings, and new conceptual formulations based on these findings, are 
emerging from the recent data analyses, it is not appropriate, at the point in 
time at which this report is being prepared, to attempt a detailed simmiary of 
the year's developments. Instead, a brief outline of major recent directions 
will be presented here. 

(1) Dtiring l*i years of collaborative research Drs. Vtynne and Singer have 
assembled fifteen large loose-leaf notebooks of published and unpublished majiu- 
scripts. A primary goal this year has been to review this material, to gain 
perspective about both the data obtained and the evolving concepts used, and 

to distill as much of the material as possible for publication. 

(2) This process of review has stiggested several ways in which the data 
should be re-examined which, fortunately, can now be done more expeditiously 
than in the early days of this research because of the advent of computerized 
data processing. Follow-up data on families originally studied as long ago 
as 1958 are being incorporated into the computerized data pool, although a 
shortage of research assistance has made this follow-up less systematic and 
comprehensive than would have been desirable. 

(3) An effort is being made to review past clinical data about both index 
family members (the original presenting patients and their counterparts in 
normal control families ) and all of the other family members to see how fully 
new diagnostic schedules can be applied to case records which were begun years 
ago before current standardized diagnostic assessments were possible. (These 
assessment schediiles have emerged primarily from the WHO International Pilot 
Study of Schizophrenia in which Dr. Vlynne was an original principal investi- 
gator and which is described elsewhere in the work of the Psychiatric Assess- 
ment Section). 

(U) Drs. Wynne and Singer, with the able assistance of Mrs. Margaret Toohey 
and the consultation of Dr. John Bartko, have been analyzing and comparing 
data on families from several sources. In addition to llU diverse families 
comprehensively studied and followed-up in Bethesda, 59 families were tested 
and less fully examined in Houston. Earlier, these data from psychological 
tests, especially the Rorschachs, and a variety of demographic and clinical 
data, were examined in an over-all quantitative fashion, for example, comparing 
the frequency of communication deviances in parental Rorschachs. This year 
progress has been made in a much more detailed qualitative breakdown of these 
data, applying factor analytic and multivariate statistical techniques and 
evaluating a nimiber of specific hypotheses. As Just one example, Drs. %nne 
and Singer have hypothesized earlier that certain types of communication de- 
viances would be very frequent in the parents of schizophrenics but infrequent 



25 



in the schizophrenics themselves, and vice versa. This clinically derived 
hypothesis has now been confirmed and spelled out. Similarly, earlier hypotheses 
about the nature of the attentional problems of parents of schizophrenics have 
been confirmed. 

(5) Three other sources of family data have also been studied in detail and 
compared with the earlier Bethesda and Houston data. First, clinical and 
Rorschach data from fifty Japanese families have been evaluated further with 
the assistance of Mieko Caudill and the late Dr. William Caudill. An extensive 
paper on the important general issue of translating cross-cultural psychological 
materials was an off shot of this work. Unfortunately, because of Dr. Caudill 's 
untimely deabh, it is not possible at the present time to assess how fully the 
Japanese data can be interpreted without his assistance. 

Second, Rorschachs from parents in Uo London families, 20 having a schizophrenic 
offspring and 20 a depressed offspring, have been examined. Although Drs. 
Steven Hirsch and Julian Leff, the London collaborating investigators, had 
written a paper last year in which they attributed positive findings to an 
artifact having to do with the word count of the subjects, they now agree that 
this interpretation was mistaken. Unfortunately, their work does not represent 
a replication of the Bethesda family studies because of gross, systematic errors 
in the way in which their parental Rorschachs were administered. However, 
certain useful information is nevertheless forthcoming from this work, mainly 
from a study of the reliability of scoring with the Singer-Wynne Rorschach 
manual. This is helpful to Dr. Singer in preparing a revision of the manual. 

Third, another source of new data has been the Rorschach from 50 parents (25 
pairs) made available from the adopti -n studies by Wender and Rosenthal at 
NIMH. Earlier, Wender and Rosenthal had found that the mental health ratings 
and certain other measures, such as Zahn's word-association indices, failed 
to differentiate the adoptive parents of schizophrenics from the adoptive 
parents of normals, whereas the biologic parents of schizophrenics clearly and 
more severe, enduring symptomatic difficulties. In striking contrast, when 
aberrant parental communication was evaluated blindly in the parental Rorschachs 
by Dr. Singer, she found that the adoptive parents of schizophrenics had the 
most deviant communication, followed by the biologic parents of schizophrenics, 
with the adoptive parents of nonnals showing a lower frequency of deviances 
(a statistically significant difference). Indeed, Dr. Singer was able to pre- 
dict with 100^ accuracy which pairs of parents had a schizophrenic offspring 
versus a non-schizophrenic offspring, regardless of whether or not the off- 
spring was biologic or adoptive. This finding points to the importance of 
familial interaction processes. Further analysis of the data may help clarify 
whether the deviant parental communication in the adoptive schizophrenic sample 
is likelj' to have been enduring or was secondary and associated with recent 
distress about their adoptive offspring's status. 

Along with these and other analyses of family data. Dr. Wynne has been colla- 
borating with Dr. Buchsbaum in a study of psychophysiologic and perceptual 
"response dispositions" in normal twins. This work will be described elsewhere. 



26 



Annual Report of the Child Research Branch 

Division of Clinical and Behavioral Research 

National Institute of Mental Health 

July 1, 1971 - June 30, 1972 

Richard Q. Bell, Ph.D., Chief 

Psychiatrists, psychologists, and social workers were brought together 
in this branch in 1959 to carry out a longitudinal study, the purpose of 
which was to illuminate the development of social, emotional, and cog- 
nitive behaviors in the early phases of the life cycle. The period from 
early marriage through early childhood was selected so as to make it 
possible to specify whether certain characteristics of parents preceded 
or were a reaction to those shown by a child. A separate identification 
of parent and infant contributors to development was to be achieved by 
studying husband and wife characteristics prior to the birth of the first 
child, and the child's characteristics early in life before there could 
be any impact of the family environment. 

Section chiefs were selected who had long experience or special train- 
ing relevant to one of these phases, and who would agree to carry out 
their research as part of a coordinated branch study. Given very general 
objectives to achieve, each section chief was then permitted a period in 
which to prepare for the longitudinal study. They selected and tested 
measures, and carried out preliminary studies required to explore the be- 
havioral domain. To provide for independence of measurements between 
periods, the failure of which had been a serious shortcoming in previous 
longitudinal studies, four sections were organized with separate personnel 
to study (a) the newlywed period and later stages of marriage, (b) pregnancy 
and parent-infant interaction in the first year of life, (c) the newborn 
period, and (d) the early preschool and school ages. 

After the four teams were organized between 1959 and 1961, preparatory 
studies were carried out, and a trial series of cases was processed from 
the period of early marriage through the preschool years (Cohort I). The 
main Cohort of 2162 couples (Cohort II) was launched in 1966 by studies 
of early marriage that continued through 195 9. Between 1967 and 1970 the 
pregnancies, newborns, and three- and eleven-month-old infants were studied. 
Studies of the preschool phase were started in 1970 and will continue until 
1973. Samples for the phases after early marriage range from 100 to 130. 

We have mentioned that it was necessary for the scientists in our 
program to accept a limitation in their freedom to pursue various lines of 
investigation. This limitation was offset by the fact that they were 
selected on the basis of their known interest in pursuing research largely 
within the domain to which they were assigned. Nevertheless it was 
necessary for them to concentrate theoretical and methodological efforts 
within one area. Because of the need tc maintain similar measures for an 
entire cohort of cases, they had to maintain sustained data gathering 

27 



operations in which month -to -month or year-to-year variations could not be 
tolerated. However, I believe I can speak for the entire staff in saying 
that the rewards of being part of a larger research program, and of being 
concerned with common theoretical problems, have offset the disadvantages 
of not having complete freedom. It has been exciting to be part of an 
enterprise that is unique in attempting to put together a theory of the 
early phases of the life cycle. The common conceptual interest has led 
to a further advantage for the investigators, the fact that there was 
an interested and critical group of scientists always available to review 
and intensely analyze scientific reports prepared by any one of us. Hie 
longitudinal program also provided a ready sapply of cases for the prep- 
aratory studies, since teams studying earlier stages could readily pass 
along their cases at later stages for the next team. Bius there have 
been operational advantages that have complemented the theoretical 
advantages . 

Since each section is at a different point in the process of data- 
gathering, primary data reduction, secondary analyses, and reporting, 
the task of understanding the overall functioning of the branch at a 
given point in time is quite complex. Furthermore, many of the sections 
are still reporting results from preparatory studies. It will be necessary 
to keep in mind the distinction between preparatory studies, and between 
Cohort I and II. Some of the preparatory studies were not a part of 
Cohort I. 

Office of the Chief 

Interest in a 1970 biennial report on the status of our research was 
so great that it was necessary to order an additional 1000 copies of the 
pamphlet we had prepared. In addition to responding to requests, we have 
distributed the pamphlet to major investigators in the field of psychology 
and psychiatry. Our remaining supplies will be distributed to investigators 
in the field of sociology, social work, marriage and family life, and 
pediatrics. This biennial report was prepared with a scientific readership 
in mind, rather than professionals in the service occupations, or for semi- 
professional, or lay readership. We are now preparing the biennial report 
for 1972. 

It was not possible to undertake the second phase of organizing our 
data bank for Cohort II. During the previous year, we had completed the 
first step, consisting of a summary tabulation of tests, procedures, and 
interviews obtained for all subjects and all phases of the study finished 
to date. The second projected step was to organize a central branch data 
bank, in which would be deposited copies of final summaries of longitudinal 
data gathered in each section, with identifying information on case numbers, 
phases of the study on which data has been gathered, and completeness and 
adequacy of the data. As we complete our data gathering for the second 
cohort, and after each of the sections has analyzed and reported findings in 
which they have primary interest, it is planned that the branch will move 
into a period in which it will serve as a national data resource for 



28 



visiting scientists from the United States, and all over the world, who 
wish access to this unique kind of longitudinal data. Ihe launching of 
the second step was delayed by demands placed upon our administrator 
resulting from an unusually high volume of errors in payroll data, and 
from the special problems of administering our program during a period 
in which a personnel freeze and grade roll-back have made administration of 
the branch very difficult. It is hoped that we can make some progress on 
the data bank in this coming year . 

Scientific activities of the office of the Chief consisted largely 
this last year in synthesizing the results from preparatory studies, and 
reporting these results at various meetings in this country and abroad. 
At an International symposium concerned with society, stress, and disease, 
convened by the Karolinska Institute at Stockholm, I provided summary 
reports of the implications for stress contained in our research on 
(a) the process of early marriage, (b) the effects of children on parents, 
and (c) the relations of newborn and preschool behavior, A serendipitous 
result of attendance at this conference was that I received valuable help 
on some other data I have been analyzing from our studies of newborns and 
preschoolers. These data seemed to indicate that preschoolers whose 
mothers had received high levels of pre-delivery medication, for sedative 
purposes, were more assertive in barrier situations in the preschool period, 
A neonatal cardiologist at the conference, and two investigators who 
specialize in hormonal effects of stimulation in early infancy, suggested 
that the long-term results could have been due to the effects of anoxia 
on the infant, acting as a stressor on the hypothalamic-pituitary-adrenal 
cortex axis. Maternal sedation might have the effect of permanently 
resetting the level of the functioning of the infant's adrenal cortex 
system. If this were the case, one would expect the same results that 
have been obtained both in studies of lower animals as well as in one 
human study of vaccination in early life, namely that early stimulation 
produces greater body weight or height in later life, in addition to 
behavior differences. With this hypothesis in mind, when I returned from 
the Stockholm conference, I re-analyzed our data and found, as anticipated, 
that at least in one of our samples, the males, higher levels of maternal 
sedation were associated with above-average height in the preschool period. 

At the Winter Conference on Brain Research in Colorado, I discussed 
the above findings in a workshop group that had special expertise in this 
area. The discussions that developed from this workshop have led to ten- 
tative plans for a coordinated program of animal and human research 
designed to (a) test this hypothesis more directly, (b) test the action 
of specific drugs that are commonly used in obstetrical practice, and 
(c) identify a variety of later outcomes in development that might be 
expected on the basis of this original finding. Current plans call for 
a conference of Victor Dennenberg from the University of Connecticut, 
Yvonne Brackbill from Georgetown University, Evelyn Thoman from Stanford 
University, and myself, to lay plans for such a research program. My own 
participation in the project will be limited to analyses of data available 
in the branch longitudinal program, because our data gathering resources 



29 



are completely consumed in our own longitudinal study. 

The plan for a coordinated and comprehensive program of animal and 
human research in this area is an exciting one, and has considerable 
potential for benefit to the public. It has long been known that some 
sedatives given the mother during labor are transmitted to the infant, and 
tend to concentrate in the brain. However, it has been thought that the 
effects were temporary, and primarily affected the liveliness of the 
infant's feeding and response to the mother. Now, Dr. Brackbill's work 
in the first few months, and ours, covering a longer time span, indicate 
that there are likely to be long-term effects of maternal sedation that 
must be reckoned with. 

From the Stockholm conference I went to Nijmegan, Netherlands, for 
the first symposium of the International Society for the Study of Behavioral 
Development. At this symposium I reported the gist of our findings on 
behavioral relations between the newborn and preschool period. From the 
Nijmegan meeting I went to visit M. P. M. Richards, who is carrying out a 
longitudinal study at Cambridge, England. We had an opportunity to further 
discuss the findings on the long-term effects of drugs. Dr. Richards has 
data supporting both Dr. Brackbill's and our own findings, and further 
indicating the need for opening up this new area of research. At that 
time we discussed the possibilities of collaboration in order to utilize 
data from one other longitudinal study carried out in England, in which 
there is excellent information on maternal sedation and later development. 

Later in the year I attended the Third Symposium on Oral Sensation 
and Perception in Bethesda, for which I provided summarizing and perspec- 
tive comments on the overall conference. At this conference, a specialist 
on histological study of the development of the skin provided information 
that may contribute eventually to understanding both the decline over days 
in tactile threshold that we have noted in newborns, as well as the rela- 
tionship of absolute level of the tactile threshold to later preschool 
behavior. Apparently, free nerve endings grow very rapidly in response 
to an increase in oxygenation that occurs after birth. The decrease in 
threshold could be due to this response to oxygenation, and those who show 
high thresholds during the newborn period, and assertiveness in barrier 
situations during the preschool period (just as the infants whose mothers 
received high levels of sedation during labor) may be less adequately 
oxygenated than those whose thresholds are low and who are unassertive in 
later development. Consistent with the picture of low oxygenation for the 
high threshold infant is the fact that their respiration rates are usually 
characteristically low. 

At the La Jolla conference on self-regulation, sponsored by the 
University of California, Berkeley, I presented a paper on biological 
contributors to self-regulation. Ihis paper summarized evidence from our 
own newborn to preschool studies, as well as findings from studies of 
heritability, that there is a substantial constitutional contributor to the 
dimension of extraversion-introversion, and that four components of this 



30 



dimension can be identified as early as the second or third year of life. 
Exploratory behavior is also important in self -regulation, and here again, 
congenital contributors have been identified in our research. Finally, 
hyperactivity was pointed out as a very salient defect involving self- 
regulation; a stronger congenital contributor has been identified in 
this area than in any of the others, namely the association of minor physical 
anomalies with hyperactivity. 

In March I assisted on a site visit to a project at the University of 
Rochester that is searching through the neonatal period for differences in 
behavior between infants born to schizophrenic mothers versus mothers with 
personality disorders or neuroses. It was very gratifying to see the ex- 
tent to which this project had been built upon findings from our own studies 
of newborns and of early infancy, and the extent to which our experience in 
longitudinal studies has assisted the development of their research strategies, 

Section on Family Development 

Since this section launched the studies of the second Cohort, it is 
the first to complete the process of primary data reduction, and has essen- 
tially moved into a phase involving higher order data analysis and report- 
ing. New methods have been developed for clustering self-descriptive terms, 
and for identifyi^ng sequences in marital interaction data. Factor analyses 
of interaction data have been carried out to check results from Cohort I. 
Our concern t±iat this trial cohort would not be representative of a broader 
sample of marriages has been allayed by the replication in the Cohort II data 
of the factors previously obtained. However, the increased size of the 
Cohort II sample permitted the extraction of some additional factors . 

Current reports from the section indicate application to issues and 
hypotheses in the larger field of marriage, as well as to our longitudinal 
data. For example, our marriage data have been used to demonstrate that 
previously reported decreases in marriage satisfaction, following having a 
child, are primarily a function of the wife's feeling that her husband has 
become less attentive to her. One other paper attacks the generality of the 
concept of power in family relations, and suggests new distinctions between 
kinds of power. One report taps not only the longitudinal data, but other 
samples the section has been studying, in order to describe unconventional 
marriages. The report indicates that our affluent society has contributed 
to the development of such marriages, that they show some novel features, 
such as the handling of sexuality and tension, but that they also show 
some of the attributes of conventional marriages. All in all, the section 
shows great versatility in the range of its scientific reports, from highly 
empirical and sophisticated methodological studies through to impressionis- 
tic explorations into new forms of relationships . 

Section on Parent -Child Behavior 

The personnel of this section were the second team to be in contact 
with Cohort II, in the case of the marriages that led to pregnancies in the 
first three years. Blanche Jacobs has supervised research assistants 

31 



engaged this past year in coding, processing, and preliminary analyses of 
data from interviews, questionnaires, home observations and laboratory 
studies, extending from pregnancy to home visits at eleven months postpartum. 
Mrs. Jacobs has made excellent progress with the data, supplying the section 
and project chiefs, both of whom are in foreign countries this year, with 
the results of ongoing analyses. She has constantly adjusted the activities 
of the branch to changes in direction that were supplied. Much of the data 
has been carried beyond the point of computer storage to first level analysis, 
such as the derivation of combination and pattern variables. 

If this section is able to continue at its present pace, the data will 
largely have reached a stage sufficient for higher order analyses that can 
be carried out by the section chief on return in the fall. These analyses, 
in turn, will make it possible to begin interrelating the data from preg- 
nancy, the newborn period, and early infancy. 

Section on Infant Development 

The section was the third in order to study the Cohort II cases in 
which pregnancies had occurred. They concentrated on the newborn period, 
even though it occurs between two phases of development being studied by 
the previous section. The practical difficulties of carrying out studies 
in hospitals, and with a subject whose viability is still tentative, re- 
quires specialized personnel such as nurses, and different approaches to 
data gathering. Ray Yang has directed the data analysis since December of 
1971 and, with the help of two of the three nurses who carried out the 
newborn assessments, has brought the task of primary data reduction very 
near to completion. It is some indication of the magnitude of this task, 
and of the morale problems engendered in maintaining day-to-day coding, 
that it has been necessary to translate over 35,000 feet of polj'graph 
tracings into forms that could be analyzed by computer. 

In addition to bringing the primary data analysis close to completion, 
Dr. Yang has prepared a report this year on neonatal responses to tactile 
stimulation. The stimulation was produced by an apparatus that programmed 
increases in the intensity of air jets delivered to the skin, and that 
produced repeated stimulations once threshold levels had been reached. 
Most studies carried out by other investigators have indicated the relative 
absence of an orienting response to stimulation in the neonate, as would be 
shown by deceleration of heart rate above pre-stimulus levels. They have 
found an acceleration, as would be expected in a defense reaction. Our 
data have confirmed this general picture, despite the addition of a feature 
that might have altered the function. Most of the prior investigations have 
not used stimulus levels adjusted to the infant's own threshold. No sex 
or state differences have been found in the heart rate response to tactile 
stimulation, and thus it will be possible to use it in the longitudinal 
study without elaborate adjustments. 

Since previous studies in this section have indicated that factor 
analyses and other higher order forms of data analysis have little to add 
to the longitudinal validity of the neonatal data. Dr. Yang is preparing to 



32 



move from the primary stage of data analysis directly to the task of relat- 
ing newborn data to variables from pregnancy and later infancy. The pace 
of data analysis in this section, and in the Section on Parent-Child 
Behavior, seems to be favorable for joint efforts in the coming year. 

Section on Child Behavior 

The major task of this section, the last team to study Cohort II cases, 
is to maintain a consistent set of procedures and observations through 1973, 
at which time all of the children bom to Cohort II families in the first 
three years following the marriage studies will have passed through the 
early preschool phase. The preschool follow-up has proceeded far enough 
that we can estimate a final sample of approximately 130 children from 
Cohort II. This is a somewhat larger sample than has completed some of the 
other phases, such as the newborn period, since the Section on Child Behavior 
has undertaken the assessment of all cases studied in early marriage, whether 
they have completed the intermediate studies or not. It is not necessary for 
cross-stage analyses starting from different points of time to utilize 
exactly the same sample. In fact, the larger the sample available for any 
given comparison the better, providing there is no selective factor operating 
to produce differences between cases that have not missed a phase versus 
those who have. 

The effort to accommodate the maximum number of cases studied in earlier 
phases has resulted in overloading the schedule for processing groups through 
the nursery school, and the staff of this section is to be commended for the 
sacrifice of the usual vacation periods, as well as interim periods between 
groups, ordinarily used to catch up on data gathering, in order to study as 
many children as possible at the time they reach the age range which has been 
set for the study. 

This section is currently conducting intra-branch case conferences for 
selected children and families that have completed the preschool phase. It 
is quite a task to collate the vast amount of information available from 
early marriage through to the preschool period, even for a single family. 
Currently, each section prepares a written summary on two children and 
families to be contrasted in the case conference. The case conference 
itself is largely devoted to discussion of these summaries, and their 
integration by the staff members who have had a prior opportunity to study 
all reports. The summary reports include a final study of the marriage 
as such, based on interviews conducted by the section on family development 
when the child and family have completed the preschool period. It is grati- 
fying to reach a stage in our studies where we can have such case conferences. 
In past preparatory studies, these conferences have led our staff to reorient- 
ations, such as toward the appreciation of the impact of children on their 
parents . The insights we obtain have not only led to important contributions 
to the child and family development field at large, but have helped us to 
adjust our analysis of the data to trends that can be seen in individual 
cases but that might not appear in surveying data from large samples. 



I 



33 



Despite being involved in a very difficult and demanding data gathering 
process, the Section on Child Behavior has been able to make some progress 
in preparing reports from our preparatory studies on relations between 
preschool and early school-age behavior. These results were reported at 
scientific meetings in the last year, and are now being prepared for publi- 
cation with some of the feedback in mind that was received at the national 
meetings . 

Summary 

When the study of Cohort II was launched in 1966 it seemed to many 
scientists in the field, and even to those of us who have been engaged in 
preparing for the study since 1959, that it was an extremely ambitious 
undertaking to try to keep four teams of investigators working together for 
seven years on phases of the human life cycle differing as much as early 
marriage and child rearing. However, some basically new information on 
human lives can only be gained by trying new approaches , and at this point 
in the story of our longitudinal study we are far enough along that we can 
at least say that the task of data gathering and analysis will be completed. 
The coming year should bring the first glimpses into the relations between 
stages. In the meantime, our enthusiasm for the task is maintained by the 
many exciting developments that have come out of preparatory studies that 
led to Cohort II. In past reports I have mentioned one finding alone from 
these studies that, in terms of public benefit, could more than return the 
cost of our years of study. I am referring to the finding of an association 
between minor physical anomalies, that can be assessed as early as the 
newborn and third month of life, with hyperactivity in later childhood. 
Hyperactivity is one of the most frequent bases for referral to treatment 
centers in early childhood. 

In the present report I have mentioned an equally promising development. 
If our findings on the long-term consequences of sedatives given mothers 
during labor should lead to a new series of studies on drugs and infant 
hormonal response, there is a prospect of revision in current thinking 
about the effects of this aspect of obstetrical practice. Again, the 
benefits to the general public in understanding the later consequences of 
obstetrical procedures could be considerable. 



34 



Annual Report of the Laboratory of Clinical Psychobiology 
National Institute of Mental Health 
Frederick Snyder, M.D., Chief 
July 1, 1971 — June 30, 1972 

The metaphor which seems most apt to describe the Laboratory of 
Clinical Psychobiology during the past year is that of an amoeba contracting 
and extending at the same tirae--sending out vigorous pseudopods despite 
continuing diminution of its total corpus. Termination of the clinical 
research and treatment unit which had been the heart of our earlier program 
involved very significant reductions in our professional staff which will 
proceed still further at the end of this fiscal year. Yet a new clinical 
project has been successfully launched without the use of a nursing unit, 
one devoted to outpatient insomniacs, while the small remaining staff has 
given good account of itself in strong psychobiological projects employing 
patients from other organizational units, normal volunteers and 
experimental animals. 

The most conspicuously successful efforts this year have been 
those on the psychobiology of aggression in the rat, for which 
Dr. Burr S. Eichelman was co-winner of the A.E. Bennett Research Award 
in Basic Science from the Society of Biological Psychiatry. This is the 
second successive year in which this Laboratory has been so honoured, 
since Dr. Richard J. Wyatt received the same prize last year for his work 
on the biochemistry of human sleep carried out here. Although 
Dr. Eichelman 's approaches to rodent aggression are wide ranging, encompassing 
(a) genetic differences, (b) experimental manipulations, such as hunger, 
thirst, stress, sleep deprivation and alterations of sensory input, and 
(c) brain lesions, perhaps his most profitable directions have involved 
various pharmacological manipulations and biochemical measures in 
collaboration with members of the Laboratory of Clinical Science. They 
have enabled him to generate a categorical division of rat aggressive 
behavior into three types having quite distinct biochemistry underlying 
them. Predatory behavior appears to be influenced by serotonergic and 
cholinergic systems, spontaneous intra species aggression seems related 
to dopamine, while irritable aggression, such as results in the standard 
shock-induced response, is most consistently associated with norepinephrine 
and is facilitated by activation of norepinephrine receptors. This 
reconceptualization of the biology of aggression has already served to 
make sense out of a great deal of evidence which had previously seemed 
contradictory and chaotic, and may well be pertinent to future thinking 
about human aggression. To make this still more a "year of aggression" 
for the Laboratory, Dr. Eichelman organized a series of seminars on the 
study of animal models of aggression during which we were privileged to 
hear from a number of the most outstanding experimentalists now 



35 



pursuing that topic in this country. 

A second yery profitable new area has been Dr. Redford B. Williams' 
pursuit of the cardiovascular correlates of varying transactional 
behaviors both in human and animal subjects. Like Dr. Eichelman's 
contribution, these studies promise to clarify much past confusion about , 
the concept of physiological arousal, so crucial to psychiatric thinking. 
In essence they suggest that the somatic correlates of arousal have 
directional as well as intensity properties depending upon whether it is 
in response to internal or external stimuli. Behaviors associated with 
attentive observation of the environment give rise to a norepinephrine 
pattern of bodily response resembling that of peripheral sympathetic 
nerve activation, while rejection of environmental stimuli or attention 
to internal stimuli yield an epinephrine pattern of cardiovascular response, 
like that due to adrenal medullary activation. If attentiveness to i 
environmental stimuli is an important determinant of cardiovascular 
response, then persons who differ in terms of characteristic ways of attending 
to stimuli might be expected to differ in terms of their typical cardio- 
vascular functioning. That possibility has been tied in with the interest 
of Dr. Monte Buchsbaum of the Laboratory of Psychology in "augmenters" and 
"reducers" of incoming external stimuli, augmenters proving different 
from reducers both in their resting cardiovascular measures and in their 
responses to experimental arousal . 

Dr. Williams' studies appear to have at least one important 
clinical implication for plotting the course of somatic arousal over the 
natural history of acute psychoses. Serial studies of forearm blood flow 
in a number of acute schizophrenic patients have now documented marked 
increases in forearm blood flow, presumably reflecting escalation of 
anxiety levels, just prior to major change in clinical status, most 
frequently resolution of psychotic symptoms, but in a few instances prior 
to thetr recurrence also. 

Along the same lines, collaboration between Drs. Williams and 
Eichelman has resulted in some provocative findings regarding the 
psychobiology of blood pressure responses in the rat. Specifically, rats 
of certain genetic strains shocked in pairs and fighting in their 
usual stereotyped fashion were shown to have a blood pressure fall 
immediately afterwards, although the same rats receiving shocks alone 
exhibit only disorganized escape attempts and have a subsequent blood 
pressure increase. Going on to elucidate the physiology underlying this | 
curious "social" influence on hypertensive response, they demonstrated 
that hypotension after paired fighting depends upon intact peripheral 
and central sympathetic nerve activation, while an intact adrenal medulla 
is equally necessary for the blood pressure rise found after the escape 
response to shock alone. Further evidence indicates that the strains of 
rats with blood pressure increases after fighting have low serum dopamine- 



36 



B-hydroxylase levels, while all strains with blood pressure decreases under 
the same conditions have higher levels of dopamine-B-hydroxylase. 

The above studies illustrate how important it is to a unit as 
small as this one htat it has such rich and flexible opportunities for 
collaboration with other units of the NIMH Intramural program, as well as 
with other Institutes at NIH. The value of collaboration in the face of 
depleted staff is also exemplified by our partnerships with two alumni, 
Drs. Wyatt and Gill in, who continue to channel large portions of their 
efforts into project here even while building an independent sleep research 
facility in the Laboratory of Clinical Psychopharmacology, St. Elizabeths' 
Hospital . Only by virtue of their initiative have we been able to continue 
studies of sleep biochemistry and pharmacology during the past year, 
examining effects of histidine, ^^Tetrahydrocannabinol , carbohydrate active 
steroids and various catecholamine precursors on human sleep. Other 
promising collaborations begun during the past year are with Dr. Robert 
Coursey of the Department of Psychology, University of Maryland, who has 
joined our efforts to fathom the psychological make-up of insomniacs, as 
well as with Miss Evelyn Elwell of Catholic University, Department of 
Nursing, who is undertaking a doctoral project with us on the changes in 
sleep patterns prior to and following open heart surgery. We are also 
most grateful for the help of Dr. Andrew G. Morrow, Chief of NHLI Surgery 
Branch, for welcoming our studies of sleep in his cardiac patients at the 
time of surgery. Not all collaboration work out, however, and several 
we had undertaken with the Walter Reed Institute of Research fell by the 
wayside during the past year. Projected studies of spontaneous rhythms 
in waking psychophysiology and of effects of adversive conditioning stress 
on sleep of monkeys were begun, but had to be abandoned when Dr. Tom Frazier 
left Walter Reed and Dr. William Orr was reassigned to other duties. As 
discussed in a recent review of available evidence about sleep patterns in 
psychiatric illness, effects of chronic stress on sleep is a crucial 
question still unanswered. If the anticipatory stress of impending 
open heart surgery is a natural and human counterpart to the stress we were 
attempting to produce experimentally in monkeys, we may soon be able to 
remedy that deficiency. 

Another experimental approach to the consequences of stress now 
underway employs the widely used model of immobilization stress in 
laboratory rats. In keeping with findings from the Laboratory of Clinical 
Science on central biochemical changes resulting from that procedure, 
our Laboratory has found concomitant changes in aggressive responses 
or blood pressure, and work still in progress appears to demonstrate 
even more striking changes in the nature of sleep, drastic attrition of the 
REM phase qualitatively similar to that we have previously described in 
acute schizophrenic and manic psychoses. 



37 



Throughout our many years of studying sleep in psychiatric 
patients there was the nagging question of what sleep patterns might be 
like in less ill persons who complain only of inability to sleep. Might 
the sleep of the millions who call themselves insomniacs be even more 
disturbed and abnormal than the anomalies we have found in severely depressed 
or acutely schizophrenic patersons? The problem was that insomniacs could 
not be enticed to spend their nights in our laboratory while we recorded 
their sleep patterns. Dr. Bernard Frankel finally overcame that 
difficulty during the past year by offering a therapeutic trial of 
"transcerebral electrotherapy" (the so-called electrosleep widely 
employed in the Soviet Union and eastern Europe but tried very little in 
this country) to insomniacs in exchange for our access to their sleep 
patterns. Although the number of respondents has not been over-whelming, 
by this means we have been able to initiate a more thorough study of 
insomniacs and their sleep patterns than any now available in the world 
literature. The possible effects of transcerebral electrotherapy would 
be of interest in themselves if we could demonstrate them. Unfortunately, 
results of that treatment thus far have not been encouraging in our 
population of insomniacs, except insofar as they have given us the chance 
to take an objective look at insomnia. Contrary to some rather sketchy 
earlier reports, we do find abnormalities of sleep corresponding to the 
Insomniacs' complaints. Compared to age-matched controls their sleep is 
delayed, abbreviated and fragmented, yet the degree of such impairment is 
rather slight compared to the extent of the patients' complaints and 
obsessive concern. Nevertheless, since sleep EEG patterns alone may not 
reveal everything unusual about insomniacs, we shall continue our studies 
of them on a broad front, gathering every accessible information about 
their psychology and physiology during waking as well as during sleep. 

Fully interpreting the significance of alterations in the internal 
architecture of sleep, whether the rather minor ones of insomniacs or the 
much more drastic ones of psychotic depressives, will not be possible until 
we have achieved much addittonal understanding of the basic biological 
significance of sleep and its component states. It is to that end that 
our long-term program of comparative studies of sleep is devoted, looking 
for clues in the varied manifestations of sleep to be found in diverse 
animal forms, as well as in the effects of experimental variables similar 
to those encountered in the natural course of animal life. Devising the 
technical means to achieve such studies has been a long and still 
continuing struggle. We have arrived at satisfactory, albeit still very 
laborious expedients, which do now provide the necessary information. 
With them we pursue our longstanding interest in the prototypical 
characteristics of mammalian sleep as found in a number of expecially 
primitive forms, but have also begun to examine sleep in some of the 
most highly evolved end-products of evolution, such as the ungulates. 



38 



Just as the overall adaptations of these creatures are highly specialized, 
so they also appear to have sleep patterns most extremely modified from 
the primitive mammalian form and much more sensitive to influence by 
environmental variables. 

The charting of such variations in the comparative biology of sleep 
in relation to other specializations of ecological adaptation promises 
an exciting quest. Thanks to the opportunity for a long over-due foreign 
work assignment, the Chief of Laboratory of Clinical Psychobiology will 
attempt to continue that quest during the next year through a field project 
in Africa, collecting sleep-waking patterns from a variety of that 
continents' very special animals by long-range telemetry. While he chases 
giraffes through the thorn bush, the small remainder of the Laboratory of 
Clinical Psychobiology staff will, he hopes, continue their diligent 
labours in Bethesda. 



39 



Annual Report of the Laboratory of Clinical Science 
National Institute of Mental Health 

Irwin J. Kopin, M.D., Chief 
July 1, 1971 through June 30, 1972 

Introduction 

The scope of investigations conducted in the Laboratory of Clinical Science 
includes fundamental research on the biochemical, neurophysiologic and 
hormonal processes which control neuronal function, inquiries on how drugs, 
humoral agents and environmental factors influence the development and 
function of the nervous system and clinical studies to determine the altera- 
tions in the fundamental processes which attend neuropsychiatric illnesses and 
how they may be corrected. 

The LCS consists of the Office of the Chief (which includes the Units on 
Clinical Biochemistry, Clinical Pharmacology, Analytical Biochemistry, 
Psychosomatics and Histopharmacology) and the Sections on Pharmacology, 
Medicine, Psychiatry and Experimental Therapeutics. The diversity of talents 
and individual approaches to research provide a unique opportunity for inter- 
action of clinical and fundamental investigations. The compiling of clinical 
problems which can be attached at a basic level and of basic observations 
which are rapidly applied to clinical situations has proved to be particularly 
fruitful. 

Section on Pharmacology 
Julius Axel rod, Ph.D., Chief 

The interests of the Section on Pharmacology have continued along three areas 
of research: catecholamines, tryptamine and the pineal gland. 

Dr. Richard M. Wei nshil bourn, who last year reported the presence of dopamine- 
beta-hydroxylase in human serum, found that the dopamine-beta-hydroxylase level 
is markedly reduced or absent in children with Familial Dysautonomi a . He also 
found that the serum levels of the enzyme gradually increase from birth to 
puberty. Dr. G. Frederick Wooten has found a rapid increase in dopamine-beta- 
hydroxylase release into the blood during stress and cardiovascular responses 
to cold, tilt, etc. In collaboration with Dr. Nguyen B. Thoa (Section on 
Medicine), Dr. Wooten has been examining the process of neurotransmitter 
release from the sympathetic nerve endings. 

Dr. Joseph T. Coyle has continued his work on the development of the adrenergic 
system in brain. He has devised a sensitive method for measurement of tyrosine 
hydroxylase in brain and examined its distribution in various areas of the rat 
brain. 

In the rat brain, the enzymes involved in the biosynthesis of norepinephrine 
(tyrosine hydroxylase, dopa decarboxylase and dopamine-beta-hydroxylase) appear 
five days after gestation. At first they are located mainly in the cell 
bodies, but reach the nerve terminals 18 days after gestation. Two days later 
(20 days after gestation), the brain norepinephrine level appears to be 
strikingly elevated. 



41 



Drs. Wooten and Coyle have found that both tyrosine hydroxylase and dopamine- 
beta-hydroxylase move down the axon by a rapid transport process involving 
microtubular elements. Repeated administration of reserpine caused an increase 
in axonal tyrosine hydroxylase and dopamine-beta-hydroxylase, but caused no 
change in the transport of the enzymes. 

Dr. Roland Ciarnello induced phenyl ethanol ami ne-N-methyl transferase (the 
adrenaline-forming enzyme) in sympathetic ganglia of newborn rats with 
dexamethasone. Drs. Juan Saavedra and Axel rod have developed a specific 
sensitive enzymatic assay for tryptamine and found the amine to be normally 
present in brain and other tissues. The intracerebral administration of 
tryptamine-C^** resulted in the formation of methyl tryptamine and dimethyl - 
tryptamine. An enzyme that forms methyl tryptami ne and dimethyl tryptamine 
from tryptamine has been found in both the human and rat brain; an inhibitor 
for the enzyme was also detected. 

Drs. Takeo Deguchi and Axel rod have developed a sensitive assay for measuring 
N-acetyl serotonin in the rat pineal gland. The enzyme can be induced in the 
pineal gland about 20-fold by dopa, noradrenaline, isoproterenol and monoamine 
oxidase inhibitors. The induction of the enzyme can be prevented by the prior 
administration of the beta-adrenergic blocking agent, propanolol. Sympathetic 
nerve denervation of the pineal gland causes a superinduction of N-acetyl - 
serotonin transferase in the pineal gland (100-fold) by beta-adrenergic agents. 

Section on Experimental Therapeutics 
Thomas N. Chase, M.D., Chief 

The research conducted in the Section on Experimental Therapeutics is directed 
towards elucidation of the mechanism of action of drugs which influence central 
nervous system function. 

Preclinical studies carried out with Drs. Larry K.Y. Ng, Robert W. Col burn and 
Kopin indicate that 5-hydroxy tryptophan enhances the release of both dopamine 
and serotonin from brain tissues. The observations that the enhanced release 
appeared dependent on the decarboxylation of 5-hydroxytryptophan to serotonin 
and that the enhanced release was substantially diminished in tissues where 
catechol ami ne-containing terminals had been selectively destroyed by 
6-hydroxydopamine suggest that dopamine may be released by serotonin derived 
from the decarboxylation of 5-hydroxytryptophan in catechol ami nergic neurons. 
Exogenously administered 5-hydroxytryptophan decarboxylated to serotonin may 
displace endogenous catecholamines, thereby offering a possible explanation for 
some of the behavioral and neurologic effects of 5-hydroxytryptophan loading in 
man. 

Attempts to study naturally occurring or drug- (phenothiazine) induced 
involuntary movement disorders have long been hampered by the lack of a suitable 
animal model. Intraventricular or intracerebral administration of 6-hydroxy- 
dopamine significantly increases the susceptibility of monkeys to involuntary 
movements induced by L-dopa (the precursor of dopamine) or apomorphine (a 
dopamine-receptor stimulator). The findings support the contention that 
denervation supersensitivity of central catechol ami nergic receptors may be 
involved in the production of dyskinesias during L-dopa treatment of patients 



42 



with extrapyramidal disease and suggest that 6-hydroxydopamine-pretreated 
primates may provide a useful paradigm for future studies of the relationship 
between catechol ami ne-containing neural systems and human dyskinesias. 

The probenecid-induced accumulation of monoamine metabolites in cerebrospinal 
fluid has been used to provide an index of their rate of formation and to the 
central turnover of the parent amines. In patients with idiopathic Parkinson's 
disease, the basal concentrations and probenecid-induced accumulations of 
homovanillic acid are considerably below those of control subjects. Although 
steady-state levels of 5-hydroxyindoleacetic acid did not differ significantly 
from normal values, there was a substantial dimunition in the response of the 
serotonin metabolite to probenecid. Pretreatment severity of parkinsonian 
rigidity and bradykinesia, but not tremor, correlated Inversely with the 
probenecid-induced rise in both monoamine metabolites. No association was 
found, however, between the therapeutic response to L-dopa and either the 
severity of parkinsonian signs prior to therapy or the magnitude of the defect 
in monoamine metabolism. Our results cast doubt on the prevailing notion that 
the ability of L-dopa to ameliorate parkinsonian signs is solely contingent on 
its conversion to dopamine in surviving dopaminergic neurons. In contrast to 
naturally occurring Parkinson's disease, normal or slightly elevated 
probenecid-induced accumulations of homovanillic acid were observed in patients 
who developed parkinsonian signs while receiving psychotropic phenothiazines 
or related neuroleptics. The ability of L-dopa to ameliorate parkinsonian signs 
in schizophrenics who had developed extrapyramidal dysfunction during chronic 
neuroleptic therapy also continues to yield favorable results. Our 
observations support the contention that pharmacologic parkinsonism may be the 
consequence of a drug-induced blockade of dopaminergic receptors. 

Studies carried out with Drs. Hinrich Cramer and Ng have shown that probenecid 
significantly elevates 3 ',5 '-adenosine monophosphate (cyclic-AMP) concentrations 
in the lumbar spinal fluid of patients with various neurologic disorders. 
Because experiments in the laboratory animals indicate that probenecid does not 
affect brain cyclic-AMP levels, our clinical observations suggest that 
probenecid may inhibit the efflux of cyclic-AMP from the spinal fluid 
compartment. The rate of cyclic-AMP rise during probenecid treatment may thus 
provide a means for estimating the central turnover of the nucleotide. Mrs. 
Edna K. Gordon developed an improved gas-liquid chromotography method for 
measuring cerebrospinal fluid levels of 3-methoxy-4-hydroxyphenyl glycol (MHPG), 
a major product of norepinephrine metabolism. In studies of more than 60 
patients, we found MHPG concentrations to be similar in ventricular and lumbar 
spinal fluid. About one-third of the MHPG from either source occurred as the 
sulfate conjugate. The oral administration of alpha-methyl -para-tyrosine (an 
inhibitor of catecholamine biosyntheses) substantially reduced MHPG in all 
patients tested. Because relatively little Intravenously infused, isotopically 
labelled MHPG enters spinal fluid, our results suggest that MHPG levels in 
lumbar spinal fluid may provide an index to central norepinephrine metabolism 
in man. 

Current clinical studies in patients with Huntington's chorea indicate a 
characteristic abnormality of dopaminergic, but not serotonergic, mechanisms. 
Probenecid-induced accumulations of 5-hydroxy1ndoleacet1c acid were found to 
be normal in the spinal fluid of patients with Huntington's chorea. In doses 



43 



sufficient to substantially affect the spinal-fluid content of 5-hydroxy- 
indoleacetic acid, neither L-tryptophan (a precursor of serotonin) nor 
para-chloro-phenylalanine (a specific inhibitor of serotonin biosynthesis) 
altered motor or behavioral function. On the other hand, the response of 
homovanillic acid to probenecid was significantly diminished in choreatic 
patients, although the degree of abnormality appeared independent of the 
severity of clinical signs. The oral administration of L-dopa consistently 
exacerbated the involuntary movements, while alpha-methyl -para-tyros ine (an 
inhibitor of catecholamine synthesis) tended to ameliorate hyperkinesis. 
Because the nigrostriatal dopaminergic system remains morphologically intact 
in Huntington's chorea, we hypothesize that the reduction in dopamine 
metabolism in the disorder occurs as a secondary phenomenon, possibly owing 
to an interneuronal feedback mechanism. 

A long-term study of the antiparkinsonian efficacy and toxicity of L-dopa 
alone and in combination with a peripheral decarboxylase inhibitor (MK-486) 
has now entered its third year. Results in stateside patients with idiopathic 
parkinsonism and in Guamanians with Parkinsonism-dementia (in collaboration 
with Dr. Jacob A. Brody) affirm the substantially improved therapeutic to toxic 
ratio reported last year. In contrast, the administration of 3-0-methyldopa, 
alone or with MK-486, failed to benefit patients with idiopathic parkinsonism. 
Because levels of apparent L-dopa in plasma and homovanillic acid in lumbar 
spinal fluid approximated levels found in patients receiving therapeutically 
effective doses of L-dopa, our findings raise some question about the conven- 
tionally assumed mechanism of action of L-dopa. Clinical studies of fusaric 
acid, a new dopamine-beta-hydroxylase inhibitor, have recently been conducted 
in patients with various extrapyramidal disorders. Use of fusaric acid alone 
or together with a fixed dose of L-dopa failed to alter parkinsonian signs. 

Section on Medicine 
Irwin J. Kopin, M.D., Chief 

The Section on Medicine has continued to study the mechanisms controlling 
enzyme levels and amine synthesis in adrenal glands and adrenergic neurons. 

Repeated stress is associated with elevation of levels of enzymes required to 
synthesize catecholamines. The mechanism of change in rate of enzyme synthesis 
involves release of catecholamines and stimulation of formation of cyclic-AMP. 
Enzymes are synthesized in the cell body and transported to the nerve ending 
where they are essential for replacement of released neurotransmitters. 
Dopamine-beta-hydroxylase, the enzyme responsible for the final step in 
norepinephrine formation, is stored in synaptic vesicles of adrenergic neurons 
and IS released along with norepinephrine. Interference with axonal transport 
by application of drugs (colchicine and vinblastine) which disrupt neurotubules 
in the axon initially results in accumulation of dopamine-beta-hydroxylase- 
after one or two days, however, the synthetic processes in the cell body are 
switched to formation of proteins required for structure (membranes 
neurotubules) rather than enzymes required for function. * 

Iwl!^S^K"'^"'n°!-*-^"""'"fr '"^^ease, which appears to involve exocytosis. is 
blocked by colchicine, vinblastine and cytochalasin B, presumably as a 
consequence of interference with neurotubules and/or neurofibrils 



44 



Prostaglandins diminish and phenoxybenzamine enhances stimulation-induced 
release of both dopamine-beta-hydroxylase and norepinephrine from the guinea 
pig vas deferens, presumably as a consequence of interaction with calcium ions 
which are required for transmitter release. 

Neurotransmitters can be replaced by chemically related, but less effective, 
compounds which have been called "false transmitters." Replacement by dopamine 
of serotonin in serotonergic neurons may occur when large doses of L-dopa are 
administered and may account for some of the effects of L-dopa treatment of 
parkinsonian patients. Similarly, 5-hydroxytryptophan administration may result 
in replacement of dopamine by serotonin. 

The development of methods for sustaining adrenergic tissues in vitro has 
permitted investigation of factors influencing induction of catechol ami ne- 
synthesizing enzymes and reinnervation of sympathetically denervated tissues. 
In organ culture, sympathetic ganglia cells develop axonal sprouts, which have 
the properties of nerve endings almost as soon as they form. The development 
of axonal sprouts and their ramification into other tissues are influenced by 
nerve growth factor and are blocked by drugs which interfere with neurotubular 
integrity. 

Our studies contribute to the understanding of neuronal development and function 
and how these processes may be influenced by drugs, hormones and environmental 
factors . 

Section on Psychiatry 

Irwin J. Kopin, M.D. , Acting Chief 

Frederick K. Goodwin, M.D., Chief, Clinical Research Unit 4-West 

Dennis L. Murphy, M.D., Chief, Clinical Research Unit 3-East 

The Section on Psychiatry has continued investigations on the psychobiological 
processes in affective disorders and the effects of various psychoactive drugs 
on amine metabolism as reflected by metabolites in the cerebrospinal fluid. 
The studies using cerebrospinal fluid levels of amine metabolites and the rate 
of accumulation of the compounds after administration of probenecid, a drug 
which blocks transport of the acid metabolites from the spinal fluid, have been 
shown to be valid indices of turnover of amines in brain. Differences in amine 
metabolite formation have been found after administration of amine precursors 
or psychoactive drugs. The levels and rates of accumulation are influenced by 
physical activity and are suggested in some patient groups. 

A computer-scored milieu rating scale for quantification of changes in manic 
and depressive features of mental illness was validated by cross-ward 
comparisons. Therapeutic trials based on hypotheses of the role of amines in 
affective disorders have continued. Although administration of tryptophan 
results in enhanced indoleamine formation, it has only minimal antidepressant 
effects. Tetrahydrocannabinol is not an effective antidepressant agent; 
cocaine, which potentiates the actions of catecholamines in peripheral organs, 
is definitely psychoactive, but not clearly an antidepressant. Comparison of 
the antidepressant effects of lithium and imipramine suggests that unipolar- 
and bipolar-depressed patients may react differently to the two drugs. Marked 



45 



( 



changes in verbal -learning capacity and memory were observed in mania, 
depression and after administration of psychoactive drugs. 

Blood platelets have been used to study individual differences in the cellular 
effects of anti depressive and antimanic drugs. Bipolar-depressed patients 
have been found to have platelets with reduced monoamine oxidase activity and 
increased levels of octopamine. 

Followup studies of manic-depressive patients have been completed on 60 former 
patients and their spouses and indicate correlations between clinical features 
during the manic episode and the subsequent outcome. 

Office of the Chief 
Irwin J. Kopin, M.D., Chief 

Unit on Clinical Pharmacology (Julius Axelrod, Ph.D. and Irwin J. Kopin^ 
M.D., CoHeads). The metabolism and effects of tetrahydrocannabinol have been 
examined in nafve subjects and chronic users of marijuana. It was found that 
chronic users metabolize the drug more rapidly and appear to be more sensitive 
to the agent, possibly as a consequence of more rapid formation of ll-hydroxy- 
delta'-tetrahydrocannabinol. Blood levels reach a peak more slowly after oral 
administration than after inhalation or intravenous infusion, and effects 
appear to parallel the circulatory drug levels: Initially rapid and subse- 
quently slow excretion suggests that the drug metabolites are stored in tissues. 
The acute cardiovascular effects are consistent with elevated levels of 
catecholamines excreted in the urine. 

Unit on Analytical Biochemistry (Robert W, Colbum, Ph.D., Head). The 
Unit has continued to develop methods for screening metabolite excretion 
patterns in psychiatric patients and to study the disposition of biogenic 
amines in the synaptosomes obtained from rat brain. The metabolic fate of 
norepinephrine is altered in pinched-off nerve endings by drugs such as 
reserpine and tyramine in the same manner as the drugs alter metabolism of 
amines in the peripheral adrenergic neurons. Tyramine enhances release of the 
unchanged amine by permitting its metabolism by monoamine oxidase. Synapto- 
somes appear to accumulate tetrahydrocannabinol, and its effects on amines is 
now being investigated. The effects of L-dopa on disposition of cerebral mono- 
amines in rat brain homoqenates has been studied in the model system, and Dr. 
Lorenz Ng was a recipient of the A.E. Bennett Award for the research involved. 

Unit on Psijahosomatics (Philippe V. Cordon, M.D., Head). The Unit has 
continued a variety of clinical projects in collaboration with other groups of 
the Laboratory. Therapeutic doses of L-dopa result in decreased levels of red 
cell catechol -0-methyl transferase. Studies of the effects of L-dopa alone . 

and of L-dopa plus MK-486 on plasma renin and aldosterone will soon be t 

completed in ten patients. Effects of L-dopa on gonadotrophic hormones, TSH 
and HGH have been studied in eight patients. Circulatory parameters previously 
found to be affected by L-dopa have been studied in five patients treated with 
the principal metabolite of L-dopa, 0-methyl dopa. Serum dopamine-beta- 
hydroxylase (DBH) as an index of sympathetic nerve function was studied in 
normal volunteers. Increases in DBH activity were observed during exercise, 
cold stress and as part of the psychic response to initial studies. During i 

46 



hemorrhage, DBH activity increases in parallel with increased sympathetic nerve 
activity in cats. Study of the effects of ethano'i on DBH has begun. Fusaric 
acid, known to inhibit DBH activity in animals, was found to inhibit serum DBH 
activity in man. 

Unit on Clinical Biochemistry (Edna K. Gordon^ Head). The Unit has 
continued to develop and improve methods for assay of metabolites of amines in 
various body fluids and to provide the biochemical technology required for the 
investigations conducted in the Section on Psychiatry and some o1^ the studies 
of the Section on Experimental Therapeutics. 

Unit on Histopharmaaology (David M. Jacobowitz, Ph.D.^ Head). Using 
histofluorimetric techniques, the localization of biogenic amines in brain, 
ganglia and peripheral tissues has been examined in a variety of situations. 
After 6-hydroxydopa treatment the disappearance of adrenergic neurons in brain 
has been related to changes in appetitive, water-consumption and fighting 
behaviors. Reinnervation in organ culture of peripheral tissues (iris, pineal 
gland) by axon growth from sympathetic ganglia has been demonstrated even when 
species are crossed (e.g. mouse ganglion and rat iris). Tryptamine formed from 
tryptophan after administration of monoamine oxidase inhibitors was found to be 
present in the capillary walls of the brain. 

The marked increase in phenyl ethanol ami ne-N-methyl transferase (PNMT) in the 
ganglia of newborn rats treated with dexamethasone was shown to be a conse- 
quence of proliferation of chromaffin tissue. The chromaffin cells persist 
beyond the time of PNMT elevation but gradually lose their ability to 
synthesize and store catecholamines. Using 6-hydroxydopamine implants to 
destroy adrenergic neurons in brain, movement disorders in monkeys have been 
produced. The rate and extent of destruction can be assessed by histological 
techniques. Similar studies of the autotranspl anted hearts of dogs reveal 
sympathetic reinnervation mainly localized to the left atrium and left 
ventricle. 



47 



Annual Report of the Laboratory of Psychology 

National Institute of Mental Health 

David Rosenthal, Ph.D., Chief 

July 1, 1971 - June 30, 1972 

FY 1972 has essentially been a business -as -usual year for the Lab- 
oratory of Psychology. However, during the year two investigators left the 
Laboratory to work elsewhere, and although we might have used their positions 
to generate new research programs in the Laboratory, for various reasons this 
has not as yet been possible. 

The research problems concerning the Laboratory continue to include 
brain and behavior, schizophrenia, other psychopathology - especially minimal 
brain dysfunction in children, behavioral development, communication proc- 
esses, thought processes, perception and creativity. The creativity research, 
however, will be phased out in another year. The new laboratory for infant 
studies is almost completed and should be ready for occupancy soon. The 
major accomplishments of the Laboratory in FY 1972 were as follows: 

Brain Function and Behavior in Primates: 



Cortical Mechanisms in Vision. 



In one study, lesions were placed in the superior colliculus of 
monkeys in order to determine whether the secondary visual pathway present in 
the rat, cat, tree shrew, and squirrel is also present in higher primates. 
Utilizing both the Fink-Heimer and Voneida silver impregnation techniques we 
have demonstrated that the superior colliculus sends a heavy projection to 
the inferior portion of the pulvinar, a connection which appears to be homol- 
ogous to that reported in non-primate animals. In addition the colliculus 
sends a relatively heavy projection to the nucleus centralis lateralis. 
Animals have now been prepared with lesions placed either superficially or 
deep in the superior colliculus to determine if these two pathways can be 
dissociated. Preliminary results from another study indicate that the pre- 
tectum, also involved in vision, projects to the parietal cortex through the 
lateral posterior nucleus, suggesting still another visual pathway. 

The evidence cited above in support of a transcortical pathway from 
striate through prestriate to inferotemporal cortex favors a sequential acti- 
vation model for object vision. This raises the question of whether or not 
such a model can be extended beyond the visual system to encompass stimulus- 
reward associative learning. Translated into functional anatomical terms, 
the question is whether visual objects might gain motivational and emotional 
significance through an interaction between the inferotemporal cortex and the 
limbic system. The three major telencephalic outputs from the inferoteitporal 
area are (a) to the orbital frontal cortex, (b) to the temporal pole and 
amygdala, and (c) to the fusiform-hippocampal gyrus and hippocampus. As a 
start toward investigating the possible role of these inferotemporal-limbic 



49 



pathways in visual associative learning, three groups of animals, each with 
damage to a different one of the three limbic structures, were cortpared with 
operated and unoperated controls in object reversal learning. This task was 
chosen because of its presumed sensitivity to associative learning processes. 
The results indicate that whereas the hippocampus, and by implication, pathway 
(c) , is probably not involved in visual associative learning, both of the 
other limbic structures, and by implication, both of the other pathways, are 
intimately involved. Furthermore, these two pathways (a and b) probably 
serve different functions in visual learning, since the two lesions (orbital 
frontal and temporal pole plus amygdala) yielded a double dissociation of 
deficits. Specifically, the frontal group was more impaired in suppressing 
or abandoning old habits, while the temporal group was more impaired in 
establishing new ones. 

Frontal Cortical Mechanisms in Spatially Directed Responding . 

Previous research addressed itself to the problem of determining 
whether the delay, the spatial features, or a combination of the two was the 
critical factor responsible for the classical delayed-response deficit pro- 
duced by ablation of the cortex in the monkey's principal sulcus. The re- 
sults of several studies have established that lesions in the principal sulcus 
result m marked impairments only when a task requires both spatial and 
mnemonic strategies for its solution. Vftien either a purely mnemonic or purely 
spatial ability is called for in a test, the test is no longer sensitive to 
the disorder produced by ablation of the principal sulcus but rather to that 
produced by ablation of the arcuate cortex. These studies of small focal 
lesions on a variety of spatial and nonspatial measures revealed an unantici- 
pated specialization of function within the dorsolateral region and thus dis- 
pelled the prevalent conception of a unitary dorsolateral mechanism. 

These findings have also led to a reformulation of the deficit clas- 
sically produced by frontal lesions as a modality-specific memory loss. One 
way to conceptualize this loss is in sensory-analytic terms. The fact that 
delayed-response tasks generally lack salient exteroceptive cues to guide 
spatial orientation has led many investigators to conclude that proprioceptive 
cues are involved m solving such tasks and hence to the view that proprio- 
ception IS disrupted by frontal lesions. Another way to conceptualize the 

rlTr-L^T'TV- !"""' '" '" ^"^ °^ ^ "P^^^^l ^^nosia, which is not 

iTtT^^l^ ^° <^^f^=^ent sensation. To assess the relative merits of these two 
contrasting views, monkeys with dorsolateral prefrontal lesions and normal 

two^oi^r''^ T"?^ ""^ """^ ^° ^^^ ^^^^^ 5oal box in a locomotor T-Maze under 
two conditions of illumnation - dimly lit and well lit. According to the 
sensory hypothesis , monkeys with frontal lesions should have greater diffi- 
culty m learning the runway response in the dark than in the light, since in 
the former, they must rely to a greater degree on proprioceptive cues! Ac- 
cording to the view that the deficit is "gnostic" rather thL sen'S 
frontal monkeys should perform as well as normals in the dark but mSht be 
TSs"s"tudris Itilf in"'"' Visual-spatial cues are available to c^Jase them. 
the%ienhat S ' r ntrSrcifis^^ ^\'''^''' T"^ ^^^°"^^^ ^^^^"- 
to a gnostic function. Moreote^ Sett^ Tro^ "SSa ftLr^rfai:^ JnteT 
polated between regular training trials indicate that the frontal moLe^ do 

50 



indeed pay attention to Lhe visual-spatial cues in iihe lighted milieu in 
which they are impaired while utilizing proprioceptive cues in the dark 
where they are not. This is the first evidence of its kind to dissociate the 
sensory and gnostic modes of spatial learning in frontal monkeys. 

Cerebral mechanisms for functional recovery after brain injury . 

The study of the cerebral cortex in the adult monkey is intri- 
guing because its removal produces selective, reliable, and on some tests, 
irrecoverable behavioral impairments. The investigation of cortex in the 
infant monkey ^ by contrast, interests us precisely because its removal fails 
to result in such deficits. The difference between the study of lesions in 
the infant and in the adult is more tiian one of a dissimilarity of outcome , 
however, for the two types of investigations pose quite different problems. 
Whereas the essential question confronting the investigator of cortical func- 
tion in the adult is the nature of processes intrinsic to the damaged sub- 
strate, the task confronting tlie student of the early brain-injured is the 
understanding of the capacities of residual areas, since presiomably these are 
the areas responsible for sustaining the functions of the cortex which has 
been removed. Thus, our investigations are concerned with identifying the 
neural substrates which mediate behavioral recovery in young brain-damaged 
animals , 

On the basis of studies involving selective lesions of the prefrontal 
cortex in infancy we have been able to identify two expressly different pat- 
terns of recovery. We found that monkeys given orbital lesions in infancy 
were initially as impaired as monkeys given the same lesions as adults but 
that later in development the early-operated monkeys gave evidence of dramatic 
recovery. By contrast, monkeys given dorsolateral lesions as infants were 
initially unimpaired but later in life this picture of normalcy gave way to 
one of retarded development. On the basis of such results we have proposed 
that there is a central principle governing whether or not recovery will 
occur, approximately when it will occur, and whether it will follow the pro- 
gressive or regressive pattern. The principle concerns the maturational 
status of functionally related areas that remain \indamaged by the early brain 
injury. If there remains iindamaged a related area which is relatively 
"uncommitted" to its own course of development at the time of brain injury, 
then recovery will ensue. If, on the other hand, the surviving tissue is 
already "committed" or relatively mature, then presumably it will have lost 
this capacity for reorganization, and hence will be unable to take on new 
functions. Regarding the prefrontal cortical areas, the available evidence 
suggests that the orbital cortex becomes "committed" considerably earlier in 
ontogeny than does the dorsolateral area. Thus, it seems reasonable to 
suppose that in monkeys given orbital lesions in infancy, the remaining dorso- 
lateral cortex could come to assume the functions of the orbital cortex but 
that the orbital region could not reciprocate for damage to the dorsolateral 
cortex. The full expression of compensatory readjustment would be delayed, 
of course, until the compensatory structure itself attained functional 
maturity. Thus, the finding that dorsolateral lesions do not produce serious 
impairments in monkeys until they reach two years of age, together with the 
fact that only monkeys given orbital lesions as infants show recovery at the 
two-year stage provide strong evidence for this view. 

51 



Another aspect of Uiis problem concerns the status of subcortical 
structures during development. It is well established that the prefrontal 
cortex is anatomically and functionally related to the caudate nucleus The 
dorsolateral cortex, for exairple, projects to the anterodorsal sector of the 
head of the caudate nucleus. It is of interest, therefore, that lesions 
placed in this part of the caudate in infants produces serious impairments 
on just those tasks and at just those ages when dorsolateral cortical lesions 
do not We interpret this finding to mean that the caudate nucleus becomes 
functionally mature earlier in development than the dorsolateral cortex and 
that it is capable of mediating many of the behaviors that the dorsolateral 
cortex will ultimately assume. According to this view, the caudate does not 
"take over" the functions in a compensatory sense but at early ages is the 
structure primarily responsible for carrying out these functions. In the 
course of development, these functions become "encephalized" , so to speak, 
with the maturation of the cortex and the caudate then loses its functional 
autonomy . 

These studies have been profitable from several points of view. 
First, they have provided a new line of evidence to support the theory that 
there are two functionally distinct subdivisions of the prefrontal cortex. 
Secondly, they provide some clues as to the limiting factors and hence to the 
mechanisms underlying recovery of function in developing organisms. Thirdly, 
they indicate something about the normal course of brain development, a sub- 
ject about which little is known. Finally, these investigations have bridged 
a gap previously existing between animal studies and the clinical literature. 
The present results parallel the findings in man by establishing evidence for 
both progressive and regressive sequelae of early injury to the brain. In 
this kind of correspondence lies the hope that the outcome of investigations 
on nonhuman forms can ultimately be extrapolated to conditions of develop- 
mental neuropathology in man. 

Cortico-subcortical mechanisms in the regulation of behavior. 

One of the siibcortical structures having intimate anatomical 
relationships with the prefrontal cortex, particularly with the orbital sys- 
tem, is the hypothalamus. While many studies have demonstrated similarities 
between the frontal cortex and the hypothalamus in the motivational and emo- 
tional functions which they siobserve, none has considered whether or not there 
are also similarities in cognitive f imctions . We did so in a recent study 
which involved placing lesions in the hypothalamus of monkeys and testing 
them on a battery of tests of frontal-lobe function. Large lesions involving 
different divisions of the hypothalamus resulted in a pattern of deficits 
which are characteristic of damage to the orbital frontal system. Smaller, 
selectively placed lesions, though resulting in impairments, did not yield a 
pattern of deficits unequivocally characteristic of one or the other of the 
frontal-lobe systems. Further analysis of the anatomical and the behavioral 
data is underway to attempt to factor out the discrepancies. 

The medial dorsal nucleus of the thalamus is another subcortical 
structure having divisions which are differentially anatomically related to 
the dorsolateral or the orbital frontal cortex. It would be expected that 



this nucleus would have functions similar to those of frontal cortex, and 
that the functions of its two divisions would be dissociable. However, in 
several studies, some of them our own, even very large lesions involving 
virtually all of this nucleus have not resulted in impaired performance on 
tests of frontal-lobe function. Nevertheless, since the anatomical relation- 
ships are so compelling, we undertook to investigate this problem again with 
slightly different procedures. The results of this study clearly indicate 
that lesions in this nucleus can result in profound deficits on these tasks. 
To determine which factor is critical in producing the impairment is the 
subject of current work. 

Somatosensory Perception . 

This year an attempt was made to localize more precisely the part of 
the anterior removal in the postcentral gyrus which was responsible for a 
profound somatosensory deficit. On the basis of electrophysiological studies 
revealing two separate and detailed representations of the hand within the 
area of the anterior removal, the area was divided into two parts and the 
subareas characterized by slowly-adapting and quickly-adapting units were 
separately removed. A deficit of the same magnitude and generality as that 
following the total anterior removal was found after destruction of the 
slowly-adapting population, whereas a milder impairment affecting only the 
first (softness) and the last (roughness) tasks of the series was produced 
by destruction of the quickly-adapting units. 

The nature of the impairment after the anterior postcentral lesion 
was explored in several ways. As described last year, we found that monkeys 
with this lesion (or even with more extended removals encompassing the entire 
postcentral gyrus and parietal operculum of both hemispheres) either retained 
or quickly recovered normal sensitivity of the hand to punctate tactile 
stimuli, as tested by a graded series of modified von Prey hairs. Thus, 
their deficits on the original battery of tasks could not be ascribed to a 
simple hypesthesia. This result led us to investigate the effect of varia- 
tions in the procedures which had revealed the severe deficits. We escplored 
in one group of animals the effects of intensive preoperative training on all 
tasks, and in another, the effects of allowing a recovery period of six months 
following the anterior postcentral removal. Neither of these modifications 
ameliorated the deficits, thus providing strong support for our original 
finding of an impairment which was much more severe than any reported by other 
investigators who have studied the effects of postcentral removals with tasks 
much like the ones we employed. We therefore believe that the lesions made 
previously by others might have spared tissue in the depths of the central 
sulcus, the siibarea which our experiment indicated was the most important. 
The fact that our procedural variations did not ameliorate the deficit sug- 
gests that the lesion causes a loss of somatosensory capacity, rather than a 
modality-specific learning disability or a deficit secondary to the ataxia 
commonly found in the weeks following a postcentral ablation. But how to 
characterize this postulated loss of capacity (since it is not a loss of 
tactile sensitivity, as noted above) remains unclear. There is evidence from 
electrophysiological studies suggesting that it may be primarily kinesthetic 
in nature, and future experiments will explore this possibility. 



53 



One research project explored the effects of lesions in the postcen- 
tral gyrus, the parietal operculum, and the posterior parietal "association" 
area on a type of somatosensory discrimination not hitherto studied in our 
laboratory, namely, the perception of differences in temperature. Monkeys 
were trained by a series of steps , starting with a task involving perception 
of thermal pain, then a gross temperature discrimination in the non-painful 
range, and finally a series of threshold determinations which terminated when 
the animal could reliably discriminate a difference of less than 2° C. in the 
cool range (24° vs . 26°) . Compared with a normal control group tested for 
retention, deficits in the operated groups have been found in trials to cri- 
terion on the painful and on the non-painful gross discriminations, as well 
as in the trials taken to meet the final threshold criterion. However, all 
animals eventually reached this final criterional level, thus indicating that 
the capacity for discriminating fine temperature differences still existed. 
The operated groups which showed the above-mentioned deficits had either bi- 
lateral parietal lobectomy, bilateral removal of the postcentral gyrus and 
the parietal operculum, or bilateral removal of the postcentral gyrus plus 
contralateral removal of the parietal operculum. Other groups whose lesions 
did not involve the postcentral gyrus in both hemispheres failed to show 
significant deficits, although a bilateral postcentral lesion by itself was 
likewise insufficient to produce impairment. 

It appears from these results that temperature perception, like that 
of simple touch, is extremely resistant to cortical lesions, and that these 
forms of somatosensory discrimination are in this respect very different from 
those involving softness , texture , size , or shape cues . 

Schizophrenia : 

A review of the literature on the offspring of schizophrenics was 
undertaken. The various studies, taken as a whole, indicate that there is 
an increased incidence of two types of pathological character structures in 
these offspring, besides the increased incidence of schizophrenia. There is 
a high incidence of antisocial characters , appearing as impulsive , hyper- 
active , delinquent children, and as adult psychopaths or "schizoid psycho- 
paths." There is also a schizoid group appearing as withdrawn, anxious chil- 
dren and as eccentric, socially isolated adults. The pathological types in 
in the young offspring of schizophrenics were found to be similar to the 
types found in retrospective studies of a group of pre-schizophrenics. 

Previous studies of social class and schizophrenia have demonstrated 
a relationship between the two but have been unable to dissect out the factors 
mediating the relationship. Employing the data from our Denmark studies, we 
have used the technique of adoption to separate the roles of genetic and 
environmental effects. Our findings indicate that: (1) the relationship 
between schizophrenia and lower social class is not clearcut in our popula- 
tion, (2) that the tendency for schizophrenics to be of lower socioeconomic 
class is the consequence of their "downward drift", and (3) that lower class 
rearing does not appear to provoke or induce schizophrenia. The generality 
of these findings is limited because of the special nature of the populations 
employed; these limitations are discussed in the summary of this research. 



54 



In further analyses of our Danish siobjects, we found that individuals 
who had a proband biological relative in the schizophrenia spectrum emigrated 
much less frequently than control subjects. This finding was surprising 
since the literature on the relation between migration and schizophrenia sug- 
gests that schizophrenics emigrate more often than controls. We interpret 
this finding to mean that individuals who harbor genes associated with schiz- 
ophrenia have less initiative, are less adventurous, and more averse to 
abrupt change than are other persons. In fact, their behavior parallels a 
trait called neophobia , which schizophrenics show in certain experimental 
tasks . 

We also came up with the surprising finding that on multiple reaction 
time tasks, our subjects who were reared by schizophrenia spectrum parents 
performed more poorly than subjects not reared by such parents. Since re- 
action time is one of the best discriminators of schizophrenics and controls, 
and since genes are implicated in schizophrenia, one might have expected an 
association between relatedness to a schizophrenic and poor reaction time , 
but this was not the case. 

Our adoption study in New York is at the point of having concluded 
almost all the data collection. Our Israeli material is still being analyzed, 
but already many new significant findings have turned up. These will be 
reported next year. 

Previous findings had indicated that chronic and acute schizophrenics 
do not exhibit a generalized deficit in the responsivity of the autonomic 
nervous system, but show such a deficit selectively, particularly in response 
to meaningful stimuli and to "stressors" such as task performance. In a 
study of monozygotic twins, most of whom were discordant for schizophrenia, 
we found that this specific deficit in autonomic responsivity was correlated 
with the severity of symptoms and behavioral disturbance. 

Other Psychopathology . 

Average evoked response studies of minimal brain dysfunction (MBD) 
children showed increased amplitudes, especially at high stimulus intensities, 
in comparison with age-matched controls. In MBD children who showed a pos- 
itive clinical response to amphetamine, AER diminished with drug treatment; 
in nonresponders , AER increased. 

Similar individual differences in drug response were seen in studies 
of L-dopa infusion in patients with affective disorders. In both studies, as 
well as in studies of attention in normal subjects, early and late AER com- 
ponents behaved quite differently, suggesting the possibility of some bio- 
chemical dissection of the as yet poorly defined AER. Further, the finding 
of interactions between intensity response functions and level of attention 
makes possible some neurophysiological assessment of attention. 

It was found that lithium is of no appreciable therapeutic benefit 
for minimally brain dysfunctioned children refractory to other forms of 
treatment. Our findings indicate that MBD children appear to be "augmenters"; 



55 



controls do not "augment." Furthermore, it appears that MBD children who 
respond to stimulant medication demonstrate diminished augmentation with such 
treatment whereas non-responders show increased augmentation. We have found 
apparent biochemical correlates of differences in conditioning in inbred 
strains of rats. Preliminary findings are that animals who avoid with dif- 
ficulty but who respond to amphetamines with increased rates of conditioning 
show diminished rates of norepinephrine turnover. This finding remains to 
be confirmed. 

The Unit on Psychophysiology has been active in the development of 
systems for on-line real-time collection of psychophysiological and electro- 
encephalographic data directly from human subjects or from analog tape. The 
combination of the real-time data collection programs, on-time interactive 
data editing programs and statistical analysis within the same computer - 
all operating together on a time-share basis - make the SEL system one of the 
most sophisticated psychophysiological experimental systems yet developed. 

Behavioral Development . 

In one study, kibbutz and residential institution were compared with 
respect to the time spent by caretakers with their infants and in behaviors 
by caretakers to infants and by infants to their caretakers. The analysis 
was performed separately for periods spent in caregiving (feeding, diapering, 
dressing, bathing) and for periods when caretakers were in their infants' 
vicinity but not ministering to their physical needs ("pure-social time"). 

Analyses of the periods caretakers spent in their infants ' vicinity 
showed that, compared to kibbutz caretakers, institution caretakers spend 
about twice as much time in ministering to their infants' physical needs - 
caregiving, and about three times as much time in the vicinities of their 
charges when not ministering to those needs - pure-social time. This differ- 
ence appears to reflect the facts that kibbutz mothers do much of the care- 
giving during the first 8 months of their infants' lives - the period inves- 
tigated, and that institution caretakers are scored as being near an infant 
when they minister to nearby children. 

Compared to kibbutz caretakers, institution caretakers showed more 
Smiles and Fine-contact responses. However, in the institution, the care- 
takers were the only ones who ministered to their charges while, in the 
kibbutz, caretakers shared this role with mothers. 

With respect to infant behaviors to their caretakers while receiving 
physical care institution infants showed more looking at, smiling, and vo- 
calizing to their caretakers, but these differences dropped out when adjust- 
ment was made for differences in caregiving time. 

• . In. periods when institution and kibbutz caretakers were not minister- 
ing to their infants ' physical needs, institution caretakers sho^ ^re Fine- 
contact Talk, and Gross-contact behaviors than did kibbutz caret^e^ but 

S\he vrci:;rty :f':^:1h'if ^^^:. ^^^ ^^°-^ -- -^^-^ed forlim^sp^nt 
m the vicinity of the children, the caretakers were found to differ only in 



56 



the incidence of Gross-contact; institution caretakers showing more of this 
behavior at two months, the same amount at six months, and less at eight 
months. During "pure-social" settings, no differences were found between 
groups in infant behaviors to^ those caretakers. 

Within the two settings, caregiving and pure-social, the correlations 
between caretaker and infant behaviors were, overall, higher for the kibbutz 
than for the institution environment, and the within-setting correlations 
were higher than the between-setting correlations for kibbutz infants , while 
they were not at all different for institution infants. Thus, as a unit, 
kibbutz infants and caretakers appeared to behave differently in pure-social 
than in caregiving periods, but institution pairs did not behave differently. 
This same overall pattern holds as well for infant behavior intercorrelations 
and for caretaker behavior intercorrelations. This pattern is therefore a 
general one. 

Within the kibbutz, mothers spent more time than did caretakers with 
their infants during the first 8 months of life: in caregiving settings, 
where caretaker time remains constant through the eight months, mothers spent 
50 times as much time at two months, and twice as much time at eight months; 
in pure-social settings, where both mothers and caretakers spent increasing 
time with their infants with age, mothers spent about twice as much time with 
their infants as did caretakers. After behavior scores were adjusted for 
pure-social time in the presence of mother and caretaker, it was found that 
more Vocal sounds and Motor acts were exhibited by infants to their mothers 
than to their caretakers. Correlations within and between caregiving and 
pure-social periods were invariably of higher magnitudes between mother and 
infant behaviors than they were between caretaker and infant behaviors . This 
result suggests a better organization between the behaviors of a mother and 
her infant than between a caretaker and the same infant. 

In a comparison of the kibbutz with two other environments , that of 
the youngest-child and that of only-child family (both urban middle-class) , 
the correlational pattern between the behaviors of a mother and her infant 
was found to be reliably higher in magnitude in the kibbutz than in either 
the youngest- or the only-child environments . Correlational patterns between 
adult and infant behaviors were reliably higher for older (8 months) infants 
than for younger (2 months) infants. 

Perceptual Development . 

An investigation which compared the efficacy of (a) repetitive , 
(b) color-varying, and (c) form-varying visual reinforcers in maintaining the 
operant behavior of three-month-olds demonstrated that form variation was 
more effective than color variation and, hence, that the three -month-old is 
perhaps more sensitive to form than color differences . A second investigation 
sought to determine which features (eyes, nose/mouth, contour) predominate in 
the four-month-olds perception of the human face and to what extent they are 
seen as isolated elements or as structured configurations. Previous research 
had yielded equivocal results regarding the discriminability of regular from 
scrambled f<gces and "eyes-only" from eyeless faces up to four months of age. 



57 



In the present experiment total fixation time to a regular schematic face was 
compared for groups of infants following prolonged exposure to differing dis- 
tortions of the face (presumably, the greater the perceived difference between 
the regular face and the previously familiarized distortion, the longer the 
looking time to the former) . The distortions were applied to four areas - 
eyes, nose/mouth, contour, and all features combined - and were of four gen- 
eral types: (a) elimination of feature, (b) scrambling, (c) positional dis- 
placement, and (d) orientation change. A control group was given prolonged 
exposure to the regular face. Preliminary analysis of the data indicates that 
in the face perception of the four-month-old (1) the eyes are more salient 
than the nose/mouth, (2) the orientation of the contour more critical than the 
orientation of the features, and (3) the horizontal arrangement of the eyes 
more important than their precise orientation. 

This experiment on the determinants of reinforcer efficacy demonstrates 
that visual change is more effective in maintaining the infant's commerce with 
the surround than visual redundancy, and suggests that an environment contain- 
ing much visual contrast and variation will recruit more of the infant's at- 
tention than a homogeneous environment, and that this is perhaps a prime req 
uisite for early discriminative learning. 



Communication Processes . 



I 



Psycholinguistic research in the Laboratory focuses on speech percep 
tion, its guiding hypothesis holding that listeners process "chunks" of speech 
which are identified on the basis of intonational patterns. These units, 
phonemic clauses, are held in short-term memory and processed as patterns of 
sound, syntax, and sense. As a subject listens to speech a gradient of pu- 
pillary dilatation occurs over the course of a phonemic clause, while it is 
being loaded into short-term memory . 

Since the pupil is richly and complexly innervated and a variety of 
processes are affecting its moment-to-moment diameter, signal averaging tech- 
niques are required in order to separate out the hypothesized psycholinguistic 
effect from "noise." The course of the project this year has involved re- 
peated attempts to match a set of experimental stimuli to a Line computer 
program in such a fashion as to be able to test the pupil diameter hypothesis. 

With respect to listener responses, attention this year has focused 
on its developmental aspects. It had been found earlier that adult-type 
listener responses are quite rare in small children. They seem to be confined 
to a fairly limited number of situations where the speaker's need for them is 
especially strong so that he all but demands them. In addition, many of the 
children's responses are quite different from the adult ones: they are likely 
to involve very slight movements, visible to the observer only on repeated 
viewings of the videotape, and thus difficult to conceive as communicative 
in the ongoing conversation. Also, many of the responses in children are de- 
layed, unlike those of adults, indicating perhaps a slower rate of understand- 
ing speech. One expectation based on past work has been confirmed: individual 
differences in this sort of behavior are very large. In spite of the varia- 
bility, younger children clearly emit fewer listener responses than adoles- 
cents and adults . 

58 



The listener response appears to have a dual role, one for the speak- 
er's benefit (that is, to let the speaker know that he is explaining things 
understandably) , and the other for the listener's benefit. This latter seems 
especially true of movements so small as to serve no communicative function 
for the speaker. These two roles point to futnre research in two directions, 
one toward language development at later ages , and the other toward social 
development, with special attention to educational maturity and to develop- 
mental diagnosis. 

Thought Processes . 

In an experiment in which a computer program controlled a special 
adaptation of the traditional selection paradigm of the attribute identifica- 
tion task, tlie amount of work required to elicit sufficient information for 
a solution was found to be a far less important determiner of the total effort 
than were tlie redundant inquiries made before the correct interpretation was 
produced . 

Work continues in the direction of increasing the computer's partic- 
ipation in administering typical psychological experiments. The present pro- 
gram participates in four stages of this task: (1) it automatically applies 
a 4 X 4 factorial design with constrained randomization of a sequence factor 
as it assigns Ss to tasks; (2) it manages the instructions to S and tests for 
comprehension; (3) it administers the assigned display sequence and records 
S's responses; (4) it provides a typed summary data report immediately after 
each run. 

This program executes the reception paradigm of an attribute identi- 
fication task designed to evaluate a person's ability to perform three types 
of reasoning: (1) inference from knowledge of a sufficient set of relevant 
factors, (2) inference from knowledge of a sufficient set of irrelevant fac- 
tors, (3) inference from knowledge of a combination of relevant and irrelevant 
factors that is just sufficient to support a conclusion. Only about one-third 
of the number of subjects planned for this experiment have completed their 
assignments; it is too early to hazard a guess about its outcome. 

An Attribute Identification System (a computer simulation) that 
"solves" this type of problem by heuristics specified in current theories has 
been developed to provide sufficiency tests on any theory that is appropriately 
explicit and concise. The heuristics of two theories - Restle's "hypothesis 
testing" theory with replacement and the "local consistency" theory - have 
been tested and found to agree only moderately well with the means and stand- 
ard deviations obtained from human subjects. However, certain extensions of 
the "local consistency" result in matches that do not differ significantly 
from hviman performances. This type of testing merits considerable extension. 

Perception . 

Perception of Time and Form . 

Normal individuals often experience a transient disorientation 
for time and place when awakened from a deep sleep. Young adults were awakened 

59 



periodically during the night and tested briefly for the ability to discrim- 
inate short time intervals. Initially no clear- effect of depth of sleep was 
evident, but with more coirplete data a moderate slowing in the subjective rate 
of passage of time was detected. This effect is not closely associated with 
variations in body temperature, EEG, or other physiological indicators. Al- 
though stable in spite of differences in gross physiological state, the time 
sense appears to change in a way similar to habituative or adaptational shifts 
characteristic of basic perceptual processes. 

Investigation of the physiological basis and developmental aspects of 
visual form discrimination has grown enormously in recent years. A difficulty 
hampering this effort, however, has been the lack of a psychologically adequate 
means of specifying the essential parameters involved. The concepts of 
Euclidean geometry generally used were derived initially in connection with 
surveying and other problems of physical measurement not primarily concerned 
with biologically relevant shapes and patterns. But perceptual processes pre- 
siomably evolved in relation to the necessity for discriminating irregular and 
varying patterns of curvatures and densities rather than points, straight 
lines, and right angles. A preliminary test of the applicability of a bio- 
logically-oriented geometry of form to the perception of the orientation of 
ellipses has been undertaken. This geometry postulates a basic parameter, the 
symmetric axis, which was varied in the ellipses used. The precision of judged 
orientation was significantly correlated with the length of the symmetric axis 
rather than with the lengths of the major diameter and focal axis, which are 
conventional geometric properties of the ellipse. The relationship of response 
to the ratio of major and minor diameters was equally good, but this ratio is 
specific to a limited class of forms. The importance of the symmetric axis is 
that it is a property of all forms. If tlie concepts involved in this geometry 
have general applicability, they could be of great utility in understanding 
the development of form perception. 

Creativity . 

The objective of this research has been to examine the validities of 
several well-known paper-and-pencil tests alleged to measure "creative poten- 
tial" by comparing them to two criterion measures of "manifest creativity" in 
science and to a number of variables theoretically related to the concept of 
scientific creativity. Since the meaningfulness of criterion measures in this 
field has been questioned, an additional objective was to examine the construct 
validities of the criteria themselves by relating them to the same reference 
variables as used in the assessment of the test measures. The principal find- 
ings were: (1) that, although the evidence of construct validity was generally 
favorable for both criteria, one criterion (an index of social recognition) 
consistently behaved more in accord with theoretical expectation than did the 
other (an evaluation of a science fair project) ; and (2) that there was no 
evidence for the validity of any of six creativity tests - none were related 
to either of the criteria or to any of the reference variables in the expected 
manner. ^ 

Noting that all of the tests which they had investigated had been de- 
rived from theories which conceptualize creativity as an ability trait ^e 
investigators decided to examine an alternative approach. Many theorists have 



i 



conceptualized creativity as a personality trait and have presented descrip- 
tions of the "creative personality." These theoretical descriptions were 
utilized in the construction of an illustrative personality test of creativity. 
The validity of this test was then assessed using the same procedures that 
had earlier been applied in the evaluation of the ability tests . 

The findings indicated that the creative personality test pos- 
sessed a high degree of construct validity. It was found to be positively 
associated with the recognition measure and with measures of achievement in 
science and in other creative areas of endeavor (e.g., art, literature, music), 
with self -ratings of creativity, and with several personality traits theoreti- 
cally related to the concept of creativity. As hypothesized, it was unrelated 
to any measures of academic aptitude or academic achievement. 

Taken together with the earlier results, these findings raise serious 
questions about the utility of theories which conceptualize creativity as an 
ability trait and support the conceptualization of creativity as a personality 
trait. 

Some corollary findings were uncovered with regard to the personality 
functioning and psychiatric help-seeking of the sample of high and low crea- 
tive subjects: (1) The prevalence of psychiatric help-seeking in the entire 
sample was remarkably high, 23%, as compared to 6 percent of college students 
in general. (2) Specific problems of adjustment to college, e.g., feeling 
out of place or having low grades, appeared to be the primary source of mo- 
tivation for help-seeking. (3) The functioning of students who received 
psychiatric treatment at college tended to decline rather than to improve over 
time. This decline was not confined to any particular area of functioning, 
and the extent of change was strongly related to both intensiveness and du- 
ration of treatment. Students who received more than 20 sessions of psycho- 
therapy exhibited the greatest negative change; those who received fewer than 
five sessions of vocational counseling actually changed in a positive direc- 
tion. (4) An interaction was found between mental health status during high 
school and type of college attended. Students who evidenced psychiatric prob- 
lems during high school and attended extremely selective, competitive colleges 
were very likely to experience adjustment problems, to enter treatment, and 
to become increasingly impaired. Conversely, students already impaired and 
who attended less selective colleges, tended not to experience adjustment 
problems, not to enter treatment, and to improve over time. Among students 
who appeared psychiatrically healthy d\iring high school, those who were most 
talented, forceful, and well-integrated were the ones most likely to become 
frustrated at college, to enter treatment, and to become psychiatrically im- 
paired. In the help-seeking group as a whole, students who already had clear 
psychiatric problems during high school were a minority, representing about 
one-third of the group. 



61 



ANNUAL REPOR.T OF THE LABORATORY OF SOCIO -ENVIRONMENTAL STUDIES 

National Institute of Mental Health 

July 1, 1971 through June 30, 1972 

Melvin L. Kohn, Chief 

Dr. William Caudill, a valued member of the Laboratory since 1960, 
died of cancer on March 24, 1972. 

Caudill had the anthropologist's faith that nothing is ever explained 
until you understand it in context of the system of which it is a part. He 
combined this faith with an adamant unwillingness to accept half-truths and 
superficial solutions. Whatever he studied- -whether it was the adjustment 
of Japanese-Americans in Chicago during World War II, the social structure 
of the mental hospital, the interrelationship of biological, personality, 
and cultural systems, or the transmission of culture from mother to child- - 
the same qualities stand out. He wouldn't let go of a problem at the point 
where most scholars would long since have thought they had found the answer. 
He always had to discover the real reasons why things fit together, not 
just the apparent reasons. And so he leaves behind not only an impressive 
set of scholarly achievements, but also a model of scholarship, of inquiry, 
of the pursuit of truth, for all of us to treasure and to emulate. 

At the time of his death, Caudill was deeply involved in a major 
cross-national study of how culture is transmitted from mother to child. 
In essence, it is a longitudinal observational study in Japan and the United 
States of the behavior of parents and children. During 1961-64, thirty 
Japanese and thirty American middle-class mother-infant pairs were selected 
for systematic observation. The infants were first-born, normal babies, and 
were three-to-four months of age at the time of observation. The first 
twenty Japanese and the first twenty American cases were selected for follow- 
up study at 2\ years of age, and observations in the home were completed 
during 1963-67. These same children were studied for a third and final time 
at six years of age during 1967-70, and all observations have been completed. 

Caudill discovered that even by three-to-four months of age Japanese 
and American infants show characteristic, culturally-appropriate differ- 
ences in behavior. He also demonstrated that these differences are meaningfully 
linked to observed differences between Japanese and American mothers' child- 
rearing practices. His interpretation was that the imprint of culture-- 
transmitted from mother to child--could be seen even at this early age. 
This interpretation was buttressed by a study of Japanese-American mothers, 
which found them to be much more like other American than like Japanese 
mothers in their style of interaction with their infants; correspondingly, 
Japanese-American babies behave more like other American babies than like 
Japanese babies. The data thus argue against a genetic interpretation of 
the behavioral differences between Japanese and American infants. Instead, 
they suggest that characteristic differences in the behavior of Japanese 
and American infants stem from culturally-prescribed differences in maternal 
practices. 

63 



Shortly before his death, Caudill completed preliminary analyses 
of the data gathered when the children were 2% years of age. The analyses 
give a striking indication of continuity in cultural differences in the 
behavior of both mothers and children. These preliminary, cross-sectional 
comparisons do not yet take advantage of the longitudinal nature of the 
data. But they do indicate that processes of cultural transmission begun 
at so early an age probably have great continuity. 

Caudill had intended to continue these analyses on three levels-- 
a cross-cultural analysis of continuities and discontinuities in child- 
rearing practices and child behavior; a more detailed statistical appraisal 
of situational variability in mother-child interaction; and a clinical 
assessment, on a case by case basis, of the individual families. It is a 
sad truth that much of what he intended cannot be carried through by anyone 
else; it required his first-hand knowledge of the data and his unique 
combination of statistical and clinical skills. But the main thrust of the 
intended statistical analysis can be carried out, and Caudill 's long-term 
collaborator, Carmi Schooler, has agreed to do so. And Caudill 's wife, 
Mie, who did many of the observations in Japan, may do a more intensive 
analysis of the individual families. 



i 



It has been a difficult year, perhaps the most difficult in the 
history of the Laboratory. Even before William Caudill 's tragic illness, 
the tone of life had been one of struggling against adversity. As is now 
almost habitual, we have had to keep our research going with barely adequate 
personnel arrangements. This year we also faced the very real danger that 
a major new endeavor, Leonard Pearlin and Frederic Ilf eld's study of the 
social-structural origins of stress, might not be funded. The uncertainty 
led to considerable anxiety, not only for these investigators, but for 
everyone else who cares about NIMH's ability to continue supporting social 
science research in its Intramural program. The issue has been favorably 
resolved, at least for the present. 

The remainder of this report summarizes the accomplishments of the 
Laboratory this past year. We simply note in passing those studies in 
which the principal activities were data-collection or the preparation of 
data for analysis--specif ically, Carmi Schooler's experimental studies of 
the social, psychological, and physiological functioning of schizophrenic 
patients; Gordon Allen's research on behavior genetics; and Lindsley 
Williams's analysis of the relationships between urban social structure and 
individual psychological functioning. 

THE DEVELOPMENT OF PROSOCIAL BEHAVIORS 

( OR KINDNESS COMETH^ ) 

h.v. h °''^'' ^ "'^^^'^ °^ ^^^'''' ''^^'^" ^'^^^ ^^^^°" ^"'i Caroline Zahn Waxier 
have been engaged in research on the development of prosocial behaviors in 
young children, that is, studies aimed at identifying conditions that ai" 



64 



or hinder the development of concern for other persons. Details of their 
substantive findings have been reported in previous annual reports. A 
general conclusion from their experiments, one relevant to their present 
plans for extending this program into investigations involving older 
children, is that the child's learning and practicing of altruism is 
largely a function of the parents' or teachers' own capacities for commit- 
ment to altruism. Children under the care and tutelage of adults whose 
commitment was only at the level of verbalized moral principles expressed 
altruism only in the form of moral judgments and principles. They did not 
develop altruism when they were cared for by adults who were warmly altruistic 
toward other people but who treated them coldly and unempathically. When 
the caretakers were genuinely responsive to others' needs for help and 
comfort, verbalized their values regarding respect for others, and were 
warmly responsive to the child, the children developed altruism, generalized 
both in principle and in behavior. 

Experimentally contrived social situations are widely used in the 
investigation of children's social learning, yet there are few guidelines 
or criteria for determining what kinds of laboratory manipulations are 
effective and valid representations of social processes. Yarrow and Waxier 
have therefore made the experimental situation itself an object of study. 
Through planned variations in their own experimental procedures, and from 
an analysis of the research literature, they have demonstrated that findings 
vary as the dimensions of the experimental situation vary. Conclusions emd 
generalizations arrived at from a large body of experiments, all using 
structurally similar situations, may have much less theoretical generality 
than is often assumed. Furthermore, experimental situations devised for 
young children do not always have the same meaning to children as to inves- 
tigators. Similarly, situations assumed to be conceptually equivalent are 
not always so. 

The data discussed by Yarrow and Waxier show that such facets of the 
experimental situation as ambiguity, bizarreness, test-like quality, and 
artificiality or reality have significant effects on children's responding. 
Further, although various experimental situations produce similar behaviors 
in children, the cognitive and affective accompaniments of these behaviors 
are not always the same, nor do they always conform to what the investigator 
has assumed. 

As Yarrow and Waxier plan for extending their studies to older 
children, many new experimental difficulties arise, particularly in making 
laboratory situations plausible and meaningful. These limitations push for 
the development of new experimental approaches to field designs. Their 
current work on observational procedures in fluid settings, such as in the 
family, is providing methodological footings to aid them in extending their 
studies of prosocial behavior; this work should contribute as well to basic 
methodology in social research, 

DEVELOPMENT OF SELF-CONCEPTION IN CHILDREN 

In past reports about Morris Rosenberg and Roberta Simmons 's study 
of self-esteem in black and white children, we emphasized their finding 

65 



that black children's levels of self-esteem are as high as are those of 
white children--despite the widespread belief to the contrary among social 
scientists and laymen alikeo Now, with the completion of their analyses 
(soon to be published as a monograph by the American Sociological Association), 
it is possible to address the theoretically more important question: just 
what does matter in determining levels of self-esteem of both black and white 
children? 

The findings consistently emphasize the impact of the immediate 
social environment on the child's self-esteemo Of particular importance is 
the concordance or discordance of the individual's social characteristics 
with those of the people with whom he interacts. Consequences of contextual 
consonance or dissonance are varied, some beneficial, others injurious. 
For example, at the secondary school level, black children attending pre- 
dominantly black schools are more likely than are black children in pre- 
dominantly white schools to have high self-esteem; but they are also more 
likely to obtain low marks in school. Whatever its other costs, then, a con- 
sonant social context appears to protect the self-esteem of the black child. 
A black child in a racially segregated context has little direct exposure 
to white children, and is thus unlikely to experience direct prejudice. 
He is exposed to circumstances that are less likely to make him aware of 
the deprecatory views of whites. If he comes from a separated/never-married 
family, he is less likely to feel deep personal shame at the fact, since 
the stigma attached to this family type is less strong in this environment. 
Although his school performance tends to be poorer than that of whites, 
he is not necessarily disturbed by this, for he usually compares himself 
with others of his race. Finally, a consonant social environment is more 
hospitable to the use of certain psychological mechanisms for protecting 
self-esteem. 

In this study, four protective mechanisms have been observed: the 
inflation mechanism (e.g, , the tendency for children to believe that 
society ranks their race, religion, or father's occupation higher than it 
actually does); selective interpretation (e.g., the child who does poorly 
in school is not likely to believe that low marks signify low intelligence); 
selective perception (e.g., the child who does poorly in school perceives 
his parents as considering him intelligent); and value selectivity (e.g., 
the academically unsuccessful child is less likely to stake his feeling 
of self -worth on intelligence). All these protective mechanisms are espe- 
cially likely to be employed in consonant social contexts, which are 
particularly hospitable to their use. 

Finally, the individual's self-attitude is strongly influenced by 
his perception of other people's evaluations of him; this will be especially 
true for those who play an important role in his life. In this respect, 
the black child appears to fare as well as the white. Black children are 
just as likely as whites to believe that their mothers, friends, and 
teachers hold favorable opinions of them. Furthermore, these perceptions 
are at least as strongly related to the self-esteem of black as of white 
children. These processes thus serve to protect the self-esteem of the 
black child against the deprivations to which he is subjected. 



66 



In sum, the data suggest that the immediate environment of the 
child constitutes an important crucible within which his self-image is 
forged. Even in a hostile larger environment, this immediate environment 
can be protective of the child's self-esteem. 

HEALTH ORIENTATIONS OF CHILDREN 

From comparisons of mothers' and children's definitions of illness, 
John Campbell found that with increasing maturity people typically adopt 
a more sophisticated definition of illness, one that is broader, more 
psychosocial ly oriented, more precise, and more subtle. Using a composite 
measure of definitional sophistication, he found that, with age statisti- 
cally controlled, the correlacion between mothers' and children's "sophisti- 
cation" scores were negligible. This evidence provides little support to 
the idea that, in defining illness, the child adopts his mother's conceptual 
style. Moreover, correspondence between mother and child in definitional 
sophistication was not enhanced by facets of the mother-child relationship 
that one would expect, from past research, to be favorable to the inter- 
generational transmission of attitudes and concepts. To a considerable 
extent, then, children's concepts of illness develop from their own exper- 
iences, rather than from the direct transmission of maternal concepts. 

Although children may not directly adopt their mothers' conceptions 
of illness, mothers do serve as gatekeepers for the child, legitimizing 
his illness or imposing a label of illness on him; this is particularly 
true for younger children. Furthermore, after age differences are 
statistically eliminated, the child's propensity to view the behavior of 
other family members as critical in defining illness is clearly linked to 
his past health history--the healthier the child has been, the less likely 
he is to view the behavior of other family members as critical in defining 
illness. 

Another dimension of the illness concept is whether or not a child 
will interpret particular symptoms as indicating that he is ill. In general, 
both mothers and children think that they are less vulnerable than other 
people to illness. This tendency is enhanced with age. Above and beyond 
the effects of age, the principal determinants of whether or not a child 
will interpret a given set of symptoms as indicating that he is ill are 
his perception of whether or not illness brings rewards, his assessment of 
his mother' s own approach to being sick, and his own standards for function- 
ing in the sick role. If he sees his mother as more attentive, affectionate 
and indulgent when he is sick, if he reports that she herself readily 
accepts the sick role, and if he thinks that it is acceptable to express one's 
emotions openly when sick, then, given specified signs and symptoms, he is 
more likely to see himself as ill. In short, to the degree that a child 
perceives the general milieu as providing support for adopting the sick role, 
he will readily attribute illness to himself. 

THE SOCIAL-STRUCTURAL ORIGINS OF STRESS 

As reported in some detail last year, Leonard Pearlin and Frederic 
Ilfeld are in the midst of a large-scale study of the social origins of 

67 



stress, i.eo, emotional burdens experienced by individuals from which 
they attempt to remove themselves. The main thrust of their investigation 
is to trace the influence of social structure--especially race, class, sex, 
and age- -on people's exposure to potentially stressful situations, their 
experiencing these situations as stressful or nonstressful, their modes of 
coping with stressful situations, and the longer-term consequences of these 
experiences. 

The principal accomplishments of the project this year have been a 
refined conceptualization of the stress process, particularly of coping, 
and the development and pretesting of a complex interview schedule. The 
final wave of pretests was conducted in Chicago by a professional survey 
organization, using a random sample of 100 respondents. These pretest 
interviews made possible the sharpening of questions and development of 
indices. Statistical analysis of these interviews also demonstrated that 
it is possible for respondents to differentiate among potentially stress- 
arousing experiences and to distinguish between situationally-induced 
stress and more pervasive anxiety. For example, a majority of people who 
report problematic experiences in one area of life do not report them in 
others; of those who say they do have problems in one or another area, 
most say that the problematic experiences do not create felt stress; and 
of those reporting stressful reactions in one area, most are likely to 
report none in other areas. This independence of responses to different 
parts of the interview insures that statistical analyses of the stress- 
process can be meaningful. 

The study is scheduled to go into the field shortly. It is to be 
conducted in Chicago, the goal being to interview a representative sample 
of 2,000 people, plus special subsamples of another 300, 

THE DEVELOPMENT OF CONSCIENCE 

In his experimental studies of conscience-development in young 
children, Roger Burton's focus this year has been the investigation of how 
a mother's presence in the experimental situation and her specific child- 
rearing practices are related to her child's behavior in a test of cheating. 
A child's performance on a simple game of motor skill provided measures of 
his honesty or dishonesty in the face of a strong temptation to cheat. 
Deviation from the rules of the game was necessary to achieve a good score. 
All children were first tested alone. A week later, their mothers were 
chlS l°Jf r '5^ while they were retested. Interactions of mother and 
child were observed from behind one-way mirrors. 

Ph.n..H^^"^K^^''' T^^^""^ "^^^ present, significant numbers of children 
changed m their observance of the rules; the majority changed to cheating 

oX2TslVe:T,olTTn,-t'' '^°"''^^'' ^ control^group reteLed alone S 
ocnerwise identical conditions remained stable in either chpflt-inc r,-,- k^,-„„ 
honest. Among children who cheated only when mother was prlsei^' tLre ' 

silJen^^S^Se^tlndicatiS^ :;rt:in ::iuct" 'T^'T' ''^" ^°"^ ^°"- 
hand, some children who ^ad^LS^^^ HLrint^^^edt^^i:"'^ 



mothers' presence. These contradictory processes do not support the notion 
that the presence of an adult will necessarily result in what has been 
described as "externalization of conscience" or "transfer of superego," in 
which the child shifts responsibility for control from himself to the 
adult. 

Reviews of research on conscience development have often concluded 
that parental warmth is positively associated with early and strong develop- 
ment of conscience. In this study, though, maternal warmth was related to 
cheating, under both experimental conditions. Further analyses that dis- 
tinguished those expressions of warmth contingent on the child's behavior 
in the game from noncontingent warmth provided a clearer understanding 
of the processes involved. Noncontingent warmth, a measure similar to 
"general warmth" as usually employed, was unrelated to any of the measures 
of the child's behavior, whereas contingent warmth was significantly related 
to cheating, whether or not the mother was present in the experimental sit- 
uation. These findings suggest that the broad notion of warmth, which has 
served as the basis for assessing the nurturant relationship, may be mis- 
leading. Warmth may be more adequately conceptualized as a specific resource 
that is manipulated rather than as a general quality of a relationship. The 
data do fit predictions from social learning principles that a mother's 
requiring successful achievement as a condition for showing warmth, or 
withholding emotional support when the child performs badly, would lead to 
cheating. 

Besides warmth, the mother's behavior was scored in the areas of 
rejection, dominance, harmony, and achievement orientation. The findings 
generally indicate that the more the mother focused her attention on 
achievement and directed the child toward achievement, the more likely was 
the child to cheat. This general pattern received confirmation from a 
factor analysis of the rearing measures, 

THE SOCIAL PSYCHOLOGICAL CORRELATES OF OCCUPATION 

The most recent analyses of Melvin Kohn and Carmi Schooler's data on 
the social psychology of occupation have centered on whether occupation 
affects or only reflects personality. Their approach to this problem is 
based on studying dimensions of occupation, in contrast to the traditional 
approach of studying some one occupation. To disentangle the intercorrelated 
dimensions of occupation, they have secured a large sample of men, inventoried 
their job conditions, and differentiated the psychological concomitants of 
each facet of occupation by statistical analysis. 

Virtually all of the many occupational conditions examined in this 
study are significantly related to one or another facet of psychological 
functioning. But relatively few occupational conditions- -thirteen in all-- 
are significantly related to more than one facet of psychological functioning, 
independently of education and of all the other pertinent dimensions of occu- 
pation. Although few in number, these occupational conditions are sufficient 
to define the structural imperatives of the job, for they identify the man's 
organizational locus, his opportunities for occupational self -direction, 

69 



the principal job pressures to which he is subjected, and the principal 
uncertainties built into his job. These occupational conditions have an 
appreciable bearing on men's subjective reactions to their jobs, their 
values, their orientation to self and to society, and even their intellectual 
functioning. 



Kohn and Schooler's preferred explanation of the linkages between 
occupational conditions and psychological functioning is that job conditions 
affect men's orientations to, and behavior in, both occupational and non- 
occupational realms of life. But there are other possible interpretations, 
which they have tested. The two most important are that the findings re- 
flect a tendency for men to mold their conditions of work to meet their 
needs and values, and that men are selectively recruited to and retained 
in jobs to which they are well suited. 

Job molding . Several lines of evidence suggest that men's molding 
of their jobs can take place only within rather narrow limitations. Most 
important of all the evidence: occupational conditions are structurally 
interrelated. Thus, a man who does substantively complex work stands a 
greater risk of being held responsible for things outside of his control 
than does a man who works at simpler tasks. The risk increases if the job 
is not only substantively complex but also time-pressured, and increases 
further if the man stands high on the supervisory ladder or is an owner. 
From this perspective, an increased risk of being held responsible for 
things outside of one's control is the price one pays for holding an inter- 
esting and responsible job. Each of the other occupational conditions can 
also be seen as part of an interlocking network. This structural interre- 
latedness means that one has to accept some occupational conditions as the 
price for securing others. 

Selective recruitment and retention . To deal with the possibility 
that the relationships between occupational conditions and psychological 
functioning come about because of selective recruitment and retention, the 
investigators reconstructed each respondent's job history. The emphasis 
was on one pivotal facet of occupation that could be reliably assessed, the 
substantive complexity of the job. The question is: To what extent has 
the substantive complexity of men's jobs been influenced by their psycho- 
logical functioning, and to what extent has their psychological functioning 
been influenced by the substantive complexity of their jobs? 

The analyses indicate that psychological functioning plays, at most, 
a small part in determining the substantive complexity of men's past and 
present jobs. Moreover, no matter which aspect of psychological functioning 
is examined, it is more affected by, than a determinant of, the substantive 
complexity of the job. Occupational self -selection undoubtedly does take 
place, but does not provide the major explanation of the findings. There 
IS a continuing interplay, throughout the career, between man affecting 
job and job affecting man. 

These findings have several implications. First and most generally, 
they contribute to the growing sense that we have for too long fixated on 

70 



I 



the importance of early, especially childhood, experience in the shaping of 
personality^ The potentiality for change persists throughout men's 
occupational careers. 

Second, the findings should help reshape our conceptions about what 
is important in occupational experience. Variables that have been at the 
center of interest in the study of occupations- -status, interpersonal 
relationships, organizational structure—prove to be less pertinent for 
psychological functioning than do the immediate realities of men's jobs. 

Third, the findings provide some insight into the processes by 
which occupational efxperience affects psychological functioning. The 
linkages between particular facets of occupational experience and particular 
facets of psychological functioning suggest that men learn to cope with the 
realities of their jobs and then generalize these lessons to nonoccupational 
realities. These findings thus argue for a learning-generalization model, 
as opposed to a reaction-formation or compensatory model. 

Finally, these findings bear directly on the issue of whether men 
similarly located in the structure of society come to share beliefs and 
values because they have experienced similar conditions of life or because 
of some process of value- transmission. Marx and the structuralists would 
have us believe that the former is basic, theorists as diverse as the 
"human relations of industry" and "culture of poverty" schools stress the 
latter. These findings come down solidly in support of the structuralists. 
Men learn from their own experience. Social structure matters because it 
helps shape this experience. 



71 



Annual Report - July 1, 1971 - June 30, 1972 

Laboratory of Brain Evolution and Behavior 

National Institute of Mental Health 

Paul D. MacLean, M.D., Chief 



By July 1, 1972, the Laboratory of Brain Evolution and 
Behavior will have spent one year in its new quarters at the 
NIH Animal Center near Poolesville, Md. This splendidly equipped 
and beautifully situated laboratory, for which planning began in 
1958, makes provision for large indoor and outdoor quasi-natural 
habitats for research on evolutionary, developmental, and 
ecological factors relating to brain function and behavior of 
animals. With this multifaceted approach, the Laboratory 
represents a unique facility and a new departure in brain research. 
The relevance of comparative animal studies to programs concerned 
with mental health is readily appreciated when it is realized 
that in its evolution the human brain expands along the lines of 
three basic patterns common to all mammals. 

The move into the new buildings went smoothly so that there 
was virtually no interruption in the ongoing experiments conducted 
indoors. One of the major research efforts of the program is to 
develop prototypes for outdoor habitats. The pond for the wild 
fowl habitat is nearing completion, and an uplands habitat, also 
near completion, has the promise of affording an inexpensive 
means and labor-saving method for enclosing large areas for 
small mammals. The main laboratory building is especially 
designed to allow easy access for the investigators to the out- 
door habitats . 

Several Calhoun-type , indoor habitats are available for 
observations on small mammals. One of them has been especially 
designed as a prototype for a "socioenvironmeter" that will partly 
compensate for the limitation of observers to record continuously 
the activities of many animals . It provides an automated data 
acquisition system which records the place, time, and direction 
of movements of animals in various compartments of the habitat 
set aside for nest boxes, feeding, and drinking. Instrumental 
behaviors can also be continuously recorded. It is estimated 
that the performance capacity of the system is equivalent to 
that of 900 observers. 

The Laboratory's first year in its new quarters has been 
remarkable because of the lack of frustrations and inconveniences 
usually experienced in settling into new buildings. The morale 
of the Laboratory has also benefited by lively, weekly seminars 



73 



and enthusiastic visits by scientists from this country and 
abroad. Finally, as mentioned in the individual reports, the 
year has been further notable because of signal, scientific 
recognitions of certain members of the senior staff. 

Section on Comparative Neurophysiology and Behavior 
Paul D. MacLean, Chief 

In its evolution the human forebrain has expanded along the 
lines of three basic patterns characterized as reptilian, paleo- 
mammalian and neomammalian. In this respect it has similarities 
to the brains of all higher mammals. The three basic brain types 
are radically different in chemistry and structure, and in an 
evolutionary sense are eons apart. Despite extensive investi- 
gation under standard laboratory conditions disappointingly little 
has been learned about the functions of the two evolutionary older 
formations of the brain. With its new facilities at the Poolesville 
Center the Section on Comparative Neurophysiology and Behavior 
will be able to conduct comparative brain and behavioral studies 
on animals living under semi-natural conditions. Studies of this 
kind have the potential of revealing brain-and-behavior relation- 
ships that would not be seen in the confines of a laboratory. 

STUDIES ON THE STRIATAL COMPLEX . In mammals the striatal 
complex (corpus striatum + globus pallidus) represents the major 
counterpart of the reptilian forebrain. The reported findings 
that large destructive lesions of the striatal complex may result 
in no motor incapacity is evidence against the clinical view that 
It primarily subserves motor functions. Projects of this Section 
are designed to test the hypothesis that the striatal complex 
plays a basic role in genetically constituted forms of behavior 
such as establishing and defending territory, hunting, homing 
mating, breeding, and forming social hierarchies. Experimental 
work of this kind is also calculated to reveal information about 
neural mechanisms underlying compulsive, repetitious, ritualistic, 
imitative and other propendent forms of behavior. 

Species-specific and imitative behavior . A long-term study 
IS utilizing the innate genital display behavior of the squirrel 
monkey as a means of identifying parts of the brain involved in 
species-specific behavior and associated imitative factors. 
Large bilateral lesions in many parts of the brain have no effect 
on the display In the past year, additional evidence has been 
^l^^i^^v ^^ lesions of the pallidal part of the striatal complex 
may markedly alter or abolish display behavior, although there is 
no evident motor incapacity. The results, therefore, indicate 
that the striatal complex may be part of a neural repository for 
species-specific forms of behavior. ' 



74 



Since the display behavior also involves imitative factors, 
the above findings are relevant to the important question of 
neural mechanisms of imitation, about which almost nothing is 
known. Imitation serves in many ways to maintain group identity 
and to promote group survival. The devastating effects of an 
incapacity for natural imitation are illustrated by cases of 
childhood autism. Since the early 19th Century, emphasis has 
been given to the use of imitation for training mentally 
retarded children, 

Effects of 6-hydroxydopamine on striatal function . 
6-Hydroxydopamine (6-OHDA) is known to destroy dopaminergic 
endings in the corpus striatum. Experiments have been performed 
in which squirrel monkeys are challenged by parenteral injections 
of L-dopa or apomorphine after the deposit of 6-OHDA powder in 
the corpus striatum. Under such conditions, monkeys that are 
apparently unaffected by 6-OHDA alone, develop athetoid movements 
and other dyskinesias. It has been shown that the same symptoms, 
(e.g., athetoid movements of the contralateral foot) can be 
elicited when animals are challenged a year later. The results 
are compatible with the clinical hypothesis that dyskinesias 
seen in the treatment of Parkinson's disease with L-dopa may 
be the result of a hypersensitivity of striatal dopamine 
receptors . 

Effect of 6-OHDA on striatal fluorescence. The use of the 
technique of Falck and Hillarp has revealed that in the foregoing 
type of experiment the deposit of 6-OHDA powder in the striatum 
may result in a loss of fluorescence for a distance of about 
2 mm from the center of the lesion. In addition, this experimental 
approach has provided new information about the course of 
nigrostriatal dopaminergic fibers in the monkey. Axons with 
injured terminals show up as brightly fluorescent beaded fibers. 
The main contribution of fibers to the rostral striatum appears 
to follow the course of the ansa lenticularis . Some fibers fan 
out in the globus pallidus in their approach to the putamen 
and caudate, whereas others veer from the ansa and follow the 
internal capsule. 

Additional findings . In extending the comparative study of 
striatal functions, some pilot experiments are being conducted 
on the effects of lesions of the paleostriatum in reptilian and 
avian forms. Tom turkeys are being used in one set of experiments 
because the group gobbling response (G.G.R.) provides a paradigm 
for investigations on imitative behavior. Preliminary findings 
indicate that a unilateral vascular lesion of the paleostriatum 
may be sufficient to produce a marked alteration of the G.G.R. 



75 



STUDIES ON LIMBIC SYSTEM . The mammalian limbic system 
(limbic cortex H- its primary brain-stem connections] represents 
an inheritance from lower mammals. The Section's research on the 
limbic system has continued to focus on the important question of 
the nature and function of intero- and exteroceptive inputs to 
the limbic cortex. 

Interoceptive inputs . In a microelectrode study of vagal 
projections to the limbic cortex an improved method has been 
devised for applying stimuli to the vagus nerve in chronically 
prepared awake, sitting squirrel monkeys. Additional evidence 
has been obtained that vagal volleys evoke discharges of units 
in the middle part of the cingulate gyrus with latencies ranging 
from 10-40 msec. The observations gain added significance from 
the finding that intravenous microinjections of serotonin, a 
known excitant of visceral receptors, affects the firing of 18% 
of units in the same cortical region, with the ratio of excitatory 
to inhibitory effects being 3 to 1. The present results are to 
be considered in the light of the known autonomic functions of 
the cingulate cortex and the alleged role of this part of the 
limbic system in morphine addiction. 

Two incidental observations in connection with this study 
should be mentioned: (1) Information has been obtained for the 
first time about the physiological effects of intravenous serotonin 
in the monkey, with penile erection being one of the manifestations i 
ihis latter finding which has not heretofore been described in 
any species, invites further investigation in regard to the 
disputed role of parachlorophenylalanine (a serotonin depletor) in 
sexual arousal of animals and man. (2) Attention is drawn to 
Project No. M-LBEB-CN-5 , describing the case of a monkey in which 
premature ventricular contractions, ECG signs of myocardial 
infarction, and cardiac myocytolysis developed following vagal 
in^tS^?t^h; f"^ significance of this finding is to be considered 
m the light of growing clinical evidence that a sizeable 



nS?her^?L°^-^^^^T^ ^^^"^ ^^°"^ ^^^^^ myocardial ischemia show 
infarction ^""^ °^ coronary thrombosis nor gross myocardial 



Exterocep tive connections . Although more is known ahoni- i-h^ 
anatomy and physiology of the olfactory^npSt to the TimSic cortex 
than other sensory systems, information is lackLg aboifthe 
influence of various components of the olfactory prelections on 
behavior The development of an improved olfactometer wi?S a 
fully automated system for testing olfactory disc?imina5on in 

Change in detection'tSLjo^SrfoS'So^rs^burSvrno SSntJon'^ 
of an overlearned discrimination task. RelearnJng S? the ^^°'' 
discrimination, however, is eventually possible'^LSicating that 



76 



other projections of the olfactory bulb afford a partial 
restitution of function. The present study provides essential 
background for planned investigations on (1) neural mechanisms 
required for the discrimination of pheromones; (2) the role of 
olfactory cues in "bait shyness" (Project No. M-LBEB-CN-9) ; and 
(3) the sensory control of fighting behavior (Project No. 
M-LBEB-CN-11) . 

Section on Comparative Biopsychology 
Walter C. Stanley, Chief 

This Section conducts comparative and ontogenetic studies 
for the purpose of gaining insights into adaptive and maladaptive 
behavior of human beings. A basic question is, "How do the 
consequences of early behavior affect later behavior?" Dogs are 
used as experimental subjects because they have a greater 
psychological affinity to man than any other domesticated animal 
and are ideally suited to biopsychological studies of the develop- 
ment of social learning and motivation. Previous investigations 
of this Section have shown that puppies under 2 weeks of age are 
capable of learning by classical and operant conditioning. The 
results suggest that in terms of the fundamental process, neo- 
natal learning is continuous with that of adult learning. This 
conclusion has far reaching implications because it means that 
neonatal learning takes place before the myelination of cortical 
structures. 

Temporal organization of neonatal ingestive behavior . Data 
on stimulus control in neonatal dogs indicate that under some 
conditions inhibitory processes are either weak, transient, or 
absent in the very young. Either the presentation or omission of 
a strong positive reinforcer such as milk can be scheduled so that 
sucking at a high rate slows to a low rate. Previously, reliable 
low rate sucking has been obtained only for short periods . In 
the past year, the use of a computer-controlled, milk-delivery 
schedule has made it possible to train subjects to slow their 
sucking so that milk is obtained 50 to 99 percent of the time. 
The schedule that results in this reliable effect combines the 
response-suppressing properties of multiple milk deliveries with 
the response-maintaining properties of single milk presentations. 
These findings clearly demonstrate that infant dogs have the 
capacity to suppress responses. 

Effective stimulus sites for milk reinforcement . Milk obtained 
by the normal intraoral route serves as a reinforcer in a variety 
of learning tasks involving different response requirements in 
neonatal dogs. Intragastric injection of milk, however, is in- 
effective in producing and maintaining learned key-lifting, al- 
though it is sufficient to maintain a nipple latch and to initiate 

77 



sucking. In view of these findings it was significant to learn 
whether or not, the oral ingestion of milk would still be an ef- 
fective reinforcer it it did not enter the stomach. Findings on 
an esophagostomized puppy resulted in an affirmative answer to 
this question. 

Maladaptive adjunctive behavior in neonates . If a neonatal 
dog is required to head-lift a key many times before obtaining 
milk from a nipple, other responses tend to occur right after 
each milk reinforcement. Such adjunctive behaviors may be of a 
normal kind such as crawling away from the nipple or may be 
maladaptive hypertonic states that interfere with getting more 
milk. The maladaptive behavior is characterized by lingual 
spasms in which the tongue is pressed against the roof of the 
mouth (TOR) or on the floor of the mouth (TOP) . In addition, 
there usually are dyskinesias of the head, trunk, and limbs. It 
was found that the experimenter could produce the TOR response 
by applying repetitive pressure below the tongue, and the TOP 
response by repetitive insertion of a nipple above the tongue. 
These functionally induced dyskinesias possibly reflect the 
incomplete maturation of the basal ganglia and suggest how some 
childhood tics might stem from maladaptive behaviors acquired 
during the nursing phase. 

Discriminated instrimiental crawling in neonatal dogs . Neo- 
natal dogs are capable of acquiring stable differential crawling 
responses to tactual or thermal cues presented on successive 
trials with only one of the cues being associated with milk 
reinforcement. Training on a new discrimination task is 
facilitated by inclusion of a previously positive cue, but is 
unaffected by a previously negative one. The findings agree 
with earlier observations that neonatal dogs, unlike adults, 
are not influenced by negative cues. 

Attachment behavior. Attachment behavior is operationally 
defined as behavior initiated and maintained by reinforcing effects 
of social stimulation. It has previously been shown that contact 
and interaction with a person can serve to maintain approach 
behavior m a variety of breeds of dogs. In juvenile Basenji 
puppies approach behavior previously established by the presence 
of a passive person extinguishes at the same rate whether or not 
exposure to the person has been on a continuous or intermittent 
schedule. _ Recent experiments have shown that beagle puppies, 
under similar test conditions, fail to show extinction. This out- 
come IS quite the reverse of what is found in beagle puppies 
reared m total isolation. In this case, the presence of a pass- 
ive person results m an improvement of running behavior with 
vnn^fn K^^^ ' ^^^5^^^ ^^ the absence of this stimulus, the 
running behavior habituates and extinguishes. The different 
findings m the two test situations possibly reflects the important 

78 



role of early exposure to human handling. 

Section on Behavioral Syst ems 
John B. Calhoun, Chief 

The research of this Section, with its emphasis on ecology, 
attempts to gain a better understanding of the interrelation- 
ships of organisms and their environment. Studies in this area 
have a special urgency because of the exponential growth of the 
world's population with its associated psychopathology , depletion 
of natural resources, and the pollution of the environment. 

Rats and mice are used as experimental subjects because of 
the extensive knowledge of their biology and behavior and because 
of their short reproductive cycles. Observations are made on (1) 
large populations, (2) small groups, and (3) animals in isolation. 

The research of the past year has been mainly concerned with 
obtaining additional behavioral and chemical data on members of a 
large population of about 2,000 mice that exhausted its capacity 
for continued procreation. This population initially began with 
four pairs of mice which were introduced into a habitat of 16 
"living units" consisting of nesting boxes, nesting materials, 
food, water, and "public space." Population growth terminated 
when the density reached about 180 mice per unit, representing 
about 20 times the number of mice that would be expected to 
inhabit this amount of space under ordinary conditions. In the 
beginning the units had been occupied by well-organized social 
groups exhibiting adequate territorial, reproductive, and maternal 
behavior. When the number of progeny exceeded by five times the 
number of animals in the original socially organized groups, there 
were four behaviorally distinct types of males: Cll territorial, 
dominant males; (2) males that infrequently left the nesting 
boxes and grew to maturity without developing normal social and 
reproductive behavior (hereafter identified as "nest dwellers"); 
(3) males that congregated in large numbers in the public spaces; 
and (4) v/ithdrawn, isolated animals. 

Irreversible behaviors resulting from crowding . Represent- 
ative mice of the four above types were reconstituted in optimal 
sized groups in new habitats containing four living units. In 
these groups the same kinds of abnormal behavior persisted, with 
a resultant failure to form a stable, structured social organiza- 
tion. Reconstituted groups of males and females from the over- 
crowded habitat showed impaired reproductive behavior: less than 
the expected number of females became pregnant; those that went 
to term made poor nests and appeared incapable of nursing and 
retrieving their young, with the result that only a few pups 



79 



survived. The provision of normal females did not improve the 
sexual behavior of the males. When females from the overcrowded 
habitat were paired with normal stud males in individual cages, 
reproduction was more successful, but there was more than the 
expected number of cases of embryo resorption and spontaneous 
abortion, as well as instances of maternal neglect and cannibalism. 

The apparent irreversible behavioral changes of animals 
exposed to the crowding serves as a v/arning of possible similar 
consequences to human beings living under congested conditions. 

Catecholamine metabolism . On the basis of an earlier study- 
it was expected that representatives of the different behavioral 
types in the overcrowded habitat m.ight show differences in levels 
of catecholamine synthesizing enzymes. Assays were made of the 
levels of tyrosine hydroxylase (TOH) and phenylethanolamine-N- 
methyl transferase (PNMP) in the brain and adrenal glands. The 
animals that lived singly or in pools showed a significantly 
higher TOH activity in the brain and a higher PNMP activity in 
the adrenals than the dominant animals. Interestingly, the 
socially uninvolved nest-dwellers had enzyme levels comparable 
to the successful dominant animals. 

While on the subject of chemistry it may be pointed out that 
previous studies in this Section showed that rats maturing in 
crowded populations exhibited marked increases in vitamin A 
content of the liver. This finding, together with the abnormal 
behaviors observed in these animals , should serve as a caveat 
in regard to the desirability of large doses of vitamins that 
has recently been proposed in writings on orthomolecular 
psychiatry. 

Social velocity . Social velocity refers to "a measure of 
the degree of physical activity and alertness of an animal." 
Observations on groups of animals ranging from four to two 
thousand indicate that as the group size increases beyond an 
optimiom, social velocity decreases. In groups in which members 
have lost their capacity for effective social organization most 
individuals exhibit a reduced velocity approaching a minimiom 
value. 

Rhythms of spontaneous behavior (RSB) . The behavior of an 
animal over time consists of a sequence of discrete behavioral 
states, each of which starts, continues, and then stops, after 
which It IS replaced by another behavior. A previous analysis of 
data derived through the use of a RSB apparatus led to the 
Identification and calculation of five probabilities concerning 
the initiation, continuance, termination, and sequencing of 
behavioral states. In the large population of mice described 
above, sixteen groups were identified, each of which exhibited 

80 



a distinctive 24-hour cycle of activity. These findings indicate 
that when an increase in population leads to an interference with 
access to resources, there is a capacity of the social system to 
reduce conflicts by utilizing resources at different times. The 
"socioenvironmeter" described in the introductory section on 
habitats will provide an improved means for investigating sequences 
of behavior in social groups. 



81 



AnniJial Report of the Laboratory of Cerebral Metabolism 

National Institute of Mental Health 

Louis Sokoloff, Chief 

July 1, 1971 through June 30, 1972 

The Laboratory of Cerebral Metabolism has continued 
during the past year to carry out investigations in its 
established research projects with no major reorganizations or 
re-orientations. Substantial progress has been made in most of 
these projects so that despite the maintenance of the same goals, 
the actual research activities have progressed to new and more 
clearly defined questions at more advanced levels. The program 
of the Laboratory is still broad and divided among the three 
Sections, each pursuing its own specific research problems. The 
Sections benefit, however, from their membership in the 
Laboratory through the communality of service modules and major 
items of equipment, the exchange of theoretical and techno- 
logical knowledge, and continued education provided by the 
Laboratory seminar program. 

Section on Developmental Neurochemistry 
Louis Sokoloff, Chief 

This Section has continued to pursue a broad program of 
investigations of normal and pathological mechanisms underlying 
normal and abnormal growth, development, and maturation of the 
central nervous system. These studies are carried out at both 
the physiological and biochemical levels. Although the 
emphasis is on basic and fundamental mechanisms, there is full 
recognition, consideration, and concern about the relevance of 
all findings to the prevention and treatment of CNS diseases of 
developmental origin. 

The thyroid hormones are known to play an essential role 
in the development and maturation of the nervous system. 
Thyroid deficiency in early postnatal life leads to physical 
dwarfism and mental retardation, a condition known as cretinism. 
The elucidation of the mechanism of action of thyroxine, the 
major thyroid hormone, has been a long and continued interest of 
the Section, and its studies led several years ago to the 
discovery that thyroid hormones stimulated protein synthesis. 
This action is now recognized as the basis of many of the 
numerous and diverse physiological effects of the hormones. The 
Section has been engaged in studies of the molecular mechanisms 
of the thyroxine stimulation of protein synthesis in brain and 
other tissues. It has been found that the stimulation of 
protein synthesis is not a direct effect of the hormone on the 
process of protein synthesis but is mediated by the product of 
a prior energy-dependent reaction between the hormone and the 
mitochondrial fraction of the cell. These studies led to the 



83 



explanation of the loss of thyroxine-sensitivity which occurs in 
brain as the brain matures and the failure of thyroxine treatment 
to reverse the mental retardation of cretinism after a critical 
age is achieved. Mitochondria of immature brain are capable of 
reacting with the hormone in the initial essential reaction, but 
the mitochondria of mature brain have lost this capability. The 
identity of the active product of the thyroxine-mitochondrial 
reaction and the chemical nature of this reaction are obviously 
key questions to be resolved, and the pursuit of these questions 
are major goals of the Section. Substantial progress has been 
made in determining the properties of the active factor, and 
these properties have been utilized to design purification 
procedures. Its exact identity is still unknown, but steady 
progress has been made. 

Progress in these studies was unfortunately temporarily 
interrupted during the last year by two reports in the literature 
which claimed evidence that thyroxine could stimulate protein 
synthesis directly without involvement of any prior reaction with 
mitochondria. Because of the importance of these claims to the 
basis of the Section's investigations, it was necessary to 
examine these alleged effects. Extensive studies in this 
Laboratory have proved beyond any doubt that these mitochondria- 
independent effects are not effects on protein synthesis but are 
technical artifacts in the procedures used by the other 
investigators. The nature of the artifacts has been definitely 
established and identified, and the results of these studies 
will be published as an example of the hazards of uncritically 
studying chemical reactions with radioactive compounds without 
establishing the chemical identity of the radioactive substrates 
and products of the presumed chemical reaction. This is a 
timely warning in this age of the widespread use of radio- 
isotopes in biochemical investigations. 

Studies have been continuing on defining the differences 
between mature and immature brain mitochondria. One of the 
differences which was previously found in this Laboratory was 
xn regard to their content of D-P-hydroxybutyrate dehydrogenase, 
an enzyme whxch is important in the utilization of ketone bodies. 
This enzyme, which IS confined only to the mitochondrial 
fraction of the cell, is low in the brain at birth, rises to a 
peak during maturation, and then, in contrast to other mito- 
chondrial oxidative enzymes which remain constant declines 
again in the mature brain. Since starvation prodAcelan increase 
in availability of the substrate for this enzyme aSa ?esint n? 
fat degradation, it is likely that this enzyme is of ma ior 
importance for the protection of the brain from nu?ri??onal 
deficiency during starvation. Recent studies in thT^iK ^ 
have Shown that the entire developmental patLJn ^^^^^^^aboratory 
ie^!^",^-^"g maturation is acc^lL^a'^ed'a'nHhi^ted'on t^he^'"^' 



time scale to a younger age in infantHT v, ^^^"ed on 
y uiigei dge in mtantile hyperthyroidism. 



On 



84 



the other hand, thyroxine acting directly on the enzyme inhibits 
its activity by competitive inhibition of the affinity of the 
enzyme for its substrates. These results suggest that on one 
hand thyroxine promotes and accelerates the biochemical 
maturation of the brain but, on the other hand, may reduce the 
resistance of the brain to nutritional insufficiency. 
Furthermore, the action of thyroxine on this dehydrogenase may 
serve as a model for its primary mechanism of action. Studies 
are currently in progress directed at the solubilization and 
purification of the enzyme so that definitive studies of the 
mechanism of its inhibition by thyroxine can be studied at the 
molecular level. 

The interaction of thyroxine with mitochondria has long 
been known to release latent mitochondrial ATPase activity. In 
contrast, studies in this Laboratory have demonstrated that the 
hormone inhibits microsomal ATPase activity. Microsomes have a 
number of ATPases which are stimulated by various ions and are 
believed to be involved in the transport of the ions in and out 
of the cells. Ion transport is fundamentally involved in the 
maintenance of membrane potential and excitability as well as 
many other cellular functions. Thyroxine inhibits all the ion- 
stimulated ATPases. The effect was originally found with liver 
microsomes, but studies in the last year have shown that the 
effect is even more prominent in brain preparations. This effect 
may be related to some of the changes in CNS function in thyroid 
disease states. The mechanism of the effect remains under study. 

Protein synthesis in brain is relatively high early in 
life and declines progressively during development until it 
reaches a relatively low level at birth. Much of this decline 
is attributable to a change in the protein synthetic activity 
of the ribosomes. It is interesting that the decline in 
protein synthetic activity bears an almost inverse relationship 
to the development of the hormone-sensitive cyclic AMP system 
in the brain. Since cyclic AMP is now known to act by stimu- 
lating protein kinase, an enzyme which phosphorylates proteins, 
the possibility has been considered that the change in ribosomal 
activity reflects the effects of phosphorylation of brain 
ribosomal proteins. Recently initiated studies have shown that 
brain ribosomal proteins can, in fact, be phosphorylated by 
cyclic AMP-stimulated protein kinase. Studies are currently in 
progress to determine whether there are age-related changes in 
this process . 

Collaborative studies with Dr. Neil H. Raskin, Department 
of Neurology, University of California, on the biochemical 
mechanisms of alcohol tolerance and the alcohol-withdrawal 
syndrome are continuing. This project was responsible for the 
first demonstration of alcohol dehydrogenase in brain. Recent 
studies have shown that chronic alcohol intake causes a rise in 



85 



the brain enzyme level of about 50%. Whether this rise can 
explain the development of tolerance to alcohol and can contributei 
to the symptoms associated with alcohol withdrawal is still under 
study. 

Studies of the changes in local cerebral blood flow with 
maturation of the brain have been completed. These studies have 
demonstrated that blood flow in gray matter is low at birth and 
rises as neuronal activity increases with maturation of the 
brain. Blood flow in white matter is also low at birth, rises 
to a peak at the time of maximum rate of myelin synthesis, and 
then declines again as maturation is achieved. The changes in 
blood flow probably reflect the changes in energy metabolism 
associated with the energy demands for biosynthetic and 
functional activities. The cerebral circulation in the newborn 
has been found to be markedly more sensitive to even moderate 
increases in the oxygen content of inspired air than it is later 
m life. Studies have been completed which show that continuous 
exposure to these elevated oxygen concentrations in the immediate 
postnatal period retards brain growth, nucleic acid synthesis 
and cell proliferation. These results indicate that oxygen ' 
therapy in the newborn for various respiratory and cardiovascular 
diseases can be deleterious to brain maturation and should 
therefore, be used with caution. ' 

^u ^ifnificant progress has been made in the development of 
a method for the simultaneous quantitative determination of 
glucose utilization in all the discrete component structures of 
the brain in animals. The method is almost ready for use in 
^nH i^^h°i *^^ influence of various physiological, pharmacological, 
and pathological states on local energy metabolism. It is hojed 
that such studies can be initiated in the coming year. 

Section on Myelin Chemistry 
Marian W. Kies, Chief 

continue^!?! ^nv 11^^ T^"" ^^^ Section on Myelin Chemistry has 
continued its investigation of the relationship between 
structure and activity of myelin basic protein (MyBP) and the 
mechanisms involved in the pathogenesis of experimental allergic 
fold'Surpolf'^The^'^'l-- ""^^'^^^ ^^^^^^ on^MyBrserve a'^^L''^ 

: 1° L--Ft-^"°- ^^ ----a!--- 

reSrSto ?he h?o? ""^^^^^J^ ^as important implications with 
a:?:ii;ne\':acti^n°^in ?h^CNs! °' "^"" ^" ^^^ ^"^^^^^ °^ - 

19 argin^nes'^irthe rnvMi'T'"^ ''^ °'^""" *^^* °"^ °f ^he 18 or 
arginmes m the myelin basic protein molecule was partially 



•methylated, and it was suggested that partial methylation of a 
single basic residue might explain the microheterogeneity of 
myelin basic protein first observed by Dr , Martenson. That 
methylation of one residue could not explain all of the observed 
microheterogeneity was obvious because of the existence of more 
than three components in the total protein. Mrs. Deibler 
undertook the difficult task of developing an analytical 
procedure for the detection of methylated amino acid derivatives 
in protein hydrolysates . Her analyses of the methylated 
arginines in the components of guinea pig myelin basic proteins 
demonstrated that the ratio of monomethylarginine to dimethyl- 
arginine remains constant, bearing out the contention of this 
Laboratory that methylation of arginine 107 cannot explain the 
observed microheterogeneity. The method which Mrs. Deibler 
developed for these analyses is a general technique for 
determining methylated derivatives of amino acids and will be 
useful for detection of these compounds in other proteins as 
well . 

Attempts by Dr. Alvord and co-workers to correlate charge 
heterogeneity with the multiple precipitin lines which they had 
observed in immunoelectrophoretic patterns of antigen-antibody 
reactions involving myelin basic protein were not successful. 
However, the observation that three precipitin lines are present 
in immunodiffusion patterns obtained with each of the individual 
components strongly suggests that partial methylation of Arg 107 
may be the cause of the multiple lines. If so, the major 
antigenic site on the molecule must contain this residue. 
(Antigenic site in this context refers to antibody-combining 
site, rather than to encephalitogenic site.) 

Last year this Laboratory reported that certain rodent 
myelins were different from other mammalian myelins in that they 
contained two different size basic proteins. Studies of these 
two rat proteins indicated that they differed in size by about 
40 amino acid residues. By analogy with published information 
on amino acid compositions of bovine and human myelin basic 
proteins. Dr. Martenson predicted the location and nature of the 
deletion which accounts for the differences between the large 
and small molecules. Tryptic peptide analysis of rat S protein 
confirmed this prediction. Although the deletion does not 
prevent the small protein from functioning satisfactorily as a 
structural protein of myelin, it markedly modifies the 
encephalitogenic site known to be responsible for its activity 
in guinea pigs. Myelin BPs have also been isolated from CNS 
tissue of the submammalian species chicken, turtle, frog, carp, 
and shark. All were inactive when tested in guinea pigs and, 
therefore, like the small rat myelin basic protein, probably 
have modified tryptophan regions. Three of these proteins — 
chicken, turtle, and frog — are, however, encephalitogenic in 
rats, as is the small rat protein. Thus it is clear that the 



87 



sequence responsible for encephalitogenic activity in rats is 
different from the encephalitogenic site active in guinea pigs. 

Previous studies in this Laboratory demonstrating that 
guinea pigs can be made tolerant to the encephalitogenic activity 
of MyBP through pre- immunization with moderate amounts of this 
protein in the absence of mycobacteria have been extended to 
include experiments on therapy. Guinea pigs in which clinical 
signs of EAE have already been established were given multiple 
daily injections of basic protein in incomplete adjuvant. The 
first therapy trials were carried out on inbred Strain 13 guinea 
pigs. The uniformly successful results (9 of 10 guinea pigs 
responded favorably to treatment) were surprising in view of 
earlier observations by Dr. Alvord that treatment was only 
partially successful. The effectiveness of treatment was 
confirmed in two more experiments. Because of earlier reports 
of partial success in treatment of Hartley guinea pigs after 
EAE had developed, similar experiments were carried out with 
outbred NIH guinea pigs, and it was also found that treatment 
was much less effective in these animals (only 3 of 9 animals 
responded favorably to treatment with encephalitogen) . The 
possibility that immune response genes are somehow related to 
(and controlled by?) genetic factors has been suggested by 
recent work on simple synthetic antigens. Thus this observation 
may have considerable significance, especially in view of recent 
reports that the distribution of histocompatibility antigens in 
multiple sclerosis patients is different from the distribution 
of these antigens in a normal population. Further studies on 
genetic relationships involved in experimental autoimmune 
disease of the CNS are in progress. 

Section on Membrane Chemistry 
Louis Sokoloff , Acting Chief 

A number of laboratories, including this Section, have 
observed that acetylcholine stimulates the incorporation of 
phosphate into phosphatidic acid and phosphatidylinositol in 
preparations from neural tissues. Phosphatidylinositol is an 
important phospholipid component of membranes, and it is widely 
believed that this biochemical effect is related to the mechanism 
of action of the neurotransmitter at the specific receptor site 
on the membrane of the effector cell. The mechanism of the 
action of acetylcholine on phosphoinositide metabolism is still 
^"o^°T"k.?':'^ previous workers in this Section proposed that 




R^r.^ + =.+ ^- • ., -^™"l^te phosphatidylinositol turnover 
Recent studies in this Laboratory have implicated calcium Ions 



in phosphatidylinositol turnover. EGTA, a potent chelator of 
Ca^+j has been found to markedly inhibit ^^P incorporation into 
phosphatidylinositol, and this inhibition can be reversed 
specifically by the addition of excess Ca"^"^. Evidence has also 
been obtained that Ca2+ stimulates the hydrolysis of phosphatidyl- 
inositol. In other words, Ca2+ appears to have actions similar to 
the mechanisms postulated for acetylcholine. This suggests the 
possibility that the action of acetylcholine on phosphatidyl- 
inositol turnover is mediated via an effect on free Ca2+ levels. 
Preliminary studies indicate, in fact, that EGTA also blocks the 
effects of acetylcholine. Studies are continuing to determine 
the role of Ca2+ in the mechanism of action of acetylcholine. 



89 



Annual Report of the 

Laboratory of General and Comparative Biochemistry 

National Institute of Mental Health 

Guilio L. Cantoni, Chief 

S. Harvey Mudd, Acting Chief 

The research program of the Laboratory has continued to 
develop favorably during the current year. Dr. Cantoni, Chief 
of the Laboratory, is spending the year on sabattical leave at 
the Institute of Embryology, University of Rome, Rome, Italy 
pursuing problems of gene action and differentiation in 
eukaryotic cells. 

Dr. Cantoni 's collaborators have continued fruitfully 
investigations which had previously been initiated. Dr. Boeker 
has succeeded in elucidating the subunit structure of a homogeneous 
preparation of seryl tRNA synthetase and supplied kinetic and 
other data bearing upon the mechanism of interaction between small 
molecular weight substrates, the enzyme protein, and the acceptor 
RNA. Detailed understanding of these sorts of interactions are 
expected to shed light upon a problem central to many of the major 
problems in biology, i.e. the general area of nucleic acid-protein 
recognition and interaction. Dr. Haberkern has developed a method 
of purifying the enzyme in calf thymus extracts which hydro lyzes 
specifically the RNA portion of RNA-DNA hybrids. The purified 
enzyme has been vised to characterize the substrate acted upon and 
the products formed by this unique enzyme. The biological role 
of this widely distributed enzyme represents a major puzzle, the 
answer to which will surely be useful in understanding normal and 
abnormal processes of information transfer in biological systems. 
Dr. Schmidt has taken the first steps toward a study of spermidine 
metabolism in mammalian brain. There is increasing evidence that 
this compound, or related ones, may play a role in the regulation 
of growth processes and the early indications coming from the work 
of Dr. Schmidt that there may be a correlation between the rate 
of spermidine formation and the times of most rapid brain tissue 
formation and myelinization raise important questions which will 
surely stimulate a great deal of work. 

Studies on the interactions between «-lactalbumin and A- 
protein are continuing in Dr. Klee's laboratory with the collabo- 
ration of Drs. K. S. Iyer and C. B. Klee. The A-protein has 
been found to be a component of the synaptosomal membrane and can 
readily be prepared in a soluble form from this source. Although 
this partially purified preparation is functionally indistinguish- 
able from the A-protein found in milk, the membrane bound activity 
does not interact with a-lactalbumin. Whether this is a problem 



91 



of accessibility or of modified properties of the A-protein 
itself remains to be determined, as does the function of the 
A-protein in synaptosomes. a-Lactalbumin has been prepared in 
the form of a mixed crystal with the homologous egg white protein, 
lysozyme. These mixed crystals may be useful in delineation of 
the degree of relationship between the conformation of these two 
proteins. Studies on the guanidination of a-lactalbumin have been 
initiated with the dual aim of preparing a radioactively tagged 
protein for membrane binding studies and of understanding the 
role of amino groups in the A-protein-a-lactalbumin interaction. 
The protein may be almost completely guanidinated without 
appreciable loss of activity so that a biologically active 
derivative of high radioactivity can easily be prepared. Complete 
guanidination is, however, accompanied by large conformational 
changes, aggregation, and loss of activity. These changes are 
currently being studied and may provide some clues to the 
structural basis of ot-lactalbumin activity. As discussed last 
year, these studies are all aimed at gaining an understanding of 
the manner in which the specific function of one protein may be 
modified through interaction with a second protein, a mechanism 
which opens interesting and largely unexplored evolutionary 
possibilities . 

Dr. Merril and his co-workers have performed a number of 
investigations on the effect of bacterial viruses on human cells. 
Such studies were first made with the virus, lambda, and hvutian 
skin fibroblast cells grown in tissue culture. The studies 
included electronmicroscopic observations which indicated that 
the cells are capable of taking up whole virus, DNA-RNA hybridi- 
zation which indicated that the viral genome was being transcribed 
and, finally, assays for the presence of an enzyme to document 
translation of the viral genome. The human fibroblasts used were 
from a child with galactosemia, a disease associated with mental 
retardation and caused by a defect in a specific galactose trans- 
ferase enzyme. A bacterial virus lambda derivative, Xpgal, 
appears to be capable of correcting the biochemical defect in the 
cultured galactosemic human fibroblasts. Investigations are 
currently underway to define the variables in this system. These 
studies have already led to the finding that the fetal calf serum 
used for growing cells in tissue culture contains bacterial viruses. 
Similar serum is used to grow cells for vaccine production and 
the possibility of inadvertant exposure of large numbers of 
persons to these viruses certainly deserves further exploration. 

As a consequence of the finding that bacteriophage are 
present in fetal calf serum, a survey was initiated to determine 
the possible presence of these viruses in other mammals. The 
presence of viruses which can form plaques on Escherichia coli C 
was soon demonstrated in blood samples obtained from members of 
our staff and from NIH Blood Bank donors whose occupation does 
not involve chronic exposure to high concentrations of virus. 



92 



[ 



studies have been started to determine how these viruses get 
into the blood and the possible effects they might have. 

As indicated by the very great amount of interest and 
publicity which attended publication of the early results of 
these studies, the work of Dr. Merril and his collaborators has 
opened a variety of possibilities for further investigation. 
Experimental manipulation of the genetic material within human 
cells should be useful in a great many studies of gene regulation, 
differentiation, and other basic biological problems. The fact 
that human (and calf) blood normally contains viruses, raises a 
host of questions ranging from the immediate practical conse- 
quences for vaccine production to longer range problems of the 
role of these hiterto undetected biological agents in human health 
and disease. 

The research in the Section on Alkaloid Biosynthesis has 
continued to focus on the metabolism of sulfur containing amino 
acids. Drs. Giovanelli and Datko have used the plant enzyme 
system which our previous studies had shown could utilize a 
variety of 0-alkylhomoserine derivatives as well as 0-phosphoryl- 
homoserine to set up a very sensitive enzyme assay for activated 
homoserine derivatives . This assay has been used to search for 
such compounds present naturally in plants. It has now been 
shown that plants contain a compound, preliminarily characterized 
as 0-phosphorylhomoserine, whereas 0-oxalyl-, 0-malonyl, and 
O"succinylhomoserine are not present. This finding provides 
direct evidence to support the previous indications of a key role 
for 0-phosphorylhomoserine in cystathionine biosynthesis by green 
plants. Thus, a major uncertainty as to which enzyme reactions 
are physiologically important in plant sulfur amino acid metabolism 
has been resolved. 

The studies of the plant toxin, rhizobitoxine, have been 
refined and applied to a more favorable experimental system. 
Using this systan, it has been shown that rhizobitoxine inhibits 
the enzyme B-cystathionase in vivo, and that one physiological 
consequence of the inhibition of this enzyme is an accumulation 
of cystathionine. No severe, sustained, impairment of methionine 
formation occurs, a result predicted if cystathionine is normally 
present well below saturating concentrations. If further studies 
show that the enzyme acetylhomoserine sulfhydrase, is not inhibited 
by rhizobitoxine, a potent tool will be available to decide whether 
the transsulfuration or the direct sulfhydration pathway is more 
important in plant homocysteine biosynthesis. 

Finally, continuing studies of homocystinuria in humans have 
led during the current year to definition of anew inborn error 
of metabolism, one which may be associated in at least some cases 



93 



with a reversible form of schizophrenia. Investigations of the ( 
means whereby large doses of pyridoxine alleviate the biochemical 
abnormalities in some individuals with cystathionine synthase 
deficiency appear to be providing a sound experimental basis 
for the possibility that hereditary enzyme deficiency diseases 
may be treated by specific stimulation of the deficient enzyme 
activity. 



94 



ANNUAL REPORT OF THE LABORATORY OF NEUROBIOLOGY 

■NATIONAL INSTITUTE OF MENTAL HEALTH 

Ichiji Tasaki, Chief 

The Lahoratory of Neurobiology has carried on investigations of the 
nervous system on two different levels: studies of the process of excitation 
in the nerve menibrane and the analysis of function of one part of the brain, 
the superior colliculus.. 

Experiments on nerve utilize optical methods, especially fluorescence, to 
study the nature and organization of the membrane macromolecules and how 
they change during excitation. Squid giant axons and crab or lobster nerves 
are stained with fluorescent dyes and then the characteristics of the 
fluorescent light coming from the nerve are analyzed. The intensity, spectrum, 
and fluorescence polarization of the emitted light give useful information as 
to the state of the macromolecules in the membrane. It has been found for 
example, that the membrane has a highly organized, regular, rigid structure. 
Evidence has been accumulated in support of the macromolecular theory of 
nerve excitation which postulates a hydrophobic-hydrophilic transition of 
the membrane during the action potential. 

Experiments on the central nervous system have investigated the role of 
the superior colliculus in behavior. Responses of single cells have been 
studied while an awake monkey fixated a point of light or made rapid eye 
movements from one point of light to another. Cells in the upper layers of 
the colliculus have large receptive fields but are insensitive to many 
stimulus parameters. About half of these cells respond more vigorously to 
a spot of light when the monkey is required to pay attention to the spot of 
light. Cells in the intermediate layers discharged before eye movements to 
the same area of the visual field where the receptive fields of the cells in 
the upper layers were found. Lesions of these cells in upper and middle 
layers did not decrease the accuracy of an eye movement but did lead to a 
longer latency to make the eye movement . These experiments suggest that the 
primate superior colliculus is not critical for eye movement guidance but 
instead contributes to a shift of visual attention and facilitates eye move- 
ment toward important areas of the visual field. 



95 



I 



Annual Report of the Laboratory of Neurochemistry 

National Institute of Mental Health 

Seymour Kaufman, Chief 

During the last year, significant progress was made in all 
of the major research areas of interest to the Laboratory. 
Indeed, in one of these areas, ±.e., analysis at the molecular 
level of the enzymatic defect in phenylketonuria and hyperphenyl- 
alaninemia, the results obtained during the last year represent 
the culmination of one of the lines of investigation that was 
initiated 17 years ago. At that time, the phenylalanine hydrox- 
ylating system was selected for intensive investigation for two 
reasons: a) it was known to catalyze a relatively new type of 
oxidative reaction, i^.e. , the incorporation of molecular oxygen 
into an organic molecule; an understanding of the mechanism of 
action of this kind of enzyme would expand our knowledge of how 
molecules are oxidized in the cell; b) it was known that the 
lack of this activity in the disease, phenylketonuria (PKU) , leads 
to mental retardation. Implicit in this undertaking was the faith 
that knowledge of the normal enzyme system would contribute to 
our understanding of the disease . 

One of the earlier applications of our increasing basic 
knowledge about the hydroxylating system was the precise delinea- 
tion of the defect in PKU. As it became apparent from our 
earlier work that the system that catalyzes the hydroxylation of 
phenylalanine to tyrosine is a complex one, consisting of at least 
three essential components, i^.e. , two enzymes, phenylalanine 
hydroxylase and dihydropteridine reductase, and the cofactor, 
tetrahydrobiopterin, it also became clear that the lack of any 
one of these components could be responsible for the lack of the 
overall hydroxylating activity in PKU. We showed that the reduc- 
tase and the cofactor are present in normal amounts in biopsy 
liver samples from PKU patients and that the hydroxylase is non- 
functional. This work established for the first time that 
phenylalanine hydroxylase is the affected component in PKU. 

The next question that demanded an answer is "What is the 
nature of the mutation in PKU that leads to a non-functional 
hydroxylase?" One of the classical approaches to this kind of 
problem is to prepare antibodies to the normal enzyme and to 
determine if the mutation leads to the production of an altered 
protein which is devoid of the normal enzyme activity, but can 
still cross-react with the antibodies. This is the approach that 
we have followed. 

One of the requisite steps in this line of investigation is 
to prepare the pure antigen, in this case, phenylalanine hydrox- 
lase . In the ideal application of this method, the pure hydroxylase 

97 



from normal human liver would be used as the antigen. The un- 
availability of fresh, normal human liver precluded our following 
the ideal course and instead, we have attempted to use the normal 
rat liver enzyme as the antigen. 

Pure rat liver phenylalanine hydroxylase (described in last 
year's report), was injected into sheep. The antiserum produced 
by the sheep to this foreign protein contained antibodies to the 
hydroxylase. When tested against either crude rat liver or normal 
human liver extract, using the double-diffusion technique, only a 
single precipitin line was produced, proving that the antibodies 
were specific for phenylalanine hydroxylase and that the anti- 
bodies to the rat liver hydroxylase could cross-react with the 
normal human enzyme . 

These antibodies were used to look for cross-reacting material 
(CRM) in a biopsy liver sample from a single PKU patient and from 
a single hyperphenylalaninemic patient. In neither of these 
samples could any CRM be detected. The tests were sensitive 
enough to detect CRM, if any were present, at the level of 5% of 
the normal enzyme . 

These results permit several important conclusions to be 
drawn about the molecular defect in these two diseases. First, 
they provide the final proof that phenylalanine hydroxylase is 
the affected component in PKU, as well as in hyperphenylalaninemia, 
thus extending and corroborating our previous conclusions. 
Second, they show that in PKU, the mutation is either of the 
deletion type, in which no gene product is made (hence no detec- 
table CRM) , or it is a mutation in the gene that determines the 
structure of the hydroxylase. In the latter case, the product 
of the mutated gene would be so altered that it is devoid of 
hydroxylase activity and of its ability to cross-react with the 
antibodies . 

In the case of hyperphenylalaninemia, additional data are 
available that help in the delineation of the genetic events that 
lead to the disease. Our previous work showed that liver samples 
from patients with this disease have about 5% of the normal level 
of hydroxylase. By a more sensitive immunological test than the 
double-diffusion technique, we have detected CRM in a liver ex- j 
tract from a hyperphenylalaninemic subject. Furthermore, we have 
shown that one of the kinetic properties of the hydroxylase, i.e., 
its Km for phenylalanine, is different from that of the normaT ~ 
enzyme . 

These results indicate that this disease is caused by a 
mutation in the structural gene for phenylalanine hydroxylase. 
The altered protein produced has the following properties: ^ 

98 



a) it has only about 5% of the normal hydroxylase activity; 

b) it has a significantly lower Km for phenylalanine; 

c) it interacts with antibodies to the normal enzyme, but the 
antibody-antigen complex does not precipitate completely nor 
does it lose all of its catalytic activity. 

The antibodies to pure phenylalanine hydroxylase are a 
powerful tool in the analysis of the nature of the defect in 
these diseases. At the present time, the only serious impediment 
to a more detailed analysis is the limited availability of suit- 
able tissue biopsy samples. 

In the area of the regulation of normal phenylalanine 
hydroxylase activity, an important advance was made during the 
last year. It was found that certain phospholipids, such as 
lysolecithin, can stimulate the activity 50-fold. Long-chain 
fatty acids show some activation, whereas lecithin is a potent 
inhibitor. These results indicate that lipids may play an im- 
portant role in the regulation of the hydroxylase activity in 
vivo . They point to the possibility that a secondary consequence 
of certain diseases, such as diabetes, and of altered nutritional 
states, such as starvation or excessive sucrose intake could, by 
virtue of their effects on lipid metabolism, lead to significant 
changes in the activity of the hydroxylase. 

The marked activation of the hydroxylase by certain phospho- 
lipids should also be useful in attempts to detect the hydroxylase 
activity in tissues that are more readily accessible than liver. 
If the activity could be detected in these tissues (e.g., skin, 
blood cells) , this test could facilitate the diagnosTs~of genetic 
diseases that are characterized by low levels of the hydroxylase. 

During the last year, we have undertaken a new problem, an 
investigation of brain tryptophan hydroxylase. This enzyme, 
which utilizes the pterin cofactor that was previously discovered 
in this laboratory, is believed to catalyze the i"ate-limiting 
step in the biosynthesis of the neurotransmitter, serotonin. 
Since alterations in the brain level of serotonin have been im- 
plicated in such diverse activities as sleep, agression, sexual 
behavior and drug addiction, it is clear that this hydroxylase 
may play an important role in modulating behavior. 

Although the project is still in its infancy, it has already 
led to significant insight into the parameters that can regulate 
the activity of the hydroxylase. Based on our previous work 
with the other pterin-dependent hydroxylases, we were able to 
predict with a high degree of accuracy several of the important 
properties of this enzyme . One of these is that the Km for 



99 



tryptophan varies dramatically with the pterin cof actor used; in 
the presence of the natural cof actor, the Km is only one-sixth 
as large as it is in the presence of the cof actor analogue. This 
finding clarifies what appeared to be an absurd situation: that 
the previously accepted Km value for tryptophan (determined only 
in the presence of the cof actor analogue) was 10 times higher than 
the probable brain levels of tryptophan. If this were the actual 
in vivo situation, tryptophan hydroxylase would be severely 
limited by availability of tryptophan. Based on our new value 
for the Km for tryptophan, this enzyme appears to operate with 
no unique limitation of substrate availability. 



Another important property of the enzyme that was demon- 
strated was inhibition of its activity by excess tryptophan. It 
may be possible to exploit this property in the treatment of the 
disease, malignant carcinoid syndrome, which is characterized by 
excessive serotonin production. If high tryptophan levels can 
be achieved in vivo, tryptophan hydroxylase shoule be inhibited 
and the exces¥ serotonin production may be partially controlled. 

In the area of skeletal muscle hypertrophy, we have found 
the earliest biochemical change yet detected in this adaption 
process - an increased turnover of phospholipids. The change 
is detectable within 2 hours of the onset of hypertrophy, pre- 
ceding by about one day any of the previous biochemical changes 
that have been documented. The alteration appears to be specific 
to hypertrophy; rats subjected to acute exercise and an endurance 
training program do not show this change . 

In the Section on Biophysical Chemistry, the study of 
membrane-specific proteins has been extended to two new important 
areas. The amount of insulin-receptor protein in the membranes 
of liver cells of obese hyperglycemic mice has been determined. 
The concentration of insulin-receptors was found to be reduced 
3- to 6-fold per mg of membrane protein in the obese mouse as 
compared to normal litter-mate controls. This is the first demon- 
stration of altered membrane receptor concentration in a disease 
state. The findings suggest that there may be a wide variety of 
disease states that are receptor diseases. 

In another organ, the kidney, it was found that the isolated 
brush border membranes are enriched in a highly stereospecif ic 
binding site for phlorizin, a glucose analogue that inhibits renal 
tubular reabsorption of glucose. All of the evidence indicates 
that this site is the one that binds glucose during transport . 
This identification should permit the isolation of the glucose 
carrier and should facilitate the determination of the mechanism 
of glucose transport . 



100 



I 



Annual Report of the Laboratory of Neurophysiology 

National Institute of Mental Health 

Edward V. Evarts, M.D., Chief 

July 1, 1971 ~ June 30, 1972 



This summary of the research program of the Laboratory of 
Neurophysiology will describe three areas of ongoing research: 
1) Cellular Physiology, 2) Central Control of Movement and 3) 
Neural Correlates of Learning and Memory. 

I: Cellular Physiology . This area includes the work of 
Carpenter and Rapoport. Carpenter's work has been centered on 
two general problems. The first concerns the mechanisms which 
allow nerve cells to respond to changes of temperature. A 
second area of Carpenter's research has dealt with the state of 
ions and water in living cells. 

In his work on thermosensitivity , Carpenter has made ex- 
tensive use of the large neurons in the marine molluscs, Aplysia 
and Navanax . In Aplysia neurons thermosensitivity is imparted 
to each cell by at least two separate mechanisms. The first, 
an electrogenic sodium pump, causes the cell membrane potential 
to increase with temperature. The second mechanism tends to 
depolarize and excite the cell with warming as a result of a 
greater temperature dependence of the passive permeability of 
the membrane to sodium than to potassium. 

A related problem investigated in the same species is the 
ionic basis of pacemaker discharge in Aplysia neurons . The 
endogenous pacemaker activity can be adequately explained by a 
model containing a voltage and time varying potassium conduc- 
tance in the face of a high resting sodium conductance. Meta- 
bolic processes influence discharge dramatically but are not 
directly responsible for discharge. The electrogenic sodium 
pump does not underlie the bursting discharge characteristic 
of some neurons, as has been suggested by others. A metabolic 
regulation of membrane conductance is important, but only in 
maintenance of a high membrane resistance which is necessary 
for normal pacemaker discharge. 

These studies of Carpenter are aimed at providing an under- 
standing of the elementary ionic and metabolic mechanisms of 
nerve cells. In the case of neuronal thermosensitivity he has 
nov; isolated several temperature dependent processes which can 
be tested in mammalian preparations. 

101 



The study of the ionic basis of neuronal pacemaker dis- 
charge also ha;s relevance to the mammal. The neuronal pacemaker 
functions in a manner very similar to that of the heart. In 
addition, there is accumulating a considerable body of evidence 
suggesting that there may be endogenous activity of neurons in 
vertebrates as well as invertebrates. 

A second general area of Carpenter's work concerns the 
state of ions and water in living cells. His results, to date, 
in studies of this problem suggest that ions in nerve Cell 
bodies exist in a very different state from those in axons. If 
this be true it is necessary to re-examine many of the concepts 
which were developed to explain electrical events in axons and 
which have been assumed to apply to all excitable tissues on 
the assumption that all ions are free. Moreover, it seems very 
possible that the state of ions in most cell bodies may be more 
like that in Aplysia neurons than that in squid axons since the 
cell bodies contain many more membraneous structures and a hiqher 
concentration of organic molecules (which are probably the site 
of the ion and water binding). His observations, therefore, 
may have relevance to all types of cells. 

Dr. Stanley Rapoport's work has been concentrated on two 
major topics. The first of these concerns the electrical, ionic 
and physical properties of muscle. The second area of Rapoport's 
work has dealt with transport mechanisms across membranes. His 
work on electrical, ionic and physical properties of muscle is 
aimed at providing knowledge of mechanical properties of the 
sarcolemma myofibrils, and of their relative contribution to 
tension as a function of stretch. This knowledge is required 
to understand the process of contraction and of the resistance 
of the muscle to stretch under physiological conditions. Cor- 
relation between electromicroscopic structure of the sarcolemma 
and myofibrils and their properties permits a better understand- 
ing of the molecular forces regulating tension. 

Stretch prolongs frog muscle survival and stimulates muscle 
metabolism. These effects have not been related up to now, but 
the present work shows that they may be related through the stim- 
ulation of the Na pump by stretch. The Na pump will determine 
ionic contents of the muscle, and these in turn may determine 
membrane potential and, therefore, contraction threshold. The 
effect of stretch in frog sartorius is relevant to the problem 
of stretch-induced muscle hypertrophy. 

Dr. Rapoport's work on transport mechanisms across membranes 
has provided a new model for blood-brain barrier breakdown. It 
proposes that the barrier can be broken down irreversibly, as 
it has in the past, or reversibly, by shrinkage of endothelium 



102 



I 



cells because of osmotic action. The reversible breakdown of 
the barrier could be of significance to the treatment of cere- 
bral diseases by facilitating drug passage into the brain, 

2; Central Control of Movement . This area of the Labo- 
ratory's research program includes the work of DeLong on the 
pasal ganglia, of Miles on the cerebellum and of Evarts on the 
sensorimotor areas of the cerebral cortex. Their studies have 
involved the use of the method of single unit analysis to un- 
cover the way in which nerve cells function in the initiation 
and control of movement. 

In DeLong 's studies on the functional role of the basal 
ganglia in the control of movement and posture, monkeys were 
trained to exert a steady pushing or pulling force on a rigid 
rod positioned in front of the hand, and then to rapidly re- 
verse the direction of the force on presentation of a visual 
stimulus. Extracellular recordings were then carried out during 
the execution of the task. The globus pallidus was studied in 
greatest detail initially. In subsequent studies recordings 
have been made in the putamen and caudate as well. In these 
latter nuclei, unit discharge was also found to precede the arm 
movements, especially in the putamen. A functional organiza- 
tion was observed in both the pallidum and the caudate-putamen 
whereby the majority of movement-related units are located in 
those regions which receive their input from the sensorimotor 
cortex. Studies on the function of the corpus-striatum are of 
relevance to the program of the Institute since these regions 
of the brain appear to have important integrative as well as 
purely motor functions which, when disturbed as in disease, pro- 
duce disturbances of movement, motivation, and affect. Current 
theories suggest that the site of action of L-Dopa, which abol- 
ishes symptoms in the majority of Parkinsonian patients, is upon 
the cells of the caudate and putamen via a dopaminergic nigro- 
striatal pathway. An understanding of the normal functioning 
of the corpus striatum should provide a firm basis for studies 
on the effects of disease and pharmacologic agents on these 
structures. 

In Miles' studies on the role of the cerebellum in the gen- 
eration of saccadic eye movements, microelectrode recordings are 
made in the cerebellum of conscious monkeys and a search is made 
for individual units whose firing patterns correlate with the 
animal's saccadic eye movements. The animal is trained to 
press a bar which switches on a small spot of light on a screen 
facing him, and he must release the bar when this light dims. 
Successful performance is rewarded with a drop of water, and 
all the animal's fluid intake is earned by working at this task. 



103 



Using this approach, four monkeys have been trained to fixate 
a small spot of light and maintain this fixation even when the 
spot changes position. Thus it is possible to induce the animal 
to generate saccadic eye movements of known magnitude and direc- 
tion merely by changing the position of the fixation target. 

To date, single unit recordings have been made from the 
cerebellar vermal cortex and sub-cortical nuclei in one monkey 
performing the controlled eye movements. Seventeen units were 
found to relate to saccade eye movements. The site of these 
cells was marked with small electrolytic lesions and has yet to 
be confirmed with histology, but it is felt with reasonable cer- 
tainty that they probably all lie within the fastigial nuclei. 
No Purkinje cell firing was observed to correlate with these eye 
movements. The main characteristics of saccade-related firina 
apparent thus far are: 

a) It is usually directionally selective, showing a burst 
during ipsilateral saccades and either suppression or no re- 
sponse during contralateral saccades. Occasional units generate 
a burst during all saccades. 

b) This burst can start before the saccade, but the exact 
time relationships remain to be estimated. 

^ ^ ""l ^'^^^ magnitude of these bursts is related to the magni- 
llf.t ? the saccades and there seems to be an optimum eye move- 
ment for which responses are maximal, and larger or smaller sac- 
cades are associated with less vigorous activity. 

d) At least in some units, the saccade-related burst is 
not very sensitive to the initial start position of the eye. 

tion ITi-T/^ °^ ""^^""^^ ^^^ ^^^^^ ^ith the functional organiza- 

initiate movement, what areas cnntr-oi =.r,^ ^reas or tne cortex 
;:.nH hr>,, 1-v.,.^^ wnaL. dreas control and regulate movement. 

PTB outDUt S!or ?^ ? ^"^""""^^ys have shown that motor cortex 
ulus ocSrs aSut ?ni r"" ,'"?r"'^"'= t'^iW^s-J by a visual stim- 



104 



than visual, reaction time may be considerably shorter. Pre- 
vious studies by others demonstrated that when subjects made 
responses to displacement of the arm, reaction time was as short 
as 50 msec. Results from recordings in sensorimotor cortex of 
the monkey when the animal makes a movement in response to an in- 
put delivered to the hand showed that under these circumstances 
motor cortex pyramidal tract neurons can discharge at much shorter 
latency than is the case for movements initiated by a visual 
stimulus. In the experiments carried out in man, it had been 
observed that muscular responses dependent upon the voluntary set 
of the subject occur 50 msec following stimulus. In the experi- 
ments on monkeys, changes in muscle activity depending upon the 
set of the animal occur at a latency of approximately 35 msec 
following the stimulus. These changes in muscle activity were 
preceded by activity of neurons in motor cortex. Recordings 
from the motor cortex reveal that pyramidal tract neurons became 
active at latencies as short as 20 msec following a stimulus to 
the hand. Non-pyramidal tract neurons of motor cortex became 
active even earlier, and neurons of the postcentral gyrus were 
active at still shorter latencies of 10-12 msec following the 
stimulus to the hand. In interpreting these observations on man, 
it was proposed that very short reaction times, dependent upon the 
voluntary set of the subject, might involve a setting of spinal 
reflexes. The present observations showing changes in motor cor- 
tex output at very short latencies would suggest that in addition 
to a presetting of spinal reflex mechanisms, such short latency 
responses dependent on voluntary set may also involve pre-setting 
of cortical mechanisms. 

The importance of this observation is that it shows that a 
quick output from motor area is not an automatic consequence of 
input but that it can be modified or gated depending on the voli- 
tional goals of the subject. It seems possible that certain 
cells in the motor area are more or less directly tied to the in- 
put and that neuronal networks within the cerebral cortex are 
able to facilitate or prevent the transmission of these patterns 
of discharge to the pyramidal tract output from the cortex. The 
time available for this switching to take place is brief and this 
fact means that analysis of the mechanisms underlyina the gating 
on or off of motor output may be approached more effectively than 
has heretofore been possible. 

A number of formulations concerning the nature of mental 
disorder in patients have proposed a disturbance in the cerebral 
mechanisms which underlie the maintenance of "set" or "attention." 
It appears that the present neurophysiological experiments on 
monkeys begin to get at mechanisms which are close to the atten- 
tional and set determining mechanisms of the brain. If these 
mechanisms can be better understood, it seems possible that they 



105 



will lead to a, sounder understanding of a variety of disturbances 
of psychological function. 

3. Neural Correlates of Learning and Memory . This third 
general area of the Laboratory's program includes the work of 
Niki and Mortimer. Niki is studying the way in which single 
nerve cells of the prefrontal cortex operate in the performance 
of "delayed alternation," a task involving short term memory, 
and Mortimer has been investigating cerebellar activity occurring 
in association with the startle response in the monkey, with a 
view to obtaining information on the modifications of cerebellar 
discharge associated with habituation of this response. Ulti- 
mately, Mortimer is interested in studying the role of the cere- 
bellum in motor learning. 

Niki's studies have revealed the existence of prefrontal 
neurons which discharge differently depending on the movement 
(rightwards or leftwards) which the monkey must make several 
seconds later. These cells may possibly be involved in regis- 
tration of short-term spatial memory. 

Mortimer's studies have dealt with the temporal sequence of 
cerebellar activity in relation to the initiation and control of 
movements. The general objective of this research is to under- 
stand the relationship between the cerebellar cortex and the 
cerebellar nuclei in the control and initiation of movement. 
More specifically, the aim is to discover the functional role of 
direct afferent inputs to the nuclei. In higher vertebrates the 
deep cerebellar nuclei provide the major output from the cere- 
bellum. The cells of these nuclei are controlled by two major 
inputs: an inhibitory input from the output Purkinje neurons of 
the cerebellar cortex and an excitatory input from the collaterals 
of afferents to the cortex. Two hypotheses have been proposed for 
the functional operation of the cerebellum. In the first hypoth- 
esis, the direct excitatory input to the nuclei is considered to 
provide only a steady level of background facilitation; changes 
in nuclear activity then reflect changes in the inhibitory input 
from Purkinje cells. An alternative hypothesis is that the cere- 
bellar cortex output is superimposed upon an ongoincr nuclear dis- 
charge evoked by its direct afferent input. 

Recordings of cerebellar Purkinje and nuclear cells revealed 
a temporal sequence of neuronal activity following the stimuli, 
in which changes in nuclear cell discharge preceded the earliest 
changes in Purkinje cell activity. Virtually all nuclear cells 
responded with a short-latency burst of spikes, which occurred 
several milliseconds before the earliest change in EMG activity 
associated with the startle response. Shortly after the onset 
of the EMG response, increases and decreases in Purkinje dis- 
charge rate were observed. These findings suggest that direct 

106 



excitatory input to the nuclei is capable of initiating activity, 
which is modified after a delay by the inputs from Purkinje 
cells. It is possible that the early nuclear discharge contrib- 
utes to the initiation of motor activity associated with the 
startle response. 



107 



Annual Report of the Section on Technical Development 

National Institute of Mental Health 

national Institute of Neurological Diseases and Stroke 

July 1, 1971 - June 30, 1972 

James S. Bryan, Chief 



During the past 12 months, the Section on Technical Development 
continued to fulfill its traditional role of support of NIMH and NINDS 
research efforts. Continuing assistance was made available in shop 
help, special purpose instruments, instrumentation systems, and assistance 
in computer oriented research and digital instrumentation. 

The major load on the Section in the past year has continued to he 
related to support of computer installations, principally the Building 10 
8lOB system which is now beginning to work with reasonable reliability 
in on-line experiments, and the rat-colony, data-collection system at 
Poolesville which has occupied us with problems of maintenance, expansion 
and modification. 

The Section continues as before to support three laboratory computers 
for general use. Table I gives a breakdown of their usage by Institute. 
Table II shows a breakdown of Section activity by laboratory. As usual, 
almost all research within the Section has involved collaboration with 
laboratories in NIMH and NINDS and is, therefore, reported as part of the 
projects in the laboratories involved. Exceptions to the foregoing include 
a small but continuing effort in neural modeling in collaboration with the 
Laboratory of Applied Studies, DCRT, and development of equipment to 
investigate the nature of motor deficits in patients with either dystonia 
or Parkinson's disease. 

The equipment to measure motor dysfunction has progressed to the point 
of carrying out a few exploratory measurements on Parkinson patients made 
available by the Section on Experimental Therapeutics, Laboratory of 
Clinical Science, NIMH. The results of these measurements encourage us to 
believe that we shall be able to characterize a patient ' s dysfunction in 
terms of motor-system damping expressed as a time-varying parameter, which 
in turn should yield insight into the nature of function and dysfunction 
in the gamma motor system. Since our initial measurements revealed in- 
adequacies in the torque motor used in the experiments, the system is now 
being reworked with a new motor in a form to be used in Building 10 for 
routine data collection with patients . This system should be operational 
by July 1, 1972. 

A total of 151 projects were completed in the last year. A large 
portion of these consisted of routine fabrication of various chambers, baths. 



109 



electrode holders, and jigs for experimental use as well as many small 
electronic devices. 

Major systems included: 

(1) Preparation of a large -animal EEG telemetry system with 
one -half m.ile range for study of sleep patterns in free 
ranging wild animals - Laboratory of Psychotiology, MTMH, 
(in process) . 

(2) Development of electronics for scanning microspectrophotometer 
in collaboration with the Section on Sensory Physiology, 

Laboratory of Neurophysiology, WIWDS . 

(3) Projecting densitometer for quantitative evaluation of 
autoradiograms - Laboratory of Experimental Neurology, WINDS. 

{k) Portable . System for Infant Learning Experiments - Section on 
Perception, Laboratoiy of Psychology, NIMH, (in process). 

(5) Collaborative activity with the Section on Pathology, 

Perinatal Research Branch, NIWLS in the development of a 
computerized image analysis system for grain counting in 
autoradiograms . 



TABLE I 



LABORATORY COMFOTER UTILIZATION 



NIMH 



Classic LINC 

MicroLINC 

PDP-12 



NINDS 


NICHD 


TOTAL HOURS 








2920 


2li 





1912 


6ofo 


3fo 


228U 



110 

/ 



TABLE II 



APPORTIOJMMENT OP EFFORT 



ENGIHEERING & FABRICATION TIME 



MAJOR USERS 



LABORATORY OR BRAWCH 

NIMH 8IOB Computer (includes Programmer) - - - - 

Psychologj^ ICTMH ------------ --- 

Clinical Psychobiology, NIMH ------- -- 

Brain Evolution & Behavior, NIMH ------- - 

Office of the Director, NINDS --------- 

Technical Development, NIMH-NINDS - - - 

Neurophysiology, NINDS ------ ------ 

Experimental Neurology, NINDS ----- ---- 

Adult Psychiatry, NIMH 

Behavioral Biology, NICHD _--- ---- 

Biophysics, NINDS --- __--_--_ 

General & Comparative Biochemistry, NIMH - - - ~ 
Neuropathology & Neuroanatoraical Sciences, NINDS 

Clinical Science, NIMH --- 

Neurochemlstry, NIIVE ---------- --- 

Molecular Biology, NINDS --- 

Neural Control, NINDS _-- 

Intramural Research, NINDS ----------- 

Neurophysiology, NIMH ------------- 

All other NINDS Labs -------------- 

All other NIMH Labs 



HOURS 


PERCENT 


5292 


19.17 


36U2 


13.19 


320i^ 


11.6 


23i^0 


QM 


1856 


6.72 


1663 


6.02 


lh9h 


^.hl 


1380 


^.99 


136U 


k.9h 


1096 


3.97 


969 


3.51 


hh9 


1.62 


h31 


1.58 


35^ 


1.28 


328 


1.18 


322 


1,16 


310 


1.12 


30ij- 


1,10 


301 


1.09 


297 


1.07 


172 


.62 



NIMH (Total) 
NINDS (Total) 
NICHD (Total) 



TOTAL"* 



18,509 67.05 

7,999 28.97 

1,096 3.97 



27,60k 100.0 



Not included in the foregoing totals or in the breakdown by laboratory 
are 8OO hours spent in routine maintenance internal to the Section, and 
the time of the Section Chief. 



Ill 



ANNUAL REPORT 

MENTAL HEALTH INTRAMURAL RESEARCH PROGRAM - 
Division of Clinical and Behavioral Research, and 
Division of Biological and Biochemical Research 

NATIONAL INSTITUTE OF MENTAL HEALTH 

July 1, 1971 - June 30, 1972 



VOLUME II 
Individual Project Reports 



ANNUAL REPORT 
MENTAL HEALTH INTRAMURAL RESEARCH PROGRAM - 
Division of Clinical and Behavioral Research, and 
Division of Biological and Biochemical Research 
NATIONAL INSTITUTE OF MENTAL HEALTH 

July 1, 1971 - June 30, 1972 



TABLE OF CONTENTS 
VOLUME II - Individual Project Reports 

DIVISION OF CLINICAL AND BEHAVIORAL RESEARCH Page 

Office of the Director 

M-0D-CI-5(c) Studies in Schizophrenic Conditions: Psychosocial 

and Biological Interrelationships 1 

M-OD-SW-1 Conflict between the Parents of Schizophrenics.... 5 
ADULT PSYCHIATRY BRANCH 



Office of the Chief 



M-AP (C) -14-1 Conceptualization and Dimensional Evaluation of 

Schizophrenia 7 

M-AP (C) -14-2 Principles for Scoring Communication Defects and 
Deviances of Parents of Schizophrenics in 
Psychological Test Transactions 11 

M-AP (C) -14-3 Cross-cultural Family Studies 15 

M-AP (C) -14-8 A Study of the Separation Process in Adolescents 

and Their Families 17 

M-AP (C) -14-9 The Conceptualization of Lasting Dyadic 

Relationships 25 

Family Studies Section 

M-AP (C) -15-3 Evaluation of Family Dynamics with Conjoint Family 

Art Procedures 29 

M-AP(C)-15-5 Family Art Therapy 33 

M-AP (C) -15-8 Systematic Analysis of Family Art Evaluations 35 



ftPULT PSYCHIATRY BRANai (cont'd) Page 

Family Studies Section (cont'd) 

M-AP (C) -15-9 Systematic Analysis of Brazilian Family Art 

Evaluations : A Replication. 39 

M-AP (C) -15-10 Sources of Variance in the Cross-Cultural 

Application of an Objective System for Analyses 

of Pictures Drawn by Patients and Their Families . . 43 

Section on Psychiatric Assessment 

M-AP (C) -16-1 WHO International Pilot Study of Schizophrenia.... 47 

M-AP (C) -16-3 Comparative Studies of Functional Psychoses 51 

M-AP (C) -16-4 Empirical Grouping of Psychiatric Patients 55 

M-AP (C) -16-5 Serum Enzymes in Acute Psychotic States 57 

M-AP (C) -16-6 Psychiatric History Study: The Nature and 

Reliability of the Data 59 

M-AP (C) -16-7 The Evaluation of Outcome in Schizophrenia 61 

M-AP (C) -16-8 Psychobiology of Cortisol Metabolism 63 

M-AP (C) -16-9 Research Interviews: Are They Valid? 67 

M-AP (0-16-10 The Recovery Process and Research Data in Acute 

Psychosis 69 

M-AP (C) -16-11 Investigation of the Schizophrenic Process Through 

Art Productions of Acutely Psychotic Patients 71 

Section on Personality Development 

M-AP (C) -17-1 A Study of Problems in Growth and Adaptation in 

the Personaltiy Development of the Adolescent 73 



M-AP (C) -17-2 Adolescent Ego Development in Normal Families, 



81 



M-AP (C) -17-3 Studies of Psychogalvanic Response in Family 

Therapy .....". 83 

M-AP (C) -17-4 A Follow-up Study of 37 Families Treated in the 

Study of Adolescent Identity. 87 

M-AP (C) -17-5 Cognition and Identity Development in Early and 

Late Adolescence : Longitudinal Studies 89 



II 



ADULT PSYCHIATRY BRANCH (cont'd) ^^9^ 

Section on Experimental Group and Family Studies 

M-AP(C)-18-2 Coordination "Micro-Codes" in Family Consensual 
Experience: A Study of the Responses to Speech 
Hesitancy and Fluency in Family Interaction 93 

M-AP(C)-18-3 The Effects of Progressive Isolation of an 

Individual from his Perceptual Functioning: Use of 
a Teletype-LINC Apparatus to Study the Reciprocal 
Relationship of Family Interaction and Individual 
Thinking 95 

M-AP(C)-18-6 Nurse-Doctor-Patient Interaction: An Experimental 
Study of its Role in Patient Acculturation on 
Psychiatric Wards 99 

M-AP (C) -18-10 The Effect of Stimulus Materials on Family Problem 

Solving. 103 

M-AP (C) -18-12 Family Views of Its Social Environment: Effects 

on Family Therapy Process 105 

M-AP (C) -18-13 Values and Atmosphere on a Psychiatric Ward: 

Basic Dimensions and Institution Comparisons 109 

M-AP (C) -19-1 Comparative Studies of Discordant Siblings in 

Families of Schizophrenic, Juvenile Delinquent and 
Well-adjusted Yo\mg Adults Ill 

M-AP (C) -19-2 Studies in the Development of Personality and 

Psychopathology in Identical Twins Discordant for 
Schizophrenia 113 

M-AP (C) -19-5 The Distribution and Concomitants of Schizophrenia, 
and Other Psychopathologies , in a Systematic 
Sample of 15,909 Twin Pairs 117 

M-AP (C) -19-6 The Twin Intrapair-Comparative Technique in the 
Study of the Determinants of Early Personality 
Development 121 

M-AP (0-20-1 Recognizing and Interpreting: A Differentiation 

of Perceptual and Cognitive Patterns 127 

M-AP (C) -20-4 The Consensus Rorschach and Focused Feedback as a 

Clinical Procedure 129 

M-AP (0-20-5 Psychological Studies of Patients with Affective 

Disorders 133 



ADULT PSYCHIATRY BRANCH (cont'd) Page 

Section on Experimental Group and Family Studies ( cont ' d) 

M-AP(C)-20-6 Psychological Deficits in Selected Neurological 

Disorders 135 

M-AP(C)-21-2 Studies of Perceptual and Cognitive "Styles" in 

Psychiatric and Non-psychiatric Sxibjects 137 

M-AP(C)-21~4 Perceptual and Cognitive Style in Normal Twins.... 141 



CHILD RESEARCH BRANCH 

M-CR-10 (c) Relations of Preschool and Child Behavior to 

Earlier Parent and Child Characteristics 143 

M-CR-11 (c) Relations between Himan Neonatal Behavior and 

Later Development , 147 

M-CR-12 (c) Developmental Patterns in the Young Family 151 

M-CR-22 (c) Offspring Effects on Parents 156 

M-CR-23 (c) Determinants and Dimensions of Mother-Infant 

Interaction 159 

M-CR-24 Cc) Structure and Correlates of Preschool and Child 

Behavior 163 



LABORATORY OF CLINICAL PSYCHOBIOLOGY 



Section on Clinical Studies 

M-CP(C)-18-3 Biochemical and Pharmacological Studies of Sleep.. 165 

M-CP(C)-18-8 Psychophysiological Studies of Sleep and Waking in 

Normal Subjects 169 

M-CP(C) -18-69 Longitudinal Studies of Sleep and Concomitant 

Biological Changes in Psychiatric Patients 175 

Section on Comparative Studies 

M-CP-18-6 Comparative Studies of Sleep 179 

M-CP-18-7 Factors Affecting Intraspecific and Predatory 

Aggression in the Rat 185 



LABO R ATORY OF CLINICAL SCIENCE Page 

Office of the Chief 

M-CS-OC (C) -04 Studies of the Interrelationships of the Nervous 

and Circulatory Systems 191 

M-CS-OC (C) -15 Studies of Pinched-off Nerve Endings (Synaptosomes) 
as a Model System for Investigating the Transport, 
Binding and Metabolism of Monoamines 193 

M-CS-OC (C) -19 Metabolism, Distribution and Biochemical Effects 

of Psychoactive Drugs 195 

M-CS-OC (C) -20 Histochemical Studies of Biogenic Amines 197 

Section on Medicine 

M-CS-M(C)-08 Formation, Release, Disposition and Metabolism of 

Biogenic Amines 201 

M-CS-M(C)-11 False Neurochemical Transmitters 205 

M-CS-M(C) -12 Growth Characteristics or Aminergic Neurons 207 

Section on Psychiatry 

M-CS-Ps (C) -18 Biochemical and Behavioral Factors in Affective 

Disorders 211 

Section on Pharmacology 

M-CS-Ph-05 Biochemistry and Pharmacology of the Adrenergic 

Nervous System 223 

M-CS-Ph-06 Tryptamine and Ohter Biogenic Amines and 

Psychoactive Drugs 227 

M-CS-Ph-07 Biochemical and Pharmacological Studies on the 

Pineal Gland 229 

Section on Experimental Therapeutics 

M-CS-ET-01 Biochemistry, Pharmacology and Physiology of 

Cerebral Amines 231 



LABORATORY OF PSYCHOLOGY Page 

Office of the Chief 

jyi_p_C-(c) -12 Studies of Heredity and Environment in 

Schizophrenia. „ . . . , . . . 239 

M-P-C- (C) -15 Reaction Time in Schizophrenia 243 

M-P-C-(C)-17 Psychophysiological Responsivity in Schizophrenia. 245 

M-P-C-(C)-36 Psychological Correlates of Cortical Evoked 

Responses 249 

M-P-C- (C) -39 Study of Heredity and Environmental Factors in 

Schizophrenia 255 

M-P-C- (C) -40 Changes in Neurological and Psychological 
Functioning in Children with Minimal Brain 
Dysfunction Receiving D-amphetautiine 257 

M-P-C- (C) -43 Lithium as a Therapeutic Agent in Hyperkinetic 

Behavior Disorders of Childhood. 259 

M-P-C- (C) -44 Individual Differences in Eye Movement Search 

Patterns 261 

M-P-C- (C) -45 The Offspring of Schizophrenics: Markers of a 

Schizophrenic Disposition. 253 

M-P-C- (C) -46 Psychophysiological Changes During the Menstrual 

Cycle 265 

M-P-C- (C) -47 Psychophysiological Concomitants of Minimal Brain 

Dysfunction in Children 267 

M-P-C- (C) -48 Autonomic Functioning in mz and dz Twins 269 

Section on Early Learning and Development 

M-P-D-(C)-30 Stimulus Conditions, Infant Behaviors , Caretaker- 
child Interaction, and Social Learning in Diverse 
Child-rearing Environments 271 

M-P-D-(C)-34 Contextual Determinants of Stimulus Power 

(Formerly: Deprivation and Satiation of Social 

Stimuli as Determinants of Their Reinforcing 

Efficacy) 277 

M-P-D-(C)-42 Evaluation of Concepts Employed for Early Learning 

and Development 279 



LABORATORY OF PSYCHOLOG Y (cont'd) Page 

Section on Personality 

M-P-P-(C)-6 The Investigation of Some Formal Characteristics 

of Speech 281 

M-P-P-(C)-22 Development of Potentially Creative Scientists: 
Personality Characteristics Associated with 
Creative Performances 285 

M-P-P-(C)-40 Body Movement as Expression of Change in 

Psychological Tension States 289 

M-P-P-(C)-41 Survey of Literature on Emotional Communication... 291 

M-P-P-(C)-42 Precocious Science Students in Psychiatric 

Treatment: a Longitudinal Study (Formerly: 
Psychotherapy Research: Models and Conceptions).. 293 

M-P-P-(C)-43 Test and Performance Measures of Creativity in 

Science (Formerly: Measures of Creative Ability 

in Science) 297 

M-P-P-(C)-44 Psychodynamic and Instrumental Learning Models: 
Implications for Personality Theory and 
Psychotherapy 301 

M-P-P- (C) -45 Developmental Factors in Conversational Behavior.. 303 

M-P-P-(C)-46 Stimulus Intensity Modification: Neurophysiologic 

and Psychoanalytic Relationships 307 

Section on Higher Thought Processes 

M-P-A-16 A Study of the Means-end Thought Processes in 

Hxoman Subjects 309 

Section on Neuropsychology 

M-P-B-2 Analysis of the Relationship Between Problem- 
solving Behavior and Certain Cortical and 
Subcortical Structures in the Sub-human Primate 
Brain 313 

M-P-B-5 Neural Mechanisms in Vision 317 

M-P-B-7 Histological Analysis of Cerebral Lesions and 

Intra-cerebral Connections in Primates 321 

M-P-B-14 The Neural Regulation of Appetitive Behavior 325 



VII 



LABORATORY OF PSYCHOLOGY (cont'd) Page 

Section on Neuropsychology (cont'd) 

M-P-B-16 Cerebral Mechanisms Underlying Functional 

Plasticity in the Developing Organism 327 

Section on Perception 

M-P-L-5 Individual Differences in Normal Perceptual 

Processes 331 

M-P-L-7 Perceptual Adaptation 333 

M-P-L-9 Discriminative and Conceptual Behavior in 

Preschool Children 335 

M-P-L-10 Discriminative and Conceptual Behavior in 

Infancy 337 

M-P-L-12 Cortical Mechanisms in Somesthesis 341 



LABORATORY OF SOCIO-ENVIRONMENTAL STUDIES 

M-S-C-11 Social Psychological Correlates of Occupational 

Position 345 

M-S-D-10 Research on the Processes of Internalization of 

Rules , Standards , and Values 351 

M-S-D-15 Occupational Experiences of Musicians 357 

M-S-D-23 Observational Learning from Nurturant and 

Nonnurturant Models 359 

M-S-D-26 An Observational Study of Maternal Models 363 

M-S-D-28 A Comparison of Methods of Obtaining Data on 

Parent and Child Behavior 367 

M-S-P(C)-23 Cultural and Psychodynamic Factors in the 

Occurrence and Treatment of Psychiatric Illnesses 

in Japan , Taiwan, and the United States 371 

M~S-P(C)-27 Parental Care and Child Behavior in Japan and the 

United States 375 

M-S-P(C)-38 The Interrelationships between Social Interaction, 
Psychological Functioning, Perceptual Style, 
Physiological Arousal and Personal History Factors 
Among Schizophrenics 379 

VIII 



LABORATORY OF SOCIO-ENVIRONMENTAL STUDIES (cont'd) Page 

M-S-PS-1 Health Orientations of Parents and Children 383 

M-S-S-12 Developmental Study of the Self-image 387 

M-S-SP-3 Variables Affecting Twin Birth Frequencies 391 

M-S-SP-4 Individual Differences in Survival and Reproduction 

Among Old Colony Mennonites in Mexico 393 

M-S-SP-5 Social Origins of Stress 395 

M-S-SP-6 Studies of Evolution of Reacting Chemical Mixtures 

Under Nearly Steady-State Conditions 399 

DIVISION OF BIOLOGICAL AND BIOCHEMICAL RESEARCH 
Office of the Director 
M-OD-BBR-2 Characteristics of Membranes in Muscle 401 



LABORATORY OF BRAIN EVOLUTION AND BEHAVIOR 

Section on Comparative Neurophysiology and Behavior 

M-LBEB-CN-1 Neural Substrate of Mirror Display in Squirrel 

Monkey ( Saimiri Sciureus) 403 

M-LBEB-CN-2 Unit Study of Interoceptive Inputs to the Cingulate 

Cortex of Squirrel Monkey. 407 

M-LBEB-CN-3 Effect of Intravenous Injections of 5-Hydroxy- 

tryptamine (Serotonin) on Unit Activity of Cingulate 
Cortex of Awake Squirrel Monkeys ( Saimiri Sciureus ) . . 409 

M-LBEB-CN-4 Physiological Effects of Intravenous Administration 
of Serotonin (5-Hydroxytryptamine) in Awake Squirrel 
Monkey ( Saimiri Sciureus ) 411 

M-LBEB-CN-5 ECG Changes and Myocardial Myocytolysis Following 

Vagal Stimulation in Awalce, Sitting Squirrel Monkey 
( Saimiri Sciureus) 413 

M-LBEB-CN-6 Transsynaptic Cellular Degeneration Following Vagal 

Nerve Section in the Newborn Rabbit 415 

M-LBEB-CN-7 Exploratory Study on Actions of Biogenic Amines in 

Squirrel Monkeys 417 



IX 



LABORATORY OF BRAIN EVOLUTION AND BEHAVIOR (cont'd) Pag e 

Section on Comparative Neurophysiology and Behavi or ( cont ' d) 

M-LBEB-CN-S Neural S'jbstrate of Olfaction in the Rat 421 

M-LBEB-CN-9 Taste and Location Aversion in Bait Shyness 423 

M-LBEB-CN-10 Aggression and Defense in Rats With Septal Lesions.. 425 

M-LBEB-CN-11 Sensory Control of Fighting in Mice 427 

M-LBEB-CN-12 Reinforcing Properties of Nesting Material During 

Gestation in Rats 429 

M-LBEB-CN-13 Functions of Avian Paleostriatal Complex. 

I. Question of its Role in Imitative Behavior 431 

M-LBEB-CN-14 Behavioral Effects of Hippocampal Destruction in the 

Virginia Opossum ( Didelphis Virginiana) 433 

Section on Comparative Biopsychology 

M-LBEB-CB-1 Temporal Organization of Feeding Sequences and 

Sucking Behavior in Infant Dogs 435 

M-LBEB-CB-2 Behavioral Effects of Response-contingent Intra- 
gastric Versus Intraoral Milk Injection in Infant 
Beagle Dogs , 439 

M-LBEB-CB-3 Schedule-induced Maladaptive Adjunctive Behavior 

in Infant Beagle Dogs 441 

M-LBEB-CB-4 Capacity for Learning in Neonatal Dogs : Parametric 

Studies 445 

M-LBEB-CB-5 Excitatory and Inhibitory Processes in Discriminated 

Instrumental Behavior of Neonatal Beagle Dogs 447 

M-LBEB~CB-6 Instrumental Escape and Avoidance Learning in 

Neonatal Mongrel Cats 449 

M-LBEB-CB-7 Attachment Behavior in Beagle Dogs as a Function of 

Social Reinforcement 451 

M-LBEB-CB-8 Behavioral Mathematics and the Logic of Measurement. 453 

M-LBEB-CB-9 Automated Apparatus for the Biopsychological Study 

of Behavior 455 

Section on Behavioral Systems 

M-LBEB-BS-1 Vitamin A Induced Alteration of Social Behavior. .... 457 

X 



LABORATORY OF BRAIN EVOLUATION AND BEHAVIOR (cont'd) Page 

Section on Behavioral Systems (cont'd) 

M-LBEB-BS-2 Social Velocity 461 

M-LBEB-BS-3 The Overliving of a Mouse Population 463 

M-LBEB-BS-4 Role of Prior Social Experience in Altering Adaptive 

Behavior 467 

M-LBEB-BS-5 Modification of Catecholamine Metabolism in a Crowded 

Mouse Population 471 

M-LBEB-BS-6 Socially Induced Dissolution of Reproductive 

Capacities in Mice 473 

M-LBEB-BS-7 Rhythms of Spontaneous Behavior. 477 

M-LBEB-BS-8 An Automated System for Monitoring in-context 

Behavior 479 

M-LBEB-BS-9 Population, Space and Mental Health 483 



LABORATOPY OF CEREBRAL METABOLISM 

Section on Developmental Neurochemistry 

M-CM-DN-1 The Mechanism of Action of Thyroxine and its 

Relation to Cerebral Metabolism 487 

M-CM-DN-2 Studies on Regional Cerebral Circulation and 

Metabolism 495 

M-CM-DN-3 Biochemical Bases of Alcohol Addiction 501 

M-CM-DN-4 Regulation of Protein Synthesis in the Brain 505 

Section on Myelin Chemistry 

M-CM-MyC-1 Biochemical Studies on Myelin and Myelin Basic 

Protein 509 

M-CM-MyC-2 Immunological Studies on Experimental Allergic 

Encephalomyelitis (EAE) 513 

M-CM-MyC-3 Studies on Delayed Hypersensitivity in EAE 517 



LABORATORY OF CEREBRAL iVJETABOLISM (cont'd) Page 

Section on Membrane Chemistry 

M-CM-MeC-1 Study of the Modulation of Central Nervous System 
Metabolism and Function through Alterations in 
Membrane Permeability and Transport 521 



LABORATORY OF GENERAL AND COMPARATIVE BIOCHEMISTRY 

Section on Proteins 

M-LGCB 16B Amino Acid tRNA Synthetases. Their Role in Protein 

Synthesis , and Interaction with tRNA 525 

M-LGCB 18 Studies on the Structure and Function of Thetin- 

Homocysteine Methylpherase and Lactose Synthetase. . . 529 

M-LGCB 35 Studies on Protein Conformation and Limited 

Proteolysis 533 

M-LGCB 56 Determination of the Effect of Small Viruses and 
Their Nucleic Acids on the Biochemistry of Living 
Organisms 537 

M-LGCB 58 Ribonuclease Specific for RNA-DNA Hybrids 541 

M-LGCB 59 Spermidine Synthesis in Rat Brain 543 

Section on Alkaloid Biosynthesis 

M-LGCB 43 Homocystinuria: Methionine Metabolism in Mammals... 545 

M-LGCB 48 Transsulf uration in Higher Plants 549 



LABORATORY OF NEUROBIOLOGY 

M-NB-1 Transient Changes in Extrinsic Fluorescence of Nerve 

Produced by Electric Stimulation. . .- 553 

M-NB-2 Sensory-motor Integration in the Primate Visual 

System 559 

M-NB-3 Metabolic Activity of Nuclear Proteins from Rat 

Brain Cells 563 



LABORATORY OF NEUROCHEMISTRY Page 

M-NC-1 The Conversion of Phenylalanine to Tyrosine.......... 565 

M-NC-2 Biosynthesis of Catecholamines 569 

M-NC-4 The Biochemical Basis of Skelet=;l Muscle 

Hypertrophy 573 

M-NC-5 The Process of Lysogeny 575 

M-NC-6 Physicochemical Investigations of Biofunctional 

Structures of Glycosaminoglycans and Glycolipids 579 

M-NC-7 The Role of the Cell Membrane in Cellular 

Organization , A Molecular Study 583 

M-NC-8 Biological and Biochemical Models for the Genetic 

Disease , Phenylketonuria (PKU) 587 

M-NC-9 The Conversion of Tryptophan to 5-Hydroxy 

Tryptophan 589 



LABORATORY OF NEUROPHYSIOLOGY 

M-NP-3 Electrical, Ionic and Physical Properties of MuscIf , 593 

M-NP-8 Transport Mechanisms Across Membranes 597 

M-NP-47 The Ionic and Metabolic Basis of Neuronal 

Thermosensitivity 601 

M-NP-48 The State of Ions and Water in Living Cells 605 

M-NP-63 The Functional Organization of the Sensorimotor 

Cortex in the Initiation and Control of Movement..... 609 

M-NP-65 Functional Role of the Basal Ganglia in the Control 

of Movement and Posture 615 

M-NP-66 The Role of the Cerebellum in the Generation of 

Saccadic Eye Movements 619 

M-NP-67 Temporal Sequence of Cerebellar Activity in Relation 

to the Initiation and Control of Movements 623 

M-NP-68 Studies on the Neuronal Activity of the Prefrontal 

Cortex 625 



Serial No. M-0D-CI-5(c) 

1. Office of Director 

2. Division of Clinical and 

Behavioral Research. 

3. Bethesda, Maryland 

PHS-HSMM-raMH 
Individual Project Report 
July 1, 1971 through June 30^ I972 

Project Title: Studies in Schizophrenic Conditions: Psychosocial and 
Biological Interrelationships 

Previous Serial Number: Same 

Principal Investigator: David Shakow 

ther Investigators : None 
Cooperating Units : None 

-an Years : 



Total : 


1.50 


Professional: 


.90 


Other: 


.60 



Project Description: 

Objectives : To bring together a large body of experimental data on schizo- 
phrenia collected over several decades into a book (with attendant individual 
papers) which develops a theory of schizophrenia, particularly of the psycho- 
biology of schizophrenia, centered around a concept of segmentalization . A 
detailed analysis of the body of experimental data already available from 
Worcester State Hospital studies and some new data gathered on our wards at 
NTMH and at St. Elizabeths Hospital will be used. 

'M ethods Employed : In relation to the already accimiijlated materials in the 
L-ea of physiology, psychophysiology, and psychology, the usual methods of 
catistical and conceptual analysis are used. Some parts of the relevant 

vzperimental literature will be used for further differentiation of the 
laterial. Related studies being carried out by other investigators in the 

Laboratory of Psychology and elsewhere in NIMH on schizophrenic, senescent, 

and brain-damaged subjects will be used in these studies for control purposes. 

Major Findings : During the year a major effort has gone into the further 
analysis and organization of data in the physiological, psychophysiological, 
and psychological aspects of schizophrenia, with a view toward developing a 
unified theory of schizophrenia. Special effort has been extended to develop 
further the segmental set theory and the detailed presentation of a theory 
of language in schizophrenia. 



S i gnificance to Biomedical Research and the Program of the Institu te : The 
studies mentioned above will contribute to the understanding of the phenomena 
of schizophrenia and eventually to a comprehensive theory of schizophrenia. 

Proposed Course of Project : Continued analysis of both published and still 
unpublished data^ in the context of the analysis of relevant data from studies 
of others at NIH and elsewhere. 

Honors and Awards : 

Special Recognition Mental Health Awards for distinguished achievement 
in the mental health field. Conferred on the occasion of the 25th anni- 
versary of the enactment of the National Mental Health Act. 

First Annua]. Distinguished Scientist Awards conferred by Section IIIj 
Division 12 (Clinical Psychology)^ of the American Psychological Asso- 
ciation^ for notable contribution to psychopathology. 

Third Annual Seymour D. Vestermark Memorial Awards for outstanding 
contributions to mental health education and research; cosponsored by 
the American Psychiatric Association and the National Institute of 
Mental Health. Lecture presented, "The education of the mental health 
researcher: Encouraging potential development in man." 

Thomas Salmon Medal of the New York Academy of Medicine, on the occasion 
of the TS^fch anniversary celebration of the New York State Psychiatric 
Institute, for distinguished service in psychiatry. 

Publications : 

Shakow, D. : Some observations on the psychology (and some fewer, on the 
biology) of schizophrenia. J. Nerv. Ment. Dis . I53: 3OO-316, I97I. 

Shakow, D. : The Worcester State Hospital research on schizophrenia 
(abbreviated version). In Offer, D., and Freedman, D.X. (Eds.): 
Modern Psychiatry and Clinical Research: Essays in Honor of Roy R . 
Grinker, Sr . New York, Basic Books, 1972, pp. 174-207. 

Shakow, D. : Conference on psychiatric education: The contribution of 
psychology in the teaching of psychiatry to medical students. J. Nei-v . 
Ment. Dis . l^k: I73-I79, I972. 

Shakow, D. : The Worcester State Hospital research on schizophrenia 
(1927-19^+6). Monograph, J. Abn. Psychol . , in press. 

Shakow, D. : Discussion of Holzman's and Silverman's contributions on 
perception in schizophrenia. Proceedings of the Conference on Schizo - 
phrenia: The Implications of Research Findings for Treatment and 
Teaching, May 30- June 2, 1970 , in press. 



Shakow, D. : The education of the mental health researcher: Encouraging 
potential development in man. Arch. Gen. Psychiat ., in press. 

Shakow, D. : Hermann ETbbinghaus. McGraw-Hill Encyclopedia of World 
Biography . New York; McGraw-Hill, in press. 

Shakow, D. : Some observations on the psychology (and some fewer, on the 
biology) of schizophrenia (abbreviated version). D. Uznadze Institute 
of Psychology, Academy of Sciences of the Georgian S.S.R., Tbilisi, 
U.S.S.R. , in press. 

Shakow, D. : Some dilemmas in psychology. Festschrift in honor of 
A. D. Zurabashvili . Academy of Sciences of Georgian S.S.R. , Tbilisi, 
U.S.S.R. , in press. 



Serial No. M-OD-SW-1 

1. Office of the Director, DCBR 

2<, Section on Social Work 

3. Bethesda, Maryland 



PHS-HSMHA-4JIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 



Project Title : Conflict between the Parents of Schizophrenics 
Principal Investigator ; Carol F. Hoover, Social Worker 

Cooperating Units ; Sections on Psychiatric Assessment, Family Studies and 

Personality Development in Adult Psychiatry Branch, DCBR. 
Center for Population Research, National Institute of 
Child Health and Development. 

Man Years ; 

Total: .5 
Professional; .3 
Other ; . 2 

Project Description ; 

Objective ; To Investigate levels of marital conflict, acknowledged 
anger and styles of coping with disagreement characteristically reported by 
the parents of schizophrenics, as compared to parents of maladjusted and 
parents of community young people. Conflict over children, particularly 
index patient coiq>ared to his siblings and to the offspring of community 
families, is a particular focus. Marital dominance and perceived couple 
interaction are also studied. 

Method Employed : A 70-itera card sort is administered to each couple 
on two separate occasions a week apart. This procedure is scored to Indicate 
conflict ratio and coping mechanisms. Marital disagreements which Involve 
particular children are also reported. 

Major Findings ; A total of 154 individuals have been tested, either 
at the N.I.M.H. or their own homes. These Include 30 couples from the 
community, located through city directories, 25 couples with maladjusted 
children, and 22 couples who have schizophrenic offspring hospitalized at 
the N.I.M.H. or elsewhere in the area. Each of these parent couples has two 
or more children between the ages of 13 and 27. 

Data from this group of subjects is now being prepared for analysis. 



Serial No. M-AP(C)-ltt..l 

1. Adult Psychiatry Branch 

2. Office of the Chief 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 20, 1972 

Project Title ; Conceptiialization and Dimensional Evaluation of Schizophrenia. 

Principal Investigators ; Lyman C. Wynne, M.D., Ph.D., Margaret T. Singer, Ph.D., 

and John Strauss, M.D. 

Other Investigators ; Helm Stierlin, M.D., Ph.D.j Winfield Scott, Ph.D.; 

Margaret Toohey; T. W. Carpenter, M.D.; Monte Buchsbaum, 
M.D. (Laboratory of Psychology); John Bartko, Ph.D. 
(Biometry Branch). 

Cooperation Units ; World Health Organization, Geneva, Switzerland; Spring Grove 
State Hospital, Maryland; Prince George County General 
HospiteuL; Laboratory of Psychology; Division of Computer 
Research and Technology, Biometry Branch. 

Man Years (not included in cooperation pro^jects ); 

Total ; . 5 
Professional; .3 
Other; .2 

Project Description ; 

Objectives ; (l) This project aims to conceptualize major features of 
schizophrenic disorders along continua or dimensions in such a vay that patients 
can be evaluated on the basis of data obtained and compared from (a) symptom- 
oriented research interviews and rating scales (see M-AP C)-l6-l; -l6-2); 
(b) individual research interviews oriented to formal or stylistic variables 
especially thought disorder; (c) psychotherapeutic work with schizophrenics 
and their families (see M-AP(C)-15-lt ); (d) interviews and records about 
pre-morbid history, kind of onset, and type of course of illness, especially 
thought disorder; (e) projective test scorings and evaluations (see M-AP(C) 
-ll*-2; -llt-5); (f) scores from tests of sensory, perceptual, congitive and 
psychophysiological variables (see M-AP(C)-21-52) . 

(2) To apply these various methods to patients from (a) a variety of 
cultures; (b) a variety of social class, educational and occupationsuL back- 
grounds; (c) a variety of families, and to study how these social variables 
do and do not affect the individual features of the various forms of schizo- 
phrenic disorder. 



4 



Serial No. M-AP(C)-14-1 

Broadly speaking, this project draws upon and helps to integrate data 
concerning schizophrenia obtained in a number of projects in the Branch and is 
especially concerned with developing improved, more comprehensive concepts and 
theories of schizophrenia. Especially relevant are M-AP(C)-14-2, 3, 5, 6; 16- 
1, 4; 21-2, 4. 

Me thod s Emp loyed ; Work is continuing on the conceptualization and 
definition of a series of dimensions to which a variety of rating scales and 
test measures can be applied. These dimensions fall into five main clusters: 
f^) arousal, including alertness, energy level, and volitional and affective 
states; (2) selectively with which attention is focused, irrelevant stimuli 
are excluded; (3) transactional sharing of foci of attention in which two or 
more persons look at the same events, ideas, or feeling states together, with 
differences along the dimensions of (a) active (doing) versus passive (under- 
going) ways of relating to other persons and stimuli, and (b) variations in 
emotional c loseness and distance ; (4) organization of the boundaries and con- 
tents of the person's sense of self and sense of identity; and (5) patterns of 
variations in the above features through time in major or segmental "sets." 
The specific methods used are described in the various projects listed above 
which are brought together for purposes of conceptualization and theory for- 
mation in this project. 

A major activity currently under way is to develop procedures for com- 
puterized analysis of the various kinds of data which have been generated. 
Data have been obtained from over 1,000 subjects in various forms; most of this 
has now been coded into complex computerized data files. 

Maj or Findings : As data analysis is being completed, the formulation 
and publication of findings, concepts, and theory are actively in progress. A 
number of types of publications, both brief and lengthy, are being organized 
and edited for publication. 

Significance to Mental Health Research ; The systematic evaluation of 
schizophrenic symptoms and processes is a fundamental necessity for further 
progress in this major area of psychiatry. This research program endeavors 
to bring together experimental and clinical approaches and to apply these to 
a variety of patients from different backgrounds. Too often in the past, 
sophisticsted, experimental approaches have been related onlv to highly unsyste- 
matic and vague clinical evaluations, and only one or two variables of patients 
have been studied in most research programs on schizophrenics. For background 
may be included in a given study. This piecemeal approach to the study of schi- 
zophrenics has led to many seeming contradictions in findings and in concepts 
which are difficult or impossible to resolve because the data obtained are not 
comparable from one study to the next. The present nroject is conceived as a 
long-term program for developing assessment methods to a higher level of refine- 
ment and reliability than is presently available, and to increase the effort to 
apply and concentualize these methods in relation to a broader spectrum of pati- 
ents. These methods of data collection lend themselves to computerized data 
processing which permit the asking, and answering, of many research questions 
previously inaccessible to investigation. 



Serial No. M-AP(C)-14-l 



Proposed Course of Project ; The data for this work are essentially 
in hand, although it would be desirable to continuing with the follow-up of 
some patients and families; collaboration in this follow-up and in some aspects 
of data analysis and writing -up of the work will continue during the coming 
year. However, this extensive program is now basically completed. Each aspect 
of the project will be of groups both within the Branch program and outside 
the Branch, as in the WHO International Pilot Study of Schizophrenia (see M- 
AP(C)-16-1). The current emphasis is on multivariate computerized analysis of 
the large amount of diverse data which have been assembled. The concepts and 
findings in this program are being assembled for publication in book form. 

Publications : 

(1) Wynne, L.C.: The Injection and Concealment of Meaning: 
Difficulties in achieving consensual validation in the familial and Psycho- 
therapeutic Relationships of Schizophrenics. Presented at the fourth Inter- 
national Sjrmposlum on the Psychotherapy of Schizophrenia, Turku, Finland, 
August 6, 1971; to be published by Excerpta Medica, Amsterdam, 1972. 

(2) Wynne, L.C.: Emerging Trends in Family Research on Schizophrenia, 
in M. Katz, R. Littlestone, L. Mosher, H. Tuma, and M. Rooth (eds.): Schizo- 
phrenia: Implications of Research for Treatment and Training , N.Y.: Basic 
Books, 1972. 



Serial No. M-AP(C)-14-2 

1. Adult Psychiatry Branch 

2. Office of the Chief 

3. Bethesda, Mairyland 

PHS -HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title : Principles for Scoring Communication Defects and Deviances of 
Parents of Schizophrenics in Psychological Test Transactions. 

Principal Investigators : Ljmian C Wynne, M,D., Ph.D. and Margaret T. Singer, 

Ph.D. 

Other Investigators : Winfield Scott, Ph.D.; John Bartko, Biometry Branch, NIMH; 
Margaret Toohey. 

Cooperating Units : Section on Twin and Sibling Studies, APB; Biometry Branch, 

NIMH; MRC Social Psychiatry Unit, Maudsley Hospital, London. 

Man Years : 

Total: 2.0 
Professional: 1.1 
Other : 0.9 

Project Description : 

Objectives : To apply previously developed theories about parental communi- 
cation for evaluating protocols of psychological test transactions to pinpoint 
selectively certain features of parental behavior which can be reliably and 
quite quickly scored from psychological tests, particularly the Rorschach, TAT, 
and Object Sorting tests; to evaluate inter-rater reliability using the scoring 
manuals; and to evaluate the effectiveness with which the scoring manuals can 
be used to differentiate parents of psychiatrically different offspring. 

Methods Employed : In previous studies, l^nne and Singer have developed a 
series of principles for evaluating the forms in which persons engage and com- 
municate in interpersonal relationships; parental styles of communicating in 
standardized situations are hypothetically linked to the occurrence and form 
of schizophrenic disorders in offspring. Wynne and Singer have hypothesized 
that communication problems of parents could affect the development of core ego 
functions which are, in fact, impaired in schizophrenics, including, most im- 
portantly, defects and deviances in the manner in which foci of attention are 
shared. These problems lead directly into a variety of other schizophrenic 
difficulties in such areas as the use of language, task orientation and inter- 
personal relations . 

In evaluating these hypotheses , psychological test materials have been 
evaluated in ways quite different from their traditional use. The emphasis in 
the present approach is to regard these test protocols as "interpretive trans- 



11 



Serial No. M-AP(C)-14-2 

actions" in which they are considered samples of communication obtained in a 
relatively standardized way in which the how (form) aspects are given more 
emphasis than the what (content) aspects of attending and communicating. Par- 
ental junctioning in test transactions is studied with the viewpoint that the 
forms of this functioning (not the content) have certain counterparts in daily 
parental roles with the growing child, namely, showing the child (or, in the 
test situation of the individual Rorschach, the tester-listener) where to look, 
what it is he is to try to understand with the parent, and how he demonstrates ( 
his or her overall roles as a reasoning, communicating person. The tests were 
used to infer the effect the parent has on the other person transacting with 
him or her, and to analyze how the parent shares or fails to share a focus of 
attention with another person. 

The scoring manuals have been designed for use with the Object Sorting 
test, individual Rorschach and TAT. It is necessary that records of subject- 
tester transactions be as nearly verbatim as possible. In the Rorschach scoring 
manual there are three main clusters of categories which are scored: closure 
problems, disruptive behavior, and peculiar perception and verbalization. Under 
these main headings there are 41 specific categories which can be used to score 
each response in the Rorschach. Similarly, somewhat different categories have 
been applied to TAT protocols and Object Sorting test protocols. 

Rorschach data from a sample of 239 families (731 individuals) have now 
been analyzed with this scoring procedure. One hundred and fifteen families 
were tested in Bethesda in the APB program plus 25 pairs of parents tested 
earlier by Wender and Rosenthal (biologic and adoptive parents of schizophrenics 
and adoptive parents of normals), 40 in London, and 59 in Houston. In this 
sample, a diagnostic diversity of patients of both sexes was included, as well 
as considerable social class and education variability. In the Bethesda samples, 
each parent and offspring was given a psychiatric diagnosis so that communica- 
tion deviance scores and diagnosis could be compared for each individual and 
for parents compared to offspring. Sub-groups of families have been parcelled 
out for special study. This approach has been facilitated by computerization 
of the data (see M-AP(C)-14-1) factor analyses, multiple regression analyses, 
and a stepwise multiple discriminant analysis of the data have been carried 
out in order to assess the significance of various demographic and clinical 
variables and the relative importance in various discriminations, of the par- 
ticular categories in the scoring manual. 



i 



Major Findings : A high degree of inter-rater reliability was achieved in 
using the Rorschach scoring system. All protocols were scored entirely blindly, 
without any information about the diagnosis or relationships of any subject 



The central research hypothesis was decisively confirmed: in these intact 
families, the frequency of communication deviances of parents was significantly 
related to the severity of psychiatric illness in the offspring, and when other 
variables are held constant statistically this relationship remains. A large 
number of new findings are emerging from these data analyses and are being pre- 
pared for publication. Especially noteworthy is the finding that the diagnosis 
of the offspring in all 25 families tested by Wender and Rosenthal were correctly 



i 



I 



12 



Serial No. M-AP(C)-14-2 

identified from parental Rorschachs , including all nine offspring who were 
adoptive schizophrenics. 

Significance for Mental Health Research : This work has developed systema- 
tic, reliable scoring methods which are simple enough to be used by relatively 
untrained raters, but which make significant differentiations of parental be- 
havior. The scoring methods have been directly derived from a comprehensive 
theory of psychological development within the family context which has been 
described in detail in a series of papers . 

Proposed Course of Project : The concepts and findings in this study are 
being reported in a series of papers and in book form. The multivariate analy- 
ses of the data is in its final stages. The scoring procedure and manuals are 
being modified on the basis of the findings in the present study. The scoring 
procedure will then be applied to new samples of parents of different diagnos- 
tic, educational, social, and cultural backgrounds to discover what the limits 
of these procedures are as a predictive and screening device, applicable to 
the identification of "high-risk" versus "low-risk" subjects. Also, the proce- 
dure is being used with various special families such as adoptive families with 
families with and without a schizophrenic offspring. Such work will be valuable 
in elucidating the genetic versus the "learning" aspects of schizophrenic dis- 
orders. One study is currently in progress in V7hich the Rorschach scoring 
manual is also being applied to a sample of parents of Japanese schizophrenics 
(see M-AP(C)-14-3). 

Publications : 

1. Wynne, Lyman C. and Singer, M. T. , Schizophrenics and their Families: 

II. Research Methods, Brit. J. of Psychiatry , 1972, in press. 

2. Wynne, Lyman C. and Singer, M. T. , Schizophrenics and Their Families: 

III. Recent Rorschach Communication Findings, Brit. J. Psychiatry , 
1972, in press . 



13 



I 



Serial No. M-AP(C)-14-3 

1. Adult Psychiatry Branch 

2. Office of the Chief 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 

Project Title : Cross -Cultural Family Studies 

Principal Investigators : Lyman C. Wynne, M.D., Ph.D. and Margaret T. Singer, 

Ph.D. 

Other Investigators : Mieko Caudill ; Dr. Kenji Sakamoto, Kyoto University 

Medical School, Kyoto, Japan; Dr. Y. Kasahara, Psychiatry 
Clinic, Kyoto University, Kyoto, Japan; Dr. S. Kuromaru, 
Kobe Medical School, Kobe, Japan Dr. William Caudill, 
Laboratory of Socio -Environmental Studies. 

Cooperating Units : Kyoto University Medical School, Kyoto, Japan; Sakamoto 
Psychiatric Hospital, Osaka, Japan; Psychiatric Clinic, 
Kyoto University, Kyoto, Japan; Kobe Medical School, 
Kobe, Japan; Section on Personality and Environment, 
Laboratory of Socio-Environemntal Studies, NIMH. 

Man Years 



Total: .6 

Professional: .4 
Other: .2 

Project Description : 

Objectives : To determine whether criteria for differentiating families 
of schizophrenics and other kinds of families apply cross -culturally and thus 
have generalized validity; to specify features of schizophrenics and their 
families which are and are not cross -culturally general; to study how varia- 
tions in the sibling order of schizophrenics are related to cultural patterns 
of family life. 

Methods Employed : Clinical data and psychological tests have been 
obtained from a sample of normal control families and families of schizophrenics 
in Japan, and earlier, in Lebanon. 

This year emphasis was placed on examination of the Japanese data. 
Psychological test protocols have been received from families of 50 late 
adolescent and young adult Japanese psychiatric patients and from the parents 
of 20 childhood psychiatric patients and normal controls. These Japanese 
protocols are being translated and scored by Mrs. Mieko Caudill, a native 
Japanese, with the manual described in M-AP(C)-14-2 , with the translated 
protocols also studied by Dr. Margaret T. Singer. 



15 



Serial No. M-AP(C)-14-3 

This year special attention has been given to a detailed examination 
of the problems of translating communication samples, as found in verbatim 
Rorschach records, from Japanese to English and vice versa. This study, 
conducted with investigators from both countries revealed much about the 
latent value assumptions and implicit communication processes in both 
cultures. Extensive discussions were also carried out on the problems of J 
achieving diagnostic comparability on Japanese and American patients. U 

tfajor Findings : The project is still in progress. The preliminary 
findings indicate that the scoring manuals developed in the NIMH research can 
be used with these highly diverse psychological test samples obtained in Leba- 
non and Japan. Two papers on the special problems of conducting family therapy 
with large, extended families in a non-Western cultural setting (Lebanon) have 
been prepared . 

Significance to Mental Health Research : The cross-cultural approach 
will very greatly strengthen the significance of the findings concerning the 
families of schizophrenics which have been obtained from American samples in 
the Adult Psychiatry Branch program. The patient-family links which have been 
studied in this research are concerned with forms of thinking and communicating, 
rather than the content of thinking, so that, theoretically, the methods of 
scoring should be applicable regardless of cultural background or other 
variables if there are characteristic forms in which families of schizophrenics 
related and live with one another. Because of translating and other difficulties 
there have been questions raised in many quarters whether psychological tests f 
and interview materials can be meaningfully compared cross -culturally . The 
present study indicates that such work is practicable, if certain procedures 
and standards are used in translating and in obtaining the original protocols , 
but scrutiny of the translating problems is valuable in its own right because 
it facilitates understanding of cross-cultural differences. 

Proposed Course of Project : Data collection in Japan by Drs . Sakamoto, 
Kasahara, and Kuromaru in Japan is almost complete. Interpretation of the 
findings, completion nf publications on methodologic and substantive findings, 
and further planning of the collaborative work is in progress. 

Publications : 

(1) Wynne, L.C., Caudill, M. , Kasahara, Y. , Kuromaru, S., Higa, M. , 
and Singer, M.T. : Problem in the Cross-cultural Study of Psychopathology : 
A Comparison of Japanese and American Disorders of Thinking and Communication. . 
Lebra, W. (ed.): Mental Health Research in Asia and the Pacific, Honolulu: j 
East-West Center Press, in press, 1972. ''I 



16 



Serial No. M-AP(C) 14-8 

1. Adult Psychiatry Branch 

2. Office of the Chief 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: A Study of the Separation Process in Adolescents and Their 
Families 

Previous Serial Number: M-AP(C)-15-2 

Principal Investigator: Helm Stierlin, M.D., Ph.D. 

Other Investigators: Stanley I. Hirsch, Richard M. MacDonald, M.D., Kent 
Ravenscroft. Jr., M.D., Robert J. Savard, Ph.D., 
Miss Elizabeth Sherwood, John S. Strauss, M.D., and 
Lyman C. Wynne, M.D., Ph.D. 

Cooperating Units: Section on Clinical Psychology; Section on Perceptual 
and Cognitive Studies; Section on Psychiatric Assess- 
ment (Adult Psychiatry Branch, NIMH). 

Man Years: 

Total: 7.3 
Professional: 5.5 
Others: 1.8 

Project Description: 

Objectives ; 

The basic objectives of this study have remained the same as stated in the 
report of last year: To investigate, at the clinical and research levels, 
the individual and family factors which may further or jeopardize the separa- 
tion process throughout adolescence. By tapping a large available reservoir 
of students with school problems, the study makes use of an adolescent high 
risk population who, over the following five years, will or will not develop 
either in a psychotic or sociopathic direction. Understanding and possibly 
differentiating the separation course of these two patient groups is the 
main goal. This includes a grasp of these patients' family and peer rela- 
tions as they unfold in time. The project builds on many of the findings 
which Drs. Lyman C. Wjmne and Margaret T. Singer and their associates have 
reported during the last decade. It addresses itself now to experimential 
factors which may allow certain high risk adolescents to steer clear of 
serious psychopathology while causing others, of seemingly equal or even 
lower risk, to succumb to such psychopathology. 



17 



Serial No. M-AP(C) 14-8 

Within the framework of this broad objective, the study tries further to 
throw light on several specific related issues. These are: 

(a) Parental perceptions and expectations which specifically bear on their 
children's separation, e.g. their ability and willingness to seek partners 
outside the family or to take on responsible jobs. We have become increas- 
ingly impressed with the .importance of such perceptions as factors which 
either inhibit or promote their children's moves toward autonomy. 

(b) The individual and family dynamics of runaway adolescents. Twenty- 
six out of 37 index adolescents seen in this project had run away from home 
at least one full day and night, before they had turned 17 (some of them 
have run away frequently, getting as far away as Florida, California, and 
Canada). The project offered a unique chance to study in depth this group 
of runaways. 

(c) The often divergent developmental course of siblings who appear close 
in age and who at first sight, appear exposed to similar family influences. 

(d) The sequela of an early precocious and overstimulated development. 

(e) Psychological and perceptual sequelae of teenage drug abuse. 

(f) The potential problems and limits inherent in various treatment 
approaches-but mainly individual, couple — and family therapy — as used during 
a crucial juncture in an adolescent's life and separation process. 

(g) The impact of the adolescent's separation on the parent's image and life 
style. 

(h) The role of the peer group in facilitating or hindering the adolescent's 
growth and separation. 

An additional number of families were seen in screening sessions only. 
These families, too, were made subject to predictions so that they could be 
followed up and could serve as untreated controls to the treated index 
patients and families. 

No new families were admitted during the last year and the major focus 
shifted to the final follow-up interviews carried out by Drs. Stierlin and 
Savard. So far, approximately twenty of the follow-up interviews have been 
carried out, most of them in the families' homes. In these interviews, 
index patients, siblings close in age, and the two parents were seen for 
approximately 50 minutes each. The asessments directed to them covered 
the areas of earlier made predictions. Following these individual follow-up 
xnterviews, all family members were asked to listen to excerpts from audio 
or (.when available) video-tapes made at earlier conjoint family sessions 
and dating back up to five years. 



18 



Serial No. M-AP(C)-14-8 

Methods Employed : 

Adolescents of age 15 and 16 who attend public schools in Montgomery County 
(Maryland) supplied the bulk of our patient material, in addition to those 
referred to us by private psychiatrists and various social and psychiatric 
agencies. The various referral sources sent us adolescents who demonstrated 
school problems and whose families appeared willing to engage in family 
therapy. It was assumed that these students represented a high risk popula- 
tion both in the direction of schizophrenia and in the direction of socio- 
pathic development. Mostly unbroken families were accepted. At the initial 
screening appointment, the family was seen as a group for 50 minutes and then 
the couple and designated patient were seen each for one-half hour. If the 
family qualified and was willing to participate in the treatment and research 
project, the patient was admitted to Unit 3-West where he received or still 
receives individual psychotherapy, usually three times a week. The family 
was seen in once- or twice-weekly family therapy sessions. Couple therapy 
once a week became mandatory. Individual psychotherapy for family members 
was offered when necessary and feasible. On the ward, the intensive therapy 
of the individual adolescent was supplemented by an intensive milieu program. 
No time limits were set to the individual or family treatment except for 
those dictated by the lengths of the therapists' stay at NIl-lH. 

After the first screening interview the available historical, social, and 
dynamic data about the family were summarized and a fairly detailed predic- 
tion was made about the index patient. This prediction included ten major 
items such as employment in five years, psychiatric contacts and diagnoses, 
suicidal tendencies, delinquent tendencies, etc. The ensuing family and 
individual therapy was then used to obtain a more comprehensive picture of 
the family dynamics as they bore on the adolescent's separation problem and 
further development. The following areas were carefully observed and 
assessed: 

(1) The prevailing parental perceptions and expectations, particularly 
insofar as these bear on the adolescent's separation. 

(2) All data pertaining to runaway episodes of adolescents, e.g. overt or 
covert parental encouragement, the context of the running away episode, 
antecedents, peer contacts, etc. 

(3) The communication patterns within the family. We tried to establish how 
much each family was bound to sabotage a pooling of resources. 

(4) The nature of the family's alignments, their relative shifts and incon- 
sistencies, their strengths, and their overt- or covertness. 

(5) Family boundaries. We tried to assess how the family is integrated within 
the community and how much it might put obstacles in the way of the adoles- 
cent's associating with peers, teachers, and other figures outside the family. 



19 



Serial No. M-AP(C)-14-8 

(6) Patterns of psychological exploitation: The various ways in which a child 
(more or less covertly) was recruited to serve his parents in ways which inter- 
fered with his own growth and separation. 

(7) We tried to be alert to all data, implicit and explicit, which could 
throw light on the parents' roles in the adolescent's separation and, in par- 
ticular, on their own separation problems when they were adolescents 
themselves. 

(8) Through an actively and empathically conducted family therapy, we tried 
to get an indication of how much the family might be capable of changing its 
patterns and thereby facilitate the adolescent's separation. Also, by focus- 
ing on the evolving transferences, we tried to get further clues about the 
parents' own separation problems. 

On the basis of these assessments, which were supplemented by an individual 
interview with each family member, we made, at the end of the treatment 
period, second step predictions about the adolescent's prospective life style 
at the age of 21. These predictions covered the same items as those made 
immediately after the screening session, but they were now amplified. Also, 
we supplemented them by a narrative kind of prediction which dealt with the 
question of how much the index would become restricted or nonrestricted, 
active or more passive. In cases where there were two siblings closely re- 
lated in age, the two of them were covered by predictions. It was expected 
that the later confirmation, partial confirmation, or refutation of our pre- 
dictions would deepen our insights and sharpen our hypotheses about the 
adolescent separation process. The comparison between the first step and 
second step predictions, as outlined above, appeared as a useful means of 
alerting us to possible sources of predictive error at this early stage of 
the research project. 

While the principal clinical investigator tried to make five-year predictions 
based on the assessment of presumably crucial and lasting family features, as 
mentioned earlier, additionally obtained Rorschach tests, TAT, cognitive and 
perceptual style procedures of all family members, as well as the audio and 
video tapes , provided material for independent evaluations and predictions 
to be made either then or at later stages of the project. The availability 
of these test procedures made it further possible to utilize these families 
for other ongoing research projects of the Adult Psychiatry Branch, as 
described elsewhere. 

Further, a standardized diagnostic inventory was made in accord with guide- 
lines developed by Drs. John Strauss and Will Carpenter on all newly admitted 
index patients. This should provide us with a further means to check out 
(subjectively tinged) dynamic family data against other independently obtained 
and more standardized data. 

Altogether 37 index patients and their families have so far been included in 
the program. An additional number of families were seen in screening sessions 
only. These families, too, were made subject to predictions so that they 



20 



Serial No. M-AP(C)-14-8 

could be followed up and could serve as untreated control to the treated 
index patients and families. 

No new families were admitted during the last year and the major focus shifted 
to the final follow-up interviews, carried out by Drs. Stierlin and Savard. 
So far, approximately twenty of the follow-up interviews have been carried 
out, most of them in the families' homes. In these interviews, index patients, 
siblings close in age, and the two parents were seen for approximately fifty 
minutes each. The questions and assessments directed to them covered the 
areas of earlier made predictions. Following these individual follow-up in- 
terviews, all family members were asked to listen to excerpts from audio or 
(when available) video tapes made at earlier conjoint family sessions and 
dating back up to five years. 

The family members were then encouraged to reflect together on how the situa- 
tion conveyed by the tape excerpt did still exist and on how they all had 
changed or not changed. In the ensuing discussion there emerged often items 
and issues which had not been covered in the preceding individual follow-up 
interviews . 

Until now, five out of the originally treated 37 families have refused to be 
interviewed. It is hoped that most of the remaining families can still be 
interviewed during the current fiscal year so that the senior investigator 
can devote the major part of the next year to the evaluation of the data 
obtained. 

Maj or Findings : 

Many major findings cannot be expected before the follow-up data, just men- 
tioned, can be fully evaluated. Nonetheless, the following interesting find- 
ings have already been noted and either published or are ready for publication. 

1. The two major patterns in adolescence, called centripetal and centrifugal, 
which were mentioned in last year's report, have been further refined. With 
an ongoing focus on these differing separation patterns, the conceptual frame- 
work which emerged last year was further developed. Crucial to this framework 
is the concept of transactional parental modes which all, albeit in different 
ways, contribute to a distorted separation of adolescent children. They 
operate via parental perceptions and expectations but also imply more basic 
and mutual relational ways and styles. 

2. In line with the above, differing separation conflicts of adolescent child- 
ren could be more clearly delineated. The differing implications for the 
parent's and adolescent's growth and the resulting differing indications for 
therapeutic intervention in separation conflicts have been spelled out. 

3. The role of parental perceptions and expectations for the development of 
crucial identificatory processes in the adolescent has been further clarified. 
In particular, certain interpersonal factors bearing on varying forms of in- 
ternalizations (which include incorporations, introjections , and identifica- 
tions) could be systematically described. 

21 



Serial No. M-.\P CC) -14-8 

4. The five different types of runaways which were mentioned in last year's 
report could be more convincingly linked to characteristic family djmamics. 
This has, in turn, further illuminated the transactions which cause parents 
and adolescent children to separate or not to separate. 

5. Mainly in collaboration with Dr. Kent Ravenscroft the adolescent's family 
dynamics and separation patterns , as above conceptualized, have been examined 
in their relevance for the adolescent's peer relations. 

6. The above findings and conceptualizations have helped to clarify the family 
dynamics and separation patterns of potential schizophrenics. 

Significance to Mental Health Research : 

This study builds on findings about the structures, communication patterns, 
and boundaries of families with disturbed offspring which have been made in 
the Adult Psychiatry Branch during the past decade. With the focus on longi- 
tudinal development and the separation process in adolescence, this study 
tries to assess the significance of various - mainly experiential - factors 
in the actual outbreak of schizophrenia and other disturbances during late 
adolescence, a period which is known to be fateful in an individual's per- 
sonality development and which yields a high percentage of first schizophrenic 
breaks. The new focus on runaways appears commensurate with the increasing 
social importance of this patient group. 

In the present study, family therapy is used as a diagnostic instrument. At 
the same time, it is tried out as a possibly efficient and most economic tool 
in the prevention of the major disasters of late adolescence, 

Proposed Course of Project : 

A major effort is now being made to finish up the follow-up interviews on 
the approximately forty families who have passed through this project. After 
these data have been obtained, it is hoped that the project can be completed 
within the next fiscal year. 

Honors and Awards : 

Stierlin, H. : "Family Djmamics and Separation Patterns of Potential Schizo- 
phrenics." Paper presented at the IVth International Symposium on 
Psychotherapy of Schizophrenia, Turku, Finland, August 6, 1971. 

By invitation, participated (via extemporaneous lectures) in the Seminar on 

Family Therapy, sponsored jointly by the Danish Psychological Association, 
Danish Psychoanalytic Society, and the Danish Psychiatric Society, 
Copenhagen, Denmark, August 8-10, 1971. 



22 



Serial No. M-AP(C)-14-8 

Publications : 

Levi, L. D. , Stierlin, H. , and Savard, R. J.: Fathers and sons: The inter- 
locking crises of integrity and identity. Psychiatry 35: 48-55, 1972. 

Stierlin, H. , Levi, L. D. , and Savard, R. J.: Parental perceptions of separat- 
ing children. Family Process 10: 411-427, 1971. 

Silverman, J., Buchsbaum, M. , and Stierlin, H. : Sex differences in perceptual 
differentiation and stimulus intensity control. In press. Journal of Person- 
ality and Social Psychology. 

Stierlin, H. : Family dynamics and separation patterns of potential schizo- 
phrenics. In press, Y. Alanen (ed.): Proceedings of the Fourth International 
Symposium on Psychotherapy of Schizophrenia, Excerpta Medica. 

Stierlin, H. : Interpersonal aspects of internalizations. In press. Interna- 
tional Journal of Psycho-Analysis. 

Stierlin, H., and Ravenscroft, Jr., K. : Varieties of adolescent "separation 
conflicts." In press, British Journal of Medical Psychology. 



23 



Serial No. M-AP(C)-14-9 

1. Adult Psychiatry Branch 

2. Office of the Chief 

3. Bethesda, Maryland 



I 



I 



PHS-HSMHA-NIMR 

Individual Project Report 

July 1, 1971 through June 30, 1972 



Project Title: The Conceptualization of Lasting Dyadic Relationships 

Previous Serial Number: M-AP(C)-15-6 

Principal Investigator: Helm Stierlin, M.D., Ph.D. 

Other Investigators: None 

Cooperating Units : None 

Man Years: 

Total: .3 
Professional: .2 
Others: .1 

Project Description: 

Objectives : 

This project seeks to contribute to the theoretical base for the compara- 
tive analysis of a wide variety of human relationships. It grew out of 
conceptualizations which the investigator developed before he joined the 
Adult Psychiatry Branch six years ago and which were published in book 
form (Conflict and Reconciliation. New York: Doubleday-Anchor, 1969; 
New York: Science House, 1969). The focus continues to be on the ongoing 
transaction between two persons who are considered as subjects - that is, 
as centers of an individual orientation toward the self, the world, and 
the other - and who are changed while the relationship unfolds. The 
phenomenology and dynamics of psychological exploitation appear here 
particularly significant. The implications of a dyadic model for the 
better understanding of family and group relationships are being explored. 
Also, creativity as a response to a binding and conflictual interpersonal 
field has been made a special focus of study. 

Methods Employed : 

Study, critical evaluation and integration of a wide range of ideas and 
findings reported in the literature of human relationships. At the same 
time, the project relies increasingly on the clinical experiences and ob- 
servations provided through the clinical service of the Adult Psychiatry 
Branch and particularly the ongoing family therapies. Increasingly, the 



25 



Serial No. M~AP(C)"14--9 

issues raised and described in Project M--AP(C)-.14-8 have influenced the 
here-described conceptual efforts. 

Major Findings ; 

(1) The concept of psychological exploitation has been further developed 
and clarified and has been integrated with the concept of transactional 
modes. This is then expected to refine the conceptual base for an under- 
standing of those separation vicissitudes which are the concern of Project 
M-AP(C)-14-8 and which have been describad there, 

(2) Various more or less related subjects, mentioned already in the pre- 
vious report, have been further worked on. These include a paper on the 
German poet Friedrich Ho'lderlin (1770-1848), who became clinically schizo- 
phrenic in his mid-thirties, a paper on the quest for the self-actualiza- 
tion of the therapist, and others. 

Significance to Mental Health Research : 

This conceptual work is relevant to the understanding of schizophrenia as 
a transactional thought disorder. Beyond that, it seeks to illuminate 
various mental disorders as being linked to special types of human rela- 
tionships. The complexities of human relationships, it appears, have far 
outdistanced the conceptualizations so far at our disposal. This project 
tries to reduce the conceptual lag in this area. The concept of psycho- 
logical exploitation seems relevant to many pressing social issues. 

Proposed Course of Project ; 

The principal investigator is in the process of pulling the thoughts and 
themes developed under this project into book form. 

Honors and Awards ; None 

Publications: 

Stierlin, H. ; _ Lyrical Creativity and Schizophrenic Psychosis as Reflected 
in Friedrich Holderlin's Fate„ In George, E. (Ed. ) ; Holderlin, The Ear ly 
Mooern. Ann Arbor, University of l^chigan Press, in pTiil^ 

^^'^n^'^^n'."'' ^® '^^V^ct of Relational Vicissitudes on the Life Course 
of One Schizophrenic Quadruplet. In Kaplan, A. (Ed. ) ; Genetic Fa ctors 
in Schizophrenia. Springfield, 111., Charles C. Thomas, 1972. 

Stierlin, H. : The Interlocking Quest for Self-Actualization and Philoso- 

S;'^i,tr^T''; ^".^""°-' ^' ^Ed.); Ihe Self-Actualization of the 
Therapist. San Francisco, Jossey-Bass, in press. 

Stierlin, H. ; "The Bed - Secret Weapon of the Revolution?" Book Review 
|f^Cooper.s^^,e_p^^th^^ P^^^gh^the ^ and Social Science 

26 



Serial No. M-APCC)-14-9 

Stierlin, H. : Book Review of A. Lorenzer's Destruction and Reconstruc- 
tion of Language . Accepted for publication in The International Journal 
of Psycho-Analysis , and in Psyche . 

Stierlin, H. : Book Review: Some Comments on Reimut Reiche's Critique of 
Charles Socarides' The Overt Homosexual . Accepted for publication in 
Psyche . 



27 



Serial No. M-AP(C)-15-3 

1. Adult Psychiatry Branch 

2. Family Studies Section 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 



Project Title: Evaluation of Family Dynamics with Conjoint Family Art Pro- 
cedures 

Previous Serial Number: SAME 

Principal Investigator: Hanna Yaxa Kwiatkowska 

Other Investigators: NONE 

Cooperating Units: Section on Adolescence and The Family; Unit on Longi- 
tudinal Studies 



Man Years : 




Total: - 


0.56 


Professional: 


0.36 


Others: 


0.2 



Project Description: 

Objectives : The purpose of the project is: (1) To evaluate families through 
a technique in which art media are used as a mode of communication and self- 
expression in order to compare (a) different families in which one or more of 
the offspring is afflicted with one of a variety of mental illnesses (schizo- 
phrenic, psychoneurotic, or delinquent) as well as normal families, and (b) 
different members within a family; (2) to evaluate through the same technique 
changes occurring in the course of family psychotherapy by repeating these 
procedures in periodic follow-ups during the treatment and after discharge. 

Methods Employed : All members of a family are seen jointly in art evaluation 
sessions. The family is introduced to easy art media with no emphasis on 
artistic achievement. The structure of the session combines spontaneous self- 
expression with standardized procedures: (a) free picture; (b) family por- 
traits; (c) abstract family portraits; (d) individual pictures started with 
the help of a scribble; (e) picture done by the family jointly and started 
with the help of a scribble. These procedures are d^evised for the comparison 
of different families. The sessions are conducted by the art therapist with 
a cooperating investigator, a psychiatrist or other staff member as partici- 
pant observer. All the sessions are tape recorded, some of them video taped 
for a better study of family interaction. Abstracts of all the sessions, des- 
cribing the families ' transactions, their comments and discussions of their 



29 



Serial No M-AP(C)-15-3 



pictures as well as special observations of the investigators, are dictated 
upon completion of the session; the art productions and tapes of the ses- 
sions are studied for more accurate analysis. Each family is seen in a single 
evaluation session as close as possible after admission. Long term patients 
and their families are seen in a second family art evaluation after a minimum 
of six months of conjoint family therapy or at termination of treatment. 

The families admitted to Unit 3 West continue to participate in family 
art evalifitions. As in previous years the arc therapist had as minimal as 
possible contact with the patient or family prior to the evaluation in order 
not to be biased by information from, other sources. 

Major Findings : The investigated patient population in the period from 
July 1, 1971 consisted of a great majority of adolescents with behavioral 
problems such as delinquency and drug usage. The investigation of phenomena 
specific to families of patients with these types of mental disorders contin- 
ues. 

It was observed that many of these families required about double the 
length of time usually needed for an evaluation session and produced a great 
deal of pictorial and verbal material. While the pictures were impressively 
revealing of the families' dynamics, the investigators were amazed at the 
difficulty these families had in recognizing the problems and interrelation- 
ships so vividly displayed. The quantity of material by itself overwhelmed 
the investigators, but even careful study of tapes rarely revealed a deeper 
engagement of the family. 

In the joint endeavor (see Method (e) above), the fathers made ineffec- 
tive efforts at leadership and were frequently sabotaged by the mothers. The 
joint production was usually of an inferior quality than the family members' 
individual ones. 

The separation issue was repeatedly revealed in the pictures of the 
families of this same group of adolescents. These adolescents underlined in 
their family portraits their desire for complete separateness from the family 
unit, but upon closer investigation one discovers that there is an ambiguity 
in these representations: the adolescent pictures himself either outside of 
the carefully delimited world of the family, yet somehow still closely at- 
tached to it or in complete unreality such as hazy, drugged fantasy world or 
on a desert island. 

On the other hand, we noticed the opposite tendency in the parents. The 
myth of happiness and unity of the family was predominant, with only hints at 
scapegoating the index patient. Their pictures underlined the unity of the 
family and encircled tightly the family world. 

As in preceding years, the family art evaluation, basically a research 
proced«re has also presented clinical advantages. The pictures displayed at 
clinical conferences illustrate the family members' problems, their trans- 



30 



Serial No, M-AP(C)-15-3 



actional style, and their perception of each other. The clinicians can 
visualize and focus on specific issues represented in the concrete and dur- 
able form of the graphic projections. These issues can also be further 
worked on in family or individual therapy. 

Significance to Mental Health Research ; The development of this technique 
continues to give additional dynamic understanding of family relations to 
projects of the Adult Psychiatry Branch of NIMH. The hypotheses based on 
the empirical findings obtained through family art evaluations have been 
scientifically investigated by systematic computer analysis of the material 
and described as a separate project, (M-AP(C)-15-8). 

The researchers' and clinicians' interest in this technique continues 
to increase in the United States and abroad. As a result of the development 
of our work at NIMH, a graduate course in Family Art Techniques leading to 
a Master's Degree is offered by the Graduate School of Arts and Sciences at 
George Washington University and at Washington School of Psychiatry. 

Seminars on family art techniques, reprints of papers, and consultations 
continue to be requested. 

Proposed Course; To continue to investigate systematically the findings des- 
cribed above with the goal of categorizing the families where these character- 
istics appear most prominently. 

It is hypothesized that the unresolved separation of these fathers and 
mothers from their own parents would be crucial in the problems of separation 
of their offspring. Special additional art procedures are being planned for 
this purpose. 

Honors and Awards ; By invitation of the American Psychological Association, 
a paper, EVALUATION OF FAMILIES WITH SCHIZOPHRENIC TWINS THROUGH FAMILY ART 
PROCEDURES by Hanna Yaxa Kwiatkowska and Loren R. Mosher, M.D., was presented 
at the Annual Meeting in Washington, D.C. in September 1971. 

An Exhibit, EVALUATION OF FAMILY DYNAMICS THROUGH CONJOINT FAMILY ART 
PROCEDURES by Hanna Yaxa Kwiatkowska, was presented, also by invitation at the 
World Congress of Psychiatry in Mexico City in December 1971. 

Publications ; FAMILY ART EVALUATION: Use in Families with Schizophrenic 
Twins by Loren R. Mosher, M.D. and Hanna Yaxa Kwiatkowska, B.S., published in 
the Journal of Nervous and Mental Diseases in the September issue, Vol. 153, 
No. 3, 1971. 



31 



Serial No. M-AP(C)-15-5 

1, Adult Psychiatry Branch 

2, Family Studies Section 

3, Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 



Project title: Family Art Therapy 

Previous Serial Number: SAME 

Principal Investigator: Hanna Yaxa Kwiatkowska 

Other Investigators: NONE 

Cooperating Units: NONE 

Man Years: 

Total: 
Professional: (inactive) 
Other: 

Project Description: 

Objectives ; (a) To further investigate the pilot study where family art thera- 
py is used as the sole therapy with families of adolescents from different 
diagnostic groups; (b) To use this approach with families of different socio- 
economic backgrounds. 

Mathods Employed : All members of a nuclear family are seen jointly in family 
art psychotherapy by the art therapist and the collaborating psychiatrist. 
Art media are offered to the family as a means of communication and self- 
expression; artistic or aesthetic considerations are not emphasized. In some 
of the sessions (at the beginning of treatment and repeated every six months) 
art evaluation procedures are used. These procedures combine free expression 
with standardized tasks and their purpose is to gauge the course of therapy 
periodically. Otherwise the family is largely left to structure the session; 
they are encouraged to draw or paint whatever comes to mind. All sessions are 
tape recorded; abstracts describing the family's interaction and the analysis 
of the pictorial and verbal material, as well as the therapists' subjective 
reactions, are dictated by both therapists. In the course of therapy at least 
one session is video taped. 

tfajor Findings ; No family was investigated this year, but a study based on a 
"blind" analysis by eminent psychiatrists and analysts of pictorial material 
obtained from long term family art psychotherapy and chronologically arranged 
was completed and presented by invitation at the American Psychiatric Associa- 



33 



Serial No M-AP(C)-15-5 

tion meetings under the title "Blind Evaluation of Pictures in Family Psycho- 
therapy: Their Communicative Power," This study demonstrated: 

1. The blind judgements drawn from pictures only, without any verbal 
content were astonishingly accurate as to identity of index, diagnosis, 
course, and outcome of therapy. 

2, The observations of the judges brought more clarity on the reasons 
for a successful achievement of the therapy and helped the therapists to 
gain a more precise understanding of their experience with this family. 

Proposed Course : To complete for publication the monograph "The Use of Drawing 
and Painting as a Primary Mode of Communication in the Family Therapy of 
Schizophrenia. " 

Honors and Awards : An exhibit, "Pictures Help a Regressed Schizophrenic 
Patient to be Heard and Understood" by Hanna Yaxa Kwiatkowska, was presented 
by invitation at the Exhibition of Psychopathological Art at the Fifth World 
Congress of Psychiatry in Mexico City. 

Publications: NONE 



3i^ 



Serial No, M-AP(C)-15-8 

1. Adult Psychiatry Branch 

2. Family Studies Section 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 



Project Title: Systematic Analysis of Family Art Evaluations 

Previous Serial Number: SAME 

Principal Investigators: James K. Dent, Ph.D. and Hanna Yaxa Kwiatkowska 

Other Investigators: Lyman C. Wynne, M.D., Ph.D., Margaret T. Singer, Ph.D. 

Cooperating Units: Section on Personality Development, Section on Twin and 

Sibling Studies, Section on Clinical Psychology, Division 
of Computer Research and Technology. 

M&n Years : 

Total: 0.35 
Professional: 0.20 
Other: 0.15 

Project Description: 

Objectives : The overall objective is to explore systematically the materials 
available from the Family Art Evaluations which have been introduced by Mrs. 
Hanna Kwiatkowska and conducted for several years. Such an analysis is aimed 
at improving diagnostic procedures and increasing our understanding of the 
social psychological dynamics of psychopathology . In presenting the specific 
objectives, the longer range of objects are listed first; the immediate ob- 
jectives are listed last. 

A. Family Dynamics and Psychopathology . 

1. To differentiate, through the characteristics of their art pro- 
ductions, families in which the index is diagnosed as process schizo- 
phrenic, reactive schizophrenic, psychoneurotic, and so forth. 

2. To distinguish role positions in the family (father, mother, 
sibling, etc.), as revealed by their pictures (such as family portraits) 
and transactions. 

B. Diagnostics (A Manual for the use of the Family Art Evaluations ). 
1. To specify the relation of the diagnosis of the index to the 



35 



Serial No. M-AP(C)-15-8 



characteristics of his own art productions and those of his family. 

2. To determine which characteristics of the art productions appear 
to represent transient symptoms and which represent more enduring per- 
sonality characteristics. 

C. Measurement Objectives . 

1. To develop objective rating systems for pictures and family 
transactions in the Family Art Evaluation method. 

2. To determine the interrater agreement and the internal consis- 
tency of the scales used. 

3. To construct by combining scales, variables having stronger met- 
ric power. 

4. To analyze the significance of variables like artistic talent 
and intelligence which may confound the relation between diagnostic 
variables and characteristics of the art productions. It is important 
to separate the evidence of psychopathology in a picture from the influ- 
ence of intelligence or artistic talent. 

Methods Employed : Our methods were described in detail last year. In sum- 
mary, the pictures are blinded, randomized, and rated; one picture in four 
is check rated for studies of interrater agreement. A variety of statisti- 
cal techniques are being used, depending upon specific objectives. 

"Blind" ratings of pictures represent an independent measure of the men- 
tal status of an individual at a particular point in time. It is our plan to 
correlate these ratings with other data. Correlation with diagnosis and fam- 
ily characteristics such as socio-economic status will be greatly facilitated 
because some of these data have already been compiled in connection with the 
research done by Dr. Lyman C. Wynne. 

Major Findings ; Factor analyses across pictures reveals that there are some 
expected dimensions which are prominent and stable. For example, there is a 
dimension that might be labelled "bizarreness" which is always first or 
second in explaining variance regardless of how the factor analysis is con- 
ducted. However, there are many more independent dimensions than was antici- 
pated; that is, even though interrater agreement is high, relations among 
dimensions tend to be low. The characteristics of the pictures are not easily 
summarized in a few dimensions. 

Factor analysis across individuals indicated that there are a few dimen- 
sions which might be labelled "trait" dimensions. They extend across the 
various procedures, across two F.A.E. 's, and are correlated with intelligence 
and artistic talent. An example of such a dimension is the use of color. 
However, unexpectedly , "bizarreness" is not such a dimension; that is, an 



( 

I 



36 



Serial No. M-AP(C)-15-8 

individual who produces a bizarre "first free" picture is not likely to show 
"bizarBeness" in his last picture. 

There are a large number of dimensions which show significant differences 
between patients and siblings. These differences are almost always as one 
would predict; for example, patients' pictures are more likely to be "bizarre." 
Comparisons between offspring and their parents are difficult because the 
parents tend to show less artistic talent. Further analyses of talent-free 
dimensions are required. 

Significance to Mental Health Research : Since the art production is an inde- 
pendent, enduring representation of the mental status of an individual (or 
family) at a moment in time and in a structured family setting, it is a valu- 
able datum both for enhancing our diagnostic methods and for investigating 
family dynamics in relation to mental disorder. 

The usefulness of "drawing tests" for individual diagnosis is widely 
recognized. Considerable research has been done on the Draw-A-Person test. 
More recently there have been efforts to use other types of art productions. 
Although the literature is full of ideas about how to diagnose mental illness 
from pictures, most of the research has been concerned with a much simpler 
and less useful task, viz.: To predict whether a person is mentally ill. 
Only a few systematic studies (e.g., that of Dr. Robert Kaye) have been con- 
cerned with trying to specify what aspects of a picture are predictive of 
what kinds of mental disorder, and there have been no statistical studies of 
family dynamics as seen through the art productions of the whole family. 

On the side of family dynamics, there is a rich body of research findings. 
Many of the concepts in this literature are used in the present study. More- 
over, the material is being coded for the computer in the same format as for 
other studies in the Adult Psychiatry Branch, and this will greatly facili- 
tate the comparison and integration of findings. 

Proposed Course : Analyses of diagnostic groups will be conducted. We will 
use a diagnostic system developed by L. C. Wynne together with data collected 
in connection with M-AP(C)-14-6, Pilot Study in Records Codification. We will 
also use a diagnostic system modeled on the work of Donald F. Klein of 
Hillside Hospital, New York City. 

Honors and Awards ; NONE 

Publications: NONE 



37 



1 



Serial No. M-AP(C)-15-9 

1. Adult Psychiatry Branch 

2. Family Studies Section 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Systematic Analysis of Brazilian Family Art Evaluations: A 
Replication. 

Previous Serial Number: SAME 

Principal Investigators: Hanna Yaxa Kwlatkowska and James K. Dent, Ph.D. 

Other Investigators: Dr. Carlos Paes de Barros, Dr. Aroldo Rodriques, 

Sylvia Beatriz Machado Joffely, Vera Polio Flores, 
Luiz Duprat. 

Cooperating Units: Institute of Psychology of the Catholic University in Rio 
de Janeiro, Brazil, Department of State Committee on Inter- 
national Exchange of Persons (Fulbright Commission). 

Man Years : 

Total: 0.10 
Professional: 0.05 
Others: 0.05 

Project Description: 

Objectives : The overall objective is to explore the differences and similari- 
ties appearing in the systematic analysis of pictorial material obtained from 
Brazilian families with the material obtained from American families, here, 
in the identically structured situation of the "Family Art Evaluation. " The 
specific objectives are: 

1. To investigate and compare the characteristics of pictures drawn by 
Brazilian families where a family member has a specific psychiatric 
diagnosis with the characteristics of pictures of diagnostically similar 
families in the United States. 

2. To define if eventual differences observed through this analysis 
could be attributed to cultural variations. 

3. To study the differences in roles of family members in both countries 
as seen in the different procedures of the family art evaluations. E.G., 
in her work with Brazilian families Mrs. Kwiatkowska has observed that 
the family portraits of Brazilian families frequently include the exten- 



39 



Serial No. M~AP(C)-15-9 

ded family, thus' bringing to light the roles of substitute parents. Is there 
a correlation between the recurrent inclusion of such substitute parent in the 
family portraits and the degree of pathology in the family? What is the role 
of the natural parents in such families? 

(4) To investigate and compare the interrater agreement on the same items 
of the rating system in the United States and Brazil. This could also shed 
light on cultural differences. 

Methods Em.ployed : The manual used for the NIMH study was translated into 
Portuguese by the Staff of the Institute of Psychology at the Catholic Univer- 
sity in Rio de Janeiro. It was edited by Hanna Yaxa Kwiatkowska; staff mem- 
bers were trained by her personally to conduct a study parallel to the NIMH 
study. 

A psychologist, Mrs, Vera Polio Flores, with the consultantship of Miss 
Sylvia Beatriz Machado Joffely, is in charge of the study and under the direc- 
tion of Dr. Carlos Paes de Barros, Chairman of the Department of Psychology. 
Other staff members of the Institute were designated as coordinators and 
trainers of the raters. The ratings were done by students as part of their 
regular curriculum for credit. Dr. Aroldo Rodriques, Research Psychologist, 
is a consultant for the statistical aspect of the study. 

The patients referred to the Clinic at the Institute of Psychology are 
mostly children or adolescents in their early teens. Jointly with their fami- 
lies they all have a family art evaluation as part of their routine psycholo- 
gical work-up. A considerable amount of material has been accumulated since 
the evaluations were introduced there in 1966. In selecting sample families 
for the present study we were, nevertheless, limited by the age group; we did 
not want to include families where the index would be less than ten years old. 
Diagnostically the sample includes families of severely neurotic or behavior 
problem children, all out-patients at the Clinic. Records of all investigated 
Brazilian families were obtained and translated from Portuguese into English 
in order to obtain data (symptoms, onset, premorbid history) to be used in 
establishing diagnoses of the Brazilian subjects. 

Major Findings ; Factor analyses reveal that there are some similarities with 
and some differences from the factor structure of pictures drawn by our fami- 
lies here in Bethesda. 

Significance to Mental Health Research : Family art evaluations provide a 
situation which offers a good deal of stability in the manner material is 
gathered for comparative studies. The basic material (pictures) is collected 
in an experimental setting structured as identically as possible with the 
NIMH setting. The methods used for the computer analysis of these data are 
also identical. The possible flaws in the translation and interpretation of 
the scoring manual, whether of linguistic or cultural nature are being inves- 
tigated in a separate study (M-AP(C)-15-10 "Sources of Variance in Cross- 
cultural Application of an Objective System for Analyses of Pictures Drawn by 



ko 



{ 

I 



Serial No. M-AP(C)-15-9 



Patients and their Families"). 

Proposed Course : Further analysis awaits the clarification of certain omis- 
sions and discrepancies in the Brazilian data. Communication about these 
discrepancies is difficult when one is dependent upon letter writing. We 
have been fortunate in the past that Mrs. Kwiatkowska was able to visit the 
Institute and establish face-to-face communications. 

Honors and Awards ; NONE 

Publications: NONE 



I 



kl 



Serial No. M-AP(C)-15-10 

1. Adult Psychiatry Branch 

2. Family Studies Section 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Sources of Variance in the Cross-Cultural Application of an 
Objective System for Analyses of Pictures Drawn by Patients 
and Their Families. 

Previous Serial Number: SAME 

Principal Investigators: James K. Dent, Ph.D. and Hanna Yaxa Kwiatkowska 

Other Investigators: Dr. Carlos Paes de Barros, Dr. Aroldo Rodrigues, 

Sylvia Beatriz Valerio Machado Joffely, Vera Polio 
Flores 

Cooperating Units: Institute of Psychology of the Catholic University of 
Rio de Janeiro, Brazil 

Man Years: 

Total: 0.04 
Professional: 0.04 
Others: 0.00 

Objectives : A system has been developed for objectively classifying pictures 
drawn by patients and by members of their families in the Family Art Evalua- 
tions at NIMH (M-AP(C)-15-8). This rating system which consists of about 
fifty dimensions has been translated into Portuguese and is being used to 
describe pictures drawn by mental patients and their families in Brazil, 
(M-AP(C)-15-1). In application, the two measurements may not be equivalent 
for several reasons: 

(a) Various pictorial symbols may have different significances in culture 
A (American) from those in culture B (Brazilian). 

(b) The English and Portuguese translations may not be equivalent. 

(c) Research group A may have particular frames of references not common 
to their own culture. 

(d) Research Group B may also have particular frames of references. 

The objective of this project is to begin to sort out some of these various 
sources of error and variance. 



^3 



Serial No. M-AP(C)-15-10 

Methods Employed ': Sixty-eight pictures selected at random from about one 
thousand pictures (American families) have been or are being rated as follows: 

Ratings 1 and 2: 

Two members of research group A have independently rated each of the pic- 
tures using the English translation. 

Rating 3: 

These raters discussed their differences and prepared a check rating repre- 
senting the best judgment of research group A for each picture. 

Rating 4: 

Using the English translation, the pictures have been rated by two American 
college student volunteers working alone (no contact with the research 
group), each doing about half of the pictures. 

Rating 5: 

Using the Portuguese translation, a bilingual American college student 
volunteer rated the pictures alone (no contact with the research group). 

Ratings 6, 7, and 8: 

These are like ratings 1, 2, and 3 but are being done by Brazilian members 
of research group E in Brazil, from slides of the same pictures rated at 
NIMH. 

For the 50 dimensions in the rating system, comparison among these 
ratings should permit us to isolate translation difficulties and some of the 
group effects. Presumably differences not attributable to these two sources 
of variance represent cultural factors in interpretation or individual rater 
biases. (A study of individual rater biases is included in M-AP(C)-15-8) . 
Because of the small number of pictures and of having only one bilingual rater, 
the results will have to be considred tentative. This project is essentially 
a pilot study for this type of investigation. 

Major Findings : The Brazilians were able to rate only about half of the pic- 
tures we sent them. Analysis of this half indicated clearly which dimensions 
have a constant meaning in both centers, which have different meanings but are 
reliable within centers (translation problems), and which dimensions are so 
poorly defined they have little meaning in either center. 

Proposed Course ; Findings will be written up in the next fiscal year. 

Significance to Mental Health Research : The precise description of mental 
disorders across cultures is hampered by a paucity of culture-free methods of 



( 



kk 



Serial No. M-AP(C)-15-10 

assessment. Frequently the problem is dealt with by using the inferential 
judgments of particular clinicians who evaluate patients in two or more cul- 
tures. Agreement among them about particular patients is interpreted as 
constancy in measurement. This system which is biased by language, dialect 
and status problems may not provide replicable descriptions; i.e. there are 
no assurances that another group of clinicians with differing backgrounds 
would provide the same description, or even a common one. 

At the other extreme, one is impressed by the almost universal under- 
standing and appreciation of works of art. The messages of enduring repre- 
sentations of art seem on the one hand to be an expression of the different 
cultures and on the other hand to convey emotions universally accessible. One 
is also impressed with the high quality of communication in pure science. 
Where ideas are precisely defined in observable terms cross-cultural communi- 
cation is facilitated. For these reasons objective descriptions of art pro- 
ductions may be an important way of achieving cross-cultural communication in 
description of mental disorders. In addition to being tangible the communica- 
tion is not limited and/or biased by the language or dialect problem and the 
professional has a direct access to the experience of the patient. 

Honors and Awards ; NONE 

Publications; NONE 



h5 



Se rial No. M-AP(C)-16-1 

1. Adult Psychiatry Branch 

2. Psychiatric Assessment Section 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: WHO International Pilot Study of Schizophrenia 

Previous Serial Number: M-AP(C)-16-1 

Principal Investigators: John S. Strauss, M.D. 

William T. Carpenter, Jr., M.D. 
Lyman C. Wynne, M.D., Ph.D. 

Cooperating Units: John Bartko, Ph.D., Biometrics Branch 
Prince Georges General Hospital 
Spring Grove State Hospital 
Morris Cafritz Memorial Hospital 
World Health Organization 

Man Years: 

Total: 2.0 
Professional: 1.0 
Other: 1.0 

Project Description : 

Objectives : (1) To develop standard interview and rating schedules that 
can be used cross-culturally for the evaluation of psychotic patients. 
(2) To evaluate a cohort of patients from the catchment area of Prince 
Georges County, Maryland with these Instruments and to compare these findings 
with similar evaluations being carried out by investigators In eight other 
psychiatric centers in Colombia, Czechoslovakia, Denmark, Great Britain, India, 
Nigeria, Taiwan and the USSR. (3) To work toward a consensus with investigators 
from these other countries about criteria derived from the interview Instruments, 
for classifying patients as schizophrenic. (4) To compare these WHO diagnostic 
evaluations with clinical evaluations and ratings of the same patients made with 
other methods such as the Lorr IMPS scale and projective tests. (5) To compare 
social and demographic data on patients evaluated by the standard instruments 
to understand more completely how these factors are related to schizophrenia 
as defined through the use of the standard diagnostic schedules. (6) To 
compare course of illness in patients from the collaborating centers by 
conducting a follow-up study on patients seen in the original sample. 

Methods Employed : Standardized forms have been developed for evaluating 
mental status, history, social function, and outcome. Initial evaluations 
were completed using these forms on 135 patients from each center. Data 
is being analyzed to compare the patients from the nine centers in terms 



^7 



Serial No. M-AP(C)-16-1 

of initial diagnosis, social function, and follow-up status. Alternative 
diagnostic techniques have been applied to evaluate their validity. 

Major Findings : In the past year the final draft of Volume One of the IPSS 
report has been prepared. This report described methods and findings of the 
first phases of the IPSS. These phases include (1) the preparation, translation, 
pretesting, and revision of the data collection instruments; (2) the application 
of these instruments to 1,202 patients in nine different centers; (3) the evalu- ^ 
ation of reliability of the interview schedules; and (4) diagnostic comparisons 
of the patients seen in the nine centers. 

The preparation and translation of data collection schedules of this kind with 
collaboration of psychiatrists from nine centers is, in itself, a significant 
contribution to the methodology available to future cross-cultural studies. 
In evaluating the applicability and reliability of the schedules, two findings 
were especially significant. First, it was possible to use the same standard- 
ized mental status interview (in translation where necessary) in all of the 
collaborating centers and reliability of ratings within each of the centers was 
high. The reliability of the ratings across centers was at a lower but still 
acceptable level. Because history and social description data had to be 
collected in different ways in the different centers, and because these data 
depend so much for their psychiatric significance on the cultural milieu. It 
was more difficult to evaluate the comparability of these kinds of Information 
from center to center. However, the schedules provided a useful means of 
collecting these data and represent a first step towards the development of 
comparable methodology in this area as well. ' 

The comparison of similarities and differences in patient types seen in the 
different centers has been given considerable attention. The Inherent complexity 
of such a comparison, even of patients within one center, is often under- 
estimated, but was highlighted by the cross-cultural nature of this project. 
Three different methods for defining diagnostic types were used. The results 
of these three different methods were then compared. In the first diagnostic 
method, the Interviewing psychiatrist assigned the patient to one of the conmonly 
used clinical diagnostic categories. The categories defined by the Inter- 
national Classification of Diseases were those most frequently used; however, 
some centers tended to use special diagnostic categories. Analysis of symptom 
profiles of the different diagnostic types showed broad similarities across 
centers for the general diagnostic categories such as schizophrenia, and manic- 
depressive psychosis. It indicated further that patients with some of the 
common defining characteristics of these diagnostic categories were seen In all 
centers. Comparison of symptom profiles to diagnostic labels applied by 
investigators from the centers also clarified many differences in the way in . 
which psychiatrists from different centers used symptom information in reaching ' 
a diagnosis. 

A second diagnostic method used to analyze the types of patients seen in this 
study was a computer program developed to simulate clinical diagnoses as they 
might be made by the psychiatric school led by Kurt Schneider. Using data from 
the mental status examination and psychiatric history, this computer method 



U8 



Serial No. M-AP(C)-T6-1 

(Catego) was able to duplicate, to some extent, the broad clinical diagnoses 
such as schizophrenia, and psychotic depression given to the patients by the 
investigators in the centers. This method represents considerable progress in 
developing a technique for applying diagnoses to patients which can be applied 
in different centers with complete reliability. 

The third method used for assigning patients to diagnostic categories employed 
cluster techniques. With these mathematical techniques for defining groups of 
patients, it was possible to arrive at categorizations that were somewhat 
similar to both clinical and Catego diagnoses. The cluster techniques also 
provided a means for defining certain subgroups of patients that were seen in 
only one or two centers. The results of these three methods were compared and 
combined to describe basic similarities and differences among patients seen in 
the different centers. 

The data from the study is also being used as source for other closely related 
investigations: (M-AP(C)-16-3, M-AP(C)-16-4) . These studies involve more 
intensive investigation of certain aspects of the data obtained during the IPSS 
and comparison of these data with similar information obtained from other 
sources. 

Significance to Mental Health Research and the Program of the Institute : 
The difficulty in comparing psychiatric patients from different cultures has 
made it impossible to evaluate accurately the etiological importance of cultural 
factors in psychiatric disorder. The absence of standard methods for evaluation 
and diagnosis of psychiatric patients has also made it difficult to ccri'pare 
incidence and prevalence rated in different cultures and to compare usefulness 
of treatment methods employed in different centers. Until these comparisons 
can be performed, it is not possible to test many crucial hypotheses regarding 
the nature and etiology of psychiatric disorders. The difficulties in estab- 
lishing standard instruments are considerable, not only in the writing and 
testing of such Instruments, but in the extensive negotiations and communications 
necessary with the various Investigators from different countries with diverse 
backgrounds and orientations. Nevertheless, in this study it has been possible 
to develop such Instruments that can be applied in a useful way in a variety of 
cultural settings. These Instruments were used with patients in nine different 
countries and proved to be applicable and useful for this purpose. 

While methods of evaluating patient characteristics must be developed in order 
to perform cross-cultural studies, it is also essential to develop methods for 
categorizing patients once their characteristics have been elicited and rated. 
In the current studies, three different methods were used to categorize patients 
and to compare patient types among the different centers. Through applying 
these methods, it is possible to show in what sense patients seen in the differ- 
ent centers are similar and in what sense they are unique. The combinations 
of these methods can also be used to determine in what sense the statement, 
"schizophrenia is found in all of the nine centers," is true, and in what sense 
the statement omits recognition of real differences of "schizophrenic" patients 
from the different centers. 



k9 



Serial No. M-AP(C)-16-1 

The completion of a follow-up study on the patients originally interviewed adds 
the crucial dimension of course of illness to the evaluation. By having 
standardized, comparable infcnnation on patients from different countries at 
two points in time, it will be possible to compare course of illness cross- 
culturally and to investigate further the use of outcome of psychiatric illness 
to validate the original diagnoses. 

Proposed Course of the Project : In the coming year the data from the ^ 
follow-up phase of the IPSS will be further analyzed and preparation of Volume 
Two of the IPSS report will be undertaken reporting follow-up results and several 
substudies from the early phases of the IPSS. 



50 



Serial No. M-AP(C)-16-3 

1. Adult Psychiatry Branch 

2. Psychiatric Assessment Section 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Comparative Studies of Functional Psychoses 

Previous Serial Number: M-AP(C)16-3 

Principal Investigators: William T. Carpenter, Jr., M.D. 

John S. Strauss, M.D. 

Cooperating Units: John Bartko, Ph.D., Biometrics Branch, Prince Georges 
General Hospital, Spring Grove State Hospital, Morris 
Cafritz Memorial Hospital, World Health Organization, 
3-E and 4-W Nursing Units, Clinical Center, NIH, Section 
on Psychiatry, Laboratory of Clinical Science. 

Man Years : 

Total: 0,4 
Professional: 0.3 
Others: 0.1 

Project Description: 

Objectives : (1) To utilize standard interview and rating schedules to 
collect data on manic-depressive patients. (2) To utilize this data and 
data collected on a larger group of schizophrenic patients in a comparable 
manner to investigate similarities and differences in symptomatology within 
these diagnostic categories. (3) To provide a sufficiently large sample of 
manic-depressive patients to enable comparison with similarly diagnosed 
patients from other field centers in the WHO International Pilot Study of 
Schizophrenia. (4) To obtain data with which to test the hypothesis that 
many of the usually accepted criteria for a depressive illness (i.e., biological 
signs, psychosomatic complaints, sleep difficulties, decrease in libido, etc.) 
do not have high order discriminatory function between depression and other 
forms of mental disturbances. (5) To generate a sufficient sample of depressed 
patients to explore the hypothesis that a diagnosis of schizophrenia is often 
used for a person who otherwise is comparable to a psychotic depression but 
has a bizarre delusion or the presence of an hallucinatory phenomena which 
many clinicians in practice do not identify as part of a depressive illness. 
(6) To elucidate the concept of schizo-affective schizophrenia by examining 
the signs and symptoms present in cases so diagnosed comparing them with 
depressed patients and schizophrenic patients during illness and through 
a follow-up period. (7) To test empirically current diagnostic systems for the 
psychoses. 



51 



Serial No. M-AP(C)-16-3 

Methods Employed : The standard instruments were developed for the WHO 
International Pilot Study of Schizophrenia, They were developed, revised, and 
extensively pretested on at least 24 patients from centers in eight countries 
and have been used in the past year on a cohort of 135 patients from each 
center. Four basic interview forms comprise the standard instruments and are 
described in project No. M-AP(C)-16-1. Using these schedules on a sample of 
patients not included in the IPSS, 37 manic-depressive patients have been inter-- 
viev/ed from wards 3-E and 4-W in the Clinical Center, Nllffl. Computerized * 
statistical methods are being developed to analyze the data collected from these 
groups of patients to develop empirical "clusters" of patients based on the 
symptoms they demonstrate. In addition the material on certain sub-groups of 
patients (i.e., schizo-af fective schizophrenia) will be examined by the prin- 
cipal investigators in an effort to clarify descriptive and conceptual aspects 
of the diagnostic categories. 

Maj or Findings : It has been possible to accumulate systematic symptom 
and sign data on large groups of patients assigned to various functional 
psychotic subcategories. This date permits testing of major diagnostic con- 
cepts and to contrast symptom profiles among various diagnostic categories. 
The most important finding to data comes from the first empiric investigation 
of Kurt Schneider's diagnostic concept. Schneider's identification of patho- 
gnomonic symptoms of schizophrenia has influenced diagnostic practices through- 
out most of the world. Despite general acceptance for over forty years, his 
diagnostic system has never been empirically tested. Using the patient data 
described above, we were able to demonstrate that the first rank symptoms are 
not pathognomonic for schizophrenia, but occur in one-third of manic-depressive 
patients and in ten percent of neurotic and character disorder patients. We 
have been able to replicate these findings with the data from each of the other 
eight centers in the IPSS, 

These data have been used with a number of diagnostic procedures to iden- 
tify groups of patients to test hypotheses related to outcome in schizophrenia 
(see Project Serial No. M-AP(C)-16-7) . 

Significance to Me ntal Health Research and the Program of the Institute : 
There is a paucity of data in functional psychoses using standardized inter- 
view techniques. Evaluating diagnostic groups and comparing them with similar 
groups from the various field centers in the WHO International Pilot Study of 
Schizophrenia offers an opportunity to clarify the use and misuse of the 
diagnostic categories and to describe more clearly phenomena represented in 
each and the distinguishing features of the various diagnostic categories. 
The ability to identify homogeneous and comparable groups in various centers 
IS fundamental for all human research of the psychoses. 

Proposed Course of the Proiect- During the coming year we will test other 
diagnostic concepts. We will use follow-up information and premorbid data in 
an effort to validate and invalidate diagnostic groups. Mathematical approaches 
to this data can help identify the critical symptom variables in diagnosing. 
Revision of diagnostic concepts will follow in order to maximize their ability 
to discriminate between patient groups based on signs and symptoms that occur 
frequently and are readily observed by clinicians, 

52 



Serial No. M-AP(C)-16-3 

Presentations : Presented by Dr. William T, Carpenter, Jr, 

1. The Search for Pathognomonic ity in Schizophrenia, presented to the 
Eleventh Annual Conference of the Mental Health Career Development 
Program, New Orleans, Louisiana, 1972. 

2. Pathognomonic ity in Schizophrenia: An Empiric, Cross-Cultural 
Investigation of Kurt Schneider's Diagnostic Concept, presented at 
the Annual Meeting of the American Psychiatric Association, 1972. 

3. Diagnostic Concepts in Schizophrenia, presented to the Department of 
Psychiatry, University of Kentucky Medical School, 1972. 



53 



Serial No. M-AP(C)-16-A 

1. Adult Psychiatry Branch 

2. Psychiatric Assessment Section 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Empirical Grouping of Psychiatric Patients 

Previous Serial Number: M-AP(C)-16-4 

Principal Investigators: John S. Strauss, M.D., John Bartko, Ph.D., 

William T. Carpenter, M.D. 

Cooperating Units: Biometrics Branch, NIMH, Computer Center, NIH, World 
Health Organization 

Man Years: 

Total: 0.3 
Professional: 0.2 
Other: 0.1 

Project Description: 

Objectives : (1) To develop methods for grouping psychiatric patients 
empirically. (2) To determine whether patients as defined by their symptoms 
fall into natural groups or vary along continua. (3) To evaluate methods 
commonly used for the empirical grouping of patients. 

Methods Employed : In the process of analyzing the data generated by the 
WHO IPSS (M-AP(C)-16-1) , some difficulties with commonly used clustering and 
factoring procedures for grouping patients became apparent. The investigators 
have used a series of statistical techniques to locate where in the process 
of data analysis the difficulties arose and to understand the relationships 
between cluster techniques and the underlying discrete or continuous structure 
of data. 

Major Findings : The results of the commonly used clustering and factoring 
techniques for grouping psychiatric patients have been demonstrated to be less 
stable than is generally recognized. It has been possible to identify the 
variables that are significant in causing this instability. The inability of 
even the improved techniques to create stable clusters from psychiatric data 
suggests that psychiatric patients may represent continua rather than discrete 
categories. 

Significance to Mental Health Research and the Program of the Institute : 
Because of the unreliability of psychiatric diagnoses and their limited 
utility, many investigators have turned to mathematical models to define more 
meaningful groups of psychiatric patients. These efforts may one day be 

55 



Serial No. M-AP(C)-16-4 

important in defining groups of patients with similar causes and courses of 
their disorders and similar responses to treatment and thus provide consider- 
able progress in research, treatment, and prevention of psychiatric disorders. 
The mathematical models currently in use have many weaknesses that must be 
recognized and eliminated before such a step can take place. By comparing 
different methods of data analysis with the same group of patients, we have 
identified some of these weaknesses, attempted to develop a more useful tech- 
nique of data analysis with more meaningful and stable output and to use this 
technique to study how appropriate typological diagnostic concepts are to the 
nature of psychiatric disorder. 

Proposed Course of the Project : The work completed has been prepared for 
publication. Further efforts continue along two major directions: (1) the use 
of different techniques to define more of the problem areas and to develop 
more satisfactory methods for grouping patients; (2) an alternate direction, 
the developing of dimensions of psychiatric function for Identifying psychiat- 
ric patients rather than attempting to place patients into discrete groups. 

Publications : Bartko, J. J., Strauss, J. S. , Carpenter, W. T., Jr.: 
An evaluation of taxometric techniques for psychiatric data. Classification 
Society Bulletin , 2(3), 1971. 

Presentations : Diagnostic Models and the Nature of Psychiatric Disorder. 
Invited paper presented at the Annual Meeting of the Classification Society, 
Chicago, April 24,25, 1972, by John S. Strauss, M.D. 



56 



Serial No. M-AP(C)-16-5 

1. Adult Psychiatry Branch 

2. Psychiatric Assessment Section 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Serum Enzymes in Acute Psychotic States 

Previous Serial Number: M-AP(C)-16-5 

Principal Investigators: John S. Strauss, M.D.; Herbert Meltzer, M.D.; 

William T. Carpenter, Jr., M.D. 

Man Years : 

Total: 0.2 
Professional: 0.1 
Others: 0.1 

Project Description: 

Objectives : In an attempt to determine relationships between 
biochemical findings and psychotic conditions. Dr. Meltzer has demonstrated 
that creatine kinase and serum aldolase levels are often elevated in acute 
psychotic states. The objective of this project is to determine more 
precisely in which psychotic conditions these enzymes are elevated. By the 
use of standardized diagnostic interviews to obtain information on a wide 
variety of symptoms and environmental conditions it will be possible, using 
a sample of patients to define more clearly the correlations of individual 
symptoms with enzyme elevations. It will be possible in this way to evaluate 
how reliably these enzyme methods differentiate schizophrenic patients from other 
psychotic and borderline conditions. 

Methods Employed : A series of patients is being interviewed using 
standardized mental status, history and social description interviews. 
Blood is drawn at the time of the mental state interview and analyzed employing 
methods currently in use by Dr. Meltzer for determining serum aldolase and 
creatine kinase. 

Major Findings ; An initial sample of patients has been tested with the 
techniques described and preliminary findings suggest that degree of 
"cognitive disorganization" as defined by a group of mental status items, 
correlates more closely than other parameters with elevated enzyme levels. 

Significance to Mental Health Research and Program of the Institute : 
There is much interest in determining whether schizophrenia and other psycho- 
tic conditions can be related to particular biochemical and other physiological 
measures. Although there is some evidenze for such relationships in regard 

57 



Serial No. M-AP(C)-16-5 

to certain affective psychoses, evidence for similar relationships in schizo- ■ 
phrenia is mere controversial. Dr. Meltzer has been able to demonstrate ■ 
relationships between creatine kinase and serum aldolase in psychotic condi- ■ 
tions but it is not clear yet to what extent elevations in these enzymes are 
related to (1) the acuteness of the psychotic conditions, and (2) particular 
clinical pictures. In the present study, it will be possible to help clarify 
some of these relationships as well as to evaluate by replication Dr. Meltzer 's 
earlier work. 

Proposed Course of the Project ; A larger series of patients is being 
evaluated. On completion of the data collection, sjTuptom patterns will be 
compared to the results of the enzjnne determinations to see whether a 
meaningful relationship exists. 



58 



Serial No. M-AP(C)-16-6 

1. Adult Psychiatry Branch 

2. Psychiatric Assessment Section 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Psychiatric History Study: The Nature and Reliability of the 
Data 

Previous Serial Number: M-AP(C)-16-6 

Principal Investigators: John S. Strauss, M.D., William T. Carpenter, Jr., M.D. 

Other Investigators: Ruth E. Boesman, R.N. 

Cooperating Units: John Bartko, Ph.D., Biometrics Branch, Nursing Units, 
4-E, 4-W, 3-E, 3-W, NIH, Clinical Center 

Man Years : 

Total: 0.1 
Professional: 0.07 
Others: 0.03 

Project Description: 

Objectives : (1) To identify different types of data ordinarily obtained 
in psychiatric history interviewing. (2) To study the reliability for these 
data as obtained from the patient compared to that obtained from his relative. 
(3) To study the effect of when in the course of hospitalization data is ob- 
tained on the nature of the data elicited. (4) To learn how psychiatric 
history is obtained in various psychiatric settings. These data will be used 
to examine the hypothesis that there is a greater variability in psychiatric 
history information than is usually expected and that the nature of the data 
obtained relates to the degree of variation. 

Methods Employed : Standardized psychiatric history and social description 
interview schedules developed for the International Pilot Study of Schizophrenia 
were utilized in interviewing. The first 20 admissions to one of the psychia- 
tric nursing units who also had relatives available as informants were inter- 
viewed. The patient and relative were interviewed within one week of admission 
and again six weeks later. The same interview schedules were used in each 
interview and the interviewing was rotated between the three investigators 
listed above in an effort to keep the interviewer as naive as possible to 
patient information other than that obtained during the interview. 

A questionnaire was sent to a large number of facilities that admit 
psychiatric patients in the United States. This questionnaire requested 



59 



Serial No. M-AP(C)-16-6 

information about who interviews whom and at what time to obtain psychiatric 
history information. Data has been collected from 20 patients and their 
relatives and is being analyzed to determine reliability. Narrative summaries 
of the interviews and certain key items are being examined by the investigators 
in order to determine comparability of the less structured aspect of psychiatric 
history evaluation. 

Major Findings ; Results show that data obtained by structured questions 
is most reliable. Several areas of data such as duration of illness, acuteness 
of onset and precipitating factors have low reliability. These findings chal- 
lenge the validity of many concepts of psychiatric disorder that are based on 
results from unstructured collection of these data. 

Significance to Mental Health Research and the Program of the Institute : 
The relationship of past experience to present behavior is fundamental to most 
psychological theories of behavior and mental function. There is a paucity 
of data testing the reliability and validity of background information obtained 
from psychiatric patients and their families. This study will attempt to 
identify the various means of collecting past history from psychiatric inpa- 
tients in various settings and to identify the pitfalls involved in interpret- 
ing this information. 

Proposed Course of the Project : The findings are being prepared for 
publication. 



60 



Serial No. M~AP(C)-16-7 

1. Adult Psychiatry Branch 

2. Psychiatric Assessment Section 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: The Evaluation of Outcome in Schizophrenia 

Previous Serial Number: None 

Principal Investigators: John S. Strauss, M.D. 

William T. Carpenter, Jr., M.D. 

Man Years: 

Total: 1.1 

Professional: 0.8 

Other: 0.3 

Project Description: 

Objectives ; (1) To describe the characteristics of outcome in schizo- 
phrenia. (2) To study the predictors of outcome in schizophrenia including 
premorbid history, social background, duration of illness, diagnosis, and 
symptomatology. (3) To use outcome measures as means for evaluating the 
validity of different diagnostic systems. 

Methods Employed : Two-year follow-up results from the patients seen by 
the staff of the Psychiatric Assessment Section for the International Pilot 
Study of Schizophrenia (M-AP(C)-16-1) were rated with scales developed for 
the study. These outcome results were compared with patient diagnoses as de- 
termined by the criteria of the Diagnostic and Statistical Manual of the APA, 
Kurt Schneider's first rank symptoms, and Langfeldt's criteria for true 
schizophrenia. Outcome results were also compared with individual symptoms and 
sixteen items rating areas of premorbid functioning. 

Major Findings : Results showed that outcome itself is not a unitary 
concept, but consists of at least four dimensions: social functioning, sjrmp- 
tomatology,need for hospitalization, and ability to work. Each of these 
variables was independent enough from the others to suggest that outcome 
represents an open-linked system comprised of several semi-independent variables. 
This view of outcome was further supported by the fact that each area of outcome 
was best predicted by the corresponding area of premorbid function: outcome 
social function by premorbid social function, outcome symptoms by previous 
duration of symptoms, outcome need for hospitalization by previous hospitaliza- 
tion, and outcome ability to work with previous ability to work. On the other 
hand, none of the diagnostic systems or individual sjmiptoms were able co predict 
outcome to a significant degree. Together, these findings suggest that outcome 

61 



% 



Serial No. M-AP(C)-16-7 

( 
is far more determined by longitudinal dimensions of function than by particular 
sjrmptoms or sjiaptom patterns. 

Significance to Me ntal Hea lth Research and the Program of the Institute ; 
There has been much doubt whether certain symptom patterns are adequate to define 
psychiatric "diseases" with predictable outcomes. Such a conception would imply 
a concept of psychiatric disorder very similar to many medical-surgical illnesse 
The current study suggests that this conception of psychiatric disorder is in- 
correct and that the major determinants of outcome are enduring personality 
structures rather than a particular "disease" process. This implies that the 
causes and treatments for prolonged disability might best be aimed at personality 
variables rather than at a supposed disease process. 

P roposed Course of the Project ; The initial sample of 140 patients is 
being augmented by addition of the patients admitted to the 4-East clinical- 
research ward. More intensive investigation into the functional determinants 
of outcome will be carried out to understand the outcome process more clearly. 

Publications ; Strauss, J.S.; Carpenter, W.T., Jr. The Evaluation of 
Outcome in Schizophrenia, To be published in Life History Research in Psycho- 
pathology, Vol. 3. Edited by Thomas, A., Roff, M. , and Ricks, D.F. University 
of Minnesota Press , Minneapolis . 

Presentations ; Presented by John S. Strauss, M.D. 

1. The Fate of Schizophrenic Patients , presented at the Annual Meeting of the 
Mental Health Career Development Program. New Orleans, March 1972. 

2. The Evaluation of Outcome in Schizophrenia , presented at the annual meeting 
of the Society for Study of Life History and Psychopathology. New York, April 
14-15, 1972. 

3. Diagnostic Criteria and Outcome in Schizophrenia , presented at the annual 
meeting of the American Psychiatric Association. Dallas, May 1-5, 1972. 



62 



C 

i 



Serial No. M-AP(C)-16-8 

1. Adult Psychiatry Branch 

2. Psychiatric Assessment Section 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Psychobiology of Cortisol Metabolism 

Previous Serial Number: None 

Principle Investigator: William T. Carpenter, Jr., M.D. 

Other Investigators: William E. Bunney, M.D., John S. Strauss, M.D., 
Laurence Drell , M.D. 

Cooperating Units: Section on Psychiatry, Laboratory of Clinical Science, 
Section on Cognitive and Perceptual Studies, APB 

Man Years: 

Total: .2 
Professional: .15 
Other: .05 

Project Description : 

Objectives : (1) To utilize sophisticated techniques for determining 
metabolism of Cortisol in psychiatric patients. (2) To evaluate manic- 
depressive patients with a battery of investigations that provide comprehensive 
information regarding their Cortisol metabolism. (3) To investigate the re- 
lationship between Cortisol metabolism, psychophysiology, and psychopathology. 
(4) To determine if Cortisol variability relates to schizophrenic diagnostic 
subgroups or outcome. 

Methods Employed : Radioisotope dilution methodology was used to determine 
production rates and metabolic clearance rates of Cortisol. Plasma concentra- 
tion at various hours of the day and 24-hour urinary output of Cortisol was 
determined with routine laboratory procedures. 

Standardized clinical assessment techniques are now being employed to give 
detailed clinical information to relate to steroid variability. Perceptual and 
cognitive test procedures are being carried out in collaboration with 
Dr. Buchsbaum. 

In a cohort of depressed patients, it was determined that central mech- 
anisms controlling Cortisol metabolism functioned abnormally. The mechanisms 
which determine response to dexamethasone suppression, methopyrapone stimula- 
tion, ACTH stimulation and circadian rhythm were intact in depressed patients. 
However, determining metabolic clearance rates and production rates of Cortisol 

63 



SeriP.l No. M«AP(C)-16-8 

suggests that depressed patients produce more Cortisol and metabolize it more 
rapidly, while maintaining normal plasma concentration. On recovery, these same 
patients reduce their production rates while maintaining an abnormally high 
metabolic clearance rate, and, consequently, reduced plasma concentration. 
These findings suggest two interesting possiblities : (1) That psychological 
and biological effects of rapid turnover of Cortisol may be critical in de- 
pressive illness; and (2) the finding of reduced plasma concentration and 
production rate on recovery v^lle an increased clearance rate is maintained, 
suggests the possibility that relative adrenal insufficiency may be related to 
the biological vulnerability to depression. 



Significance to Mental Health Research and the Program of the Institute : 
The results of this work have focused attention on the need for sophistication 
in technical approaches to Cortisol research in psychiatry. Static measures 
alone (e.g., plasma concentration for 24-hour excretion rate) may be misleading 
about the physiologic activity of Cortisol. Findings to date require a re- 
consideration of Cortisol metabolism regarding manic-depressive disorders. The 
possibility of relative adrenal insufficiency in depressive disorders reopens 
an area of research which has been dwarfed by the number of findings based on 
static measures suggesting either normal or Increased adrenal function with 
depressive Illness. If there is a biological vulnerability based on adrenal 
insufficiency, this may be obscured by stimulated Cortisol production during 
the distress of depressive illness. Studying patients during recovered, low 
stress periods provide an opportunity to identify basic biological dispositions. 

Proposed Course of Project : Studies of Cortisol metabolism are being 
incorporated into the 4-East clinical unit's research program. In keeping with 
the major thrust of the work on 4-East, there will be careful attention to the 
clinical variables related to altered steroid metabolism and the possibility 
of using biological variables such as steroid metabolism as validating criteria 
to test classifcation systems. The relationship between steroids, psychopath- 
ology and psychophysiology will be investigated in collaboration with the 
Section on Perceptual and Cognitive Studies, APB. 

Honors and Awards: None 

Publications: 

Carpenter, W. T., Jr., Bunney, W. E.: Adrenal Cortical Activity in 
Depressive Illness, Amer. J. Psychiat . 128 : 31-40, 1971. 

Carpenter, W. T., Jr., Bunney, W. E.: Dirunal Rhythm of Cortisol in 
Mania, Arch. Gen. Psychiat . 25^: 270-273, 1971. 

Carpenter, W. T., Jr., Bunney, W. E.: Behavioral Effects of Cortisol 
in Man, Seminars in Psychiatry 3: 421-434, 1971. 

Carpenter, W. T., Jr., Strauss, J. S., Bunney, W. E.: The psychobiology 
of Cortisol Metabolism: Clinical and Theoretical Implications, to' be published 
in Psychiatric Aspects of Medical Drugs , R. I. Shader (ed.). Raven Press, 



I 



6k 



Serial No. M-AP(C)-16-8 

Presentations: 

The Serotonin Depletion Hypothesis in Depressive Disorder, presented by 
Dr. Carpenter to the Tenth Annual Conference of the Mental Health Career 
Development Program, Tucson, Arizona, 1971. 



65 



Serial No. M-AP(C)-16-9 

1. Adult Psychiatry Branch 

2. Psychiatric Assessment Section 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 



Project Title: Research Interviews: Are They Valid? 

Previous Serial Number: None 

Principal Investigators: Michael H. Sacks, M.D. 

John S. Strauss, M.D. 



William T. Carpenter, Jr., M.D, 



Man Years : 




Total: 


.2 


Professional: 


as 


Other : 


.05 



Project Description: 

Objectives : To test the validity of structured mental status interviews 
used for research and clinical purposes. 

Methods Employed : Twenty patients admitted to a research unit for acutely 
psychotic patients were interviewed within the first week of admission using 
the Psychiatric Assessment Interview (PAI), a modification of the Present State 
Examination (PSE) used in the International Pilot Study of Schizophrenia. Two 
weeks after admission, the patient's psychiatrist filled out a PAI schedule 
utilizing information obtained from the patient, family, spouse, nursing staff, 
etc. The initial evaluation interview and the schedule completed on the basis 
of all information available was then compared. 

Major Findings : (1) The ratings on the two week PAI generally described 
more pathology than those from the initial PAI. (2) This difference was 
especially marked for observed behavioral data (signs) and minimal for reported 
symptoms. (3) Patient classifications based on the two interviews were iden- 
tical for each patient if a diagnostic system such as Kurt Schneider's symptoms 
as criteria were used. For those systems such as cluster analysis depending 
more on both signs and symptoms, patient classification often changed markedly 
from the initial to the second interview. (4) Diagnostic categories such as 
catatonic schizophrenia which are most dependent on behavioral ratings were 
especially likely to change when initial interview and the second schedule 
were compared. 

Significance to Mental Health Research and the Program of the Institute : 
Structured mental status interviews have become a major instrument in studies 

67 



Serial No. M-AP(C)-16-9 



of psychiatric patients. They have been used» for example, as basic data col- 
lection instruments, the International Pilot Study of Schizophrenia and the 
United States-United Kingdom Study of Psychiatric Disorder. With structured 
interviews of demonstrated reliability, large amounts of data accumulated by 
different psychiatrists at different centers can be collected and compared. 
However, the degree to which these interviews provide data that accurately 
reflects all information available about the patient's current psychiatric 
status has not previously been evaluated. The results of the present study 
suggest that for certain diagnostic systems and certain psychiatric conditions 
such mental status interviews are very adequate, but for these diagnostic 
system.s or psychiatric conditions depending more on observed behavior, results 
from strucured interviews must be accepted with reservation. 



Serial No. M-AP(C)-16-10 

1. Adult Psychiatry Branch 

2. Psychiatric Assessment Section 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: The Recovery Process and Research Data in Acute Psychosis 

Previous Serial Number: None 

Principal Investigators: Michael Sacks, M.D. 

William T. Carpenter, Jr., M.D. 
John S. Strauss, M.D. 

Man Years: 

Total: .2 

Professional: .18 

Other: .02 

Project Description: 

Objectives : (1) To define the different phases of the psychotic process 
as the patient moves from severe decompensation toward recovery. (2) To 
describe the kinds of research Investigations the patient is able to par- 
ticipate in as he passes through these phases, and the implications of this 
phasic process for interpreting results of research on psychosis. 

Methods Employed : Acutely psychotic patients were observed during the 
course of their Illnesses as they participated or failed to participate in 
different research projects. Independent behavior ratings were compared with 
the patients' research performances. These observations were supplemented 
by interviews with the patient, held prior to discharge, regarding his views 
on the research procedures. 

Major Findings : Distinct phases of patient's illness have been identified. 
The three phases are: (1) The out-of-contact phase during which patients 
typically were unaware of research expectations. Thought processes are 
fragmented and delusional. During this time the patient is unavailable for 
any kind of research that involves active cooperation with another person or 
cognitive engagement in a task. (2) Double-awareness phase during which 
the patient is still delusional, but has become aware of the ward research 
program. A capacity for insight of his symptoms has begun and the patient 
begins to modify his behavior despite severe symptoms. Participation and 
cooperation in complex research tasks, although tedious, are now possible 
even though delusional interpretations of procedures may suggest a danger 
to the patient and. In fact. Influence the way in which he takes the test. 
(3) The recovery phase during which the patient is able to realistically perceive 
and evaluate the research and his participation in it comes with significant 
clinical improvement. When the patient fails to cooperate In research procedures, 



Serial No. M-AP(C)-16-10 



1 

nit I 

I 



he has clear reasons for refusing— which reflect his attitude toward the un 
or his doctor. Themes about the research which were present in delusional 
form during earlier phases may continue, but are now expressed more 
rationally in a therapeutic relationship. Research that can be carried out is 
restricted by the phase through which the patient is passing. In the more 
disturbed phase, no information is obtainable about either response or other 

5S reqi 

spects 



aisturoea pnase, no inrormation is obtainable about either response or other ■ 
measures requiring active collaboration of the patient; as the patient improves* 
more aspects of his function can be evaluated. ■! 

I 



Significance to Mental Health Research and the Program of the Institute : 
The major focus of experimental research on psychosis in the past has 
often been on chronic patients. Only recently has greater attention been 
directed toward the acute patient. This study attempts to define phases of 
the acute process and to demonstrate their interrelationship to the research 
findings and conclusions that can be drawn from them. Identifying the psycho- 
logical set during collection of data provides a framework for interpreting 
results which enriches the disease model or simple behavioral rating approach. 



TO 



Serial No. M-AP(C)-16-11 

1. Adult Psychiatry Branch 

2. Psychiatric Assessment Section 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Investigation of the Schizophrenic Process Through Art 
Productions of Acutely Psychotic Patients 

Previous Serial Number: None 

Principal Investigator: Harriet Wades on 

Cooperating Unit: 4-East Nursing Unit, Clinical Center, NIH 

Man Years : 

Total: 0.6 
Professional 0.5 
Other: 0.1 

Project Description: 

Objectives ; (1) To obtain art productions from acutely psychotic patients 
at intervals during the course of their hospitalization and follow-up. (2) To 
utilize the art productions in conjunction with other clinical assessments for 
the purpose of diagnosis. (3) To compare and study the art productions and the 
patients' associations to them in order to gain a greater understanding of the 
schizophrenic process by: (a) investigating longitudinal changes by comparing 
pictures made during acute psychosis, recovery, and follow-up; (b) studying, 
in detail, delusions, hallucinations, and other manifestations of schizophrenic 
thinking as revealed in the art productions; (c) comparing art productions of 
different patients with one another in order to delineate subgroups of schizo- 
phrenic ideation; (d) contrasting the art productions of schizophrenic patients 
with those of manic and depressed patients. 

Methods Employed ; All patients on a research ward for the study of acute 
schizophrenia are evaluated in individual art therapy sessions shortly after 
admission, just prior to discharge, and at follow-up. Some patients have add- 
itional sessions during the course of hospitalization if there is marked change 
in the patient's condition. Patients are provided with simple media and en- 
couraged to express themselves freely and to free associate to their pictures. 
At each session they are requested to make three pictures: (1) whatever they 
want to draw; (2) a self portrait; (3) a picture of the illness. If there is 
indication that a patient is hallucinating or has in the past, he is asked to 
make a picture of it. If there are other pictures that patients particularly 
want to produce, either during the session or at another time, they are encour- 
aged to do so and to discuss them with the investigator. To date 18 patients 



71 



i 



Serial No. M-AP(C)-16-11 

have been studied. Each session is recorded on audiotape and a suirrmary is 
written by the investigator. 

Ma.jor Findings: Although it is too early to report any solid findings, 
certain trends have appeared which are being studied further. The parameter 
of organization in the pictures seems to be particularly revealing of intra- 
psychic states. The changes in balance between richness and impoverishment 
in the pictures (the latter is often indicative of depression [H, Wadeson, 
Characteristics of Art Expression]) both within the same patient and among 
patients provides important data on the process of the illness. Changes in 
self-concept during the course of psychosis and recovery and differences in 
self-concept among patients is an important discriminator. Pictures of hal- 
lucinations, delusional systems, and other manifestations of schizophrenic 
functioning are extremely useful in furnishing greater understanding of the 
patient's experience of his psychosis. 

Significance to Mental Health Research and the Program of the Institute; 
There is little data of a comparative nature on the art productions of any 
particular population. Most of the writing in this area is directed toward 
therapeutic benefits rather than diagnosis and evaluation. Where such reports 
exist, they are primarily speculative and do not report characteristics of a 
designated population that has been studied systematically. The purpose of 
this project is to help counter this lack. In a broader sense, although the 
outward manifestations of acute schizophrenia are readily studiable, (symptoms, | 
progress, etc.) the inner experience of the affected individual is much less 
accessible. Hopefully, this investigation will provide data in this area. 
Finally, in conjunction with other parameters of assessment, it is hoped that 
the data obtained from the art evaluations will add to the clarity of differ- 
ential diagnostic dimensions in acute schizophrenia. 

Proposed Course of the Project : During the coming year the sample will 
be enlarged and the developing trends investigated systematically. Also, new 
trends will be noted and studied. In addition, the data from this project will 
be compared with data from art productions of manic and depressed patients, of 
which the investigator has accumulated an abundance on past projects. 

Publications ; 

Wadeson, Harriet: Characteristics of Art Expression in Depression. J. Nerv. 

Ment. Pis. , 153(3), Sept. 1971. 
Wadeson, Harriet, Fitzgerald, Roy: Marital Relationship in Manic-Depressive 

Illness: Conjoint Psychiatric Art Evaluations. J. Nerv. Ment. Dis. , 153 (3), | 

Sept. 1971. ■ 

Wadeson, Harriet: Conjoint Marital Art Tlierapy Techniques. Psychiatry . Feb. 

1972. 
Wadeson, Harriet: Portraits of Suicide. Publication of exhibit. Annual Meeting, 

American Psychiatric Association, Washington, D.C., May 1971. 

Awards : Rush Bronze Medal Award 



72 



Serial No. M-AP(C)-17-1 

1. Adult Psychiatry Branch 

2. Section on Personality Development 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: A Study of Problems in Growth and Adaptation in the 
Personality Development of the Adolescent 

Previous Serial Number: None 

Principal Investigator: Roger L. Shapiro, M.D. 

Other Investigators: Carmen Amoros-Cabrera, M.S.W.; Carl Feinstein, M.D. ; 
Stuart Hauser, M.D. ; Richard MacDonald, M.D. ; 
Winfield Scott, Ph.D.; Robert Winer, M.D. ; and 
John Zinner, M.D. 

Cooperating Units: Unit 3-West 

Man Years 

Total: 3.9 
Professional: 3.3 
Other: .6 

Project Description: 

Objectives . Our investigation of personality development in the 
individual adolescent focuses upon study of the family group and the social 
group of which he is a part. We assume that there is a correspondence 
between the structure of the individual personality system and the structure 
of external reality which has impinged on that personality throughout 
development, especially the social system and its subsystems. Personality 
theory generally relies heavily on the individual's account of his own 
developmental experience in interpersonal, family, and group situations, 
to understand his personality formation and functioning. In our program 
of research we observe directly the individual adolescent in interaction 
with his family group and social group. These observations provide an 
objective measure against which to assess the individual's statements about 
his own experience. Such observations are a necessary step in verification 
of theory postulating social determinants of personality functioning. In 
addition, such observations clarify the individual's psychological meaning 
to significant others. This is crucial to understanding their behavior 
towards him and its effect upon his psychological functioning. 

Methods . Our early studies of adolescents in emotional crises over 
separation from their families included psychotherapy of hospitalized 
adolescents and research interviewing and psychological testing of the 
adolescent and his parents separately. A comparison group of adolescents 

73 



Serial No. M-AP(C)-17-1 

1. Adult Psychiatry Branch 

2. Section on Personality Development ' 

3. Bethesda, Maryland 

who were developing normally was studied in individual interviews and 
family interviews. A difference was found between patient families and 
normal families in the capacity to tolerate autonomous behavior in the i 
adolescent and none-the-less maintain relatedness to him; that is, the i 
patient families manifested difficulties in these areas while the normal 
families did not. 

We noticed repeated discrepancies in the patient families between 
the adolescent's statements about parental attitudes towards his 
independent functioning and the parents' own statements of attitude toward 
independent behavior in the adolescent. We became interested in these 
discrepant views and in order to investigate them further, began to study 
the adolescent and his parents in interaction. We added conjoint family 
therapy to our treatment program. We could now observe directly transactions 
between adolescent and parents. This has remained a major focus of our 
study. We have developed methods for defining characteristics of parent- 
adolescent interaction and formulating the relation of these behaviors to 
the identity problem of the adolescent. We define characteristics of the 
boundary between the family and the individual adolescent. We find a 
relation between this and the nature of self boundaries which have developed 
within the adolescent. In addition, we consider how characteristics of 
self boundaries in the adolescent determine the role boundaries he establishes \ 
in new interpersonal and group situations. 

The unique feature of our research is the design and conduct of a 
program in which, in addition to intensive individual study of the adolescent, 
he is studied within his family group and in his role behavior in a group 
situation in the treatment unit or (in the case of our normal sample) in 
the school. For the past two years our psychiatric unit has had an 
entirely adolescent population which has greatly facilitated our ability 
to study the role the adolescent takes in peer relations and authority re- 
lations in the group life of the residential treatment unit. 

During the past four years we have worked with normal adolescents at 
the Sidwell Friends School in Washington. For purposes of comparison, we 
have studied these adolescents in situations similar to those in which we 
study disturbed adolescents. We have seen them in individual research 
interviews, in family study groups with their parents, and in weekly 
groups studying peer relations and authority relations in the school setting, i 

The adolescents we have hospitalized in our treatment unit have been 
between ages 14-21 with a wide range of disorders. These have included 
adolescents manifesting a variety of behavior disorders including school 
and work failure, drug problems, sexual disturbances, running away, and 
other kinds of antisocial acting out; we have also studied adolescents 
with neurotic disturbances manifested by anxiety symptoms and depression. 



Serial No. M-AP(C)-17-1 

as well as adolescents with borderline disorders or psychoses. We have 
treated these adolescents and their families for periods ranging from 
6 months to 2 years, first as inpatients, later as outpatients. 

Our residential treatment program includes individual psychotherapy 
for the adolescent, conjoint family therapy, and study of the hospital 
group in which the adolescent lives and works. It combines three hours 
per week of individual psychotherapy for the adolescent with a weekly 
one-hour conjoint family therapy session; one hour per week of marital 
therapy for the parents; and four patient-staff meetings per week, including 
one which is a study group examing peer relations and authority relations 
on the psychiatric unit. This program has evolved over the past 12 years 
during which time increasing integration of the functions of study and 
treatment has occurred. We have designed the program to study situations 
which articulate the psychological maturation of the individual adolescent 
with hisexperience within his family, within his peer group, and within 
the social institution of which he is a part. 

We define the following tasks which we implement within the program: 

(1) To explore and modify the internalizations of childhood experience 
which have rendered the adolescent's ego vulnerable and unable to develop 
relative autonomy and individuation. This is the task of individual 
psychotherapy . 

(2) To explicate and modify the actuality of current family dynamics 
which are interfering with adolescent individuation and separation. This 
includes clarification of the nature of the boundary between the parents 
as a marital pair and the adolescent. This is the task of conjoint family 
therapy and marital therapy. 

(3) To study and modify the adolescent's functioning in a new 
social organization away from the family in which he has the opportunity 
to develop a more mature and responsible relationsHjp to peers and to 
authority figures than was present in his family relations. This is the 
task of the unit study group. 

The task we define for the individual psychotherapy situation includes 
study of the internalizations of the adolescent through his projections 
in the transference. In our patients these internalizations interfere with 
capacities maturing in the adolescent for making new relationships outside 
of the family. We define characteristics of the adolescent's internal 
objects which militate against new relationships through engendering anxieties 
over separation, sexual anxieties, or anxieties deriving from deficient 
models for adult roles and relationships. These characteristics of inner 
objects are externalized in transference phenomena and their study is a 
central task in the work of psychotherapy. 



75 



Serial No. M-AP(C)-17-1 

The integration of individual psychotherapy with family therapy 
includes study of the correspondence between transference phenomena in 
individual therapy and the actual current parent-adolescent relationship 
family therapy. 



1 

cond Hi 



We utilize the conjoiiit family therapy situation to implement the se 
task defined above, that of explicating and modifying the actuality of 
current family dynamics which are interfering with adolescent individuation 
and separation. The boundary between the individual adolescent and his 
family as a group is studied. We conceptualize transactions across this 
boundary through use of the concept of delineation and through a related 
concept, that of unconscious assumptions in the family as a group. 

Delineation is a concept closely linked to observable behavior. We 
define as delineations, behaviors through which one family member communicates 
explicitly or implicitly his perceptions and attitudes — infact, his mental 
representation of another family member — to that other person. Through use 
of the concept of delineation we make formulations involving three levels 
of inference from observations of family interaction. A first level of 
inference is that specified behaviors in one person imply a particular 
delineation of the other person. 

A second level of inference is about the determinants of delineation. 
Delineations may communicate a view of the other person which appears to 
be predominantly determined by his reality characteristics. However, in 
the families of disturbed adolescents we find that delineations frequently 
communicate a view of the other person which is predominantly determined by 
mobilization of anxiety and defense in the delineator. We call these 
defensive delineations. We pay particular attention to the parents' 
defensive delineations of the adolescent. When parents' delineations are 
observed to be distorted, stereotyped, and over-specific, contradictory, 
or otherwise incongruent with the range of behaviors manifested by the 
adolescent, we make the inference that these delineations serve defensive 
aspects of the parents' personality functioning. That is, they are not 
simply realistic responses to the current characteristics of the adolescent 
but are behaviors through which parents defend against anxiety. We find 
that these parents, through their defensive delineations, seek to hold the 
adolescent in a relatively fixed role which serves to mitigate their own 
anxiety. Projective identification is of central importance as a mechanism 
of defensive delineation. 

In addition, we make a third level of inference, that of characteristics 
of the family group as a whole. From excerpts of family interaction 
containing defensive delineations, we accrue evidence of shared or comple- 
mentary characteristics of the family as a group and of the unconscious 
determinants of these characteristics. We consider coordinated, shared 
complementary behavior in the family to be evidence of a level of unconscious 
fantasy and defense in the family group organized around particular 
unconscious assumptions. 



76 



Serial No. M-AP(C)-17-1 

The third task defined above is that of study and modification of the 
adolescent's functioning in a new social organization away from the family 
in which he has the opportunity to develop new roles and a new relationship 
to peers and to authority figures. The situation we have developed in our 
program for implementation of this task is the Unit Study Group. This is 
an intergroup meeting consisting of all of the patients, the chief psychiatric 
nurse representing the nursing staff, the unit administrator representing 
the individual and family therapi.?ts, and the clinical director representing 
the research project chiefs and senior psychiatric staff. The task of this 
meeting is study of authority relations and peer relations in the group 
life of the psychiatric unit. This is not a decision-making meeting, but 
one in which the dynamics of roles and role relationships are studied, 
including attitudes toward those in authority roles. The work of the meeting 
is the examination of roles individuals take or are put into by the group 
in the hospital with whom they live and work. A whole range of issues of 
group life in the hospital are discussed in the meeting. In particular, 
phenomena defining the boundaries of the self are attended to in the group, 
the roles taken by the patients and the new roles which evolve in their 
relations with each other and with authority. 

In a new investigation. Dr. Robert Winer is continuing his study of 
the use of mind-altering drugs by youth in a multi-faced research project. 
Relying primarily on interview data, he is explaining the meaning of 
drug use to adolescents and to their families. The study is at present 
proceeding on four fronts, with a fifth area to be investigated in the 
future. 

Three of the sub-studies focus on the hospitalized adolescent population. 
While drug use was not a criteria for admission to the ward, two-thircfe of 
the patients have made extensive use of "street-drugs" prior to their 
admission here. The first sub-study consists of interviews with each of 
in-patients in which the primary focus is on motivational aspects of their 
drug use. Clear patterns of social and interpsychic determinants of drug 
use are becoming apparent, and it appears that the more disturbed adolescents 
primarily used drugs in attempts to resolve internal, rather than external, 
conflict. The impact of the adolescents' peer mileau, both prior to and 
during hospitalization, on their attitudes about drug use is significant. 
Normative peer expectations provide a baseline for adolescents from which 
they judge their own behavior. 

The second sub-study involves interviews of these adolescents with 
their families. As these families are also seen weekly in ongoing family 
therapy, data from the research interviews will be correlated with material 
obtained from family therapists. In these interviews areas focused on 
include the family members' attitudes and fantasies about drug use, and 
the families' past and present modes of responding to the adolescent's 
known or suspected drug use, including modes of response within the research 
sessions. It is becoming clear that the parents' own conflict over drug 
use finds expression in the adolescents' behavior; that conflict over 
drug use becomes a focal point in the family for the negotiation of broader 

77 



Serial No. M-AP(C)-17-1 



m 



family conflicts; and that, more specifically, a frequently found conspiracy 
of silence in the family on the drug use issue reflects the family's abortive 
efforts toward integration. 

The third sub-study examines the adolescents' experience with their 
pro~tem family, the psychiatric staff, in working through conflict over 
drug use. Patterns observed in the family sub-study are also seen in this 
arena. Since the psychiatric staff is committed to the fact of finding 
constructive means for dealing with drug use, it is possible to explore 
the interaction of the adolescents' attitudes, values, and behavior with 
those of the staff. 

A fourth sub-study is explaining motivational aspects of drug use in 
a group of late adolescents and young adults who have made extensive use 
of mind-altering drugs , but who have not sought or received psychiatric 
help. While the importance of intrapsychic, as opposed to social deter- 
mination of drug use is important here, as in the hospitalized group, the 
specific nature of the determinants appear to differ, being apparently 
more related to the working through of appropriate life stage conflicts 
than to the resolution of neurotic conflict. 

Finally, an anticipated sub-study will investigate data obtained 
in group meetings with non-hospitalized youths who have made extensive 
use of drugs. The emergence of group attitudes, and their impact on 
individual members will be explored. 

Major Findings . The methods of observation and inference which have 
been described are utilized to define in each of our adolescent patients 
the characteristics of his internal psychological boundaries and the 
relation of these to characteristics of the boundaries between the individual 
adolescent, his family, his peers, and authorities in the institution 
in which he lives. We find in examining the boundary between the adolescent 
and his family that parental delineations of the adolescent are determined 
by defensive needs in the parents rather than by realistic perceptions of 
the adolescent. These defensive needs in the family are the key to 
formulations of the unconscious assumptions of the family as a group. 

We find in the unit study group that patients tend to repeat roles 
they have taken and are taking in their families . In the work of the 
group we examine this phenomenon and explore with the adolescents the 
degree to which new possibilities in role behavior are available to them 
in relation to peers and to people in authority roles in the institution. 
We find the range of role behavior limited and difficult to change in the 
patient group. They are an extremely dependent group. They manifest a 
range of responses of anxiety, rage, suspiciousness and fear of exploitation 
in relation to authority. These responses prove to be highly resistant to 
change. In contrast we find in the group of normal adolescents in the 
classroom study group at Sidwell Friends School greater capacity to take 
and maintain work leadership in the group and to cooperate with authority. 



78 



Serial No. M-AF(C)-17-1 

They show more flexibility in role behavior, more capacity to experiment 
in the group, and less suspiciousness and anger. We are now beginning 
detailed comparisons of these group behaviors. 

Significance to Mental Health Research . This study now includes methods 
and findings for studying the adolescent peer group as well as studying 
the adolescent and his family. With these methods we will more fully 
comprehend adolescent personality development from the perspective of 
identity formation. Our findings thus far clearly indicate that the presence 
of impaired development of adolescent ego autonomy reflects impaired 
parental ego functions. We want to consider in what ways and to what extent 
the peer group can be used to alter and mitigate deleterious consequences 
of family relationships. We are interested in the implications of these 
findings both for the highly important task of deepening our understanding 
of disturbance in adolescence and for improving our techniques of therapy 
and rehabilitation. 

Proposed Course of Project. Next year we will introduce a more 
systematic study of the individual therapy of the adolescent himself. We 
want to expand the observations in individual therapy from which we infer 
the characteristics of the self boundaries of the adolescent. We also 
want to focus upon evidence of the individual's internalization of 
experiences in the family group and the unit study group as it is mani- 
fested in individual therapy. In addition, we will continue more detailed 
comparison of behavior of adolescents in the psychiatric unit study group 
and the classroom study group at Sidwell Friends School. We will also 
continue the study of adolescent drug use in the ways that have been discussed. 

Honors and Awards : 

Roger L. Shapiro, M.D. , Principal Investigator: 

Director of a Group Relations Conference, sponsored by The A. K. 
Rice Institute of The Washington School of Psychiatry, Amherst 
College, August 27-September 1, 1971. 

Senior Staff, Conference on Authority and Leadership, sponsored 
by the Centre for Applied Social Research of the Tavistock 
Institute of Human Relations, London. University of Leicester, 
England, April 5-18, 1972. 

Senior Staff, Group Relations Conference, sponsored by The A. K. 
Rice Institute of The Washington School of Psychiatry, Mount 
Holyoke College, June 3-16, 1972. 



79 



Serial No, M-AP(C)-17-1 

Presentations: 

Roger L. Shapiro, M.D. , Principal Investigator: 

"The Adolescent, the Family, and the Group: Boundary 

Considerations." Presented at the 17th Annual Chestnut 
Lodge Symposium, Rockville, Maryland, October 8, 1971, 
and at Tufts New England Medical Center, Boston, Massachusetts, 
December 16, 1971, 

Publications : 

Shapiro, R. L. Adolescence and the Family. In the Proceedings of 
the Ninth Annual Conference on The Handicapped Child. Alfred I. 
DuPont Institute, Wilmington, Delaware, 1971. 

Shapiro, R. L. and Zinner, J. Family Organization and Adolescent 
Development. Task and Organization , ed. Eric Miller. 
Tavistock Publications. In press. 

Zinner, J. and Shapiro, R. L. Projective Identification as a Mode 
of Perception and Behavior in Families of Adolescents. Int. J. 
of Psychoanalysis . In press. 



Serial No. M-AP(C)-17-2 

1. Adult Psychiatry Branch 

2. Section on Personality Development 

3. Bethesda, Maryland 



June 1, 1971 through June 30, 1972 

Project Title: Adolescent Ego Development in Normal Families 

Previous Serial Number: NONE 

Principal Investigator: Roger L. Shapiro j M.D. 

Other Investigators: Stuart Hauser, M.D. ; John Zinner, M.D. 

Cooperating Units: Sidwell Friends School, Washington, D. C. 

Man Years : 

Total: .7 
Professional: .6 
Other: .1 

Project Description: 

Objectives . This study attempts to specify some of the crucial 
determinants of identity formation in normal adolescents. We hypothesize 
that delineations of the adolescent by his family and his peer group 
provide much of the content of his self concept and that the manner in which 
the delineation is communicated will influence the way in which it is 
internalized. We further hypothesize that the adolescent will utilize 
peer group experience in an attempt to reorganize conflicting elements 
in his self concept which have derived from conflicting elements within 
his family. We hope to specify in detail in what ways peer group experience 
allows for development of new and innovative aspects of identity and in 
what ways it is conditioned and limited by past and' present family interactions. 

Methods Employed . During this year two classroom study groups were 
formed at Sidwell Friends School. These groups were composed of 10 students, 
ages 14-17, in the 9th to 12th grades of the Sidwell Middle School; a teacher 
and a principal, or dean; and Dr. Stuart Hauser as group consultant. The 
task of the group was to study authority relations and peer relations in the 
school, making observations about group formation, individual roles in the 
group, relations to authority in the group as we have with the Unit Study Group 
on the adolescent inpatient unit. Particular attention was paid to the 
capacity of these adolescents to define themselves verbally in relation to 
authority figures and peers. The range of attitudes toward self and others 
and capacity to tolerate differences and to work with the boundaries established 
by authority were foci of attention. Tne groups met for 13 weekly sessions 
of an hour. 

81 



Serial No. M-AP(C)-17-2 

Major Findings. In the Classroom Study Group far less anxiety and 
inhibition was seen in group function and activity than was seen in the 
Unit Study Group. The students were quickly highly verbal and involved in 
clearly defined ways. The principal and the teacher had difficulty 
representing their actual school roles in the group and still feeling 
a part of the group. Their presence focused much of the group's attention on 
authority relations although explicit discussion of attitude toward teachers 
and school administration was far less common than expression of implicit 
attitudes. The Classroom Study Groups demonstrate the feasibility of such 
groups in the Sidwell School setting. This is the second year of working 
with such groups, following last year's tliddle School Group, also done with 
Dr. Hauser, 

Significance to Mental Health Research . The study of peer relations 
and of family relations of normal adolescents provides a contrast to our 
studies of peer relations and of family relations of disturbed adolescents. 
This increases the precision of our formulations of the pathological 
processes in adolescent disturbance and thereby contributes to a better 
understanding of the etiology of adolescent personality disorder. At the 
same time the study provides data on the ways in which peer and school 
experience contributes to normal identity formation and thereby contributes 
to an understanding of normal development. 

Proposed Course of Project . We want to begin to analyze the develop- 
ment and processes within these groups in more detail, and in relation to 
our patient groups (the unit study group) . 



82 



Serial No. M-AP(C)-17-3 

Adult Psychiatry Branch 

Section on Personality Development 

Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Studies of Psychogalvanic Response in Family Therapy 

Previous Serial Number: M-AP(C)-17-3 

Principal Investigator: John Zinner, M.D. 

Other Investigators: David Reiss, M.D. and Roger Shaprio, M.D. 

Cooperating Units: Experimental Group and Family Studies Section, APB; 
Unit 3-West 

Man Years 

Total: 1.25 
Professional: .50 
Other: .75 

Project Description: 

Objectives ; The family psychophysiology project was initiated to provide 
quantifiable information about subjective experience during family interaction 
that would supplement self reports of family members and inferences made from 
observable behavior. 

Studies of interaction in families of emotionally disturbed adolescents 
carried out by this section in the past and concurrently have consistently 
focused attention on the subjective experience by family members of one another 
as important determinants of family group behavior. In particular, we have 
found clinically that family members often behave in such a way as to reduce 
anxiety in the family group as a whole or within particular members. In the 
case of emotionally disturbed adolescents the psychopathologic outcome may de- 
rive at least in part from the patient's attempts to diminish parental anxiety 
over parental intrapsychic conflict. 

Because family members may not be aware of anxiety during family sessions 
and because anxious members may choose to remain silent and not report their 
feelings or demonstrate it overtly in their behavior, we undertook to monitor 
continuously autonomic indicators of anxiety during family therapy sessions. 
The study therefore adds a psychophysiologic dimension to our ongoing investi- 
gations of the interplay between subjective experience and behavior in family 
interaction. Since the unit of study is conjoint family therapy, an opportunity 
is provided for exploration of the process of family therapy witihin individual 
sessions and on a long term basis, as well as the physiologic reactions of family 
members to the interventions of the psycho-therapists. 

83 



Serial No, M-AP(C)-17-3 

Method . The sample consists of families of adolescent patients admitted 
to our treatment program as well as families of "normal" adolescents inter- 
viewed in the "Sidwell Project." 

The Psychophysiologic variable selected for initial study was the galvanic 
skin response (GSR) which is known to be a rather good indicator of anxiety 
occurring in an interpersonal context. In addition, the GSR has the value of 
being discrete, unidirectional, easily visualizable and proportional in ampli- 
tude to the experienced intensity of the emotional stimulus. 

During conjoint family interviews, the GSR of family members and thera- 
pists are monitored continuously on a Grass Polygraph by way of electrodes 
attached to two fingers of each subject's non-dominant hand. A timing device 
and polygraphic recording of speech permits the accurate synchronization for 
retrieval of physiologic responses and concurrent verbal behavior. In 
addition, sessions may be video-taped using a split-screen technique which 
records and displays simultaneously both the family in interaction and the 
polygraph record. Playback of these videotapes permits an analysis of the 
sequential unfolding of family behavior and subjective experience of family 
members . 

Progress and Major Findings . A small sample of families of "normal" and 
"hospitalized" adolescents has been monitored physiologically during family 
sessions. Each family has been tested on at least two occasions to evaluate 
the stability of the physiologic variables. There is a close relationship, 
between occurrence of GSRs and the operation of psychological defense 
mechanisms. GSRs can be peripheral indicators of central anxiety "signals." 
These are subjective phenomena which stimulate the operation of psychological 
defenses preventing the eruption of a greater intensity of anxiety. Psycho- 
logical defenses which limit anxiety limit the further occurrence of GSRs. 
In the family therapy situation, however, there are stimuli beyond the control 
of the family, such as therapists' interpretations, which challenge defense 
mechanisms and generate anxiety, with a corresponding increase in GSR ampli- 
tude and frequency. Individuals in whom anxiety is, in general, poorly bound 
demonstrate marked degrees of GSR activity on polygraph records. At the other 
end of the spectrum are those individuals with hypertrophed defense operations, 
marked ego restriction and almost quiescent electrodermal activity. Thus the 
physiologic recordings, conform to psychoanalytic concepts of anxiety which 
postulate that primitive arousal mechanisms are incorporated and modulated by 
the ego so that they may perform a signal function for the operation of psycho- 
logical defenses. 

This year, all the physiologic data has been scored as have the transcribed! 
audiotapes of the family sessions. The data has been reduced in a search for 
new physiologic variables which would be relevant to testing of hypotheses 
derived from clinical theory. Most variables used in the literature were not 
useful for this purpose. Variables developed in our study which measure rela- 
tive rather than absolute degrees of electrodermal activity are more valid. 
In the coming year these new physiologic variables will be employed in tests 
of hypotheses related to family interaction. One such experiment is being 
planned in collaboration with the alcohol Research Center at St. Elizabeth's 
Hospital. In this instance, physiologic measures will test the stabilizing 

8^ 



Serial Ho. M-AP(C)-17-3 

effect of drinking behavior of marital dyads in which one or both members 
are alcoholics. 



85 



I 



Serial No. M-AP(C)-17-4 

1. Adult Psychiatry Branch 

2. Section on Personality Development 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 

Project Title: A Follow-Up Study of 37 Families Treated in the Study 
of Adolescent Identity 

Previous Serial Number: M-0D-CI-SW-9(c) 

Principal Investigators: Carmen Amoros-Cabrera, M.S.W. and Roger Shapiro, M,D. 

Other Investigators: Carl Feinstein, M.D. 

Cooperating Units: Unit 3-West 

Man Years 

Professional: .40 
Other: .20 
Total: .60 

Project Description: 

Objectives . To obtain information about the current adjustment of 
the adolescent and his family as related to (1) the problems that motivated 
their admission to the project, and (2) their individual perceptions of 
the effects of therapy and the relationship of therapy to any changes that 
may have taken place. 

Methods Employed . The family group, the adolescent, and the parents 
are seen in separate interviews with the goal of providing information 
which will allow for the isolation and identification of various factors 
comprising the therapeutic experience, such as the impact of the adolescent's 
hospitalization, ward milieu, family therapy, couples therapy, and individual 
therapy. The outcome of each aspects of the therapeutic program is 
emphasized, and outcomes will be evaluated for a number of categories still 
being defined. 

Progress . Sixteen families have been seen in the follow-up study 
this past year, and a paper was written on the preliminary findings 
focusing on couple's therapy with the parents and their status at follow-up 
interview. While adolescence and adolescent turmoil are frequently seen 
as an opportunity for the growth and development of the child, little 
attention has been given the possibilities of change for the parent during 
his child's adolescence. The findings of our study indicate that parents, 

87 



Serial No. M-AP(C)-17-4 

precipitated intp couple's psychotherapy by the adolescent turmoil of their 
children, have considerable capacity for psychic change at that time. 

On the basis of follow-up interviews and evaluation of data from 
long-term therapy with 22 parental pairs, three stages of regression and 
progression through which these couples pass during the therapeutic process 
were defined: (1) loosening of ties to the original family, (2) renewed 
adolescence and early m.arriage, and (3) return to parenting. 

Of the 27 follow-up cases, there was evidence of drug use in 11 of 
the index patients (the adolescent). Using a scale of -5 to +5 to 
evaluate adjustment, each adolescent was rated for factors such as capacity 
for independent living, socialization, heterosexual adjustment, ability to 
handle finances, productive application of time and energy, and sustained 
level of health. The results were: 



1 


case 


+5 


5 


cases 


+4 


1 


case 


+3 


1 


case 


+1 


1 


case 





1 


case 


-3 


1 


case 


-4 



Of these cases, six continued in therapy after discharge as we recommended. 
Five of them had married and seemed to be functioning adequately in 
relation to their family responsibility; 4 of the 11 had completed college 
and were successfully employed. T\i?o adolescents showed no indication of 
progress. One continued to be extremely delinquent, a child of very unstable 
parents, and his involvement with drugs has become increasingly serious. 
The other had presented clear indications of psychotic content since 
admission, had shown marked recovery periodically, but had failed to sustain 
an adequate level of functioning and was hospitalized. 

Significance for Mental Health Research . We are particularly 
interested in learning about the success of the therapeutic plan in 
clarifying the index patient's identity problems and in understanding and 
modifying the parents' delineations of the adolescent. This study will 
be useful in isolating factors contributing to the precipitation of serious 
adjustment problems during adolescence and in evaluating the outcome of a 
treatment program derived from research findings. 

Proposed Course of Project . A paper is being developed on the three 
phases of couple's therapy. A predictive criteria is being developed to 
relate to anticipated progress after discharge. A correlation between 
index patient progress and parents progress is being made, and we are 
studying the siblings of index patients in terms of the development of 
siblings with "static parents" versus that of siblings with "dynamic parents.' 
We are also assessing the impact of parental therapy on the quality of 
interaction between parents and younger siblings when those siblings 
reach adolescence. 



Serial No, M-AP(C)-17-5 

1. Adult Psychiatry Branch 

2. Section on Personality Development 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 



Project Title: Cognition and Identity Development in Early and Late 
Adolescence: Longitudinal Studies 

Principal Investigator: Stuart T. Hauser, M.D. 

Other Investigators: Roger L. Shapiro, M.D. 

Cooperating Units: Ward 3-West, Normal Volunteer Office 

Man Years : 

Total: .50 
Professional: .30 
Other: .20 

Project Description: 

Objectives . An earlier longitudinal study of identity formation in 
lower socio-economic class boys (Hauser, S. T., Black and White Identity 
Formation , N. Y., Wiley, 1971) suggested several areas for further investi- 
gation. A clear difference in identity formation patterns was found 
between the black and white adolescent subjects. Two questions of interest 
emerging from this earlier investigation and orienting the current studies 
were: 

1. What variants of identity formation are found in other groups of 
adolescents, such as girls, other social classes, and psychiatric patients? 

2. What are other aspects of psychological functioning which are 
associated with varying identity formation patterns? In particular, 
cognitive processes appear to be related to modes of self-image perception. 
How then are these cognitive areas linked with identity development 
patterns, more complex patternings of self-images? Are certain cognitive 
or perceptual processes more powerfully linked to identity development? 

Methods Employed . To approach the preceding questions, several 
populations of subjects are being sampled: 

1. Adolescent male and female patients of middle and upper socio- 
economic class status (24 subjects). 



Serial No. M-AP(C)~17-5 

2. Adolescent male and female high school and early college age 
students, also of middle and upper socio-economic class status (35 subjects), 

Each of the subjects from these samples is studied longitudinally for 
two years, being seen every six months. The sequences of meetings and 
instruments used, with rationale for their use, is the following: 

1. Groups of seven to eight subjects from each of the samples 
meet with the senior investigator for a series of four meetings, focused 
around "the study of roles and perceptions of the self and others in the 
group." 

2. From the tapes of these meetings, a separate Q-sort deck is 
generated for each group. The deck, consists of 3X5 cards, on each being 
an "I" statement made by a group member which reflected a particular 
personal emotional, ideological, or general descriptive position about 
himself. There is an equal number of statements from each group member, 
including the leader. 

3. Each subject is individually interviewed following the conclusion 
of the four group meetings, the thrust of the individual sessions being 
around self-conceptions, current and past. Inquiry is also along the 
lines of developmental and family history. 

4. The following week the subject takes the Q-sort task. In this 
method he is asked to sort the deck from his group (described in #2, above) 
for a series of seven different self-images. These include self-images 
from temporal, idealized, and peer realms. There are a total of seven 
self-images, always requested in the same order by the experimenter. 

5. In the following testing one to three weeks after the Q-sort, 

the subject is tested with a series of cognitive measures. The techniques, 
their rationale and their order of being taken are: 

a. The Pettigrew Category Width Scale. This is to measure the 
breadth or narrowness of a subject's categories. 

b. The Concealed Figures Test. For determination of degree of 
field articulation, of "differentiation." 

c. The Object Sorting Test. To determine the size and number 
of categories generated by a subject; and, in addition, to analyze his 
reasons underlying his categories (conceptualizations) . 

d. The Twenty Questions Task. To measure the type and degree 
of efficiency of a subject's problem-solving strategy. 

e. Draw-A-Person Task. The drawing of persons obtained will be 
analyzed using the scales devised by Witkin and Associates for measurement 



90 



Serial No. M-AP(C)-17-5 

of "sophistication of body image," a variable highly associated with 
differentiation. 

Steps three through five are repeated every six months for a two-year 
period. Thus each subject will be interviewed and tested a total of 
four times . 

The self-image measurements which are being obtained from these 
instruments include correlational indices, general measures of relatedness 
and of discrimination (all obtained from the Q-sorts) ; indices of the 
sources of self-image components (also from the Q-sorts) . Specific 
cognitive variables from each of the cognitive instruments are simultaneously 
being determined. 

Techniques for analyzing the complex data is along several lines in 
order to investigate inter-relationships of the variables at single points 
in time, and over time; and to investigate consistencies within individual 
subjects and between groups of subjects. Two basic statistical tools will 
be analyses of variance and factor analyses. Both these approaches and 
their implementation have been worked out with Dr. John Bartko, statistical 
consultant, and the computer center. 

Major Findings . At this point three to four waves of interviews and 
testings have been completed on most of the controls and patients. The 
data obtained from the first round has been analyzed for measures noted 
earlier. Correlational analyses of the Q-sort data are completed and 
have been written up in "The Differentiation of Adolescent Self-images," 
to be presented at the annual American Psychiatric Association meetings. 
The major finding is in the differential sensitivity of various self-images 
(idealized, temporal, peer) to variables of sex and patienthood. Implications 
of these differences are being studied, and further elaborated. 

A second aspect of the sample is in the black-white comparative 
studies. Data from the original New Haven sample was re-analyzed using 
new tools: information statistics (for analysis of structural complexity 
of self-image and over-all relatedness) and drawing analyses for study 
of differentiation. The structural complexity analysis of the older 
longitudinal data is consistent with lessened structural complexity 
(more polarized) self-image for several of the blacks' images. 

Significance to Mental Health Research . These studies are directed 
toward an increasingly intensive analysis of self images from several 
perspectives: Their "inner characteristics of meaning and structure, their 
relation to one another, their modes of change over time, their relation 
to other modes of personality functioning which appear highly relevant, 
such as cognitive processes. One important application of such quantitative 
studies is as a means of following the course of an adolescent during 
psychotherapy comparing other measures with independent observations such 
as those of nurses or the patient's therapist. A second application is to 



91 



Serial No. M-AP(C)-17-5 

the comparison of adolescent development with and without psychotherapy, 
and under different modes of psychotherapy (half the patient population 
is receiving only group therapy, the other half is in group and individual 
therapy) . 

The operationalizing of major concepts such as "identity formation" 
and "psychosocial moratorium" is still a third important consequence of 
this kind of research. Through such operationalizing the concepts are given 
clearer empirical definition and rendered more susceptible to rigorous 
quantitative research. Moreover, the way is opened to study of these 
much discussed phenomena (identity development) in many varied groups 
ranging from ones within our own culture — ethnically , racially , psychia- 
trically, socio-economically differentiated — to cross-cultural comparisons. 

Course of the Research . The plan is to complete data collection 
for a two-year period on all of the subjects. This will involve four 
waves of interviews and testings on each subject. The complex data is 
being analyzed using analysis of variance models : two and three-way 
ANOVA's for cross-sectional, and repeated measures model for longitudinal. 
A second facet of the research is content analysis of the interview 
materials along the lines of different self-images and their changes. 
A technique involving quantitative analysis of five-minute interview 
segments has been developed and applied with the help of the late Dr. William 
Caudill. 

A preliminary outline for the eventual integration of the findings 
in monograph form, "Lines of Adolescent Development," has been written 
up. Specific discussions of new methodological and substantive findings 
during the progress of the studies are complete. The first of these 
papers, "The Differentiation of Adolescent Self-images," is to be presented 
at the annual APA meetings. 

Honors and Awards : 

1. Hauser, S. T. and Shapiro, R, L. "Differentiation of Adolescent 
Self-images." Presented at the Adult Psychiatry Branch Seminar, NIMH, 
March, 1972. 

2. Hauser, S. T. and Shapiro, R. L. "Differentiation of Adolescent 
Self-images," presented at the Annual Meeting of the American Psychiatric 
Association, Dallas, Texas, 1972. 

3. Hauser, S. T. "Black and White Identity Formation." Presented 
to Grand Rounds, St. Elizabeths Hospital, November 1971. 

4. Hauser, S. T. Recipient of Research Scientist Development Award 
Grant. 



92 



Serial No. M-AP(C)-18-2 

1. Adult Psychiatry Branch 

2. Section on Experimental 
Group and Family Studies 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 - June 30, 1972 

Project Title: Coordinating "Micro-Codes" in Family Consensual Experience: 
A Study of the Responses to Speech Hesitancy and Fluency 
in Family Interaction. 

Previous Serial Number: M-AP(C)-18-2 

Principal Investigator: David Reiss, M.D. 

Other Investigators: None 

Cooperating Units: None 

Man Years: 

Total: . 1 
Professional: .0 
Other: .1 

Project Description: 

Objective : The card-sorting experiment and previous studies by Reiss 
as well as by Strodtbeck, Mishler, and Waxier, et al. , support the notion 
that families can be distinguished by the shared experience, of their 
members, of their environment. Furthermore, it appears as if this shared 
experience serves as a major regulator of moment-by-moment family interaction 
in a variety of settings. In order to maintain such consensual experience 
and to utilize it to deal with environment events as they occur on a moment- 
by-moment basis, family members must be exquisitely sensitive to each other's 
ideas and feelings at all times. The project was part of a card-sorting 
experiment in which family members could communicate only by voice; thus 
each member had to utilize the others' vocalizations to remain continuously 
integrated in this delicately balanced family process. Recent experimental 
evidence suggests that family members may utilize changes in each other's 
patterns of speech hesitancy and fluency for this purpose. We postulated 
that all families will show significant moment-by-moment response to changes 
in the fluency patterns of each member. However, some families — which we 
have termed "environment-sensitive" — are predicted to respond to hesitant 
speech as a signal pointing to a difficulty or incogrulty perceived by the 
speaker in the laboratory puzzle itself. Other families — ^we call them 



93 



Serial No. M-AP(C)-18-2 

"consensus-sensitive" — ^will interpret hesitancy as a sign of the speaker's 
perception of or response to the family itself. These family types are 
defined by a consensual experience model and identified by their non-verbal 
performance on a card-sorting procedure. Thus, this study is a further test 
of the consensual experience model which predicts that family members will 
respond to minimal changes in each other's speech in ways determined by 
their over-all shared experience of the environment. These minimal speech 
changes could then be viewed as a personal, family "micro-code" serving to 
regulate its interaction in moment-by-moment harmony with its shared experi- 
ences and views. 

Method ; The verbal interaction in the second family problem of the 
card-sorting task was recorded on a specially prepared 4-channel tape record- 
ing system and transcribed by polygraph to give a visual, objective record 
of patterns of vocalization. A timing signal permitted coordination of the 
polygraph record with a tjrpescript of the content of the family's discussion. 
Changes in fluency were measured by methods of Boomer and Dittman, and 
Goldman-Eisler, using the polysraph record. The family's response to fluency 
changes in any member was measured using interaction codes developed by Reiss 
and Mlshler and Waxier, using the typescript, and also measures of the card 
sort and trial times. 

Progress : All the polygraph and typescript records have been obtained. 
The Boomer and Dittman scoring procedures have been successfully adapted for 
use with the data collected in this study. In addition, the Level of 
Abstraction Code, from previous work by Reiss, and the Responsiveness Code, 
from work by Mishler — two coding procedures for measuring verbal interaction — 
have been adapted for the present project. All three coding procedures are 
nearly complete. Programming has begun to utilize Attneave's information 
transmission statistic to analyze relationships among the three codes 
through time. Coding procedures have continued very slowly during the past 
year. Completion of this project is being hampered by lack of adequate 
number of research support staff. 



9h 



Serial No. M-AP(C)-18-3 

1. Adult Psychiatry Branch 

2. Section on Experimental 
Group and Family Studies 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 - June 30, 1972 

Project Title: The Effects of Progressive Isolation of an Individual 
From His Family on His Perceptual Functioning: Use of 
a Teletype-LINC Apparatus to Study the Reciprocal Rela- 
tionship of Family Interaction and Individual Thinking. 

Previous Serial Number: M-AP(C)-18-3 

Principal Investigator: David Relss, M.D. 

Other Investigators: None 

Cooperating Units: None 

Han Years: 

Total: .1 
Professional: .0 
Other: .1 

Project Description: 

Objective : Previous experiments in this Section have demonstrated that 
family Interaction does have a specific, predictable short-term effect on the 
thinking and perception of its members. A critical question is: of all the 
flux and nuance of family interaction, which aspects are the most critical 
for regulating the thought and perception of its members. In the card-sorting 
and micro-code experiments. Dr. Reiss explored the role of various details of 
the vocalized portion of family interaction — excluding all forms of non-vocal 
performance. In the current experiment, the question is: to what extent do 
families differ In the amount of objective information — concerning the 
problem solution — they can obtain and distribute among its members; and, 
further, how does this obtained and distributed Information reeulate per- 
ceptual processes in their members. In other words, in what way does an 
individual's perceptual process — occurring in the midst of a familv problem- 
solving task — deoend on the quality and quantity of information provided him 
about the problem by his family, disregarding all other aspect of the family 
interaction of which he is a part. It is predicted that families will differ 
in the amount of relevant information they can discover about the problem, 
their effectiveness in distributing it to all members of the family and the 



95 



Serial No. M-AP(C)-18-3 



use each member makes of Information provided to him by others in the family. 
Specifically, we expect families we have designated as environment-sensitive 
will extract a great deal of problem-relevant Information from their environ- 
ment, will effectively distribute it amongst members in the family and each 
member will utilize the information insofar as it assists him in a logical, 
consistent and comprehensive problem solution . Individuals in families 
designated as consensus-sensitive will work to obtain, distribute, and 
utilize problem-relevant information only insofar as it permits a family 
solution at a desired level of wlthin^member agreement . In the present 
experiment the procedure progressively isolates each member from his family. 
In the first condition all information obtained by all members about the 
problem is transmitted Immediately to each individual along with the identity 
of the family member who obtained lt~the "public mode"; in the second 
condition the information is transmitted after a variable delay without the 
identity of the member who obtained It — the "anonymous mode"; in the third 
condition no Information is transmitted between members—the only information 
available to each monber is what he obtains himself and that provided by an 
Impersonal, extra-family source — the "standard mode." It is predicted that 
members in environment-sensitive families will maximally utilize information 
from any source whereas members in consensus-sensitives will utilize informa- 
tion from their past when it comes from an impersonal source. In order to 
provide immediate and standardized information transmission between the family 
members and between the family and the impersonal environment a teletype-LINC 
apparatus was constructed and programmed. This permitted the conduct of 
experiments entirely under the control of computer. It further permitted 
every item of family interaction, i.e. transmission of information by use of 
teletypes, to be precisely recorded in time. Thus, at the conclusion of the 
experiment it is possible to know not only what interaction has occurred but 
precisely when. This will permit an exact correlation of the various events 
comprising the flux of family interaction in this experimental setting. The 
teletype-LINC apparatus represents a major innovation in experimental social 
psychology and this project, in addition to its exploration of a particular 
hypothesis about family interaction, serves as an Initial study of this 
innovation. 

Method: Four family members, the parents and two children, are seated 
in booths so they cannot see each other. Each has a teletype and is Instructed 
in its use. They are told that they must discover a class of symbol sequences 
that, when typed, will result in plus (+) being typed in return — automatically. 
Their understanding is that the plusses are typed in a systematic way and 
their job is to discover the system or pattern. Each member is given an 
example (e.g. CSTTTTTTTS which represents the class of "plus sequences" 
beginning with CS followed by n number of Ts and concluding with an S) , Then 
each member tries out his own sequences in turn. In the "public mode" each 
sequence Is automatically typed, immediately, on the other members' teletypes, 
with a symbol indicating whose sequences It was and when it received a plus 
or not. In the "anonymous mode" the sequence is typed, along with its plus or 
minus, after a variable delay in a way concealing its authorship. In the 



96 



Serial No. M-AP(C)-18-3 

"standard mode" the sequence t5rped by each member Is not typed on anyone 
else's teletype; instead, a sequence from a standard library, stored in the 
computer, is typed on everyone else's teletype., Each mode is introduced by 
detailed instructions and considerable practical experience for the family 
so that they become fully familiar with its distinctive features before 
beginning the actual problem-solving. Preceding and following each experi- 
mental problem each member is given a objective test of his ability to 
predict the class of sequences that will get a plus; this serves as a test 
of his ability to recognize relevant patterns. 

Progress ; In the first study, four families designated as consensus- 
sensitive were compared with four environment-sensitive families. The 
distinction between these two groups was made by the use of card-sorting 
procedure. The consensus-sensitive families were those that sought to 
achieve consensus at the price of accurate problem solution. The two groups 
were carefully matched for a number of variables including intelligence and 
social class. The results were very striking and clear even though, in this 
pilot study, the sample was small. We used a matched-pair design in which an 
environment-sensitive family was matched with an consensus-sensitive family. 
In each pair the consensus-sensitive family showed a progressive improvement 
in problem-solving ability as intermember access was reduced from the public, 
to the anon3rmous to the standard mode. In sharp contrast each environment- 
sensitive family showed no change or a slight decline in problem-solving 
ability as intermember access was reduced. 

A second study, using a wider sample of 15 families, studied the more 
detailed processes of hypothesis testing in the two groups of families. 
Correlational studies suggested that members in families with a marked deficit 
in the public mode relative to the standard mode, used others' h3rpotheses as 
a basis for their own hypothesis testing less often than members in families 
without such a relative deficit. Moreover, in the public deficit, members 
were less willing to risk the construction of incorrect hypotheses. These 
findings were predicted by a consensual experience model: It states that 
members in environment-sensitive families (with no public deficit) use each 
others' experiences with the environment as a way of augmenting their ovra 
experience and understanding of it, whereas consensus-sensitive families, 
since they are oriented to achieving an agreed-unon internal version of 
experience, tend to ignore the others interaction with the environment. The 
unwillingness of these individuals to risk negative feedback, for their 
hjrpotheses. confirms our view that they experience negative feedback as 
censorious rather than information-giving; this attitude is consistent with 
their vi«w of the environment as hostile and unknowable. 

After completing the two studies described above, the program for the 
teletype experiment was substantially revised to: (a) make the three modes 
more nearly identical in the type and quantity of feedback for subjects' 
hypotheses and (b) to more completely automate the procedure; this now 
includes some automatic instruction and testing of subjects. Pre-experimental 
trials, during the past year, have indicated that the changes have improved 

91 



Serial No. M-AP(C)-18-3 



the efficiencYs standardization and comprehensibility of the procedure. 
Serious delays in completing data collection have been caused by lack of 
adequate number of research support staff. 



Honors and Awards ; 

1. Reiss, D. : Invited address. "The Faiaily's View of Its Environment; 
Laboratory Studies of Its Origins and Functions." Faculty of the 
Department of Psychiatry, Montefiore Hospital and Medical Center, 
Bronx, New York, March, 1972. 



Publications : 

1. Reiss, D. : Intimacy and problem solving: An automated procedure 
for testing a theory of consensual experience in families. 
Arch . Gen . Psychiat . 25: 442-455, 1971. 

2. Reiss, D. : Varieties of consensual experience I. A theory for 
relating family interaction to individual thinking. Fam . Process 
10: 1-28, 1971. 

3. Reiss, D. : Varieties of consensual experience II. Dimensions of 

a family's experience of its environment. Fam. Process , 10; 28-35, 
1971. 

4. Reiss, D. : Varieties of consensual experience III. Contrast 
between families of normals, delinquents and schizophrenics. 
J. Nerv. Ment . Pis . 152: 73-95, 1971. 

5. Reiss, D. : Competing hypotheses and warring factions; Applying 
knowledge of schizophrenia. Schizo. Bull. In press. 



Serial No. M-AP(C)-18-6 

1. Adult Psychiatry Branch 

2. Section on Experimental 
Group and Family Studies 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 - June 30, 1972 

Project Title: Nurse-Doctor-Patlent Interaction: An Experimental Study 
of Its Role In Patient Acculturation on Psychiatric Wards. 

Previous Serial Number: M-AF(C)-18-6 

Principal Investigator: David Relss, M.D. 

Other Investigators: None 

Cooperating Units: Richard Almond, M.D. , Department of Psychiatry, 

Stanford University Medical School, Palo Alto, California 

Man Years: 

Total: .8 
Professional: .6 
Other: .2 

Project Description: 

Objectives : The major objective of the study is the direct measurement, 
under controlled conditions, of nurse-doctor-patient interaction as it occurs 
on psychiatric wards. The hypotheses of the study are derived from previous 
work by Dr. Almond which suggest that particular forms of nurse-doctor- 
patient interatlon are crucial to inducing change and improvement in patients. 
Moreover, his previous studies suggest that certain value orientations by 
the staff serve to control or perpetuate these crucial interactions and many 
patients, after modifying their behavior during interaction with professional 
staff (and other patients), accept these values. This study seeks to relate 
value orientations of the staff, concerning t3rpes and process of treatment 
as well as personal preferences for t3rpe8 of interaction in group involve- 
ment, with the way they interact with each other and with patients. Specif- 
ically, we attempt to predict how a nurse and doctor will Interact with 
each other from a knowledge of their value orientations; then we seek to 
predict how the nurse-doctor dyad will Interact with a patient, based on 
their behavior when interacting as a dyad. This is the first direct experi- 
mental study of Interpersonal processes amongst psychiatric personnel and 
therefore the project also serves the general purpose of examining the value 
of experimental techniques in this area of clinical Investigation. 



99 



Serial No. M-AP(C)-18-6 



Method : Dr. Almond has modified a questionnaire he used in his original 
studies in New Haven. It has a broader range of items and is now suitable 
for administration to nurses and doctors as well as patients. The results 
of this questionnaire were used to evaluate nurses' and doctors' value 
orientations. These orientations, in turn, were used to predict nurse-doctor 
interaction. Two value orientations were selected as independent variables. 
1) the subjects' expressed valuation of social openness and involvement in 
the ward (SOWI) by patients and staff; 2) the subjects' expressed wish to be 
included in the control groups (FIRO). Sixteen nurse-doctor dyads were 
formed so that they could be divided into four subsamples of equal size; 
8 dyads were highly discrepant on SOWI (snore higher) and 8 had similar 
scores; half of each of these subsamples had highly discrepant FIRO scores 
(more higher) and half were the same. Each dyad was tested separately in a 
small-group-type laboratory where they were isolated in booths and could 
communicate only by microphone. They worked on a standard set of problems, 
provided by the experimenter, requiring them to group a set of fictitious 
patients into activity groups. After a series of such problems, they were 
joined by a patient and continued to work on a set of similar problems as a 
triad. A number of objective indices of social interaction in the dyads and 
triads were derived from the card placements and objectively recorded times 
of various phases of the experimental task. These variables sought to 
measure the extent to which the dyads and triads 1) agreed or disagreed on 
problem solutions; 2) blindly followed a potent leader or worked inter- 
dependently with each individual making a substantial contribution; 3) 
utilized the full range of ideas elaborated by each person working alone; 
4) "objectified or dimensionalized" the problem rather than seeing each 
fictitious patient and grouping as unique and personal. 

Progress : Data analysis and written reports are complete. The basic 
findings are these: There is a substantial difference in the effects of 
independent variables early in the task, when the nurse and doctor are being 
acquainted and where the dyad meets the patients for the first time, and 
later in the task when all three have been working together. The findings 
are these: 1) Where the nurse has a tendency to dominate groups and the 
doctor wants to be dominated (FIRO compatibility) and the nurse has higher 
SOWI values, the doctor and nurse form a very tight consensus but are unable 
to include or assimilate the patient. Here the dominant nurse shows evidence 
of using her more differentiated values as a club forcing the doctor to accept 
her views. These findings were also obtained where the nurse and doctor are 
equal in values and neither is dominating or wishes to be dominated (FIRO 
incompatible) . Here the lack of any differences between the two on value 
orientation appears to produce an enui exaggerated by incompatibility and 
papered over by an artificial consensus. 2) Where the nurse and doctor 
are equal in values and FIRO compatible, and where the nurse is superior in 
values and the dyad is FIRO incompatible, the nurse and doctor form a 
flexible and varying consensus and very effectively include the patient in 
this consensus. In the former, interpersonal compatibility enables the dyad 
to reach an affable agreement which is well able to include a third person. 
In the latter, some interpersonal incompatibility focusses the dyad away 

100 



Serial No. M-AP(C)-18-6 



from the task of simply gratifying one another. Rather they concentrate on 
preparing for the patient's entrace. The nurse's high SOWI values enable 
her to take an important role in assimilating the patient when he does arrive. 
The findings indicate that both independent variables are Important and have 
an interacting effect. A difference in values appears crucial for stimulat- 
ing the nurse-doctor dyad to consider various approaches and reach a meaning- 
ful consensus; however, if the nurse tends to dominate the dyad and the 
doctor acquiesce, the nurse will use her distinctive value position as a 
club. Tension between nurse and doctor will be papered over with a forced 
consensus and the patient will be excluded. 



101 



Serial No. M-AP(C)-18-10 

1. Adult Psychiatry Branch 

2. Section on Experimental 
Group and Family Studies 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 - June 30, 1972 

Project Title: The Effect of Stimulus Materials on Family Problem Solving. 

Previous Serial Number: M-AP(C)-18-10 

Principal Investigator: David Relss, M.D. 

Other Investigators: None 

Cooperating Units: None 

Man Years: 

Total: .1 
Professional: .1 
Other: .0 

Project Description: 

Objective : In the work done in our laboratory almost all family 
problem-solving tasks have utilized pattern recognition tasks in which 
patterned stimuli have been generated by one or another type of finite state 
grammar (as originally described by Chomsky and Miller). These problem 
materials have a ntimber of advantages for studying complex perceptual and 
cognitive processes. Nonetheless, they represent a restricted model of the 
types of stimulus experience families may encounter In their everyday lives. 
Tt is important to establish that our findings concerning family problem 
solving can be generalized to different kinds of stimuli. Other feattires 
of the card-sorting procedure, such as the partial self -administration 
features, ease of observer recording of sorting performance, uniformity of 
physical characteristics of the stimulus materials. Isolation in booths, 
have solved a number of long-standing methodological problems. Thus, it 
seemed imprudent to change the basic card-sorting procedure itself. However, 
a change of the content of the cards seemed useful to test the generality of 
our findings. 

Method ; Accordingly, we designed a procedure, adapted from Tlen's 
Organic Integrity Test, which required subjects to sort cards according to 
objects pictured on the cards. Three sets of 15 cards were developed: two 
were used for initial and final individual task and a third for a family 



103 



Serial No. M-AP(C)-18-10 



task between the individual tasks. Thus, the procedure has the same formal 
structure as the letter syllable and number-sorting tasks. In each of three 
tasks the cards can be grouped in at least three ways: by color of object, 
use of object (e.g. tool, wearing apparel or sporting equipment) or by sex 
of user (male, female or neutral). A maximally effective sort would pre- 
sumably use one of these three with complete consistency (corresponding to 
recognizing the finite state grammar in the basic sorting procedure). Also, 
families could vary in the amount of sorting similarity between members and 
across trials. Therefore, the same variables of problem-solving ability, 
coordination and closure were obtainable from this procedure as the basic 
procedure. 



Progress ; Data collection is continuing. 



lOi^ 



Serial No. M-AP(C)-18-12 

1. Adult Psychiatry Branch 

2. Section on Experimental 
Group and Family Studies 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 - June 30, 1972 

Project Title: Family Views of Its Social Environment: Effects on 
Family Therapy Process. 

Previous Serial Number: None 

Principal Investigator: David Relss, M.D. 

Other Investigators: Ronald Costell, M.D. and Loann Drake 

Cooperating Units: Section on Personality Development, APB, IR, NIMH 

and Psychiatric Institute of the District of Columbia 

Man Years: 

Total: 2.0 
Professional: 1 
Other: 1 

Project Description: 

Objective: During the past 6 years a series of laboratory studies have 
revealed that families — functioning as a group — develop shared and vivid 
concepts of the structure of the larger social community in which they live 
and work. Some families see their social environment as being patterned 
and engrossing. Other families see their social environment as threatening, 
chaotic and overwhelming. Evidence suggests that these shared family 
constructions of their environment are typical and enduring and dominate a 
family's response to any novel or stressful challenge in their social 
environment. We hjrpothesize that this is particularly true when a family 
must Involve Itself in an entirely new social community. Then, their typical 
reaction patterns play a major role in shaping their adaptations to and 
involvement in the Institution^ social processes. This kind of encounter 
between family and the new institution is very well exemplified by a 
psychiatric hospital that emphasizes family treatment. When the index 
member is admitted to the hospital, the whole family is actively engaged in 
the treatment program. Thus, the family — as a group — must orient itself to 
a set of novel and stressful challenges. This study is designed to test the 
relationship between family reaction patterns, as measured in the laboratory, 
and their adaption during the first six weeks of family-oriented in-patient 
psychiatric treatment. The laboratory measures will be used to predict the 

105 



Serial No. M-AP(C) -18-12 



degree to which the family will become involved and engrossed in the treat- 
ment program or withdraw and protect itself from the hospital eomnunity and 
its programs. The interaction between family and hospital will also be 
viewed as protypical of interactions between families and a variety of 
institutions in their social environment. Later, we plan studies of the 
interaction between families and schools and families and occupational 
settings. 

Method s One independent variable is the family's problem-solving 
behavior in the laboratory. Based on this, a family can be placed in one of 
three categories! environment-sensitive, consensus-sensitive and distance- 
sensitive. The second variable is institution; the families are either 
admitted to the Psychiatric Institute or NIMH. It is planned to set up a 
system whereby families can be randomly assigned to one or the other 
institution with a stratification procedure that assures family comparability 
along several dimensions. Thus,, the basic design is a 3 (family types) x 2 
(institutions) factorial one. 

The dependent variables are selected to measure various aspects of the 
family's adaptation to the hospital community and its treatment program. 
Several of the procedures utilize the family interaction laboratory but are 
specifically designed to measure the family's perception or collective 
experience of the hospital social community. The most important is the Ward 
Perception Q-Sort. Our theory states that a family's t3^ical approach to 
construing novel social situations will determine its shared experience of 
the ward community. This shared experience is a variable intervening 
between family type and adjustment to the treatment program. The Ward 
Perception Q-Sort is intended as a direct estimate of this shared perception 
in the family. Specifically, it measures four aspects of the family's shared 
perceptions! accuracy, stereotypy coherence and the similarity between 
members. The procedure requires family members, each individual in his own 
booth, to sort a group of 36 cards into 7 categories. Each card contains a 
description that might be applicable to the psychiatric ward and the 7 
categories are labeled in descending order from "most characteristic" to 
"least characteristic." The family is urged to discuss together, thru an 
intercom, how to categorize the cards. Objective scores are computed to 
estimate the four aspects of family perception from their sorts. 

Two other procedures permit a direct assessment of family-hospital 
interaction; they are utilized directly on the ward. Both depend on the 
family's participation in a multiple-family therapy group— a major treatment 
modality at both the Psychiatric Institute and NIMH. 

The first procedure is direct observation and measurement of the 
family's interaction with other family and psychiatric staff in the group. 
Over a series of sessions the family's seating arrangement and the frequency 
and direction of their speech will be carefully recorded by an observer. 
The family's engagement and involvement in the ward community will be indexed 
by its willingness to disperse itself physically in a group rather than stay 

106 



Serial No. M-AP(C)-18-12 



huddled together in adjoining seats; it will also be indexed by frequent 
speech directed at many individuals. 

The second procedure is the sociometric technique. It too is being 
used as a measure of family engagement and involvement. In particular, we 
are interested in the experiential boundary the family constructs between 
itself and the rest of the community. Family members are asked to choose 
others in the multiple family group whom they like and know well. Imper- 
meable boundaries will be indicated by families who choose few others and 
where members choose others in the same family. Members in families with 
impermeable boundaries should also be the object of choice by few others, 
outside the family, in the multiple family group. 

A third procedure is a group cohesiveness questionnaire adapted from 
studies of outcome and process in therapy groups of unrelated members. This 
is used to estimate the family's subjective sense of being involved in the 
multiple family group. 

A fourth procedure is the Family Perception Procedure. This procedure 
is aimed at assessing, from a different perspective, the character of the 
family's experience of the social community— in this sense supplementing 
the Ward Perception Q-Sort. Here, a family is tested immediately following 
a multiple-family group meeting. Members, working together, are asked to 
make a number of distinctions between different families and between differ- 
ent members of the same family. Following general procedures outlined by 
George Kelly, an estimate is made of the number, complexity and character of 
the dimensions the family uses to discriminate between individuals and 
families within the group. Here, we attempt to distinguish between simple, 
moralistic and superficial distinctions and complex, flexible and psycho- 
logically insightful distinctions. 

Overall, we have made the following predictions. Environment-sensitive 
families — who can develop progressively more complex, subtle and accurate 
solutions to laboratory problems, will show simple kinds of evaluations of 
the ward social community on the Q-Sort and Family Perception Procedure. 
They will also show evidence of greater engagement and involvement in the 
therapeutic process. Consensus-sensitive families — who force an early 
agreement among themselves on simple and stereotyped solutions to laboratory 
puzzles— will show similar characteristics in their conceptions of the social 
community on the ward and remain isolated and distant from the therapeutic 
program. 

Progress ; Two major achievements, crucial to the success of this 
project, have been accomplished during this first year of the study. First, 
a well worked out collaboration has been established with the Psychiatric 
Institute and the Section on Personality Development. This has included 
review of the project with professional staff and patients, testing of 
families and establishing multiple-family groups suitable for study. The 
problem of setting up a random assignment procedure must wait until the 

107 



Serial No. M-AP(C) -18-12 



future of the Adult Psychiatric Branch and Unit 3 West is secure. Second, 
all procedures for measuring the dependent variables are new in some 
respect — either they have never been tried before or they have never been 
applied to families. Thus, during the past year we have been engaged in 
extensive and intensive pilot testing and all procedures show evidence of 
being practicable and reliable. 



108 



Serial No. M-AP(C) -18-13 

1. Adult Psychiatry Branch 

2. Section on Experimental 
Croup and Family Studies 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 - June 30, 1972 



Project Title: Values and Atmosphere on a Psychiatric Ward: Basic 
Dimensions and Institution Comparisons. 

Previous Serial Number: None 

Principal Investigator: Ronald Costell, M.D. 

Other Investigators: David Reiss, M.D. 

Cooperating Units: NIH Nursing Administration, Nursing Units 3 West, 3 East, 
4 West, 4 East, and Psychiatric Institute of the 
District of Columbia 

Han Years: 

Total: .9 
Professional: .4 
Other: .5 

Project Description: 

Objective ; Studies of psychiatric wards indicate that the attitudes 
and values of staff and patients with regard to therapy-related behaviors 
play an important role in defining the therapeutic milieu and the nature of 
therapeutic transactions between patients and treatment staff. This study 
seeks to explore the relation between therapeutic milieu attitudes and 
values and aspects of Individual disposition toward interpersonal relations. 
In addition, the study seeks to explore the relation between these two 
domains and the ways in which individuals perceive the ward atmosphere. 
These relations are explored through analysis of a composite questionnaire. 
Therapeutic milieu attitudes and values are represented on the questionnaire 
by several previously studied scales includluK the Almond Social Openness- 
Ward Involvement Scale, and the Therapeutic Ideology Scale of Strauss. 
Individual interpersonal disposition items are represented by the A-B 
Therapist Scale of Whltehom and Betz, the FIRO-B scales of Schutz and the 
Machiavellianism Scale of Gelst and Christe. The Ward Atmosphere Scale of 
Moos provides the measure of perception of the social atmosphere of the 
ward. Exploration of therapeutic milieu attitudes and values, and of 
interpersonal relations disposition in conjunction with another study, in 
1969, provided interesting factor analytic factor clusters from two 

109 



Serial No. M-AP(C) -18-13 



institutions. In the current study we plan to assess the reliability of 
these factors over time and extend the perspective of the study to percep- 
tions of ward atmosphere. 

Method ! The composite questionnaire is to be administered to inpatients, 
nursing staff and professional staff on the four psychiatric units at NIMH 
and to similar groups at a large private psychiatric hospital, the 
Psychiatric Institute of D.C. Individuals from both hospitals participated 
in the 1969 study. The data consisting of score values on the various com- 
ponent scales will be factor analyzed using the principal components method. 
Reliability of Che questionnaire components and factor structure obtained in 
the 1969 study will also be assessed. The total sample of respondents will 
be about 250. 

Progress ; Questionnaire materials allowing for direct IBM card punching 
from the forms, and computer program for extracting the scale scores have 
been prepared and pretested. The questionnaires have currently been distri- 
buted on all of the four NIMH wards, and preparations are underway to 
distribute the questionnaire at the Psychiatric Institute of D.C. 



110 



Serial No. M-AP(C) 19-1 

1. Adult Psychiatry Branch. 

2. Section on Twin & Sibling Studies 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 
Individual Progress Report 
July 1, 1971 through June 30, 1972 

Project Title: Comparative Studies of Discordant Siblings in Families of 
Schizophrenic, Juvenile Delinquent and Well— adjusted 
Young Adults 

Previous Serial Number: same 

Principal Investigator: William Pollin, M.D. 

Other investigator: Martha Werner, M.A. 

Cooperating Units: 

University of California-Davis, Dr. Joe P. Tupin 
University of Connecticut, Dr. James R. Stabenau 

Man Years (Computed for the 12 month period) 

Total: .5 
Professional: .3 
Other: .2 

Project Description: 

Objectives , Methods Employed . Patient Material , and Major Findings 
of this study have been extensively described in previous years' reports. 
At present, activities are limited to completion of ten-year followup 
home visits, and integration and preparation of the data for monograph 
publication. 

Significa nce to Mental Health Research ; This project, along with the 
other ongoing studies in schizophrenia concurrently under way in the Section 
are all addressed to the two major goals of helping to define etiologic 
factors relevant to schizophrenia, and more basically, determinants of 
personality formation. As such, they are relevant to major ongoing questions 
ef the determinants of mental health and emotional illness. 

Proposed Course of Project: Integration of sibling data with that from 
twin studies (19-2 and 19-5 below) for monograph publication. 

Honors and Awards; Publications: 



111 



Serial No. M-AP(C) 19-2 

1 . Adult Psychiatry Branch 

2. Section on Twin & Sibling Studies 

3. Bethesda, Maryland 

PHS-HSMA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 

Project Title: Studies in the Development of Personality and Psychopathology 
in Identical Twins Discordant for Schizophrenia 

Previous Serial Number: same 

Principal Investigator: William Pollin, M.D. 

Other Investigators: none 

Cooperating Units: 

A. NIMH : 

Social Service Department (Eleanor Dibble) 

Computer Systems Branch, Office of Adm inistrative Management (Nils 

Mattsson) 
Center for Studies of Schizophrenia, CRB, ERPC (Dr. Loren Mosher) 

B. The George Washington University, Department of Psychology Graduate 

Facility (Mrs. Mae Leisinger, Dr. Malcolm L. Meltzer) 
Galesburg State Research Hospital, Galesburg, 111. (Dr. Harold Himwich) 

Man Years (computed for the 12 month period) 

Total: 1.3 
Professional: 1.1 
Other: .2 

Project Description: 

Objectives : 

In identical twins discordant for schizophrenia, genetic, racial, ethnic, 
social class and a variety of other variables which have seemed to bear some 
relationship to the pathogenesis of this illness are constant for both twins. 
Therefore, in studying pairs in which one twin is schizophrenic and the other 
is not, there exists an unusually favorable situation within which to attempt 
to determine what life history events, family relationship patterns and non- 
genetic biologic factors play a role in the etiology of this illness, and in 
what manner. In addition, a new method of analyzing and comparing twin and 
control data has made it possible to define probable genetic factors which 
predispose to schizophrenia. The overall picture of schizophrenia patho- 
genesis which is then possible enables one to aim at a more rational approach 
to development of new treatment modalities. 



113 



Serial No. M-AP(C) 19-2 

Methods Employed ; 

Previous reports have described the intensive multidisciplinary in- 
patient work-up of a total of 25 families with identical twins admitted for 
evaluation to the Clinical Center. 

During the past year, Mrs. Mae Leisinger, working on her Ph.D. disser- 
tation under my supervision, tested a series of hypotheses relating schizo- 
phrenia to family interaction and pathology. The conceptual frame of refer- 
ence was that shared unconscious pathology of the family system generates 
interlocking tensions which are reduced and projected onto a particular mem- 
ber. This member's fragmentation of experience, identity diffusion, dis- 
turbance of motor perception and distortion of thought and affect — some 
of the salient characteristics of schizophrenia — are hypothesized to re- 
flect to a maximum degree the distortions clinically resident in other family 
members and/or their relationship with one another. To test these hypotheses, 
an additional group of ten local, community resident families with "normal" 
twin pairs were given the same TAT and Leary Interpersonal Testlist procedures 
previously employed with the series of families of MZ pairs discordant for 
schizophrenia, and the resultant N of 30 families (120 individuals) analyzed. 
Each individual described himself, his hypothetical ideal self, and each of 
the three other family members; specialized scoring systems were used to 
measure: 1) the level of conscious communication; 2) the level of private 
perception versus pre-conscious symbolic representation; and 3) the level of 
values or ego ideal . 

Patient Material: 



See previous reports for details. Fifteen monozygotic twin pairs dis- 
cordant for schizophrenia and their families (one pair became concordant) ; 
20 control twin families. 

Major Findings : 

Previous reports have described earlier findings. Differences distin- 
guishing index schizophrenic from non-schizophrenic co-twin controls in dis- 
cordant pairs have included family perception and relationship differences, 
life history and non-genetic constitutional differences; and biochemical 
findings apparently related to schizophrenic genotypes involving catechol- 
amine metabolism. 

New findings this past year involved family interaction data. It was 
found that individuals in the schizophrenic families unconsciously perceive 
themselves as very similar ~ father similar to mother and parents similar to 
offspring. Normal family members, instead, portray themselves as different 
one from the other within the families with the father particularly being 
perceived as exhibiting a well-differentiated role identity. The data suggest 
that the normal father is the family member who customarily disentangles the 
family group, but the fathers of schizophrenics seem unable to do this. This 
similarity is, however, either unrecognized or unadmitted. This blurring of 
sex role differences seems to skew the family system, and the family is seen 
to have an "undifferentiated ego mass" as previously described by Bowen. 
Further, there is substantial evidence, consistent with Laing's formulations 

lli^ 



Serial No, M-APCC) 19-2 

that the parents perceive the schizophrenic in terms that misdefine him to 
himself. In particular, the parental message for the schizophrenic is that 
he is passive and instrumentally unable to master his environment. These 
observations are consistent with those of Tienari and Kallmann, and with the 
earlier clinical observations by this group, who had reported a pattern in the 
discordant MZ pairs, beginning in the earliest years, by which the index was 
rigidly imprinted with a role expectation of incompetence and dependence. The 
question quickly arises as to the extent to which this familial perception of 
the schizophrenic as passive and incompetent is based on the reality of the 
results of his illness. To some extent this must be the case. However, a 
most interesting relationship between such disconfirmation of the index, and 
parental intrapsychic repression, strongly suggests that this is not the 
entire story. The higher the degree of parental repression, the greater the 
degree of parental disconfirmation of the index twin. This finding presents 
an interesting parallelism to the formulation of defensive delineations pre- 
viously proposed by Roger Shapiro's group, and suggests that the disconfirma- 
tion is in part a process that is meeting unconscious psychological needs 
of the parent. Leisinger suggests "One may analogize from the wit of G. B. 
Shaw who, as Eliza in Pygmalion, says, "The difference between a flower girl 
and a lady is not how she behaves, but how she is treated,' to say, the 
difference between a schizophrenic and another twin is not how he responds, 
but how he is perceived." Clearly this is not the whole story, but the 
interesting, statistically significant relationship between parental repress- 
ion and the above findings strongly suggest that it is part of the story. 

Significance to Mental Health Research : 

Previous analysis has focused on the significance of defining a) non- 
genetic constitutional contributions toward the pathogenesis of schizophrenia, 
and b) a characteristic pre-illness life course preceding schizophrenia. 
The findings of the past two years suggest some of the genetically determined 
biological factors which contribute to predisposition to this psychosis, and 
help establish by quantitative rather than clinical data some of the relevant 
family processes . 

Proposed Course of Project : 

Continuing analysis of multidisciplinary data with further efforts to 
trace central relationships involved. Replication study as described 
below (19-5), with focus on newly available biochemical possibilities, 
including DMJ determinations (Himwich) and collaborative methyl transferase 
determinations (Wyatt and Himwich) . 

Honors and Awards : 

Pollin, William: Guest lecturer, Northern Virginia Mental Health Center 

Pollin, William: Guest lecturer. The George Washington University, 
Department of Psychology Graduate Facility. 



115 



Serial No. M-AP(C) 19-2 



Publications ; 



Pollin, W.: The pathogenesis of schizophrenia: Possible relationships 
between genetic, biochemical and experiential factors. (In press. 
Arch. Gen. Psychiat.) 

Pollin, W. : A new approach to the use of twin study data in studies of 
the pathogenesis of schizophrenia and neurosis. In Kaplan, A. (Ed.): 
Genetic Factors in Schizophrenia . Springfield, 111., Charles C. Thomas, 
1972^ pp. 374-379. 

Pollin, W. A possible genetic factor related to psychosis. Reprinted 
in Vestnik Proceedings Academy of Medical Science of USSR 5: 57-59, 
1971. 

Pollin, W. : Genetic and environmental determinants of neurosis. In 
Kaplan, A. (Ed.): Human Behavior Genetics . (In press, Springfield, 
111., Charles C. Thomas) 



116 



Serial No. M-AP(C) 19-5 

1. Adult Psychiatry Branch 

2. Section on Twin & Sibling Studies 

3. Bethesda, Maryland 

PHS-HSMHA-Nim 
Individual Progress Report 
July 1, 1971 through June 30, 1972 

Project Title: The Distribution and Concomitants of Schizophrenia, and 

Other Psychopathologies, in a Systematic Sample of 15,909 
Ts'/in Pairs 

Previous Serial Number: Same 

Principal Investigator: William Pollin, M.D. 

Other Investigator: Stephen Cohen, M.D. 

Cooperating Units: 

A. NIMH: 

Social Work Department, Mrs, Eleanor Dibble 

B. National Academy of Sciences /National Research Council, Dr. Z, Hrubec 
Georgetown University, Dr. Martin 

Human Genetics Branch, NIDR, Mr. Webster Leyshon 

Man Years (Computed for the 12 month period) 

Total: 1.9 
Professional: 1.0 
Other: .9 

Project Description: 

Objectives : 

1. To identify, contact, and recruit a replication sample for a new 
study into the pathogenesis of psychosis. (See 19-2) 

2. To determine which of the differentiating factors previously uncover- 
ed in our study of a series of identical twins discordant for schizophrenia 
can be validated by analyzing a much larger systematic series of twins dis- 
cordant for schizophrenia. 

3. To determine which, if any, of these factors are specifically rele- 
vant to schizophrenia, and which instead may predispose toward non-schizo- 
phrenic psychosis, or non-psychotic psychopathology . 

4. To evaluate the relative genetic component in the etiology of schizo- 
phrenia, in comparison to other psychopathologies; in particular, affective 
psychosis . 

Methods Employed : 

In a National Research Council sample of 15,909 pairs of male twins, both 
of whom served in the Armed Forces, and for whom extensive medical follow-up 



117 



Serial No. M-APCO 19-5 

is available, all subjects were located who were computerized as showing 
any psychiatric diagnosis, or were separated from the Service in such a 
manner as to indicate disabling psychopathology. Following analysis of the 
computer data, individual charts of the first subgroup of patients, com- 
prising 420 pairs with one or both diagnosed Schizophrenic Reaction, Involu- 
tional Psychotic Reaction, Affective Reaction, and Other Psychotic Reactions 
were called in from various parts of the country and thoroughly reviewed by a 
team of three psychiatrists-. Those charts that fulfill certain rigid diagnos- 
tic criteria for Schizophrenia and Manic Depressive psychosis have been 
identified and form the nuclear sample for further study. 

Recruitment letters have been sent by the NAS/NRC Follow-Up Agency to 
those twin pairs who met our criteria, inquiring as to their availability for 
participation in the study either in their home community or in Bethesda. 
Blood samples for zygosity detennination have been analyzed for pairs 
responding positively. 

Because of a disappointingly low yield in the affective psychosis cate- 
gory State Departments of Mental Hygiene were contacted nationwide. Three 
states currently maintain twin registries (California, North Carolina and 
New York) . A total of 366 possible referrals from the first two of these 
states have been received and are in the process of chart diagnostic review. 

Patient Material : 

Working with data obtained from 42 states' vital statistic offices, the 
NAS/NRC located 54,000 pairs of male twins, born between the years 1917 and 
1927. Of these, 15,909 pairs were identified by the Veterans Administration 
as both having served in the Armed Services. These twins represent a cohort 
born in the decade 1917-1927, and now range in age from 45 through 55; thus 
the age of maximal risk for the development of schizophrenia has been passed. 
We are currently vjorking with the 420 pairs of the 15,909 pairs for 
whom data are available, in which one or both twins have been listed as show- 
ing the diagnosis of Schizophrenia, Involutional Psychotic Reaction, 
Affective Reactions, and Other Psychotic Reactions. We will subsequently 
review the charts of twins with diagnosis for psychoneurosis and a group 
still to be selected to serve as normal controls. 

Of 229 California twins referred with possible Affective Psychosis 
diagnosis, 68 charts were selected as most likely candidates and sent to 
us for current review. 

Major Findings : 

1. The yield of potential MZ pairs discordant for Affective Psychosis, 
a key control group In our planned replication study, has been disappoint- 
ingly small, even after extension to three state hospital systems, and it 
may be necessary to give up this phase of the contemplated study design. 

2. A systematic review of the claims files of all 420 veteran twin 
pairs from the NAS/NRC twin panel of 15,909 pairs where one or both twins 
had a psychotic diagnosis revealed that the MZ pairwise concordance rate for 
schizoaffective disorder is more than two times higher than that of 

118 



I 



Serial No. M-AP(C) 19-5 

schizophrenia, but not significantly different from that of manic depressive 
illness. Monozygotic twins concordant for schizoaffective disorder had 
affective symptomatology equal to that of manic depressive twins and schizo- 
phrenic symptomatology equal to that of the schizophrenic twins. For both 
twins in MZ pairs concordant for illness, schizoaffective psychosis has a 
mean age of onset which is earlier than both manic depressive psychosis and 
schizophrenia. Seven of 21 (33%) MZ index schizoaffective committed suicide, 
as opposed to none of the 18 manic depressives and 3 of the 100 index 
schizophrenic twins. 

3. From the NAS computer tape, 5,256 psychopathology diagnoses were 
initially identified in 3,614 individuals. These included the following 
subgroups of monozygotic, discordant pairs; 401 pairs discordant for psycho- 
neurosis, 112 personality disorders, 166 for psychophysiologic disorders, 
23 affective disorders, and 354 pairs discordant for other psychopathology, 
in addition to the previously described 69 MZ pairs discordant for schizo- 
phrenia. Subsequent intensive chart review by a team of three psychiatrists 
has significantly refined these initial findings. For the first time, a 
common clinical yardstick has been applied to all subjects reviewed, and 
obvious errors located and corrected. In the 840 charts reviewed there were 
268 charts where changes in zygosity, diagnosis or disease course were made. 

Significance to Mental Health Research ; 

1. The findings concerning schizoaffective psychosis help clarify the 
diagnostic relationships of various types of psychosis. Specifically, the 
revised findings help document the conclusion that there may be a signifi- 
cantly greater genetic factor contributing to the pathogenesis of affective 
as compared to schizophrenic psychosis. They also indicate that the genetic 
mechanisms contributing to schizoaffective schizophrenia overlap with, or 
include, those of affective as well as schizophrenic psychosis. 

2. Identification of the sought for groups of MZ twins discordant for 
different psychopathologies would provide populations admirably suited for 
testing several major related hypotheses concerning schizophrenia. We have 
previously described a constellation of familial, life history, and biolog- 
ical factors, derived from intramural studies and the world literature, which 
has differentiated identical twins who become schizophrenic from their co— twins 
who do not. Comparison of the sample of MZ pairs discordant for several of 
the other psychopathologies, will make it possible a) to clarify and inte- 
grate into a conceptual schema those differentiating features which we 
replicate; and b) to determine which, if any, subgroup of these differentiating 
factors may be specific for schizophrenia, and which, on the other hand, are 
related to psychopathology in general. 

Proposed Course of Project : 

1. Continuing evaluation of additional state referrals, and completion 
of analysis of chart review. 

2. Questionnaire evaluation of selected subsamples of the above- 
described MZ pairs discordant for different definable psychopathologies, 

3. Direct study of appropriately selected subsamples to test 
previously described hypotheses. 



119 



Serial No. M-AP(C) 19-5 

Honors and Awards : 

None 

Publications : 

Cohen, S., Allen, M. , Pollin, W. and Hrubec, Z. The relationship of 
schizoaffective psychosis to manic depressive psychosis and 
schizophrenia: Findings in 15,909 veteran twin pairs. (In press. 
Arch . Gen , Psychiat . ) 

Allen, M. , Cohen, S., Pollin, W. Schizophrenia in veteran twins, a 
diagnostic review. Am. J. Psychiat. 28: 936-945, 1972 



120 



Serial No. M-APCC) 19-6 

1. Adult Psychiatry Branch 

2. Section on Twin & Sibling Studies 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 19 72 

Project Title: The Twin Intrapair-Comparative Technique in the Study of 
the Determinants of Early Personality Development 

Previous Serial Number: same 

Principal Investigators: Donald J. Cohen, M.D. and William Pollin, M.D. 

Co-principal Investigator: Eleanor Dibble 

Research Associate: Anna Nichols 

Cooperating Units: 

Section on Scientific Applications, AMCS , NIMH, Messrs. Nils Mattsson, 

Robert Rawlings , Jr., Darryl E. Bertolucci, Richard Fabsitz 
Social Work Department, NIMH 
Child Research Branch, NIMH (Nursery School), Dr. Charles Halverson and 

Gail Inoff (M-CR-24 (C)) 
Georgetown University, Washington, D.C., Dr. Martin Allen 
Children's Hospital, Washington, D.C., Drs. Beale Ong, Jerome Haller, 

and Ann Lodge 
Human Genetics Branch, NIDR, Mr. Webster Leyshon 
Department of Pathology, NIH, Dr. Louis Thomas 

Man Years (computed for the 12 month period) 

Total: 2.1 
Professional: 1.2 
Other: .9 

Project Description: 

Objectives : 

1. To develop methodologies for the study of the antecedents of person- 
ality in preschool children, based especially on the comparative study of 
pairs of twins. To study differences between children in relation to a) 
non-genetic biological differences between the twins, i.e. differences in the 
congenital endowment of the children and early differences during the first 
weeks of life; b) parental personalities and behaviors, specifically, differ- 
ences in relationship and perceptions of parents to Twin A versus Twin B; 
c) the impact of such differences in parent-child relationships, and of differ- 
ent experiences such as illness or surgery, on the children; and d) the origins 
of and differences between the children in relation to behavior problems. 



121 



Serial No, ,M-AP(C} 19-6 

2. To study the developmental roots of personality and family character- 
istics which have been related in our other studies on schizophrenia and psycho- 
pathology to the origins of serious mental illness. 



Methods Employed : 

(1) Longitudinal Study . Local obstetricians, officers of Mothers of 
Twins Clubs, and mothers familiar with our program, have referred families to 
the research program at various times during the gestation of the twins or soon 
after birth. Families were seen while the children were still unborn, and have 
been followed since that time. The children's current ages in this cohort of 
12 sets of twins range between almost 1 year of age and almost 6 years of age. 
The children in this cohort and their families have been studied with the fol- 
lowing procedures: Developmental evaluation and Bayley testing; neurological 
evaluation; psychiatric diagnostic evaluations of the twins and parents; fam- 
ily records; information from the Experimental Nursery School of the National 
Institute of Mental Health in which the children are enrolled at age 2-1/2 
years for one day of studies; evoked cortical potentials; projective psycholog- 
ical testing; and social work evaluations. The children and the parents are 
seen at regular intervals of from 3 to 6 months for evaluation and interview. 
Special forms have been developed for the taking of developmental history, 
family history, rating of behavior during Rorschach testing, and ratings of 
the children in experimental situations. 



I 

i 
I 



fli 

^ w\ 



(2) Epidemiological Study . On the basis of our studies on psychopathol 
and on the longitudinal study of normal twin development, we have initiated 
a new study titled "Childhood Personality Development: Twins and the Antece- 
dents of Personality." This epidemiological investigation aims at exploring 
the hypotheses and conclusions from the previous studies and extends the size 
of the sample, explicates and operationally defines particular variables that 
have emerged from clinical observations , and uses newly devised psychological 
instruments. The study employs a battery of psychological questionnaires and 
instruments, some newly devised and others adapted from other workers, with a 
population that will include approximately 600 families with twins between 
the ages of 1 year and 6 years of age. The major focus will be on twins who 
are monozygotic. The sample will be drawn from volunteers from Mothers of 
Twins Clubs, locally and nationally. Parents who volunteer will be sent by 
mail, in two phases, a series of questionnaires and forms, which they will 
return when completed. The 9 forms, which we call the psychological instrument, 
includes the following: 

1. Release of Information Form. This is a relatively standardized form 
which gives permission for communication with the family's obstetrician, 
pediatrician, hospitals, and schools. 

2. Family Background. This form contains questions about demographic in- 
formation and physical similarities between the children. Socioeconomic 
questions allow for the determination of social position and socioeconomic 
class (using the Hollingshead two-factor index of social position) . A 
series of questions about the children's physical similarity (height, 
weight, etc.) and about whether or not they are confused by members of the 
family and strangers allows for the determination of probable zygosity. 
The similarity and zygosity indices, newly devised by us, are based on 

122 



Serial No. M-AP(C) 19-6 

previous experience with, twins and work, done on determination of zygosity 
with adults. Validation will be achieved to collaborate with studies 
that have performed blood typing for zygosity. 

3. Pregnancy, Delivery and First Month, of Life. This form has a series 
of questions relating to problems during the pregnancy, problems during 
delivery, and problems during the first month of life for the children. 
Pregnancy form includes questions such as length of the pregnancy, diffi- 
culties during pregnancy, and medication during pregnancy. The delivery 
section relates to birth weight, problems during the first week of life, 
and time of first sustained contact between parents and children. The 
first month of life section is an elaboration of a scale which we have 
previously developed in our longitudinal study on the development of twins, 
The parents are asked questions in six operationally defined areas of 
functioning, including attentiveness , calmness, bodily functions, general 
overall development, and health. Indices have been developed for scoring 
difficulties during pregnancy , delivery and first month of life for each 
child. In addition, general questions about parental attitudes and con- 
cerns are scored separately. 

4. Twin Development During the First Years of Life. This form contains 
broad variables which have been found to be most relevant from our longi- 
tudinal study of children, and is an operational statement of the inter- 
twin comparison method. Each item is a question stated in the following 
way: Which child shows more of a particular characteristic, for example, 
which child was more cuddily. Respondent specifies two things: which 
child shews more of the personality attribute and how big a difference 
existed between the two children in relation to the personality attribute. 
Three age periods are covered: first year of life, second year of life, 
and current . 

5. The Childhood Personality Scale. This form is derived in part from 
the work of Drs. Earl Schaefer and Richard Q. Bell (Infant Behavior Scale). 
It relates to each child's characteristic behavior during the preceeding 
two months. Both socially desirable and socially undesirable character- 
istics are represented. The positive or socially desirable character- 
istics include verbal expressiveness, social response, inquisitiveness , 
vigor, etc. Negative characteristics include monotonous behavior, irrit- 
ability, destructibility , passivity, etc. 

6. Parents Report. This form concerns the way a parent feels he acts 
towards the child and a sense of how the ideal parent would act towards 
the same child. Concepts are derived from Drs. Earl Schaefer' s and 
Richard Bell's studies of parenting, and include concepts from their 
home behavior, parent behavior, and communication of marriage inventories. 
Each item is stated in the following form: I see the child's good points 
and faults. The respondent states whether this is an accurate description 
of his behavior, using a 6-point scale, and also states how the ideal 
parent would act toward the child. 

7. Recent Family Changes. This form assesses the family's perception of 
its adaptation and of the current family situation to which they feel the 
children are exposed. Specific problem areas, as well as general adap- 
tation, are covered by separate questions. Specific areas include family 
migration, recent losses, problems of marriage and finance, physical 

123 



Serial No. M-AP(C) 19-5 

illness, etc. The family is also asked to rate the degree to which the 
children are under stress, how well the children are coping with the 
stress, and an overall rating of the children's health. They are also 
asked to rate similar questions for each of the adults. Quantitative 
scores are derived from reports by both the father and mother of the 
degree of family stress. 

8. Behavior Problems. This form is derived from our clinical experience. 
The National Institute of Mental Health Psychopharmacology Study Section's 
instrument for behavioral assessment of children, Keith Conner's studies, 
and the work of other epidemiological investigators of childhood psycho- 
pathology. The form consists of items which describe particular problems 
of behavior. The respondent assesses whether the particular child has 
this problem, using a 4-point scale. The form can be scored using factors 
derived in other studies, for example, Conner's factors, quantitative 
scores relevant to the psychiatric classification system developed by 

the Group for the Advancement of Psychiatry. Thus, severity and particu- 
lar areas of psychopathology are scored. 

9. General Comments. This form consists of a general question which is 
open-ended to allow families to fill in other information which they 
think is of relevance. 

Both mother and father complete psychological forms. The mother alone 
completes the Release of Information form, the Family Background form, 
and the Pregnancy, Delivery and First Month of Life form. The mother 
and father individually complete the following instruments: Twin Develop- 
ment During the First Years of Life, Parents Report, Recent Family Changes, 
Behavior Problems, and General Comments. The father completes a separate 
form about his attitudes towards the pregnancy, which is derived from the 
larger form Pregnancy, Delivery, and First Month of Life, which is 
completed only by the mother. 

Collaborative arrangements have been established with the Section on 
Scientific Applications, Computer Systems Branch, NIMH for data reduc- 
tion and computer analysis of the data. 

Patient Materials : 

The longitudinal development of twins study consists of a cohort of 12 
sets of twins, 10 monozygotic and 2 dizygotic. The cohort for the epidemio- 
logical study will consist of approximately 600 sets of twins, 100 dizygotic, 
approximately, and the remainder monozygotic. 

Maj or Findings : 

(A) Longitudinal study : 

Eight of the sets of twins followed from the time of diagnosis of twin- 
ing in pregnancy through the current ages of 2-1/2 to 6 have been in the Child 
Research Branch, NIMH, nursery school. By June 1, 1972, all 10 sets of twins 
from this major cohort above the age of 3 will have been seen in the nursery 
school. In addition, they have all had the scheduled developmental evalua- 
tions, psychiatric interviews, social work evaluations, and projective testing. 
In general, these studies have shown a developmental sequence and set of 
interactions between constitution and family perception and behavior. 



124 



i 



Serial No. M-AP(C) 19-6 

In general, the child was more competent physiologically and behaviorally as 
a newborn tends td develop into the more articulate, coping, and socially 
competent preschooler. In contrast, his less well-endowed sibling tends to 
become more fearful and insecure. An important aspect of this developmental 
pattern relates to the better endowed child's ability to be both highly atten- 
tive to external stimulation and at the same time to be relatively calm. 
The child who is more calm and attentive is not only seen as less vulnerable 
by parents, but he also tends to have fewer physical difficulties during 
the first years of life. 

(B) Epidemiological study : 

This study has just emerged from the pilot testing phase. The major re- 
sults of this phase has been to perfect the psychological instrument and to 
establish its usefulness. 

Proposed Course of Project : 

The project will continue to study longitudinally the development of the 
children in the longitudinal cohort. It will be of particular interest to 
follow these children as they move into more formal schooling and through the 
oedipal and latency stages. A major focus of activity will be in relation to 
the large scale, epidemiological investigation of personality development of 
twins . 

Significance to Mental Health Research : 

The longitudinal study of twins has offered the opportunity to study in 
depth the contributions of genetic, non-genetic but congenital, and early 
experiential variables to the development of personality. This has made pos- 
sible the delineation of variables related both to vulnerability and to 
competence. The central role of arousal and the modulation of arousal, as 
well as the varieties of ways in which children and families can cope with 
stressful situation articulates with our other studies on schizophrenia. As 
the children in the longitudinal cohort enter the oedipal and latency stages, 
we will have the opportunity to observe the increasingly complex structural- 
ization of their behavior as they develop more complex coping and defense 
systems. The epidemiological study of twins will provide a major testing 
ground of many of our hypotheses about genetic and non-genetic antecedents of 
personality, with particular relation to our interest in the first months of 
life, family perception, and the development of competence. We believe, also, 
that the psychological instrument which we have developed will have broad 
application in other studies which aim at understanding the social and emo- 
tional development of children during the first years of life. 

Honors and Awards: 

None 

Publications : 

Cohen, D. , Allen, M. , Pollin, W. et al . : Personality development in 
twins: Competence in the newborn and preschool periods. (In press, 
J. Amer. Acad. Child Psychiat.) 

125 



n 



Serial Number: M-AP(C)-20-l 

1. Adult Psychiatry Branch 

2. Section on Clinical Psychology 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Recognizing and Interpreting: A Differentiation of 
Perceptual and Cognitive Patterns 

Previous Serial Number: None 

Principal Investigator (s) : Winfield H. Scott, Ph.D. 

Other Investigators: Monte Buchsbaum, M.D. 

Cooperating Units: Laboratory of Psychology, Division of Computer Research 
and Technology 

Man Years: (1971-1972) 

Total: .20 
Professional: .10 
Other: .10 

Project Description: 

Objectives : The purpose of the research is to study contrasting approaches 
to Rorschach responding, as a way of studying individual differences in 
thinking and perceiving, to study the relationships between these con- 
trasting approaches and contrasting varieties of symptom formation in 
psychiatric patients and differing patterns of performances on laboratory 
measures of perceptual and cognitive variables among psychiatric patients 
and normal subjects. In earlier work, two different approaches to Rorschach 
responding were identified. The first, the "Recognitory" approach, is one in 
which subjects tend to respond to qualities of blots with associations to 
things previously seen. In the contrasting "Interpretive" approach, 
subjects attribute qualities to the blots which are not innate in them, 
qualities such as movement and depth, and these become important determinents 
of responses. Both approaches can be observed among normal subjects as well 
as psychiatric patients. The objectives of continuing work on the project 
are to refine definitions of the contrasting approaches, to study their 
relationships to clinical symptomatology in psychiatric patients and to 
laboratory measures of perceptual and cognitive variables among both normal 
subjects and subjects who are psychiatrically impaired. 

Methods Employed : Normal subjects and psychiatric patients are administered 
the Rorschach in a strictly routinized fashion. In addition, they are 
administered other psychological tests, including the Wechsler Adult 
Intelligence Scale and measures of a variety of perceptual and cognitive 



127 



Serial Number: M-AP(C)-20-l 
variables. A scoring system has been developed for interpretive and 
recognitory features on the Rorschach. Thus statistical analyses are 
possible to do on the relationship between approaches to Rorschach re- 
sponding and performances on the laboratory measures of perceptual and 
cognitive variables. 

Major Findings : Factor analyses have been carried out on the associations 
of the interpretive and recognitory features in the Rorschach protocols of 
20 college students, v7ho were normal volunteers. While the recognitory 
features have emerged in a single factor, the interpretive features are 
divided into two different factors, which appear to reflect different 
styles of thinking and perceiving. The component elements of the first 
interpretive factor suggests that subjects with high scores on this 
factor tend to think and perceive in terms of ongoing processes, movement 
and change. In contrast, it suggested that subjects with high scores on 
the second interpretive factor tend to objectify processes, to think in 
terms of fixed outcomes of actions, and to think of objects in terms of j 
their uses. Subjects with high scores on the recognitory factor think 
and perceive heavily under the influence of concrete features of external 
stimuli, even to the point of stimulus-boundedness . A few relationships 
have been established among these normal subjects between interpretive 
tendencies and performances on some laboratory measures of perceptual and 
cognitive variables. Subjects who are given high global ratings on 
interpretiveness also have high scores on an Embedded Figures test, and 
on a size estimation test. They have lower scores on the Category Width 
test. Interpretive tendencies appear to be associated with field inde- 
pendence . 

Significance to Mental Health Research : The research may allow development 
of new systems of classifying patients in terms of diagnostic, therapeutic 
and prognostic variables which are associated with fundamental aspects of 
psychophysiological functioning. 

Proposed Course of Project : Both psychological test data and data on 
perceptual and cognitive variables have been gathered on a population of 
twins. It is proposed to study the relationship between interpretive and 
recognitory tendencies and laboratory measures in this population in an 
attempt to establish other relationships between perceptual and cognitive 
functioning and approaches to Rorschach responding. In addition, data 
are being gathered on a variety of acutely psychotic patients, in order to 
study variations in approaches to Rorschach responding among these patients. 

Honors and Awards : None 

Publications: 



Ulatowska, Hanna and Scott, Winfield H. Linguistic indicators of 
perceptual style. Linguistics , (in press). 



128 



Serial Number: M-AP(C)-20-4 

1. Adult Psychiatry Branch 

2. Section en Clinical Psychology 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title : The Consensus Rorschach and Focused Feedback as a 
Clinical Procedure 

Previous Serial Number: None 

Principal Investigator(s) : Winfield H. Scott, Ph.D., Elizabeth B. Sherwood, 

M.A., Carol A. Langsner 

Other Investigators: None 

Cooperating Units: Section on Personality Development 

Man Years: (1971-1972) 

Total: 1.00 
Professional: .8 
Other: .2 

Project Description: 

Objectives : The main objective of the research is to study the family as 
a small group, in order to identify salient differentiating features of 
families which may have effects on the functioning of their individual 
members. A second purpose is to explore the use of the Consensus Rorschach 
and video and audio tape feedback as a clinical technique which may be 
used in the assessment of families. Any family can be regarded as a small 
group, like other small groups which have tasks to perform, requiring a 
differentiation of roles. Each family has unique features which are likely 
to effect the functioning of the family as a whole, and the functioning of 
its individual members as well. The Consensus Rorschach provides a x%fay 
of studying these features under conditions which are standardized, but 
which provide families with an opportunity to express important features of 
the group freely. The current work also involves exploration of the 
potential applications of the Consensus Rorschach to clinical assessment. 
The family are made part of the diagnostic team in that they are asked to 
review their own performance during "feedback" sessions. In these sessions 
psychologists lead the family members in a discussion of their performance 
through the use of videotape or audiotape replay of the Consensus Rorschach 
procedure. A major objective of the research is to examine the effective- 
ness of the feedback procedure in changing the performance of family 
members in a subsequent administration of the Consensus Rorschach. 



129 



Serial Number: M-AP(C)-20-4 

Methods: Each family admitted to 3-West is asked to participate in the 
project. Both parents, the index patient and the one sibling closest 
in age to the patient take part in the Consensus Rorschach. They are 
required to see how many agreements they can reach about what an inkblot 
looks like. The procedure is recorded on both videotape and audiotape. 
Each family is randomly assigned to one of four different "feedback" 
conditions. Depending uppn the condition to which they are assigned, 
families review their performances on videotape or on audiotape, with or 
without psychologists present with them. At a third session, the 
Consensus Rorschach is repeated, as is a paper and pencil test. The pro- 
cedure produces data bearing on different effects of different feedback 
conditions, as well as on the differences among families in various aspects 
of performance on the Consensus Rorschach procedure itself. 

Major Findings : In the experimental situation, families can be regarded 
as small work groups. Families who have gone through the procedure - 
families of psychiatrically impaired adolescent children - are regularly 
unproductive or underproductive in the Consensus Rorschach procedure. But 
the reasons for low productivity vary from one family to another, and 
their identification provides a way of characterizing families and de- 
scribing salient features of those families as small groups. In some 
families, productivity is low because of relentless competitiveness among 
family members which prevents them from organizing around the task of 
reaching agreements, or precludes their modifying their individual per- 
ceptions sufficiently to reach agreements. In other families, productivity 
is low because percepts are not sufficiently differentiated for clear 
identification of real agreements to occur. In other instances, productivity 
is low because of difficulties in permitting appropriate role differentiation 
to occur, or because of the family's great discomfort in the test situation. 
Clinical observation would suggest that these differences may relate to 
the particular kinds of impairment in functioning demonstrated by the 
adolescent offspring. 

Significance to Mental Health Research : The project may result in 
identification of features of families which are likely to have effects 
on the functioning of individual members. It may also result in a technique 
useful to apply as a part of the clinical evaluation of families prior to 
their beginning in family therapy. It is likely that performance on the 
Consensus procedure and in the feedback session will have prognostic value, 
providing a basis for estimating the capacity of the family to engage in 
the process of regarding itself as a group which has effects on its 
individual members. Moreover, the project provides a way of assessing 
the effects of various "feedback" procedures now widely used in clinical 
settings . 



I 



130 



Serial Number: M-AP(C)-20-4 

Proposed Course of Project ; Eight out of an experimental series of 20 
families have gone through the three sessions of the procedure. As other 
families become available for study, they will be tested. Work is 
underway to modify the scoring system developed by Dr. Nathene Loveland 
for evaluation of communication deviances occuring in test sessions. 

Honors and Awards ; None 

Publications; None 



131 



Serial Number: M-AP(C)-20-5 

1. Adult Psychiatry Branch 

2. Section on Clinical Psychology 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Psychological Studies of Patients V7ith Affective Disorders 

Previous Serial Number: None 

Principal Investigator (s) : Edward F. Donnelly, Ph.D., Dennis L. Murphy, M.D. 

Other Investigators: Winfield H. Scott, Ph.D., James K. Dent, Ph.D. 

Cooperating Units: The Laboratory of Clinical Science, Section on Psychiatry 

Man Years: (1971-1972) 

Total: .45 
Professional: .4 
Other: .05 

Project Description: 

Objectives ; The purpose of the research is to study differences in 
psychological test response patterns between patients with affective dis- 
turbances and other psychiatric patients, and to explore the relationship 
between test response patterns and a range of clinical and experimental 
variables among patients with affective disturbances. A major goal is 
to clarify distinctions between patients with unipolar and bipolar 
affective disturbances. 

Methods: Psychological test productions of patients with a variety of 
affective disturbances constitute the basic data for differentiation of 
subgroups. The test data include both objective and projective personality 
tests, as well as an intelligence scale. Patterns of psychological test 
data are studied in relation to aspects of premorbid adjustment, course of 
illness during hospitalization, and adjustment following hospitalization. 

Major Findings : Differences have been observed in the test response 
patterns of patients with unipolar depressions on one hand, and bipolar 
patients - whether depressed or manic - on the other. On the Rorschach, 
patients with unipolar depressions develop responses which are dynamically 
expressive communications while bipolar patients develop responses which 
are concretely related to the inkblots. During the past year, it has been 
established that among patients hospitalized for depression, a group of 
unipolar patients can be differentiated from a group of bipolar patients 
on the basis of patterns of responses to the MMPI . Moreover, there is a 
difference between unipolar and bipolar depressed patients in the relation- 
ship between scores on a depression scale of the MMPI and ratings for 

133 



Serial Number: M-AP(C)-20-5 

depression on the Bunney-Hamburg scales. While there was a significant 
relationship between the two for unipolar patients, there is not for 
bipolar patients. This would suggest that there may be a difference 
between the subjective experience of depression and outward manifestations 
of depression in behavior among bipolar patients. 

Significance to Mental Health Research : The research may contribute to 
a refined classification of patients with affective disturbances related 
to psychological test performances, patterns of perceptual and cognitive 
functioning, aspects of premorbid functioning and post-morbid adjustment. 

Proposed Course of Project : Further analyses will be done on data at 
hand, and additional data will be accumulated on new patients admitted 
to the Clinical Center for the treatment of depression. 

Honors and Awards: None 



Publications: None 



1 



13^^ 



Serial Number: M-AP(C)-20-6 

1. Adult Psychiatry Branch 

2. Section on Clinical Psychology 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July I, 1971 through June 30, 1972 

Project Title: Psychological Deficits in Selected Neurological Disorders 

Old Title: Psychological Assessment of Deficits in Affective Psychosis, 
Epilepsy and Schizophrenia 

Previous Serial Number: None 

Principal Investigator (s) : Edward F . Donnelly, Ph.D., Thomas N. Chase, M.D. 

Other Investigators: Norton M. Hadler, M.D., Max A. Baker, M.D. and 
Carol A. Langsner 

Cooperating Units: Laboratory of Clinical Science, NIMH and Arthritis and 
Rheumatic Branch, NIA^LD 

Man Years: (1971-1972) 

Total: .40 
Professional: .30 
Other: .10 

Project Description: 

Objectives : The objective of the research is to study patterns of deficit 
in personality, intellectual, cognitive and perceptual functioning in 
various neurological and psychiatric disorders, and to study drug- related 
changes in patterns of deficit. 

Methods : Patients with various neurological disorders such as Parkinson's 
disease, Huntington's disease and Down's syndrome are studied with 
psychological measures of intellectual, personality and central nervous 
system functioning. These include the Halstead-Reitan Battery, the MMPI 
and the Wechsler Adult Intelligence Scale. Behavioral observations are 
recorded on the Bunney-Hamburg scale. 

Major Findings : A study of the possible effects of L-dopa on intellectual 
and memory functioning reveals that I.Q. increments reported by prior 
studies can be explained as a function of practice effect, a variable 
difficult to control in longitudinal studies requiring testing and retesting. 
A long term followup of patients on L-dopa therapy suggests that there are 
no deleterious effects on intellectual functioning, although there is a 
slight (and non significant) decline in the scores on the Comprehension 
subtest of the WAIS for a portion of the patients. 



135 



Serial Number: M-AP(C)-20-6 

Si gnificance to Mental Health Research : From both clinically and 
empirically derived data, there have been claims for the improvement in 
intellectual functioning attributed to treatment with L-dopa. Observations 
would suggest, however, that the improvement can more likely be attributed 
to practice effect on the tests than to L-dopa induced effects. 

Proposed Course of Project : It is anticipated that during the coming year, 
patients with a variety of neurological disorders will be studied to 
establish what aspects of intellectual and personality functioning may 
be effected by the neurological disorders. In addition, the effects of 
drugs on the^e patterns of deficit will be studied. 

Honors and Awards: None 



Publications: 



Chase, T.N., Watanabe, A.M., Brodie, H.K.H. and Donnelly, E.F. 
Huntington's Chorea: Effect of serotonin depletion. Archives of 
Neurology, 26: 282-284, 1972. 



^ 



136 



Serial No. M-AP(c)-21-2 

1. Adult Psychiatry Branch 

2. Section on Perceptual and 
Cognitive Studies 

3. Bethesda, Maryland 

PHS -HSMHA-NIMH 
Individual Project Report 
July 1, 1971 - Jujie 30, 1972 

Project Title: Studies of Perceptual and Cognitive "Styles" in Psychiatric 

and Non-psychiatric Subjects. 
Previous Serial Number: Same 
Principal Investigator: Monte Buchsbaum, M.D. 

Other Investigators: Lyman C. Wynne, M.D., Ph.D.,; Stephen Landau, M.D. 
Thomas Bittker, M.D.; John S. Strauss, M.D.; Dennis 
Murphy, M.D.; Frederick K. Goodwin, M.D.; and 
William P. Carpenter, Jr. M.D. , Helm Stierlin, M.D. , 
Ph.D. 

Cooperating Units : Laboratory of Psychology, NIMH 



Man Years: 




Total; 


2.0 


Professional: 


1.0 


Other : 


1.0 



Project Description: 

Objectives; To relate individual differences in sensory perception and 
cognitive functioning in human subjects to psychiatric clinical dimensions 
and to neurophysiological measures; to develop and implement clinically 
valuable computerized measures of perceptual and cognitive functions . 

Methods Employed ; Research in this section focuses on disturbances in per- 
ceptual and cognitive behavior in psychiatric patients. Its work is closely 
coordinated with basic electrophysiological and perceptual research in the 
Unit of Psychophysiology, Laboratory of Psychology, NIMH. 

The finding of perceptual and attentional deficits in a variety of 
psychiatric patient groups has encouraged the development of theories of 
psychiatric illness and personality structure based on perceptual style. 
However, the psychiatric patient's report of his perceptions might reflect 
poor motivation, poor cooperation, failure to attend to instructions or in- 
ability to communicate with the examiner, rather than any actual perceptual 
difference. For this reason the section has emphasized electrophysiological 
correlates of perceptual behavior using averaged evoked response techniques. 

Major Findings; Affective Disorders. Off -drug average evoked response 
data have been collected on a population of 83 bipolar and unipolar patients 
and ^4-8 mat-ched normal controls. Earlier findings that bipolar patients 



137 



Serial Wo. M-AP(c)-21-2 

5. Narcotic Addicts. A group of narcotic addicts in a methadone 
research program at the VeterajD.s Administration Hospital is being studied 
both on and off methadone treatment on a single blind basis. Our interest 
in this group stems from study of a perceptual dimension termed "stimulus 
intensity control". This dimension is based on a series of studies of 
individual differences in responsiveness to sensory stimulation. Two differ- 
ent ways of accepting sensory input ha-ve been hypothesized: the "augmenter" 
who tends to increase the perceived intensity of stimuli and the "reducer" 
who tends to decrease it. Reducing, like habituation, may represent attempts 
to cope with sensory overload. The stimulus intensity control is being 
inferred for measurements of the average evoked response to varying inten- 
sities of auditory and visual stimulation. Opiates, which modify responses 
to painful or intense stimulation, would be expected to affect the evoked 
response at high intensities differently than low intensities. We have 
further hypothesized that narcotic addicts may differ from the control popu- 
lations in their baseline off -drug electrophysiological response to stimuli 
of various intensities. Tests of prognostic and diagnostic significance 
might develop from this program. 

Significance to Biomedical Research and the Program of fahe Institute; 
This project, in helping to give a neurophysiological basis to psychiatric 
diagnosis and prognosis, contributes to the effort to understand the 
mechanisms of psychiatric disease. 

Proposed Course of the Project : 

1. Comparison of clinical groups. During the next year, extensive 
analysis of data collected on affective disorder, schizophrenic and normal 
populations will be analyzed. New mathematical techniques being developed 
for the analysis of evoked response will be applied to this pool of data. 

2. Patient testing. We will continue to test patients with affective 
disorders and schizophrenia. Several new drug studies are planned with the 
affective disorder patients and emphasis will be on collecting off -drug data 
on schizophrenic patients . 

3. Twin studies will enter a data analysis phase with emphasis both 
on the determining Mz and Dz differences and using psychophysiological and 
psychophysical data to predict perceptual differences in Mz pairs. 

k. Collaboration with the Unit on Psychophysiology will continue 
on basic, perceptual and psychophysiological research on attention, 
habituation and stimulus intensity in order to increase our biochemical, 
psychological and clinical meaning of certain a^^erage evoked response 
components and their parametric changes . 

Honors and A.-rarls: jlone. 



138 



Serial No. M-AP(c) - 21-2 

showed larger amplitude evoked responses and especially at higher inten- 
sities ("augmentation") in comparison with unipolar patients have heen 
replicated. Of special interest is the finding that the "bipolar -unipolar 
difference was the greatest among patients with early onset of symptoms 
(less than age ko) since several investigators have demonstrated a greater 
genetic component in the affective illness in the early onset vs. late 
onset patients. In addition to the amplitude findings, changes in evoked 
response latency across stimulus intensity have also been found. Age, sex, 
biochemical data and behavioral ratings collected in conjtmction with the 
evoked response data are also undergoing analysis. 

2, Schizophrenic patients. A battery of tests including four average 
evoked response measures, perceptual tests, autonomic physiology and psycho- 
motor function have been collected so far on fifteen schizophrenic patients 
off drugs. Data collection will continue until a larger sample is collected. 

3. Twin studies. In order to assess the relative importance of genetic 
and environmental backgrounds, monozygotic and dizgotic normal twins are 
being studied using measures of autonomic and psychomotor functioning, average 
evoked response procedures, a battery of perceptual tests, questionnaires and 
interview data. Thus far approximately 60 twin pairs have been tested. The 
project is currently entering the data analysis phase. In addition family 
groups, both normal and psychiatric, have also been evaluated. 

k. Constancy of perceptual effects. Do the perceptual differences 
observed in psychiatric patients reflect an underlying and fixed biological 
characteristic or are they related to the attentional, affective and autonomic 
arousal state of the individual at the moment of the perceptual behavior? 
At a clinical level our approach to this problem is to compare two clinical 
groups, those with affective disorders and those with schizophrenia using 
only periods when the patients are off drugs. Comparisons are made between, 
on the one hand correlations between perceptual behavior and day to day 
clinical rating, and on the other hand correlations between perceptual 
behavior and historical, demographic, and genetic features. In comparing 
perceptual behavior in periods of mania or depression in cyclic patients 
with periods of depression in unipolar depressed patients, diagnostic 
categories determined by patient history appear to be more closely related 
to perceptual behavior and neurophysiological data than current patient 
mood as measured by nurse or physician ratings. Similar analyses will be 
done on the data from the schizophrenic patients. The effects of "state 
variables" such as attention and arousal are also being studied in normal 
populations. Comparisons of the effects of muscle tension, painful stimula- 
tion and shifts of attention toward or away from evoked response stimuli 
have demonstrated the importance of each of these factors but also have 
highlighted the importance of underlying individual differences in the 
habitual deployment of attention or channeling of arousal. 



139 



Serial No. M-AP-(c) 21-2 

Publications: 

Buchsbaum, M. : Average evoked response techniques and applications . Schiz. 
Bull . Winter, 1970. pp. 10-18. 

Buchsbaunij M., King, C. and Henkin, R. I,: Average evoked responses and 

psychophysical performance in patients with pseudohypoparathyroidism. 
J. Keurol. Neurosurg. Psychol. In press. 

Buchsbaum, M., Goodwin, F., Murphy, D«, and Borge, G. AER in affective dis- 
orders. Ajner. J. Psychiat , 128: 19-25. 1971. 

Borge, G., Buchsbaum, M., Goodwin, F., Murphy, D., and Silverman, J.: 

Neuropsychological correlates of affective disorders. Arch. Gen . 
Psychiat. 2k: 501-50^+, 1971. 



Gillin, J. C, Jacobs, L. S., Fram, D. H. , Williams, R. , Buchsbaum, M. and 
Snyder, F. Partial REM phase deprivation and schizophrenia: An 
experimental reappraisal. Arch. Gen. Psychiat . In press. 

Silverman, J., Buchsbaum, M. and Stierlin, H. : Sex differences in 
perceptual differentiation and stimulus intensity control. 
J. Persc Soc. Psychol, In press. 



ito 



Serial No. M-AP(c) - 21-U 

1. Adult Psychiatiy Branch 

2. Section on Perceptual and 
Cognitive Studies 

3. Bethesda 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 - June 30, 1972 

Project Title: Perceptual and cognitive style in normal twins. 

Previous Serial Number: Same, 

Principal Investigator: Monte Buchsbaum, M.D. 

Other Investigators: Lyman C. Wynne, M.D., Ph.D. 
Theodore P. Zahn, Ph.D. 
Stephen Landau, M.D. 
Winfield Scott, Ph.D. 
William Pollin, M.D. 

Cooperating Units: Unit on Psychophysiology, LP - NIMH 



Man Years: 




Total: 


3.0 


Professional: 


1.5 


Other: 


1.5 



Project Description: 

Objectives; Evaluation of the heritability and interaction of several 
sensory, perceptual and cognitive fimctions in normal volimteer tivins . 

Methods Employed : 

1) Rod and frame measure of field dependence-independence. 

2) Measure of scanning: direct monitoring of eye movements during 
a size estimation task. 

3) Auditory and -visual cortical evoked response measures designed to 
evaluate the effect of stimulus intensity, stimulus contrast, 
evoked response stability and cortical response symmetry. 

k) Rorschach inkblot test. 

5) Psychiatric background interview. 

6) Clinical rating scales (M-AP(c)-l^-l). 

7) Blood typing for zygosity (M-AP(c)-16-1). 

8) Autonomic and psychomotor functioning. 

9) Wise IQ test. 

Sixty twin pairs have been tested to date. Preliminary examination of 
the data has revealed predicted similarities in the monozygotic twins which 
are not found in dizygotic pairs. This is particularly apparent for the 
cortical evoked response wave forms and the stimulus intensity response 
amplitude functions augmenting-reducing concept. Data analysis will soon 
begin. 

ll^l 



Serial No. M-AP(C)-21-U 

Significance to Biomedical Research and the Program of the Institute; 

The concepts of field dependence-independence and stimulus intensity 
control have been relevant in predicting and explaining individual differ- 
ence in pain tolerance, sensory isolation, tolerance and response to 
stimulus overload. Preliminary studies here at the NIMH have revealed that 
there are fami.lial tendencies in perceptual styles as measured by standard 
psychophysiologic tasks and cortical evoked responses. One method of 
further elucidating the heritable nature of perceptual style is to investigate 
several perceptual functions in groups of monozygotic and dizygotic twins. 
This will allow us to draw some conclusions as to what aspects of perception 
are genetically transmitted and which ones are learned or modified by 
environmental experiences , 

Proposed Course of Project ; The cujrrent project was designed to run for 
three years. This will result in approximately 100 twin pairs tested at the 
end of that time. This large number is necessary in order to arrive at 
meaningful and significant conclusions about the objectives of the study. 

Honors and Awards; None, 

Publications ; None . 



142 



Serial No. M-CR-10 (c) 

1. Child Research Branch 

2. Child Behavior 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 



Project Title: Relations of Preschool Behavior to Present and Earlier 
Parent and Child Characteristics 

Previous Serial Number: SiME 

Principal Investigator: Charles F. Halverson, Jr. 

Other Investigators: Mary F. Waldrop, Richard Q. Bell 

Cooperating Units: Section on Twin and Sibling Studies, Adult Psychiatry 
Branch, NIMH [M-AP(C)-19-6] 

Man Years: 

Total: 9.0 
Professional: 2.2 
Other: 6.8 

Project Description: 

Objectives : 

To describe reliable and consistent measures of parent and child charac- 
teristics at the early preschool level to serve as developmental markers in 
the overall branch longitudinal research program, which includes studies of 
early marriage, newborns, early mother- infant interaction, and behavioral de- 
velopment in the first year of life. To organize and describe patterns of be- 
havior and individual differences in young children through experimental and 
naturalistic studies at various age periods in the preschool and early school 
years. Specifically, the object is to measure varieties of play, social de- 
velopment, peer behavior, assertiveness, cognition, and attentional processes 
in young children, and to measure relevant parental characteristics. 

Methods Employed : 

The final sample for the cohort presently being studied by the Branch, 
Cohort II, will consist of approximately 130 early preschool-age children and 
their parents. Explicit methodology of the research nursery school has been 
described in earlier annual reports. Groups of five children ranging in age 
from two and a half to three years of age attend nursery school for four weeks. 
Behavior measures are obtained by direct counts and timing. Play and peer 

li^3 



Serial No. M-CR-10 (c) 

behavior are also the basis for more global ratings of personality and social 
development. Measurement is directed toward attentional behavior in free and 
semi-structured play settings, social behavior in several contexts, and toward 
the quality and quantity of vigorous and assertive behaviors in various exper- 
imental situations. Cognitive and intellectual development is assessed in 
Individual tests and from analyses of ongoing speech and play behavior. 

The basic methodological considerations are (a) the stability of measures 
of play behavior during the four-week period, (b) construct validity of the 
cognitive and play variables, and (c) cross- setting generality of the various 
constructs. The planned analysis of the data calls for checking relations 
between the various kinds of measures (observations, ratings, experimental 
procedures) in different settings (indoor free play, rest, outdoor free play). 
This check will then provide the basis for composite variables describing 
more general characteristics of the child. 

All the preschool children in this cohort of the longitudinal study, in- 
cluding those who, for various reasons, cannot attend a full, four-week 
session of nursery school, are observed in a one-half-day session of free 
play. This session precedes each regular four-week session. The child and 
mother are individually transported to the research nursery school where, in 
the absence of peers, detailed records of the changes in play brought about 
by the entrance of strangers and the departure of the mother to another room 
are obtained. The mother is also interviewed about her child's social behav- 
ior and level of behavioral and social competence. At this time, the first 
in a series of detailed reviews of the child's and parent's activities for a 
week are obtained from the mother. By the end of the nursery school group, 
each mother has provided us with descriptions of three weeks in the child's 
and parent's lives. From these records we hope to check for relations between 
relevant parental behavior and the child's functioning in nursery school, as 
well as provide criterion data for material gathered on the parents at earlier 
points in time. Additional parent information is obtained by other interviews 
and rating procedures. 

Data collection on the main cohort of preschool children from our longi- 
tudinal sample has now been underway for two years and will continue to July, 
1973, to reach a total sample of approximately 65 males and 65 females. These 
cases are extremely valuable since, for most, newlywed data have been obtained 
on the parents, and the infant and mother- infant pairs have been studied in 
the first year of life. Currently, we have seen 90 of Cohort II, two-thirds 
of the core sample that we anticipate can be seen. Case loss in the first 
two years (moving out of the area, unable to contact, illness, etc.) continues 
to be approximately 25 percent. 

Major Findings : 

No analyses or results other than reliabilities can be carried out for 
this project until all the subjects have been seen. Several reports are in 
preparation based on previously seen longitudinal samples. Earlier reports 
have described studies based on a sample of children who had been studied 

Ikk 



Serial No. M-CR-10 (c) 

previously as newborns, in the research nursery school at two and a half years 
of agQ and at age' seven and a half, using a battery of cognitive tests and an 
assessment of play behavior. We are now collating these studies in a report 
for publication that shows children who were effective and assertive in pre- 
school barrier situations later, at seven and a half, were the ones who (a) 
had higher verbal intelligence and showed more imagination in play (cognitive 
domain) , (b) were more dominant in initiating peer contacts and were more vig- 
orous, less fearful and coped better with new situations (play domain). Also, 
high verbal males and females were high in verbal IQ, social maturity, and in 
amount of time exploring the free play environment. 

Also, a paper has been published delineating the rating system for the 
assessment of the hyperactivity factor in preschool children. Six facets of 
hyperactivity and three of withdrawal can be identified via teacher's rating 
scales and then combined into two factor scores. The scores can be used to 
identify hyperactive or withdrawn children in various treatment settings. 

We are also continuing a collaboration begun in 1970 with the Section on 
Twin and Sibling Studies of the Adult Psychiatry Branch, NIMH [M-AP(C) - 19-6] . 
We are now studying sets of twins that are part of a study of the early con- 
genital and experiential contributors to development. To date we have assessed 
six pairs of twins in a cohort of approximately ten pairs intensively studied 
from birth on. The final plan will be to relate our nursery school behavior 
to data collected by the collaborating section on genetic, physiological, and 
behavior variables during the early years. A preliminary clinical report based 
on the first five pairs of twins has been accepted for publication. 

Significance to Bio-Medical Research and the Program of the Institute : 

The identification of stable patterns of preschool behavior in the areas 
of assertiveness, response to caretakers, interaction with peers, and cogni- 
tive performance is important for the description of variations in human de- 
velopment. In addition, the several different developmental patterns associ- 
ated with hyperactive, impulsive behavior may provide some evidence about the 
early or congenital contributors to impulse -control problems. This type of 
behavior problem is one of the most frequent bases for referral of children 
to child guidance clinics. Studies of twins and behavioral activity in the 
preschool period provide additional evidence of the interface between genetic, 
physiological, and behavioral dimensions. The present longitudinal cohort 
even makes it possible to extend our studies of precursors to a phase in the 
life cycle prior to the infant's birth -- the preparental period. The planning 
of mental health programs, both diagnostic and remedial, will depend on such 
reliable information about development. The understanding of early develop- 
mental processes can lead to appropriate early intervention that would be more 
effective than diagnosis and treatment occurring at a much later point in time. 

Proposed Course of the Project : 

Data collection has been underway for two years, and will continue for 
one more year. An additional two years will be necessary for the reduction 



Serial No, M-CR-10 (c) 

and analysis of the vast amount of data obtained. Analyses of the preparatory 
study will continue and further reports will be prepared. 

Honors and Awards: None 

Publications: 

Bell, R. Q., Waldrop, M. F., and Weller, G. M.: A rating system for the 
assessment of hyperactive and withdrawn children in preschool samples. 
Amer. J. Orthopsychiat . 42: 23-34, 1972. 



1^6 



Serial No. M-CR-11 (c) 

1. Child Research Branch 

2. Infant Development 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Relations between Human Neonatal Behavior and Later 
Development 

Previous Serial Number; Same 

Principal Investigator: Raymond K. Yang 

Other Investigators: Richard Q. Bell 

Cooperating Units: None 

Man Years: 

Total: k.k3 
Professional: 3.25 
Other: 1.20 

Project Description: 

Objectives : 

This is a psychophysiological and behavioral study of human neonates, 
designed to provide measures of stable individual differences reflecting 
congenital characteristics of infants bom to families in the Branch Longitu- 
dinal Study. The data are to be used to: l) identify stable measures charac- 
terizing the human newborn; 2) identify continuities and discontinuities 
between the newborn period and later periods of development; and, 3) describe 
the fashion in which newborn characteristics interact with parental variables 
in producing later outcomes. 

Methods Employed : 

This section is currently reducing data (collected from I967 to 1970 on 
the Branch Longitudinal series. Cohort II) to forms amenable to computer 
analyses. Data was obtained from I38 human newborns. Each infant was 
observed in a hospital nursery and continuous recordings of selected psycho- 
physiological and behavioral functions were obtained during two consecutive 
interfeeding periods between 50 and 72 hours of age. The functions and 
responses recorded were: heart rate, respiratory rate, galvanic skin potential, 
electro -oculogram, skin temperature, body motility, tactile threshold, a 
righting reflex (the prone head response) , characteristics of non-nutritive 

IU7 



Serial No. M-CR-U (c) 

sucking, reaction to interruption of sucking, and pliyslclogical and behavioral 
changes due to swaddling. 

This section also has complete hospital records of the anesthetics and 
analgesics given the mothers of the infants during labor and delivery. In 
future analyses it is intended that these data will serve as a possible 
mediator of relations established between the newborn, and later periods of 
development . 

Major Findings ; 

The year was devoted entirely to data reduction. Tiie section faced the 
somewhat fonnidable task of reducing by hand ncre than 35,000 feet of 
poly graphic tracings to data that could be analyzed by computer. This task 
has been accomplished and the section has near completion an analysis of 
heart rate responses to threshold intensity tactile stimuli (determined by 
behavioral response) . Analyses indicated that the exclusive response was a 
monophasic acceleration above prestimulus levels that did not reach its peak 
magnitude until 9-15 seconds past stimulus onset. No heart rate responses 
were associated with sub-threshold stimulus intensities. Repetitive presenta- 
tions of threshold levels were characterized by a very rapid decrement in 
heart rate response , most of the decrement occurring between the first and 
second stimulus presentation. Neither threshold intensity nor magnitude of 
the heart rate response was affected by sex of the infant or sleep state 
(active or quiet) . There was a slight tendency for males and females to 
continue their behavioral responses to repetitive presentations of the 
stimulus during active sleep. 

Significance to Biomedical Research and the Program of the Institute ; 

Results from an earlier publication (Bell, Weller and Waldrop, Monogr. 
of the Soc. for Res. in Child Develpm. , 1971, Vol. 36, Nos. 1-2) suggest that 
paradoxical shifts in relations may occur between measures obtained during 
the newborn period and during the preschool period (2-l/2 to 3 years) : 
prognostically healthy signs at the newborn period (vigorous respiration and 
reflex responsiveness) were positively related to watching others rather than 
participative behavior at the nursery school period. These results were 
reported at a symposium on stress in Stockholm, at the International Congress 
of Psychology, in the Netherlands, and at a symposium of the American 
Psychological Association. A discussant at the latter symposium remarked 
that the same type of paradoxical shift between early and later behaviors 
had been uncovered in two other longitudinal studies, though this section's 
data on the newborns were from an earlier point in development. Thus it now 
appears that there is convergent evidence that relations between congenital 
behaviors , or other behaviors manifest in the first year of life , and later 
development , are of a different and much more complex nature than has 
heretofore been surmised. 

The elucidation of variables and relations such as these are useful not 
only in describing continuities in development, but also in locating areas 

li+8 



Serial No. M-CR-11 (c) 

of behavior in which reliable prognostic indicators of later behavior can be 
found. The data, currently being reduced to analyzable forms, will provide 
an opportunity to expand the areas in which this search can be made (extensive 
physiological and sleep data were not previously available) as well as to 
provide an opportunity to replicate the Bell, Weller and Waldrop findings. 

Proposed Course of the Project ; 

The major data reduction task should be completed early in the year. 
At that time, within-phase analyses will be undertaken to ascertain those 
variables and areas of newborn behavior that might provide fruitful relation- 
ships to data obtained with other phases of the longitudinal study. Once 
this is done, it should be possible to analyze and report on relations 
between these newborn measures and later behavior at three- and eleven-months 
postpartum, the latter obtained by one other team in the longitudinal study. 
Relations between newborn and preschool characteristics cannot be determined 
until 1975 ) since data gathering at this later phase will not be completed 
until 1973 > and reduction of the data will not be completed until two years 
later. 

Honors and Awards: None 

Publications : 

Bell, R.Q: Human neonatal behavior as a predictor of behavior in 
childhood stress situations. In L. Levy (Ed.), Society, stress 
and disease; childhood and adolescence . Oxford University Press : 
Oxford, England, to appear in 1972. 



Ik9 



Serial No. M-CR-12 (c) 

1. Child Research Branch 

2. Section on Family Development 

3. Bethesda, Maryland 

PHS-HSMHA~NIMH 

Individual Project Report 

July 1, 1971 through June 30, 197 2 

Project Title: Developmental Patterns in the Young Family 

Previous Serial Number: SAME 

Principal Investigator: Robert G. Ryder 

Other Investigators: David H. Olson, John S. Kafka, and 

Walter Sceery 

Man Years : 

Total: 5.92 
Professional: 2.52 
Other: 3.40 

Project Description: 

Objectives: 

To describe and formulate variations in relationships 
among young married couples; to describe and explicate the 
developmental history of differing patterns of 
relationships; to integrate sub-cultural, social, and 
personality phenomena into a comprehensive view of intimate 
human relationships, to investigate correspondence among 
marriage patterns, attributes of offspring and patterns of 
parent-child interaction. 

Methods Employed : 

Most of the data presently being studied were 
previously collected from a sample of 2,162 young married 
couples from the Washington, D.C. metropolitan area. The 
quantitative portion of this body of data has largely been 
collated and organized into computer files from which 
substantive analyses can be undertaken. The qualitative 
data, consisting primarily of written records and reports, 
has been altered to protect confidentiality, and recorded on 
microfilm. Original copies of most written material have 
been placed in federal storage, and will be destroyed after 



151 



Serial No. M-CR-12 (c) 
the completeness of the microfilm copies has been definitely 
established. 

Present data collection is limited to marriage followup 
studies of couples whose children have reached the preschool 
phase of the Branch longitudinal study, a group of about 80 
couples so far. Data collection includes interaction 
procedures, questionnaires and an interview. 

The Qualitative Unusual Event Sorting Technique 
(QUEST) , developed in FY 1971, has been used to generate 
clusters among self descriptive terms provided by subjects. 
All cases are presently being scored for these clusters. 
QUEST is presently being used to generate a set of clusters 
from codings of subjects' written essays about their 
marriages . 

A new technique for studying interaction sequences is 
being developed, for use with interaction data from this and 
other projects. This Sequence Correlation Procedure (SCP) 
departs greatly from traditional procedure, which generates 
transitional probabilities, requires a great deal of data, 
and can yield umvieldy results. Useful but somewhat 
different kinds of information seem obtainable vrith 
substantially more economy from SCP, VJhile more 
conventional procedure treats a sequence of events, in 
effect, as a matrix, SCP specifies a sequence as simply a 
vector, with consequent reduction in the numerical 
complexity of results. SCP should also make it possible to 
uncover sequential patterns embedded in a context of 
irrelevant events, which might be lost using other 
procedures . 

Major Findings : 

Preliminary intercorrelations among all presently 
scored questionnaire variables indicates a far higher number 
of significant relationships than v/ould he expected by 
chance. The organization of these relationships into 
dimensions, to be revised by an iterative process, is in 
progress . 

Longitudinal data has been used to partially replicate 
findings from other laboratories that having a child is 
related to a decrease in self reports of "marriage 
satisfaction". One such study also reports, in effect, that 
couples initially high in "marriage satisfaction" shov; the 
greatest decrease. The analysis completed in the present 
project also shows a decrease in "marriage satisfaction" 
that is greater for couples who have a child than for 



152 



Serial No. M-CR-12 (c) 

couples who do not have a child in the same time interval, 
and indicates that the most consistent content involved in 
this relationship is the \\-ife's self report that her husband 
is inattentive to her. IJomen who have a child, as compared 
with women who do not in the same time interval, become more 
likely to report that husbands do not pay enough attention 
to them. There was no evidence whatever to support the view 
that this effect was related to one's initial scores on 
"marriage satisfaction" . 

Longitudinal data are also being used at present to 
investigate changes in reported sexual behavior and interest 
in the first few years of marriage. There appears to be a 
general decline in both reported activity and interest 
between the spouses, somevrhat greater, on the average, for 
the wife than for the husband. 

Interaction data from the Color Matching Test has been 
factored and the factors replicated. The resulting 
dimensions are presently being adjusted to an optimal 
profile rotation, i.e., a rotation which maximally 
differentiates among couples, versus the standard 
rotational aim of maximally differentiating among variables. 
It appears that three or four dimensions are stable among 
samples of about 200 couples, as compared with two or three 
dimensions from the much smaller samples previously 
employed. Interaction data are still being coded from the 
Inventory of Marital Conflict, and the Inventory of Family 
Conflict. Data from the Inventory of Family Conflict is 
still being collected, since this procedure is used with 
longitudinal couples whose children are presently going 
through the Child Research Branch nursery school. 

Consideration of previous experience with interaction 
procedures has led to a report by David Olson called "The 
Power lessness of Family Power", in which he notes the 
extremely poor correspondence of alleged power measures 
collected from different sources. The principal 
investigator has completed a conceptual work attempting to 
delineate just what is meant by the word "power". A 
principal conclusion was that power is best viev;ed as a 
psychological concept involving motivation. "A" is said to 
have power over "B" if "A" can get "B" to do something "A" 
wants done and "B" does not want done. Three varieties of 
power were defined: contingency power, cost-effectiveness 
power, and resource power. 

Work was also advanced on global descriptions of 
particular marriage patterns. Adequate preliminary coding 
reliability was established for locating spouses in a five 



153 



Serial No. M-CR-12 (c"i 



dimensional inferential framework. Husbands vrere considered 
according to attributed effectiveness and impulse control, 
and wives according to "dependency" , attitude toward 
attention and orientation toward the marriage. 

An impressionistic report of marriages in v/hat has been 
called the counter culture has also been completed. Aspects 
emphasized in this report are a return of conventionality, 
demystification of sexuality, a general approach to tension, 
and a psychology of plenty. Conceptual links among these 
facets were noted. 



Significance to Bio-Medical Research and the Program of the 
Institute; 

There continues to be a growing interest, in the 
general marriage and family field, in the substantive 
findings and methodological advances of this project. A 
significant contribution to knowledge about concomitants of 
child bearing is one substantive matter of widespread 
interest. A popular enthusiasm for measures of family power 
is likely to be effected by the more conservative viev? we 
find supported by our data. A serious need for 
dispassionate views of the family implications of 
alternative life-styles is answered in part by the project 
work on unconventional couples . 

The primary significance of the project continues to be 
in progressing toward more differentiated ways of describing 
and viewing intimate relationships, which should be useful 
to those dealing clinically or by way of research with 
married couples, and in cooperating v/ith other projects in 
the Child Research Branch in attempting to demonstrate 
predictive relationships between kinds of young married 
couples and their subsequent offspring. 

Proposed Course of Project; 

Activities for the coming fiscal year will continue to 
consist primarily of working v/ith the data in hand- 
Quantitative and quasi-clinical studies, studies of 
particular relationship patterns, and comprehensive studies 
of dimensionality are to be carried forv/ard with a view to 
eventual integration. 



15h 



Serial No. M-CR-12 (c) 



Honors and Awards ; 

The principal investigator was nominated to be 
president of the Groves Conference on Marriage and the 
Family. 

Publications : 



DuPont, R.L., Ryder, R.G. and Grunebaum, H. : An Unexpected 
Result of Psychosis in Marriage. American Journal of Psychiatry, 
128: 6, 735-739, 1971 

Kafka, J.S.: Discussion of: An Unexpected Result of 
Psychosis in Marriage. Am erican Journal of Psychiatry, 
128: 738-739, 1971 

Kafka, J.S.: Paradox, Time and Object Constancy. 
Scientific Bulletin of the British Psycho-Analytical 
Society , 331 23-39, 1972 

Kafka, J.S.: Report on Panel on "The Experience of Time". 
Journal of the American Psychoanalytic Assn. (in press) 1972 

Olson, D.H. : The Powerlessness of Family Power: Empirical and 
Clinical Considerations, Science and Psychoanalysis, 
22: 139-147, 1972 

Olson, D.H.: Empirically Unbinding the Double Bind: 

Review of Research £ Conceptual Reformulation. Family Process, 

II: 1, 69-94, 1972 

Olson, D.H. and Rabunsky, C.C.: Validity of Four Measures 
of Family Power, Journal of Marriage and The Family, 
(in press) 1972 

Ryder, R.G.: Dimensional Structure of SPAT (The Spouse 
Adjective Test) Catalog of Selected Documents in Psychology , 
1: 17, 1971 ~ 

Ryder, R.G.: What is Power? Definitional Considerations 
and some Research Implications. Science and Psychoanalysis, 
22: 36-52, 1972 



155 



Serial No. M-CR-22(c) 

1. Child Research Branch 

2. Infant Development 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 



Project Title: Offspring Effects on Parents 

Previous Serial Number: Same 

Principal Investigator: Richard Q. Bell 

Other Investigators: Lawrence V. Harper, University of California at Davis 

Cooperating Units: DCRT, Computation and Data Processing Branch 

Man Years : 

Total: 1.0 
Professional: .4 
Other : . 6 

Project Description: 

Objectives ; 

To review the literature for evidence of offspring effects on parents; 
to provide a conceptual scheme to organize findings; to initiate studies 
in areas crucial to theories of early development. 

Methods Employed ; 

Literature search, concept development, and development of research 
methods relevant to offspring effects on parents . 

Major Findings : 

In last year's report we mentioned efforts to locate hierarchies of 
infant and maternal behaviors from home observation data between the first 
and ninth week of life. Inspection of data from a computer program pre- 
pared by DCRT for analyzing temporal contingencies in mother-infant inter- 
actions, indicates our searching method is valid. This method consists of 
scanning computer-plotted frequency distributions that show the frequency 
of first occurrences of one category of responses after varying intervals 
following occurrences of responses in another category. Scanning resulted 
in finding non-random distributions for a substantial number of our cases 



156 



Serial No. M-CR-22(c) 

for a sequence known to exist in the data on the basis of previous studies. 
That is, crying should follow fussing at other than random intervals, and 
more frequently than fussing follows crying. This proved to be the case, 
following which we searched for other elements in the sequence that have 
not already been established in prior studies. It was found that vocal- 
izing usually precedes fussing, but not the reverse, whereas general 
movement can either precede or follow vocalization. 

Thus, looking at the infant data alone, it appears we have located an 
ordered response repertoire. We can now take the step of checking this 
repertoire for age changes . Components that show age changes can then be 
checked for the influence of maternal responses. In this way we can proceed 
to test the hypothesis that infants and parents respond to each other, not 
only in terms of single events, but also in terms of each other's reper- 
toires. The research approach was reported at the April 1972 meeting of 
the Committee of Correspondents on Infancy. 

Lawrence Harper has completed a paper reviewing all sources of data 
relevant to the human infant's effect on parents or caretakers. This paper 
paralleled a previous review carried out on infra-human mammals, and showed 
that the effect of the young ranged from the impact on the physiology of 
the mother through to alteration of the relationship of the parents to 
their physical and social environment, just as was the case in infra-human 
primates. One of the challenging conclusions that Dr. Harper wasable to 
reach in the review of the paper on primates was that the young had played 
a vital role in the radiation of species into different environments, and 
that the innovative and exploratory activities of the young offset normal 
cultural transmission. Even in the primate colonies, cultural transmission 
from adults is conservative and operates to restrict the range and flexi- 
bility of animal troups . Though the evidence was of a different nature, 
similar conclusions could be reached at the human level. 

Significance to Biomedical Research and the Program of the Institute ; 

This series of conceptual, methodological and empirical contributions 
is intended to bring about a revision of socialization theory and research 
methods that have, in the main, proved relatively unproductive in recent 
years. The revised approach may make it possible to launch socialization 
research on a course that corresponds better to the realities of parent- 
child interaction, and thus increase the likelihood of generating more 
consistent results than in the past. Socialization research is, in turn, 
the basis for advice to parents as well as the basis for many social and 
family-oriented action programs. 

Proposed Course of the Project : 

All papers from this project, along with contributions to the field 
from other authors, are being collated in a volume of readings on the 
effects of the young on their parents. Ihe analyses of mother-infant inter- 
actions will be continued with the objective of locating parent response 



15T 



Serial No. M-CR-22(c) 

hierarchies, and ascertaining how these interact with infant behavior 
repertoires in the production of age changes . 

Honors and Awards ; 

Richard Bell was invited to be the keynote speaker at the first of a 
series of annual conferences on the origins of behavior, sponsored by 
the Educational Testing Service. 

Publications : 

Bell, R. Q.: Reduction of the stress in child rearing. In Levy, L. 
(Ed.): Society, Stress, and Disease: Childhood and Adolescence . 
Oxford, England, Oxford University Press, In press. 



158 



Serial No. M-CR-23 (c) 

1. Child Research Branch 

2. Section on P&rent- Infant Behavior 

3. Bethesda, Maryland 

EHS-HSMHA-Un^lH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Determinants and Dimensions of Mother- Infant Interaction 

Previous Serial Number: Same 

Principal Investigator: Howard A. Moss 

Other Investigators: Sandra J. Jones 

Cooperating Units: None 

Man Years: 

Total: i+.17 
Professional: 1.17 
Other: 3.00 

Project Description: 

Objectives ; 

The major objectives of this research are to identify primary dimensions 
of mother-infant interaction, to illuminate the determinants of these inter- 
action patterns, and to relate these findings to data provided by other com- 
ponents of the Branch longitudinal program, including the early behavioral 
makeup of the infant, the preparental relationship of the mother and father, 
and the mother's early experience with her own family. In addition, the data 
obtained from the mother-infant study vill be used to predict nursery school 
behavior when the children are studied at 2^ years of age. 

Methods Employed: 

The data collection for this project on mother-infant behavior was initi- 
ated in September, 19^7 and completed by October, 1970. Although most of the 
reliability data was collected throughout the course of the study, there vere 
some cases studied through January, 1971, for the purpose of obteiining addi- 
tional reliability information on sane of the procedures. The sample consists 
of 121 mother-infant pairs from the second cohort of the Branch's longitudinal 
program. 

All the procedures administered in the main longitudinal study of mother- 
infant interaction have been described in detail in previous annual reports. 

159 



Serial No. M-CR-23 (c) 
Therefore this annual report i-Till only provide a summarj-. 

(1) Interviews and questionnaires were administered to the expectant 

mother during the last trimester of pregnancy. 

(2) Two six-hour home observations were made of mother-infant interaction 
at three months of age. 

(3) Postpartum interviews and questionnaires were administered to the 
mother when the infant was about 3<^ months of age. ^.-Jhile these pro- 
cedures were being administered, the infant was studied in a labora- 
torj'- situation using procedures that involved vocal conditioning, 
visual attention, resistance to cuddling, and muscle tonus. 

(h) \lhen the infant; was eleven months old, a home visit was made durirg 
\7hich the mother was interviewed and the child was observed in struc- 
tured situations and in free play. Observations dealt with reaction 
to strangers, separation from the mother, imitation, socialization, 
exploratory behavior, etc. 

In addition, we have completed data collection on a subsample of 36 second- 
born mother-infant pairs for whom we have antecedent data on the first-born. 
Two six-hour home observations of matemal-infant interaction were made using 
the same measures employed in studying the first-born sample. Folloid.ng the 
second obsei*vation, the mother was interviewed briefly about differences and 
similarities between her experiences with her two infants. 

The majority of the staff effort for the past year has been devoted to 
coding, processing, and carrying out preliminarj^ analyses of data. Under a 
contract. Dr. Elizabeth Hillenbrand has completed ratings on the 121 postpartum 
interview tapes. The principal investigator conducted both the pregnancy and 
postpartum interviews but rated only the pregnancy tapes. Thus, independence 
of ratings between these two sets of data is being maintained. 

The i^l heme observation variables and the I7 global variables from the 
home observations have been standardized to correct for any differences between 
observers. Fifty- six new combination and contextual variables from the home 
observations have been generated based on patterns and sequences of scores. 
These will eventually be used \j±th our other measures in both our cross-sec- 
tional and longitudinal analyses. 

In addition, data preparation has been completed for the pregnauicy and 
postpart'.in questionnaires, the traditional family values questionnaire, the 
pregnancy and postpartum interview ratings, and the laboratory studies on vocal 
conditioning, visual attention, muscle tonus, and resistance to cuddling. The 
eleven-month study variables have been coded, reliabilities for the three ob- 
servers have been calculated, and the approximately 90 variables remaining are 
in the process of being put on IH'I cards to be added to the data decl: for each 
subject. 

160 



Serial No. M-CR-23 (c) 

Sir;nlficance to Bio-Medical Research and the Prop;ragi of the Institute ; 

The data collected from this project should provide basic information con- 
cerning the extent to which initial response tendencies in infants and various 
parental characteristics conjointly contribute to early mother-infant inter- 
action patterns. From these data we can begin to determine the variance in the 
mother-infant interaction that is attributable to infant characteristics, as 
well as the variance associated with particular maternal predispositions. The 
results of these studies should also help us understand the development of the 
mother's and infant's attachment toward one another; the emergence of social 
behavior and responsiveness in the young child; and some of the developmental 
antecedents of cognitive functioning. The results should also provide informa- 
tion concerning the basic dynamics of early personality functioning. 

Prcrposed Course of Project ; 

Data processing should be completed for all but the second-born sample 
during the coming year. All within-stage analyses of the mother-infant materi- 
al and the construction of the final set of variables to be used in the cross- 
sectional and longitudinal analyses should also be completed. The last year has 
been concentrated on data analyses. In the coming year our efforts will turn to 
the reporting and publication of findings. 

Honors and Awards ; 

None 

Publications ; 

Jones, S. J. Test of Bogartz's model on binary prediction by children. 
Psychonomic Science , In Press. 



161 



Serial No. M-CR-24 (c) 

1. Child Research Branch 

2. Child Behavior 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 



Project Title: Structure and Correlates of Preschool and Child Behavior 

Previous Serial Number: SAME 

Principal Investigator: Charles F. Halverson, Jr. 

Other Investigators: Mary F. Waldrop 

Cooperating Units: None 

Man Years: 

Total: 

Professional: 

Other: 

Project Description: 

This project has been incorporated in M-CR-IO (c) . 



163 



Serial No. M-CP(C)-18-3 

1. Laboratory of Clinical Psychobiology 

2. Section on Clinical Studies 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 



Project Title : Biochemical and Pharmacological Studies of Sleep 
Previous Serial Number; Same 



Principal Investigator : 
Other Investigators : 



Frederick Snyder, M.D. 

William E. Bunney, Jr., M.D., David H. Fram, M.D., 
J. Christian Gillin, M.D., Frederick K. Goodwin, M.D., 
Robert M. Post, M.D., Richard J. Wyatt, M.D., 



Joel Kotin, M.D., Leonard S. 
Robert I. Henkin, M.D. 



Jacobs, M.D. and 



Cooperating Units : 



Section on Psychiatry, Laboratory of Clinical Science, NIMH 
Laboratory of Clinical Psychopharmacology, SMR 
Experimental Therapeutics, National Heart and Lung 
Institute, NIH 



Man Years C1971) : 

Total : 3 
Professional: 1 1/2 
Other: 1 1/2 

Project Description : 

Objectives : 

Experimental findings over the past several years promise under- 
standing of the basic biochemical processes underlying sleep, and over 
the same period increasingly clear demonstrations of the severity of 
sleep disturbances in many psychiatric patients indicate the need for 
better means of alleviation. These practical and theoretical aspects 
are closely linked, for if biochemical understanding of sleep could be 
achieved, rational treatment of its disturbance would surely follow. 

The work of Jouvet and others in cats suggests that non-REM sleep 
is somehow related to serotonin metabolism, while REM sleep has a 
particular relationship to norepinephrine. Among the evidence for 

165 



Serial No. M-CP(C)-18~3, Page 2 



these conclusions is a specific reduction in non-REM sleep after 
parachlorophenyl alanine (PCP) administration, as well as the specific 
reduction of REM sleep by monoamine oxidase inhibitors (MAOI). Pre- 
vocative as these findings are, their human relevance was uncertain 
so long as comparable studies had not been carried out in man, and 
this has been the primary aim of our own efforts over the past 
several years,. 

Contrary to findings in the cat, we have reported that therapeutic 
doses of parachlorophenylalanine (PCP), an inhibitor of serotonin 
synthesis, produces marked suppression of REM sleep without diminution 
of total sleep, an effect which is reversed by 5-hydroxytryptophan 
(5-HTP) the serotonin precursor which by-passes the PCP inhibition 
of serotonin synthesis. On the other hand, we have found that 
inhibitors of catecholamine synthesis, alpha methyl paratyrosine 
(AMPT) or alpha methyl phenyl alanine (AMPHe) have the effect of 
elevating REM sleep levels without significant change in non-REM sleep. 
We have found that oral dosages of L-Dopa, presumably elevating 
central Dopamine concentrations, also diminish REM sleep. Thus, 
both serotonergic and adrenergic systems would appear to influence the 
occurrence of REM sleep, but in ways quite opposite to those implied 
by previous studies in the cat. 

While the main implications of these findings are being pursued by 
Dr. Wyatt at his new sleep laboratory in the Laboratory of Clinical 
Psychopharmacology, SMR, several related issues continue to be 
followed up here during the past year in a number of separate studies. 

Patient Material : 



4 medical patients 

15 psychiatric patients 

5 normal volunteers 



Methods and Findings : 

A. Effects of Intravenous DOPS and 5-HTP during Sleep 

A new approach to studying the biochemistry of human sleep involving 
the intravenous infusion of drugs during sleep with simultaneous 
monitoring of sleep patterns was described in last year's report 
together with first results. REM onset infusions of L-Dopa, 
25-50 mg. shortened the first REM period, while pre-REM infusions 
delayed the onset of the first REM period in patients pretreated with 
a peripheral decarboxylase inhibitor. 



166 



Serial No. M-CPCC)-18-3, Page 3 

During the past year the same approach has been extended to two 
other drugs affecting amine synthesis, DORA (an unnatural amino 
acid thought to be decarboxylated directly to norepinephrine without 
conversion to dopamine) and 5-HTP (the immediate precursor of 
serotonin. In the present studies eight depressed patients, pretreated 
with a peripheral decarboxylase inhibitor (MK-486, 50 mg. t.i.d.) 
were given a total of 22 DOPS infusions (50-150 mg.), 11 5-HTP 
infusions, and 28 placebo infusions. In contrast to L-Dopa, neither 
DOPS nor 5-HTP effected REM latency or the length of the first REM 
period. There were no differences in the overall nightly sleep 
patterns compared with placebo infusion. Larger doses of both drugs 
will be used in further trials. 

B. Effects of Histidine on Sleep 

As reported last year, 20 gm/day doses of L-histidine, the amino acid 
precursor of histamine, did not appear to have any effects on the 
sleep patterns of narcoleptic patients, discouraging the possibility 
that histamine is particularly implicated in the biochemistry of 
sleep and waking. Although that issue has been dormant for most of 
the past year, Drs. Gill in and Henkin have now revived it by 
beginning a series of studies at higher dosages of L-histidine 
(32 gm/day) in normal volunteer subjects. 

C. The Effects of Carbohydrate Active Steroids (CAS) on Human Sleep 

Pursuant to last year's work demonstrating significant reductions 
of REM sleep after moderately high pharmacological dosages of 
prednisone in normal volunteers, Drs. Gillin and Henkin are now 
examining the effects of carbohydrate active steroids both in normals 
and in patients with adrenal cortical insufficiency. 

The effects of CAS were studied in four patients (three with 
Addison's Disease and one with panhypopituitarism), on and off 
hormonal replacement therapy, as well as in five male volunteers 
during baseline conditions and while receiving metyrapone (reduces 
Cortisol production by inhibition of adrenal 11-B-hydrosylation). 
In both patients and volunteers decreased CAS was associated with 
significant increase in high-voltage slow-wave proportions of sleep 
and REM density (the intensity of rapid eye movement during REM 
sleep). The effects of increased CAS were studied in three 
volunteers by oral administration of prednisone 12.5 gm. 4 times/day 
and in 5 volunteers by intravenous infusions of ACTH. In both 
situations increased CAS resulted in significant decreases in REM 
and REM % and increase in REM latency. In addition, prednisone 
significantly reduced stage 3, and ACTH reduced total sleep. Since 
the same results were found in the hypopituitary patients as in the 
Addisonians, the results suggest that increased slow-wave sleep 

167 



Serial No. M-CP(.C)-18-3, Page 4 



following decreased CAS is independent of ACTH. 

D. Effects of L-Kynurenine on Human Sleep 

Earlier work here failed to explain why two precursors of serotonin, 
L-tryptophan and 5-HTP, did not have the same effects on human 
sleep. Since kynurenine is the largest metabolic pathway for 
tryptophan, it was of interest to examine the effects of 
L-kynurenine administration itself. Although this study still 
continues, data from the first three subjects given this substance 
in doses of 2 gin. before bedtime have not yielded any apparent 
effects on sleep patterns. 

E , Effects of ^ tetrahydrocannabinol on the Sleep of Psychiatric 
Patients 

In connection with therapeutic trials of A ^tetrahydrocannabinol 
we have examined sleep effects in three depressed psychiatric 
inpatients. The only consistent result, noted in all three 
patients, was a considerable reduction of REM time on the first 
night of drug administration, but not on succeeding nights. 
Additional subjects are being studied. 

Significance to Mental Health Research : 

These studies contribute to the present worldwide effort to unravel 
the complex relationships of brain monoamines to sleep and to mental 
illness. They also begin to demonstrate the possible effects of stress 
and increased corticosteroid levels in disturbing those mechanisms. 

Proposed Course of Project : 

The collaboration of this Laboratory in such biochemical and 
pharmacological studies of sleep will probably be limited to completion 
of the above studies and others immediately following from them. In 
the meantime, two of our alumni, Drs. Wyatt and Gillin, have launched 
a full scale effort along the same lines at the Laboratory of Clinical 
Psychopharmacology, SMR, where this work will undoubtedly continue. 

Publications : 

Gillin, J.C., Jacbos, L.S., Fram, D.H. and Snyder, F.: Acute effect 
of a glucocorticoid on normal human sleep. Nature , in press 1972. 

Wyatt, R. , Fram, D.H., Buchbinder, R. and Snyder, F.: Treatment of 
intractable narcolepsy with a monoamine oxidase inhibitor. 
New Eng. J. Med . 285: 987-991, 1971. 



168 



n 



Serial No. M-CPCC)-18-8 

1. Laboratory of Clinical Psychobiology 

2. Section on Clinical Studies 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title : Psychophysiological Studies of Sleep and Waking in 
Normal Subjects 

Previous Serial Number : same 

Principal Investigator : Frederick Snyder, M.D. 

Other Investigators : Redford B. Williams, Jr., M.D., J. Christian Gillin, 
M.D., Monte S. Buchsbaum, M.D., Robert I. Henkin, M.D. 
Thomas E. Bittker, M.D., Friedhelm Lamprecht, M.D. 
Frederick G. Wooten, M.D., Lyman C. Wynne, M.D., Ph.D. 
Wybren, De Jong, M.D. and David P. Henry, M.D. 

Cooperating Units : Adult Psychiatry Branch, Laboratory of Clinical Science 
and Laboratory of Psychology, CBRD, NIMH 
Laboratory of Clinical Psychopharmacology, SMD, NIMH 
Experimental Therapeutics, National Heart and Lung 
Institute 

Man Years : (1971) 

Total : 3 
Professional: 1 1/2 
Other: 1 1/2 

Project Description ; 

Objectives : 

This heading encompasses a number of varied studies each concerned with 
one or another aspect of normal psychophysiology. One, carried out by 
Dr. Redford Williams and numerous collaborators examines the 
cardiovascular correlates of varying transactional behavior. A second, 
undertaken by Drs. Christian Gillin and Monte Buchsbaum searches for 
variations in auditory evoked potentials across the night of sleep. 
A third project, extending existing data on the relationship between 
plasma growth hormone levels and stages of sleep to middle-aged and 



169 



Serial No. M-CPCC)-18-8, Page 2 



older subjects, has been completed during the past year and is 
awaiting publication. Finally, a fourth study looking for 
regularly periodic variations in waking psychophysiology under- 
taken in collaboration with the Department of Psychophysiology at 
Walter Reed Army Institute of Research had to be abandoned when 
one of the collaborators left the Arir^y and the other was reassigned 
to different duties. 

Patient Material : 



40 normal control subjects 
8 psychiatric patients 

Methods and Findings : 

A. Cardiovascular Correlates of Varying Transactional Behaviors 

In these studies two cardiovascular measures (heart rate and 
blood flow) are recorded during baseline periods (a vigilance 
task) and three experimental conditions as follovjs: 

Cl) A vigilance task eliciting attentive observation of 
external stimuli. 

(2) An interview, promoting interaction with another person. 

(3) A cognitive task (mental arithmetic or a word association 
test) directing attention inward. 

In a first study, the two cardiovascular measures were examined in 
8 normal and 8 psychiatric patients (5 schizophrenic and 3 
depressives) in conjunction with interviews and word association 
tests. Not surprisingly, baseline heart rates and forearm blood 
flows were significantly higher in the patient group and increases 
in heart rate were significantly greater regardless of condition. 
While normals showed significant increases in blood flow during the 
word association test, patients did not ~ perhaps due to their 
already high baseline levels, or perhaps related to their difficulty 
in sustaining attention to the experimental task. Changes in forearm 
blood flow during an interview were quite unexpected in both normals 
and patients, being the first instance of decreased forearm blood 
flow in response to any psychological stimulus. 

Consistent results were obtained from a second study in 
collaboration with Drs. Wynne, Buchsbaum, Bittker and Singer in 20 
normal subjects representing either "augmenters" or "reducers" of 
auditory evoked potentials. As measured by simultaneous recording 



170 



Serial No. M-CP(C)-18-8, Page 3 

of systolic and diastolic blood pressure, heart rate, forearm 
blood flow and finger pulse volume, significantly different 
patterns of cardiovascular activation were obtained under the 
three experimental conditions of outward vigilance, interview and 
mental arithmetic. Forearm blood flow provided the best differ- 
entiation, since it again went up during mental arithmetic 
(attention inward), but down during vigilance (attention outward). 

This finding (and related sub-findings) suggests that depending 
upon which cardiovascular parameter one chose to look at, one could 
say that any one of the three experimental conditions was the more 
stressful in that it resulted in a larger response. A consideration 
of the pattern of response, however, suggests that behaviors 
associated with attentive observation of the environment give 
rise to a pattern of response resembling that of peripheral 
sympathetic nerve activation, while rejection of environmental 
stimuli seems to give rise to a pattern of response resembling 
that ensuing from adrenal medullary activation. 

Support for the above interpretation was provided by the second 
finding that subjects with increased FBF during the interview 
differed significantly in cardiovascular response from those 
subjects with decreased flow. Contributing independently to this 
difference was the greater degree of attentiveness to the 
interviewer observed in subjects with decreased FBF during the 
interview. 

If attentiveness to environmental stimuli is an important determinant 
of cardiovascular response, then persons who differ in terms of 
characteristic ways of attending to stimuli might be expected to 
differ in terms of the cardiovascular parameters under study. 
Augmenters In the present study differed from reducers both in 
terms of cardiovascular response to the experimental conditions 
and in terms of resting levels of the five cardiovascular parameters. 
In general these differences were reflected in higher FBF and 
heart rate for augmenters in terms of both resting levels and 
responses to experimental conditions. 

B. Auditory Evoked Potentials during Sleep 

Previous work of Dr. M. Buchsbaum and others has shown that certain 
normal persons tend to show exaggerated increases in evoked potentials 
to increasing intensity of auditory stimulus ("augmenters") while others 
tend to dampen their responses at the higher intensities ("reducers"). 
Collaborative studies begun by Dr. C. Gill in while he was a member of 
our staff with Dr. M. Buchsbaum still continues to search for changes 
in auditory evoked potentials across the night of sleep, looking for 
differential tendencies to augment or reduce related to the several 

171 



Serial No. M-CP(C)-18--8, Page 4 



EE6 stages of sleep, 



Following a night of adaptation to the sleep laboratory and the 
auditory click stimuli, auditory evoked potentials are collected 
and averaged by computer for each of the EEG sleep stages across 
two or three nights. Pilot results suggested a clear trend toward 
reducing of evoked potentials in the progression from REM sleep 
through successive phases of non-REM sleep (stages 2 to 4). Data 
has been collected from 8 additional subjects during the past year, 
but analysis is not yet completed. 

C . Growth Hormone Release during Sleep in Relation to Subjects' Age 
and to Acromegaly 

One of the most dramatic findings of recent sleep research has been 
that of an apparent association between high-voltage slow-wave 
stages of sleep (stages 3 and 4) and peaks of plasma growth hormone. 
Until now that evidence had been limited to young adult sublects who 
happen to have large portions of slow-wave sleep and might be expected 
to have high levels of growth hormone. In collaboration with 
Dr. R. Henkin of the Experimental Therapeutics Branch, NHLI, during 
the past year we have studied such relationships in middle-aged and 
older subjects, who typically have much less slow-wave sleep as well 
as lower levels of plasma growth hormone. In addition, studies 
have been conducted on acromegalic patients who have elevated growth 
hormone levels throughout the night. The results of studies in 10 
middle-aged or older normal controls and 6 acromegalic patients have 
been reported in a paper published in Endocrinology . Although 7 
of the 10 older normals showed at least one peak of growth hormone 
early in the sleep period regardless of whether they had phases of 
high-voltage slow-wave sleep at that time, 3 of the 4 subjects over 
50 years of age failed to show sleep peaks of growth hormone despite 
the presence of high-voltage slow-wave sleep. The sleep patterns of 
the acromegalic patients were essentially normal for their ages. 
While they showed the expected elevations of growth hormone levels 
throughout the night, none exhibited any discrete peaks of hormone 
level generally found in normals. Thus, these findings suggest that 
sleep-related peaks of growth hormone tend to diminish or disappear 
with advancing years, but that this change is probably not directly 
related to the age associated decrease in slow-wave sleep. 

Significance to Mental Health Research : 

The significance of Dr. R. Williams' work on the psychophysiology of 
transactional behaviors stems from the central importance of 
"physiological arousal" to psychiatric thinking. This work 
demonstrates that physiological arousal has directional properties. 



172 



Serial No. M-CPCC)-18-8. Page 5 

depending upon whether it is in response to internal or external 
stimuli." That finding may help to clarify much past confusion 
among efforts to quantify the somatic correlates of arousal. 

The work of Drs. C. Gill in and M. Buchsbaum on auditory evoked 
potentials during sleep promises to add a significant dimension to 
present knowledge of the human neurophysiology of sleep. By means 
not applicable to human subjects, a vast amount of recent 
neurophysiology has begun to identify differences in the function 
of the brain in relation to the several electrographic stages of 
sleep. The evoked potential technique is one of a few means by 
whicR similar conclusions might be reached concerning human brain 
function. 

The studies of growth hormone release during sleep in older normals 
and acromegalics serve to confound previous assumptions about 
a direct relationship between growth hormone peaks and high-voltage 
slow-wave sleep. By demonstrating dissociation of the two under 
certain natural conditions our work implies that they are not 
directly related. 

All of these studies illustrate the necessity for the most searching 
possible understanding of normal relationships between behavioral 
and physiological variables as prerequisite for the interpretation 
of abnormal ones. 

Proposed Course : 

One additional study involving Drs. R. Williams, M. Buchsbaum, 
R. Wooten and D. Henry is planned this year in which they will carry 
out simultaneous measures of forearm blood flow, heart rate, 
blood epinephrine, norepinephrine and DBH levels during another 
vigilance task (continuous performance test) and mental arithmetic. 
Some subjects will be normals who have been identified as either 
"augmenters" or "reducers," and others will represent extremes of 
"field dependence" or "field independence." 

Since Dr. R. Williams is leaving the laboratory this June and 
Dr. C. Gill in has already formally left to join the Laboratory of 
Clinical Psychopharmacology, Division of Special Mental Health 
Research, St. Elizabeths' Hospital, no further studies under this 
category are contemplated during the next year. 



173 



Serial No. M-CP(C)-18-8, Page 6 

Publications : 

Carlson, H.E., Gillin, J.C., Gorden, P. and Snyder, F.: Absence of 
sleep-related growth hormone peaks in aged normal subjects and in 
agromegaly. Endocrinology , in press. 

Snyder, F.: Psychophysiology of human sleep. Clin. Neurosurg. 
18: 503-536, 1971, 

Snyder, F. and Scott, J.: Psychophysiology of sleep. In: Greenfield, N. 
and Sternbach, R. (eds.), Psychophysiology . New York: Holt, Rinehart and 
Winston, Inc., 1972. 

Awards : None 



rjk 



Serial No. M-CP(C)-18-69 

1. Laboratory of Clinical Psychobiology 

2. Section on Clinical Studies 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 

Project Title : Longitudinal Studies of Sleep and Concomitant Biological 
Changes in Psychiatric Patients 

Previous Serial Number : Same 

Principal Investigator : Frederick Snyder, M.D. 

Other Investigators : Bernard L. Frankel , M.D., Redford B. Williams, Jr., 
M.D., Winfield H. Scott, Ph.D., Robert D. Coursey, 
Ph.D., John J. Strauss, M.D. and 
William T. Carpenter, Jr., M.D. 

Cooperating Units : Section on Clinical Psychology, CBRA 

Section on Psychiatric Assessment, CBRA 

The Department of Psychology, University of Maryland 

Man Years C1971): 

Total: 3.5 
Professional: 1.5 
Other: 2.0 

Project Description : 

Objectives : 

The continuing purpose of this project is that of seeking objective 
correlates of mental illness which will provide quantifiable 
assessments of clinical course and effectiveness of therapeutic 
efforts over a broad spectrum of diagnostic entities. The collection 
of all-night sleep patterns from psychiatric inpatients has been 
suspended during the past year, while analysis of data collected in 
previous years remains to be completed. In collaboration with the 
Section on Psychiatric Assessment, APB, longitudinal studies of a 
waking psychopysiological measure, forearm blood flow continue on 
acutely psychotic patients. In the meantime, the primary emphasis 
of the project has shifted to sleep studies of an outpatient 
category which has been very little investigated previously, that 
of primary insomniacs. The latter studies are being carried out in 
conjunction with therapeutic trials of cerebral electrotherapy. 

175 



Serial No. M-CPCC)-18-69, Page 2 



Methods Employed : 



On the inpatient side of this project, forearm blood flow, a measure 
reputed to be related to variations in arousal or anxiety, has been 
obtained on a serial basis, two or three times per week, from 
selected psychiatric inpatients going through acute psychotic episodes. 
In such manner seven patients have now been followed throughout their 
entire clinical courses here at the Clinical Center. 

The outpatient studies of insomniacs, so far encompassing fifteen 
patients, involve the following protocol. After completion of 
initial psychiatric evaluation, clinical psychological testing by 
Dr. Scott of APB and additional psychological testing by 
Dr. Coursey of the University of Maryland, all-night electrographic 
sleep records are obtained for five consecutive nights. At the 
completion of that baseline period patients receive two courses of 
cerebral electrotherapy totalling thirty daytime sessions over a 
seven week period, including intervals at two different pulse 
frequencies. Throughout the study interval patients complete an 
eleven item questionnaire each morning to provide subjective i 
assessment of the quality of their sleep. Twenty-four hour urine ' 
samples to be analyzed for 17-hydroxy steroid levels are collected 
during the baseline period and again after completion of the 
treatment course. At the end of the treatment interval five 
additional nights of sleep recordings are carried out in our laboratory. 
Both pre- and post-treatment sleep records are compared to those of 
age-matched normal control studies under the same conditions. 

Patient Material : 



18 patients (3 schizophrenics and 15 insomniacs) 

Major Findings : 

The longitudinal measures of forearm blood flow completed during the 
past year have been consistent with the findings described in two 
patients in last year's report. In each case marked increases in 
forearm blood flow have preceded onset of major changes in clinical 
status, usually improvement, but in a few instances exacerbation of 
illness. 

Data from the first seven insomniac patients has been analyzed 
with the following results: 

(1) Compared to age and sex-matched controls the insomniacs did 

indeed take longer (p<:.05) to fall asleep, spent less (p<:.05) 
time in bed actually asleep, and they also awakened more 
frequently during the night after falling asleep. In addition, 

176 



Serial No. M-CP(C) -18-69, Page 3 

there were trends toward decreased REM latency, increased REM 
sleep percentage and decreased delta sleep in the insomniacs, 
but these have not been statistically significant in the 
subsample so far analyzed. 

(2) Using a two-tailed paired t-test to compare pre- and post- 
treatment sleep record parameters, there were no significant 
changes in (a) time to fall asleep; (b) amount of actual sleep, 
number or total duration of nocturnal awakening, REM latency, 
or percentages of sleep spent in particular EEG stages. Also, 
there were no significant changes in the patients' subjective 
evaluations of their sleep or in depression and anxiety self- 
rating scales. 

Significance to Mental Health Research : 

As recently reviewed (Electroencephalographic Studies of Sleep in 
Psychiatric Illness), the worldwide effort over the past decade to 
objectify the nature of sleep disturbances in various psychiatric conditions 
does not appear to demonstrate specific or inherent anomalies of sleep 
in any diagnostic category. Rather, it would seem that the sleep 
abnormalities thus far found in all groups simply reflect the intensity 
and duration of anxiety and hyperarousal accompanying various conditions. 
Thus, sleep patterns may provide highly tangible indicators of the 
degree of patients internal distress at various phases of illness, but 
two deficiencies of present knowledge remain to be remedied. For one, 
other objective indicators of waking anxiety are needed with which to 
correlate changes in sleep patterns. The forearm blood flow measure we 
have been examining may be one such indicator. Secondly, much more 
information is needed about sleep patterns in nonhospi tali zed and less 
severely ill patients, or in normal individuals undergoing periods of 
unusual life stress. Our present studies of insomniac patients 
contribute to the second goal , and constitute one of the first serious 
efforts to investigate that very common but poorly understood problem. 

Proposed Course of Project : 

Data analysis from our extensive earlier studies of sleep in inpatient 
schizophrenics and depressives will be completed as will that from 
our current trials of electrosleep in insomniacs. It is hoped that 
during the next year the series of insomniacs studied can be enlarged, 
the measures applied to their sleep extended to include a variety of 
autonomic as well as EEG indices, and alternative therapeutic 
approaches explored, such as relaxation feed-back training and behavioral 
conditioning. Efforts will continue to find research access to patients 
suffering from acute and chronic anxiety states, and to normal subjects 
under conditions of unusual stress. In this last connection, we are 



177 



// 



Sena! No. M-CP(C) -18-69, Page 4 



about to undertake a study of EEG sleep patterns in patients prior to 
and following open heart surgery in collaboration with NHLI. As 
noted elsewhere, the effects of chronic stress on sleep are also being 
tested experimentally in laboratory animal studies. 

Publications : 

Kupfer, D.J., Wyatt, R.J., Snyder, F., Mould, G.P. and Curry, S.H.: 
Chlorproraazine Plasma levels and sleep in psychiatric patients. 
Coniiiun. Behav. Biol . 6: 237-240, 1971. 

Snyder, F.: Electroencephalographic studies of sleep in psychiatric 
disorders. To be published in the Proceedings of the First 
International Congress of the Association for the Psychophysiological 
Study of Sleep, Bruges, Belgium, in press, 1972. 



178 



^ 



Serial No. M-CP-18-6 

1. Laboratory of Clinical Psychobiology 

2. Section on Comparative Studies 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title : Comparative Studies of Sleep 

Previous Serial Number : Same 

Principal Investigator : Frederick Snyder, M.D. 

Other Investigators : Thomas C. Douthitt, Ph.D., Nellie Bugbee and 
Burr S. Eichelman, Ph.D., M.D. 

Cooperating Units : Section on Technical Development, IRPD, NIMH 
Laboratory of Clinical Science, CBRD, NIMH 
National Zoological Park 

Man Year s (1971): 

Total: 3 1/2 
Professional: 1 1/2 
Other: 2 

Project Description : 

Objectives : 

The general objective of this project is to explore the phylogenetic 
manifestations and adaptive functions of sleep by systematic 
comparative study in a broad variety of animal forms under varied 
experimental conditions. This first required the development of 
suitable instrumentation and methodology for the recording of 
electrophysiological patterns from unrestrained animals in relatively 
spacious enclosures and over extended time intervals. The achievement 
of a suitable radio-telemetry system for that purpose was described in 
last year's report, together with the first results from its 
application. 

The past year has been occupied with much more extensive data 
collection from several species of primitive mammals under a wider 
variety of experimental conditions. Further refinement of the 
telemetry system has permitted the first assessment of sleep patterns 
under quasi-natural conditions in a large, out-door enclosure. 



179 



Serial No. M-CP-18-6, Page 2 



Beginnings have been made at developing techniques for much 
longer range telemetry which should permit the study of sleep patterns 
in entirely free-roaming animals. Finally, special emphasis is 
being directed to animal models of the effects of chronic stress 
upon sleep patterns. 

Methods Employed : 

Electroencephalographic sleep-waking patterns are obtained from 
animal subjects either by implanted radio-telemetry or by cables attached 
to implanted electrodes. After at least ten days recovery from surgery 
animals are acclimated to conditions of life in 64 cubic feet, sound 
shielded enclosures under constant conditions of temperature, a 
standardized 12/12 light cycle, and feeding at the same time each day. 
Without further disturbance to the animal, recordings are then obtained 
over 24-hour periods two or more days each week for at least one month 
prior to experimental modification of conditions. Records are scored 
in 30 second epochs in terms of waking, transitional sleep, slow-wave 
sleep and REM sleep. Since gross body movement and feeding are 
identifiable from characteristic artefacts, the records actually provide 
a quantitative profile of the animals' entire daily life. 

At the completion of baseline recording, environmental conditions are 
varied in one or another respect, thus far including the following: 
Cl ) alterations of the light cycle (24-hours light or 24-hours 
darkness); (2) introduction of co-specific animals of the same or 
opposite sex; (3) changes of ambient temperature; (4) modifications of 
quantity or nature of diet; (5) reduction in size of available living 
space; and (6) experimental stress. 

Major Findings : 

A . Technical Aspects . 

1 . Improvement of telemetry signal strength 

Attempts earlier this year to apply the low powered, implanted 
telemetry system to opossums living in our large, out-door enclosure 
at the National Zoo were unsuccessful, since the signal strength was 
too weak to be reliable for continuous 24-hour reception. After 
various attempts to remedy that problem, a solution was finally 
achieved by incorporating a small, powdered iron core into the 
transmitter, thus increasing signal strength several fold without 
increase in power consumption or necessary battery weight. With 
that recent innovation, recordings are now being successfully 
obtained on a routine basis from animals living undisturbed in 
a 10,000 square feet out-door enclosure over intervals of three to 
four months. 



180 



Serial No. M-CP-18-6, Page 3 

2. Development of a telemetry system for studies of free- 
roaming animals 

The ultimate step beyond our present capability to study animals 
under the quasi-natural conditions described above would be the 
ability to obtain similar records from completely free-ranging 
animals without at all disturbing their natural patterns of behavior. 
This would require long-range physiological telemetry capabilities 
for recording el ectroencephal ©graphic patterns at distances of at 
least one-half mile, as well as tracking telemetry for following 
them over still greater distances. The tracking telemetry 
techniques have been extensively used for wildlife studies and 
this equipment is commercially available. Mr. James Bryan, 
Chief, Section on Technical Development, is attempting to meet the 
challenge of long-range physiological telemetry for us by designing 
a short-range implanted telemetry package together with a much 
higher powered, "booster" transmitter, which will be attached to the 
animals by the neck collar. The first field test of that system is 
now underway at the Pool esvi lie animal facility. 

B. Ph ylogenetic Studies 

As described in last year's report, primary emphasis has thus far 
been given to intensive study of sleep in a number of primitive 
maranals, the hope being that this will yield insights concerning 
the prototypical characteristics of mammalian sleep. Data has now 
been collected and analyzed from more extensive series of four 
species: the native marsupial, Didelphis ; two insectivores, Centetes 
ecaudatus and Erinaceus europaeus ; and the primitive rodent, 
Aplodontia rufa" ! Results to date point to some similarities and 
other differences in the sleep of these animals. It is prominent 
in the captive lives of all: 55-65% of every 24-hour period in 
Centetes , Erinaceus or Aplodontia , and up to 85% in Didelphis . However, 
the patterning of sleep through the 24-hours and its relation to the 
light-dark cycle differs considerably among them. Erinaceus appears 
to be essentially a monophasic sleeper, with sleep almost uninterrupted 
throughout the light phase of the cycle, while at the other extreme, 
Aplodontia is regularly polyphasic, with a clock-like alternation 
between sleep and waking 5-6 times each day, and with very little 
regard to light or darkness. The Tenrec, Centetes . is an irregularly 
polyphasic sleeper with only slightly more sleep interspersed during 
the dark than during light, while the opossum's small portion of 
waking is mainly in one nocturnal block. 



181 



Serial No. M-CP-18-5, Page 4 

In terms of the percentages of REM sleep within total sleep, extremes 
of 18 to 30% occur in the two most closely related forms, Erinaceus and 
Ce ntetes , while the two most remote, Pi del phis and Aplodontia have the 
similar proportions of 23 end 21% respectively (also very similar to 
the average figure in another relatively primitive mammal, Homo sapiens) . 
These results from pnmitive mammals lead us to suspect that variations 
in patterns of mammalian sleep have less to do with broad phylogenetic 
relationships than with specialized evolutionary adaptations, a point of 
view elaborated In an "ecological -adaptive" hypothesis of sleep function 
in a recent publication ( Evolutionary Theories of Sleep: What, Which, 
and Whither? ). 

From the foregoing perspective it is now of interest to explore the sleep 
characteristics of some of the more highly specialized end products of 
mammalian evolution, where sleep patterns could be expected to be most 
diverse in ways related to the overall life adaptations of different 
forms. To that end, during the past year we have begun telemetric studies 
of sleep in ungulates at the Poolesville animal facility, starting with 
the domestic goat. The goat is exclusively a nocturnal sleeper, but in 
the data collected so far has averaged less than 3 hours sleep per 
night, and only 9% of that has been REM sleep. Plans to attempt similar 
studies of more e.xot1c ungulates will be described. 

C. Experimental Modification of Sleep in Primitive Mammals 

Effects of varying environmental conditions upon primitive sleep patterns 
have thus far been most extensively studies in Erinaceus , and to a lesser 
extent in the other species enumerated. Experimental manipulations in the 
case of Erinaceus has included; (1) introduction of a co-specific animal 
of the opposite sex into the recording chamber, (2) substitution of 
continuous light or continuous darkness for the standard cycle; 
(3) total food deprivation for one day; (4) reduction in amount of living 
space from 54 to 8 cubic feet; (5) removal of the log used as a nesting 
place; and Ijo) successively lower temperatures until the point of 
hibernation. The only experimental condition which clearly decreased 
the proportion of waking was reduction In enclosure size, a change of 
about 9%. Since most animal sleep studies are done in small enclosures, 
their estimates of total sleep may be inflated, a point that should 
become clearer when we make similar measures of hedgehog sleep in our 
large, out-door enclosure. Although we expected that continuous dark 
might increase the duration of waking in this strongly nocturnal 
animal, there was no change, yet continuous light did result in a 
moderate increase in total sleep. All other variables described 
resulted in Increased waking, with increments ranging from 5% during 
a day of food deprivation to 20% when ambient temperature was lowered 
to 41 F. Similar decreases In sleep to food deprivation and lower 
ambient temperatures were demonstrated in Aplodontia . Either increases 
or decreases in total sleep of Erinaceus in response to these 



182 



Serial No. M-CP-18-6, Page 5 

experimental conditions were accompanied by decreased proportions 
of the REM phases, most marked at low temperatures, when it was cut in 
half. The same was true of Aplodontia only with respect to food 
deprivation. 

The low temperature study reflects our interest in the possible relation- 
ship between sleep and hibernation. Specifically, we expected to find 
increasing sleep at low temperatures, finally giving way to a smooth 
transition from sleep into hibernation. In the one hedgehog in which 
hibernation has occurred thus far, just the opposite occurred. Total 
sleep decreased progressively as ambient temperature was lowered, 
so that the dropping out of cerebral electrical activity signaling 
hibernation actually occurred directly out of waking. 

The experimental comparison of greatest interest has been that between 
animals living under standard laboratory conditions and those living 
under quasi-natural conditions in the out-door enclosure. Technical 
problems prevented that comparison until recently, but the first two 
studies of this nature have now been completed in opossums. No very 
striking differences in sleep patterns of those animals appeared in those 
studies, except for variations apparently related to intercurrent 
weather conditions. On two days when temperatures averaged below 40°F 
waking was reduced to about 15%, compared to 30-40% in other recordings 
from this animal. By contrast, several episodes of rain were associated 
with almost continuous waking in the same specimen. During the next 
year we shall be looking for similar responses to naturally occurring 
events in the zoo enclosure, as well as experimentally manipulating 
that situation by varying modes of feeding, introducing co-specific 
animals of the same or opposite sex, or, with proper safeguards, 
introducing a natural predator of the opossum, such as a dog or 
coyote, to observe the effects of a natural stress. 

D. Effects of Chronic Immobilization Stress on Sleep of the Rat 

The possible effects of chronic stress on sleep patterns is an issue 
directly relevant to interpretation of abnormalities found in the sleep 
of psychiatric patients, but one which could not be experimentally 
tested in human subjects. Our efforts to examine that question in monkeys 
by means of adversive conditioning had to be given up when collaborative 
arrangements with scientists at the Walter Reed Institute of Research 
proved unworkable, since we have no suitable facilities for monkey 
studies in thts Laboratory. We turned, therefore, to the use of another 
well standardized experimental model of stress, that resulting from 
tmmobiltzatton restraint in the albino rat. Recent studies here and 
in other NIMH laboratories have demonstrated marked and persistent 
changes in rat behavior (increased irritability and shock-induced 
fighting) as well as elevations of brain norepinephrine levels and 



183 



Serial No. M-CP-18-6, Page 6 



blood pressure after one month of immobilization stress administered 
two hours each day. The same effects are still apparent 15 days after 
the stress period. Hence s we have set out to determine whether 
comparable stress will be reflected in the 24-hour sleep patterns. 
Since the telemetric technique appeared to have no advantages for this 
purpose, recording is being done by wire cables connected to implanted 
electrodes. After five days baseline recording, daily immobilization 
periods are carried out for the next 30 days, while 24-hour sleep 
patterns are sampled three days per week. Control animals not subjected 
to the daily stress are housed and recorded in the same fashion. 

A pilot study by this means in one rat yielded some of the most 
dramatic changes in sleep patterns so far observed after any experimental 
manipulations. Total sleep and REM were reduced from the outset of the 
stress, but after 15 days REM sleep abruptly disappeared entirely, 
remaining absent for the remainder of the stress period and for at least 
one week afterward. The same procedure is now almost completed in 
groups of six stressed rats and six controls, with results which appear 
to be consistent but perhaps somewhat less striking. This time 
special attention will be devoted to the period of recovery from stress 
to determine the time course of sleep normalization, and whether 
there is evidence of rebound compensation for the lost REM sleep, such 
as we have described in recovering depressive-psychotics, but have 
failed to find in recovering schizophrenics. 

Significance to Mental Health : 

Despite its obvious importance in human life and its particular 
disturbance in psychiatric illness, the general biological significance 
of sleep is still entirely obscure. The investigations described are 
among efforts proceding all over the world to remedy that deficiency 
by careful phylogenetic comparison and experimental analysis. 

Proposed Course of Project : 

Work will continue on all of the fronts described. In addition, the 
principal investigator will take advantage of a foreign work assignment 
to attempt studies of sleep patterns in a number of larger African 
mammals by means of long-range telemetry. 

Publications : 

Snyder, F. : Evolutionary theories of sleep: What, which, and whither? 
To be published in the Proceedings of the First International Congress 
of the Association for the Psychophysiological Study of Sleep , in press. 

Awards : None 



18^ 



J 



Serial No. M-CP-18-7 

1. Laboratory of Clinical Psychobiology 

2. Section on Comparative Studies 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title : Factors Affecting Intraspecific and Predatory Aggression 
in the rat 

Previous Serial Number : Same 

Principal Investigator : Burr S. Eichelman, Jr., M.D., Ph.D. 

Other Investigators : Nguyen Bich Thoa, Ph.D., Jorge Perez-Cruet, M.D., 
Redford B. Williams, Jr., M.D., Friedhelm 
Lamprecht, M.D. and Keng-Yong L. Ng, M.D. 

Cooperating Units : Office of the Chief. Laboratory of Clinical Science, CBRD, 
NIMHj Section on Medicine, Section on Psychiatry and 



Section on Experimental Therapeutics, Laboratory of 
Clinical Science, CBRD, NIMH 



Man Years (1971): 



Total : 




1 


.5 


Professional : 


1 


.4 


Other: 






.1 



Project Description : 

Objectives : 

This project is designed to provide an overview of aggressive behavior 
in the rat, an overview encompassing strain characteristics and types 
of aggressive behavior, as well as their pharmacological and neuro- 
anatomical correlates. The information from these studies is also 
being contrasted with mouse aggression. 

Methods Employed : 

The studies center around three behavioral tests: shock-induced 
aggression, jump-flinch thresholds to pain, and mouse-killing 
behavior. The first two paradigms have already proved fruitful as 
areas of research in delineating aggressive behavior (Eichelman, B.: 
J. Comp. Physiol. Psychol . 74:331-339, 1971). Ancillary techniques 



185 



.y; 



Serial No. M-CP-iS-?, Page 2 



employed utilize cannula and intraci sternal application of 
pharmacologically active drugs, surgical excision or lesioning, 
monitoring of blood pressure (rat tail), and monoamine or related 
enzyme measurements. 

Sub-projects : 

(1) Strain Variability . This is a continuation of the comparative 
study of rat strains in relation to shock-induced aggression, 
pain thresholds and mouse-killing behavior. There is a 
significant variation in aggression as well as in the response 
to footshock. Osborne-Mendel rats (NIH) demonstrate a group 
probability of 0.5 for mouse-killing and shock-induced fighting 
contrasted vn'th NIH Wistar which do not show mouse-killing, 

but fight at 0.5 or Sprague-Dawley rats which have a killing 
probability of 0.1 and fight 0.2. As suggested by Wistar 
strain studied, there is no correlation between high fighting 
pairs in the shock-induced paradigm and the predatory behavior 
of mouse-killing either within or between strains. Between 
10 to 20 strains will be reported on at the termination of this 
study. This material will allow for the appropriate selection 
of strains to study in terms of high or low levels of irritable 
or predatory aggression. 

An ancillary project related to an automated system of measuring 
isolation-induced aggression in mice has proved adequate for 
short-term observations, but inadequate for long-term 
monitoring. This project has been terminated. 

(2) Sensory Input . The role of sensory input and its effect on 
aggression and pain threshold has been studied in collaboration 
with Miss Nellie Bugbee. Total olfactory bulbectoiny in the rat 
induces mouse-killing behavior. This has been validated in our 
laboratory, however, there is no change in intraspecific shock- 
induced aggression. Bulbecton^ does lower the rat's jump 
threshold to electric shock, demonstrating that an interruption 
of one sensory input changes the behavior response to another 
sensory stimulus. Removal of rat vibrissae substantially 
decreases shock-induced fighting, while blinding and decreasing 
hearing produces no change in shock-induced or predatory 
aggression. This study has been completed and will be published 
in June, 1972. However, the removal of vibrissae, does not 
effect isolation-induced aggression in mice, as shown by a study 
done in collaboration with Dr. B. Slotnick of the Laboratory of 
Brain, Evolution and Behavior, NIMH. 



186 



Serial No. M-CP-18-7, Page 3 



(3) Experimental Manipulation . Hunger, thirst, and prolonged 
swimming do not alter shock-induced fighting of Sprague- 
Dawley rats. Conversely, sleep deprivation or chronic 
immobilization increased shock-induced aggression. The 
increased aggression seen after immobilization is correlated 
with an elevation of hypothalamic norepinephrine and tyrosine 
hydroxylase, but not serum dopamine B-hydroxylase. 

(4) Pharmacological Manipulations . Catecholamine levels, turnover 
rates, and destruction of nerve terminals have been studied 

in relation to irritable aggression. Both 6-hydroxydopamine 
(which depletes both dopamine and norepinephrine and damages 
both amines' nerve terminals) and 6-hydroxydopa (which effects 
only norepinephrine metabolism in the dose used) produce an 
increase in shock-induced aggression which persisted up to 
six months. This effect appears specifically related to 
norepinephrine, since 6-hydroxydopa which effects only norepine- 
phrine has the same effect. The time course of this facilitation 
of aggression is delayed by two-three days after amine depletion. 
This, plus the fact that AMPT (alpha-methyl -para-tyrosine) and 
disulfiram — which also deplete brain norepinephrine, but do not 
damage terminals — do not alter shock-induced aggression, 
suggests that the increase in aggression may be related to 
receptor supersensitivity rather than amine depletion per se . 
Chronic use of cations such as rubidium and even potassium also 
increase shock-induced fighting while lithium decreases the 
attack rate and cesium or sodium do not change it. These 
results are now being studied in relation to effects of amine 
turnover in brain. It appears that an increase in norepinephrine 
turnover rate is associated with an increase in shock-induced 
aggression. 

In contradistinction, spontaneous aggression in the rat appears 
related to dopamine metabolism rather than to norepinephrine, 
since it is facilitated by apomorphine and also by dopa plus 
a peripheral decarboxylase inhibitor, particularly after 
6-hydroxydopamine pretreatment. This facilitation occurs even 
in the presence of a dopamine B-hydroxylase inhibitor which 
prevents the synthesis of new norepinephrine. 

These pharmacological studies have generated a unitary theory 
on irritable aggression in the rat discussed in "Aggressive 
Monoamines," Biological Psychiatry , in press. 



18t 



Serial No, M-.CP-18-7, Page 4 



(5) Hypertension . Strain differences in blood pressure and aggression 
have been studied in the rat. These parameters appear to vary 
independently. However, brain norepinephrine metabolism 
differences have been observed in the Sprague-Dawley deprived 
rats of the Brookhaven "sensitive" and "resistant" strains 
developed by Dr. L.K. Dahl . These strains differ in levels of 
aggression and also in their susceptibility toward hypertension. 
Their catecholamine metabolism will be studied in greater detail 
during the remainder of this year. 

The blood pressure changes following foot-shock to rats alone 
or in pairs noted in last year's report has been shown to vary 
with rat strain. Further, the decrease in tail blood pressure 
appears related to peripheral and central sympathetic activity, 
while the increase in blood pressure seen in rats shocked alone 
appears related to adrenal function. These conclusions were 
reached by studying rats treated with peripherally or centrally 
administered 6-hydroxydopamine (to deplete norepinephrine or 
dopamine) and with adrenalectomy. 

The cannula study for examining the central dopa-induced 
hypotensor response will be completed during the remainder of 
the year. 

Significance to Bio-medical Research and the Program of the Institute 

Aggression in the rat must be divided into at least three categories: 
irritable aggression, spontaneous aggression and predatory 
aggression. Irritable aggression appears to develop upon central 
stimulation of norepinephrine receptors. Spontaneous aggression 
appears to develop upon stimulation of central dopamine receptors. 
Predatory aggression appears more related to serotonin and 
cholinergic brain metabolism. Hypertension and irritable aggression 
appear only randomly related in the rat, but both may show correlations 
with central catecholamine metabolism. External factors such as 
stress may chronically alter aggressive behavior and brain catechol- 
amine metabolism. Expanding knowledge of the biology of aggression 
in the rat offer provocative leads for future studies of primate and 
human aggression. 

Proposed Course of Project : 

Completion of the above studies. 



Serial No. M-CP-18-7, Page 5 

Publications : 

Eichelraan, B., Thoa, N.B. and Ng, K.Y.: Facilitated aggression 
in the rat following 6-liydroxydopamine administration. 
Physiol ofly and Behavior 8: 1-3, 1972. 

Eichelman, B. and Thoa, N.B.: Aggressive monoamines. 
Biological Psychiatr^^ , in press, 1972. 

Bugbee, N.M. and Eichelman, B.: Sensory alterations and aggressive 
behavior in the rat. Physiology and Behavior , June 1972, in press. 

Thoa, N.B., Eichelman, B. and Ng, K.Y.: Effect of 6-hydroxydopamine 
and other drugs on shock-induced aggression in the rat. 
Brain Research , in press. 

Thoa, N.B., Eichelman, B. and Ng, K.Y.: Aggression in rats treated 
with dopa and 6-hydroxydopam1ne. Journal of Pharmacy and Pharmacology 
24: 337-338, 1972. 

Williams, R.B. and Eichelman, B.: Social setting: Influence on the 
physiological response to electric shock in the rat. Science 
174: 613-614, 1971. 

Awards : 

A.E. Bennett Research Award in Basic Science, 1972, from the Society 
of Biological Psychiatry. 



189 



t 



Serial No. M-CS-OC(C) -04 

1. Laboratory of Clinical Science 

2. Office of the Chief 

3. Bethesda, Maryland 

PHS-HSMHA-NIH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project title: Studies of the interrelationships of the nervous 
and circulatory systems. 

Previous Serial Number: Same 

Principal Investigator: Philippe V. Cardon 

Other Investigators: James L. Weiss, Raymond J. Matta , Thomas 

N. Chase, G. Frederick Wooten, Friedhelm 
Lamprecht, Griff T. Ross, August Watanabe, 
Jorge Perez-Cruet, 

Cooperating Units: Sections on Pharmacology, Experimental 

Therapeutics, Psychiatry, and Medicine, LCS ; 
Reproduction Research Branch, NICHHD; 
Department of Medicine, University of Indiana. 

Man Years: Total 2,5 

Professional 2.5 
Other None 

Project Description: 

Objectives : To study the interaction of the nervous and 
circulatory systems and the effects of drugs on those systems. 

Methods Employed ; Standard non-traumatic techniques for 
assessing well-known circulatory parameters in man. Direct 
measurement of analogous parameters in animals. Electrical re- 
cording of peripheral sympathetic nerve activity in animals. 
Enzymatic assay of blood. Radio-immune assay of pituitary 
trophic hormones in blood. Standard tests of renal function. 

Major Findings : (1) Effects of anti-parkinsonism drugs 
other than direct CNS effects. Three clinical studies, each 
involving 5-10 patients will be completed by the end of the 
year, but data analysis has not been completed, because the pace 
of acquiring sufficient data is limited by the rate at which 
patients receive these agents for therapeutic reasons. The 
studies are: (a) Effects of L-dopa on plasma renin and 
aldosterone, (b) Effects of L-dopa on gonadotrophic hormones, 



191 



Serial No. M-CS-OC (C) -04 

TSH . and growth hormone, (c) Effects of 0-methyl-Dopa on blood 
pressure and postural circulatory adjustments. 

In three patients receiving the dopaminergic-stimulating 
drug apomorphine, the following rapidly reversed renal ab- 
normalities occurred: 50% reduction in glomerular filtration 
rate, decreased PSP excretion, and azotemia, without albuminuria 
or abnormal sediment. Further studies of this effect in monkeys 
have begun. 

(2) Factors influencing serum dopamine-beta-hydroxylase 
activity (DBH) , In man DBH activity increases during exercise, 
cold-pressor stress, and in response to the presumed psychic 
stress of being studied for the first time. In animals it in- 
creases during hemorrhage, Fusaric acid, known to inhibit DBH 
activity in animals, also inhibits DBH activity in man. 

Significance to Biomedical Research and the Program of the 
Institut e : A thorough understanding of the effects of anti- 
park ins oliism drugs is essential for their rational use. The 
studies of DBH contribute to our understanding of the extent 
to which changes in serum DHB activity are an index of changes 
in sympathetic nerve activity. 

Proposed course of project : Further studies of similar 
nature. 

Honors and Awards : None 

Publications : 



Weiss, J.L. , L.K.Y. Ng , T.N. Chase: Long-lasting dyskinesia 

induced by levodopa. Lancet 1:1016, 1971. 

Weiss, J.L., C.K. Cohn, T.N. Chase: Reduction of catechol-0- 
methyltransf erase activity by chronic L-dopa therapy. Nature 
234:218, 1971. 

Weiss, J.L. and T.N. Chase: Levo-dopa in parkinsonism. 
Drugs 2:257, 1971. 



J 



Lemberger , L. , J.L. Weiss, A.M. Watanabe, I,M, Galanter, R.J, 
Wyatt , P.V. Cardon: Delta-9-tetrahydrocannabinol : Temporal 
correlation of the psychological effects and blood levels after 
various routes of administration. New Engl. J. Med. 286:685, 
1972, 



192 



Serial No. M-CS-0C(C)-16 

1. Laboratory of Clinical Science 

2. Office of the Chief 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Studies of pinched-off nerve endings (synaptosomes) as a model 
system for investigating the transport, binding and metabolism of 
monoami nes . 

Previous Serial NunAer: Same 

Principal Investigator: Robert W. Col burn 

Other Investigators: L. Keng-Yong Ng (Guest Worker), K.S. Rajan and Irwin J. 
Kopin 

Cooperating Units: Section on Experimental Therapeutics, LCS and Illinois 
Institute of Technology Research Institute (Chicago) 

Man Years: Total 1.0 
Professional 1.0 
Other None 

Project Description: 

Obgectives: Synaptosomes isolated from whole brain represent an in vitro 
system similar in many respects to that present In living organisms. THIrrent 
basic problems being investigated with this system are: (1) How do neurotrans- 
mitters pass through mentranes? (2) How are they bound within vesicles? 
(3) What is the mechanism for their release? A concurrent study involves 
investigation of the effects of psychotomimetic drugs on the above parameters 
for neurotransmitter substances. 

Methods Employed: Drugs used for treatment of depression or mania such as 
desmethylimipramine, lithium or narcotics are added to the synaptosome system. 
The uptake, binding and release of a variety of neurotransmitter substances are 
measured; alternatively, drugs are given in vivo prior to isolation of the 
synaptosomes. The chelation chemistry of neurotransmitters as a possible 
mechanism for binding and release in synaptosomes is studied. 

Major Findings: The synaptosomes take up, bind and release monoamines 
such as norepinephrine and serotonin much as they function in in vivo or in 
perfusion experiments. As in the peripheral sympathetic nervous system, the 
route of norepinephrine metabolism varies with the mode of its release. Uptake 
studies with neurotransmitters are of importance since reuptake is a major means 
for termination. Recent findings with the in vitro synaptosome system provide 



193 



Serial No. M-CS-0C(C)-16, Page 2 

evidence that dopamine administration at high doses displaces endogenous 
serotonin from its storage sites. 

Signifioanae to Biomedical Research and the Progrcan of the Institute: The 
drugs altering monoamine function have proved very useful in modifying mood. 
The present studies provide information on a molecular basis concerning drug 
action. 

Proposed Course of Pros eat: With the above system, large numbers of very 
similar samples can be prepared and will be used in comparing a wide variety of 
drugs using kinetic methods to determine active mechanisms. Synaptosomes will 
be further fractionated to isolate carrier or receptor proteins. 

Honors and Awards: Dr. Ng was a recipient of the A.E. Bennett Award for basic 
research of the effects of L-dopa on disposition of cerebral monoamines in rat 
brain homogenates. 

Publications: 

Colburn, R.W. and Kopin, I.J.: Effects of reserpine and tyramine on release of 
norepinephrine from synaptosomes. Bioohem. Phamaool. 21: 733-736, 1972. 

Ng, L.K.Y., Colburn, R.W. and Kopin, I. J.: Effects of L-dopa on uptake and 
release of monoamines and amino acids by synaptosomes in homogenates of rat 
brain. J. Pharmacol. Exp. Ther., in press. 



ISk 



Serial No. M-CS-0C(C)-19 

1. Laboratory of Clinical Science 

2. Office of the Chief 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Metabolism, distribution and biochemical effects of 
psychoactive drugs 

Previous Serial Number: Same 

Principal Investigator: Irwin J. Kopin and Julius Axelrod 

Other Investigators: L. Keng-Yong Ng (Guest Worker), Robert W. Colburn and 
David S. Kreuz 

Cooperating Units: Sections on Pharmacology, Experimental Therapeutics and 
Medicine, LCS 

Man Years: Total 1.5 
Professional 1.1 
Other 0.4 

Project Description: 

Methods Employed: (1) Drugs are administered; and using radioactivity or 
chemical methods, the levels in blood, urine and feces are determined. (2) The 
alterations in amine metabolism are assessed by examining the tissues of animals 
or the blood, cerebrospinal fluid and urine of man. (3) The modification of 
effects of one drug by another is examined in animals. 

Major Findings: Tetrahydrocannabinol persists for several days in the 
blood of persons receiving the drug. Blood levels of the drug and its 
metabolites, which are rapidly formed, correlate well with the euphoric effects. 
Chronic marihuana smokers metabolize tetrahydrocannabinol more rapidly than 
others, and formation of 11 -hydroxy- tetrahydrocannabinol may mediate the effects 
of the drug. 

Signifioanae to Biomedical Research and the Frogram of the Institute: The 
problem of drug usage is currently a major concern. The studies will help to 
elucidate the mechanisms of action of drugs which are abused, to indicate their 
possibly toxic effects and to suggest means for treatment of patients suffering 
from toxic effects of the drugs. 

Proposed Course of Project: Identification of metabolites, estimation of 
drug effects on amine metabolism and enzymes concerned with amine synthesis and 
with degradation and examination of drug interactions will continue. 



195 



Serial No. M-CS-0C(C)-19, Page 2 

Honors and Awards: None 

Publications: 

DaviSj J.M. , Kopin, I.J., Lemberger, L. and Axelrod, J.: Effects of urinary pH 
on amphetamine metabolism. Ann. N.Y. Acad. Sai. 179: 493-501, 1971. 

Lemberger, L., Axelrod, J. and Kopin, I.J.: Metabolism and disposition of 
delta-9-tetrahydrocannabinol in man. Pharmacol. Rev. 23: 371-380, 1971. 

Lemberger, L., Axelrod, J. and Kopin, I.J.: Metabolism and disposition of 
tetrahydrocannabinols in naive subjects and chronic marijuana users. Ann. N.Y. 
Acad. Sai. 191: 142-154, 1971. 



I 



Lemberger, L., Tamarkin, N.R., Axelrod, J. and Kopin, I.J.: Delta-9- 
tetrahydrocannabinol : Metabolism and disposition in long-term marihuana smokers. 
Science 173: 72-74, 1971. 

Lemberger, L., Weiss, J.L., Watanabe, A.M., Galanter, I.M., Wyatt, R.J. and 
Cardon, P.V.: Delta-9-tetrahydrocannabinol : Correlation of the psychological 
effects and blood levels after various routes of administration. Neu Eng. J. 
Med. J in press. 




196 



Serial No. M-CS-0C(C)-20 

1. Laboratory of Clinical Science 

2. Office of the Chief 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Histochemical studies of biogenic amines 

Previous Serial Number: None 

Principal Investigator: David M. Jacobowitz 

Other Investigators: Andrew K.S. Ho (Guest Worker), Paul D. Maclean, 

J. Stephen Richardson (Guest Worker) and Hiroshi Watanabe. |. 

Cooperating Units: Laboratory of Brain Evolution and Behavior, NIMH 1 1 

Man Years: Total 1.50 "I 

Professional 0.75 ,,, 

Other 0.75 H 

II' 
Project Description: '^*' 

Objectives : To localize, at a cellular level by use of histological 
techniques, neurotransmitters and the enzymes and receptors concerned with their 
formation, action and metabolism. The effects of drugs, hormones and environ- 
mental changes are being studied using tissues from animals or from in vitro 
organ and tissue cultures. The techniques allow precise localization o? 
biochemical changes and permit study of interaction of different neuro- 
transmitter systems (e.g., adrenergic-cholinergic interrelationships) as well 
as correlations with behavioral parameters. 

Methods Employed: (1) The morphological procedure involves the use of a 
highly specific fluorescence histochemical method for the demonstration of 
catecholamines (norepinephrine, epinephrine, dopamine) and indoleamines 
(serotonin) within monoaminergic nerves and cells. (2) Biochemical assays for 
norepinephrine, dopamine and serotonin are available. (3) Enzymes concerned 
with biogenic amine synthesis (tyrosine hydroxylase, dopamine-beta-hydroxylase, 
phenyl ethanol ami ne-N-methyl transferase) and acetylcholine synthesis (choline 
acetyl transferase) and degradation (acetylcholinesterase) are assayed in the 
brain. (4) Behavioral parameters such as water and food consumption, 
spontaneous motor activity, rectal temperature and aggressive behavior are 
measured. 

Major Findings: (1) 6-Hydroxydopa stereotaxically placed in the rat 
lateral ventricles produces a graded dose-dependent decrease in spontaneous 
motor activity, water and food consumption and norepinephrine in the brain. 
Fluorescent microscopy of brain sections shows an increase of fluorescence in 

197 



Serial No. M-CS-0C(C)-20, Page 2 

the preterminal nerve trunks in noradrenergic axons. The return of normal 
appetitive and locomotion behaviors despite reduced levels of norepinephrine 
suggests that other unknown factors such as supersensitivity are Involved in 
the recovery of the behaviors. Two to three days after injection of 6-hydroxy- 
dopa, there appears to be an increase in the tyrosine hydroxylase activity and 
a decrease in the dopamine-beta-hydro)?ylase activity in the striatum. 

Histochemical observations reveal a system of monoaminergic cell bodies in the 
region of the depleted terminals of the nucleus dorsomedialis, directly below 
the fasciculus mamillothalamions. 

6-Hydroxydopa injected intraventricularly causes a marked and persistent 
increase in the number of attacks occurring during shock-induced fighting in 
rats. The increase in attack frequency appears to be correlated with 
6-hydroxydopa ' s effect of reducing brain norepinephrine and with degeneration 
of norepinephrine terminals. 

(2) On the basis of our demonstration that reinnervation occurs in denervated 
rat irises by the superior cervical ganglion cultured in vitro , we now have 
shown that cross innervation occurs between ganglia and irises of different 
species. The mouse ganglion is capable of growing nerves onto the rat and 
guinea pig iris; the rat ganglion reinnervates the guinea pig and mouse irises, 
thus providing the first demonstration of cross-species reinnervation in vitro . 

Drugs added to the ganglion-iris preparation have been shown to influence the 
nerve terminals. 6~Hydroxydopami ne appears to deplete, and probably destroy, 
adrenergic nerves grown in organ culture. Cytochalasin B appears to disrupt 
and reduce the number of adrenergic nerves in the iris in vitro . 

(3) Histochemical observation of the rat superior cervical ganglion at various 
time intervals after application of vinblastine to the ganglion shows that 
there is an initial marked increase in the catecholamine fluorescence in the 
nonterminal axons within the ganglion for up to four days; thereafter, the axons 
are normal. The adrenergic terminals within the ganglion initially are 
diminished (24 hours) but are subsequently (four to 14 days after treatment) 
markedly increased in number. The noradrenergic terminal plexus in the iris is 
entirely absent between one and 40 days after vinblastine application. The 
occurrence of norepinephrine uptake into the nerves, however, demonstrates the 
presence of the nerve fibers and suggests that "naked" adrenergic nerves are 
present without all the synthetic machinery required for norepinephrine 
synthesis and storage. 

(4) A possible localization of tryptamine in the brain was investigated by 
administration of tryptophan in the presence of iproniazid and para- 
chlorophenyl alanine to rats. No unusual localization of monoamine fluorescence 
was noted in catecholamine or serotonergic nerves; however, green fluorescence 
was noted in the capillary endothelium and was prevented by the decarboxylase 
inhibitor MK-486. It appears that tryptophan is capable of being decarboxylated 
in the endothelium of the brain capillaries to form tryptamine. 



Serial No. M-CS-0C(C)-20, Page 3 

(5) Newborn rats treated with dexamethasone daily for one week show a marked 
increase in the number of catechol ami ne-containing chromaffin cells in the 
superior cervical ganglion. The increase is correlated with a marked increase 
in the phenyl ethanol ami ne-N-methyl transferase level within the ganglion. 
Continued treatment for 12 days appears to maintain the increased numbers of 
chromaffin cells within the ganglion although the phenyl ethanol ami ne-N-methyl 
transferase activity at this time is markedly reduced. Therefore, enzyme 
induction is not maintained along with new cell formation. After one month, 
the catecholamines in the new cells disappear. 

(6) A method was developed whereby small cell -body regions of the brain could 
be taken and smeared on slides and visualized the same day without freeze- 
drying procedures. The procedure will enable pin-point localization of 
monoaminergic cell bodies (e.g., locus coeruleus) for future studies in cell 
culture or biochemical analyses, 

(7) Explants of substantia nigra grown in tissue culture have been shown to 
survive for three to seven days. Histochemical and biochemical studies using 
uptake of dopamine-H' indicate viable cell bodies and varicose terminals 
emanating from the dopami ne-containing cells. 

(8) Studies with Gunn rats, a genetically abnormal strain of rat with a 
parkinson-like syndrome, showed by fluorescence microscopy that there is a red 
fluorescent substance within the myelin of most of the large nerve trunks within 
the brain and suggests a possible porphyri n-1 i ke substance accumulating in the 
brain. In addition, a degenerative pigment cell accumulation is observed in the 
cerebellum. Furthermore, many noradrenergic-nerve containing regions of the 
brain appear to contain a reduced content of the amine. 

(9) Studies of the adrenergic innervation within the autotranspl anted hearts of 
dogs indicate that a complete adrenergi c-nerve denervation is initially obtained 
with the procedure. Hearts of dogs maintained for two years after auto- 
transplantation showed a moderate reinnervation of nerves, mainly in the left 
atrium and ventricle with fewer nerves in the right chambers; transplanted 
hearts and other organs may become reinnervated by adrenergic nerves. 

(10) The caudate and putamen of squirrel monkeys were unilaterally implanted 
with 6-hydroxydopamine crystals in an attempt to destroy the dopamine terminals 
within the neostriatum; gross motor deficits were noted. The brain is currently 
being studied for the extent of dopami nergi c-nerve destruction. It appears that 
most of the caudate and about one-half of the putamen contents of dopamine were 
lost. The preterminal dopamine tracts are visualized and are currently being 
mapped. 

Signifioanoe to Biomedical Reseopoh and the Program of the Institute: Our 
Studies attempt to elucidate the functions of catechol- and other amines in the 
brain and periphery in normal and pathological clinical states. Precise 
localization of biochemical processes is a major advance in furthering our 
understanding of the role of particular areas of brain in control of behavior 



199 



Serial No. M-CS-0C(C)-20, Page 4 

and movement disorders and in identifying the site of drug action. 

Proposed Course of Project: Detailed mappings of the brain catecholamine 
and serotonergic nerves of the rat brain are currently being done for future 
studies using drugs and lesions in order to reveal specific functions of the 
monoamines at various sites within the brain. A similar mapping of the 
cholinergic nerves of the brain will also be undertaken. 

Honors and Awards: None 

Publications: None 



200 



Serial No. M-CS-M(C)-08 

1. Laboratory of Clinical Science 

2. Section on Medicine 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Formation, release, disposition and metabolism of biogenic 
amines 

Previous Serial No.: Same 

Principal Investigator: Irwin J. Kopin 

Other Investigators: Philippe V. Cardon, Robert W. Col burn, Andr§ Dubois 
(Guest Worker), Michael H. Ebert, Ingeborg Hanbauer, David P. Henry, 
Tomislav KaziC (Guest Worker), Friedhelm Lamprecht, Gertrude D. Maengwyn- 
Davies (Guest Worker), L. Keng-Yong Ng (Guest Worker), Stephen D. 
Silberstein, Ngueyn B. Thoa, James A, Thomas and Virginia K. Weise. 

Cooperating Units: Section on Experimental Therapeutics, LCS and Units on 
Psychosomatlcs and Analytical Biochemistry (Office of the Chief), LCS 

Man Years: Total 7.5 
Professional 6.0 
Other 1.5 

Project Description: 

objectives: (1) To determine the mechanisms which control development 
and plasticity of the nervous system. (2) To study the molecular basis for 
control of synthesis, storage, release, action and inactivation of aminergic 
transmitters. (3) To quantify metabolic rates for neurotransmitters and 
correlate them with function, drug effects and environmental influences. 

Methods Employed: Radioactive amines or their precursors are injected 
into animals, perfused through tissues or exposed to tissue slices in vitrei 
and the metabolism and disposition of the compounds are examined. Enzymes 
concerned with synthesis or metabolism are assayed in various tissues; and the 
effects of drugs, procedures, age, etc. are determined. 

Major Findings: The elevation of adrenal medullary enzymes, which 
results from repeated exposure to stress, is associated with an enhanced rate 
of epinephrine biosynthesis. The enzyme levels appear to be controlled by 
neuronal and hormonal influences which involve cyclic-AMP. Immobilization 
stress results in elevation of endogenous norepinephrine and increased fighting 
behavior. Shock-induced aggression is enhanced by destruction by 6-hydroxy- 
dopamine of catechol aminergic neurons in the brain. This effect is reversed 
by drugs which result in activation of the dopaminergic receptor. 



201 



Serial No. M-CS-M(C)-08, Page 2 

Stimulation of sympathetic nerves results in release of dopamine-beta- 
hydroxylase as well as norepinephrine; and the enzyme can be used to study the 
process of exocytcsis, which mediates release of the neurotransmitter. In the 
guinea pig vas deferens the process of transmitter and enzyme release is 
enhanced by calcium ions and phenoxybenzamine; but the enhanced release is 
reversed by prostaglandin, possibly by its action on calcium ions. Stimulation- 
induced release of neurotransmitters appears to be blocked by colchicine or 
vinblastine, drugs which interfere with the integrity of the neurotubular 
proteins. Stimulation of the hypogastric nerves results in accelerated 
synthesis of norepinephrine in the vas deferens with selective release of the 
newly formed transmitter. 

Colchicine and vinblastine, by interacting with neurotubulin, block rapid 
axonal transport. These drugs, when applied to the superior cervical ganglion 
of rats, cause elevation in levels of catecholamines and of dopamine-beta- 
hydroxylase. After the initial increase in levels of the enzyme, the amount 
of dopamine-beta-hydroxylase present diminishes. Postganglionic section or 
treatment with 6-hydroxydopamine, which destroys sympathetic nerve endings, 
results in a similar decline in dopamine-beta-hydroxylase activity with a 
similar decline in levels of tyrosine hydroxylase. Uptake of norepinephrine 
by the ganglia in vitro, however, increases at the time that dopamine-beta- 
hydroxylase and tyrosine hydroxylase fall. These observations suggest that as 
a result of axonal injury, there has been a switch in metabolism In the ganglia 
which results in decreased enzyme production and enhanced formation of 
structural components. 

Siqnifiaanoe to Biomedical Researah and the Program of the Institute: 
Catecholamines end other amines play an important role In normal physiology. 
Alterations In synthesis, activation, Inactivation or metabolism of these 
substances may be responsible for abnormal clinical states or may explain the 
mode of action of drugs or development of tolerance or addiction to drugs. 
Assessment of these various processes is important in determining the factors 
Influencing physiology, pharmacology and pathology in brain and other organs. 

Proposed Course of Project: Continued development of methods to Study 
control and to quantify synthesis rates, storage, release and metabolic routes 
of the catecholamines in isolated tissues. Intact animals and man and the 
study of these mechanisms of neurohumor inactivation in various clinical states 
of autonomic and mental disorders will be pursued. Assessment of the control 
of enzymes concerned with transmitter synthesis and their roles in control of 
neuronal function will be further studied. 

Honors and Awards: Dr. Kopin presented Invited seminars on topics in 
catecholamine metabolism and synthesis to the Department of Physiology/Schools 
of Medicine and Dentistry, Georgetown University (Washington) and to the 
Department of Pharmacology/ Co liege of Medicine, University of Arizona (Tuscon). 
He addressed the New York Heart Association Symposium on Regulation of 
Catecholamine Metabolism in the Sympathetic Nervous System (New York) and 
served as Discussant at the conference of the Psychobiology of 



202 



Serial No. M-CS-M(C)-08. Page 3 

Electroconvulsive Treatment (Dorado Beach, P.R.). He was invited to 
participate on the Ad Hoc Panel on Cardiovascular Metabolic Effects of Space- 
flight at the NASA Manned Spacecraft Center (Houston) and to chair a symposium 
on Brain Monoamines and Control of Anterior Pituitary Function at the IV 
International Congress of Endocrinology (Washington). He participated in the 
Round Table Discussion on Studies of Neurotransmitters at the Synaotic Level 
(Budapest) and in the lUPS Comnission on Neurotransmission (Munich). 

Publications: 

Gewirtz, G.P.;, Kvetnansky, R.. Weise, V.K. and Kopin, I.J.: Effects of ACTH 
and dibutyryl cyclic-AMP on catechol ami ne-synthesi zing enzymes in the adrenals 
of hypophysectomized rats. Nature 230: 462-463, 1971. 

Johnson, D.G. , Thoa, N.B., Weinshilboum, R. , Axelrod, J. and Kopin, I.J.: 
Enhanced release of dopamine-beta-hydroxylase from symoathetic nerves by 
calcium and phenoxybenzamine and its reversal by prostaglandins. Proo. Sat. 
Aoad. Soi. 68: 2227-2230, 1971. 

Kopin, I.J. and Silberstein, S.D.: Axons of sympathetic neurons: Transport of 
enzymes in vivo and properties of axonal sprouts in vitro. Pharmaaol. Rev., in 
press. 

Kvetnansky, R., Gewritz, G.P., Weise, V.K. and Kopin, I.J.: Effect of 
dibutyryl cyclic-AMP on adrenal catechol ami ne-synthesi zing enzymes in 
repeatedly immobilized hypophysectomized rats. Endocrinology 89: 50-55, 1971. 

Kvetnansky, R., Weise, V.K., Gewirtz, G.P. and Kopin, I.J.: Synthesis of 
adrenal catecholamines in rats during and after immobilization stress. 
Endocrinology 89: 46-49, 1971. 

Lamprecht, F., Eichelman, B.S., Thoa, N.B., Williams, R.B. and Kopin, I.J.: 
Ininoblizati on-induced increase in rat fighting behavior and brain catecholamine 
synthesis. Science » in press. 

Thoa, N.B., Eichelman, B.S. and Ng, L.K.-Y.: Shock-induced aggression: 
Effects of 6-hydroxydopami ne and other pharmacological agents. Brain Res., In 
press . 

Thoa, N.B., Johnson, D.G. and Kopin, I.J.: Selective release of newly 
synthesized norepinephrine in the guinea pig vas deferens during hypogastric 
nerve stimulation. Eur. J. Pharmacol. 15: 29-35, 1971. 

Thoa, N.B., Johnson, D.G. , Kopin, I.J. and Weiner, N.: Acceleration of 
catecholamine formation in the guinea-pig vas deferens after hypogastric nerve 
stimulation: Roles of tyrosine hydroxylase and new protein synthesis. J. 

Pharmacol. Exp. Ther. 178: 442-449, 1971. 



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Serial No. M-CS-M(C)-08, Page 4 

Thoa, N.B., Wooten, G.F., Axelrod, J. and Kopin, I.J.: Inhibition of release 
of dopamina-beta-hydroxvlase and norepinephrine from sympathetic nerves by 
colchicine, vinblastine or cytochalasin-B. Fpoo. Nat. Acad. Sci. 69: 520-522, 
1972. 



20k 



Serial No. M-CS-M(C)-11 

1. Laboratory of Clinical Science 

2. Section on Medicine 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: False neurochemical transmitters 

Previous Serial Number: Same 

Principal Investigator: Irwin J. Kopin 

Other Investigators: L. Keng-Yong Ng (Guest Worker), Nguyen B. Thoa and 

Virginia K. Weise [ 

Cooperating Units: Unit on Psychosomati cs (Office of the Chief) and Section t 

on Experimental Therapeutics, LCS I 

■J 
Man Years: Total 1.5 

Professional 1.0 ]" 

Other 0.5 j; 

Project Description: 

Objeatives: To determine the consequences of neurochemical transmitter 
replacement by relatively inactive substances, "false transmitters," in the 
mechanism of action of drugs, to study the possible role of these substitute 
transmitters in disease states and to investigate the mechanism of transduction 
of the nerve impulse into transmitter release. 

Methods Employed: (1) Radioactively labeled substances which are known 
or thought to accumulate in sympathetic nerves are synthesized and purified. 
(2) The effect of precursors of false transmitters on the rate of synthesis 
of catecholamines is determined using conversion of labeled tyrosine to 
octopamine and norepinephrine. (3) The central effects of L-dopa have been 
studied in animals in which the adreneraic and dopaminergic neurons have been 
destroyed with 6-hydroxydopamine. This permits study of uptake and metabolism 
of dopa and dopamine in serotonergic neurons. 

Mas'or Findings: Amines related to norepinephrine can replace it at its 
binding sites and thereby influence norepinephrine synthesis, storage and 
release. The effects deoend on the time after administration. Dopamine, 
formed from dopa, in serotonergic neurons can displace serotonin and diminish 
synthesis and release of this indoleamine. Dopamine may be a false 
serotonergic transmitter since it can be released by 5-hydroxytryptophan. 



205 



Serial No. M-CS-M(C)-n, Page 2 

Significance to Biomedical Research and the Program of the Institute: An 
understanding of the mechanisms for binding and release of catecholamines is 
basic to a meaningful hypothesis of the events related to the activation of 
transmitters and synaptic transmission. The fact that a number of inactive 
substances chemically related to norepinephrine may replace it provides a means 
for modulating the effects of nerve stimulation. It is possible that after 
drug administration or in disease states, endogenously formed false transmit- 
ters may reduce effectiveness of ??eurotransmission through certain nervous 
pathways. After admini strati ori of Udopa, accumulation of dopamine and 
replacement of other amines may result In hypotension and movement disorders. 

Proposed Course of the Project: Further investigations of replacement by 
false transmitters of other neurotransmitters such as cholinergic or seroton- 
ergic false transmitters are planned. The possible existence of other 
molecular substitutes (hormones, for example) will also be investigated. 
Studies of the possible role of false transmitters in drug action in man are 
planned. 

Honors and Awards: Dr. Kopin presented a lecture on the mode of action of 
L-dopa in the central nervous system to the Department of Neurology/School of 
Medicine, University of Maryland (Baltimore). 

Publications: 

Kopin, I.J.: Unnatural amino acids as precursors of false transmitters. Fed. 
Proc. 3": 904-907, 1971. 

Thoa, N.B., Johnson, D.G. and Kopin, I.J.: Inhibition of norepinephrine 
biosynthesis by alpha-methyl amino acids in the guinea-pig vas deferens. J. 

Pharmacol. Exp. Ther. 180: 71-77, 1972. 

Thoa, N.B., Weise, V.K. and Kopin, I.J.: Effect of L-dopa on methylation of 
H3-norepinephrine and H3-histamine. Bioahem. Pharmacol, t in press. 



206 



Serial No. M-CS-M(C)-12 

1. Laboratory of Clinical Science 

2. Section on Medicine 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Growth characteristics of aminergic neurons 

Previous Serial No.: None 

Principal Investigator: Irwin J. Kopin 

Other Investigators: Julius Axelrod, Kenneth R. Berv, Floyd E. Bloom, Ingeborg 
Hanbauer, David M. Jacobowitz, David C. Klein, Stephen 0. Silberstein and 
Steven A. Vogel . 

Cooperating Units: Laboratory of Neuropharmacology, NIMH; Laboratory of 

Biomedical Sciences, NICHD; Unit on Histopharmacology (Office of the Chief) 
and Section on Pharmacology, Laboratory of Clinical Science, NIMH 

Man Years: Total 3.5 
Professional 3.0 
Other 0.5 

Project Description: 

ObjeoHves: The development of i£ vitro techniques to study tissues in 
isolation permits examination of factors which control processes of growth and 
influence levels of functions of cells (neurons). 

Methods Employed: Tissues are removed from animals and transferred to 
vessels where they are maintained in culture and allowed to grow. The 
constituents of the culture media are varied; different tissues (such as super- 
ior cervical ganglion and irises) can be grown together, and drugs and hormones 
can be added to the media. With such in vitro techniques, the rate of change in 
enzyme levels, amine content and uptake processes can be measured, and the 
effects of various factors on growth of axonal processes can be assessed. 

Major Findings: Adrenal glands, superior cervical ganglia. Irises and 
pineal glands from adult rats survive for up to two weeks in organ culture. 
When ganglia are grown in contact with irises or pineal glands, axonal processes 
grow into the tissue. When the ganglia are grown alone, however, axonal sprouts 
form and have the properties of nerve endings (uptake, storage and release of 
catecholamines). The axonal sprouts enter tissues and carry with them vesicles 
containing dopamine-beta-hydroxylase and catecholamines. Reinnervation does not 
appear to be specific, but development of sprouts can be prevented by drugs 
which interfere with neurotubular protein. A sensitive and specific assay for 



207 



Serial No. M-CS-M(C)-12, Page 2 

nerve growth factor has been developed; nerve growth factor, which is normally 
present in ganglia and other tissues, influences the rate and extent of axonal 
ramification. 

Conditions which enhance release of catecholamines (e.g., depolarization 
induced by elevated potassium) cause induction of tyrosine hydroxylase and 
dopamine-beta-hydroxylase in adrenal glands and ganglia. 

Signifiacmoe to Biomedical Researah and the Program of the Institute: 
Understanding the factors which control neuronal growth and development is 
essential for a rational approach to investigation of a wide spectrum of 
physiologic processes (e.g., memory, maturation, endocrine control) and 
pathologic conditions (neural retardation, drug influences on brain development 
and perhaps a number of neurologic and psychiatric disorders). The study of 
neurons in isolated systems permits controlled variations of the cellular 
environment, which are not possible in the intact animal, and thus allows more 
definitive indentifi cation of the factors involved in control of the various 
functions. 

Proposed Course of Project: Tissue from brain and peripheral sympathetic 
neurons will be grown. The changes in uptake processes, enzyme levels, 
neurotransmitter formation and release and the effects of other cells will be 
examined. The rate of hormones, the effects of drugs and the differences in 
genetic variants will be investigated. 

Honors and Awards: Dr. Kopin was invited to present a lecture on recent work 
relating to functional innervation by sympathetic nerve fibers grown in tissue 
culture to the Department of Neurology/College of Physicians and Surgeons, 
Columbia Univeristy (New York). 

Publications: 

Hanbauer, I., Johnson, D.G., Silberstein, S.D. and Kopin, I.J.: Pharmacological 
and kinetic properties of uptake of norepinephrine-H^ by superior cervical 
ganglia of rats in organ culture. Neuro-pharmaoology ^ in press. 

Johnson, D.G., Gorden, P. and Kopin, I.J.: A sensitive radioimmunoassay for 75 
nerve growth factor antigens in serum and tissues. J. Neuroohem. 18: 2355-2362, 
1971. 

Johnson, D.G. , Weise, V.K., Hanbauer, I., Silberstein, S.D. and Kopin, I.J.: 
Dopamine-beta-hydroxylase activity during sympathetic reinnervation of rat iris 
in organ culture. Neurobioloay , in press. 

Kopin, I.J., Silberstein, S.D., Johnson, D.G., Hanbauer, I. and Jacobowitz, 
D.M. : Sympathetic reinnervation of the rat iris in vitro . In Costa, E. , 
Iversen, L.L. and Paoletti, R. (Eds.): Advances in Biochemical 
Psyohopharmacology J Volume VI. New York: Raven Press, Inc., 1972, in press. 



208 



I 



Serial No. M-CS-M(C)-12. Page 3 

Silberstein, S.D.: Sympathetic reinnervation of the rat iris in culture: Role 
of nerve growth factor and microtubular protein. Neurology ^ in press. 

Silberstein, S.D., Brimijoin, S., Molinoff, P.B. and Lemberger, L.: Induction 
of dopamine-beta-hydroxylase in rat superior cervical ganglia in organ culture. 
J. Neuroohem. 19, 919-921, 1972. 

Silberstein, S.D., Johnson, D.G., Hanbauer, I., Bloom, F.E. and Kopin, I.J.: 
Axonal sprouts and norepinephrine-H' uptake by superior cervical ganglia in 
organ culture. Ppoc. Nat. Acad. Sai.j in press. 

Silberstein, S.D. , Johnson, D.G., Jacobowitz, D.M. and Kopin, I.J.: Sympathetic 
reinnervation of the rat iris in organ culture. Proa. Nat. Aaad. Soi. 68: 
1121-1124, 1971. 

Silberstein, S.D., Lemberger, L., Klein, D.C., Axelrod, J. and Kopin, I.J.: 
Induction of adrenal tyrosine hydroxylase in organ culture. Neuropharmaoology^ 
in press, 

Silberstein, S.D., Shein, H.M. and Berv, K.R. : Catechol -0-methyl transferase 
and monoamine oxidase activity in cultured rodent astrocytoma cells. Brain 
Res.f in press. 

Vogel, S.A., Silberstein, S.D., Berv, K.R. and Kopin, I.J.: Stimulation-induced 
release of norepinephrine from rat superior cervical ganglia in vitro . Eur. J. 
Fharmaool.f in press. 



209 



Serial No. M-CS-Ps(C)-18 

1. Laboratory of Clinical Science 

2. Section on Psychiatry 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Biochemical and behavioral factors in affective disorders 

Previous Serial Number: Same 

Co-Principal Investigators: Dennis L. Murphy, Frederick K. Goodwin 

Other Investigators: Max A. Baker, Thomas C. Goldman, Joel Kotin, Robert Post, 
Halbert Miller, Steven Ablon, Gabrielle Carlson, 
David Fischer 

Biochemists: Edna K. Gordon 

Other 

Collaborating 

Scientists: William E. Bunney, Jr., Monte S. Buchsbaum, 

Frederick Snyder, Richard Wyatt, Christopher Gillin, 
Edward Donnelly, Michael H. Ebert, Jorge Perez-Cruet 

Psychiatric 

Social Workers: Yolande Davenport, Carol F. Hoover, Walter Sceery 

Psychiatric 

Consultants: M.B. Richmond, P. Chodoff, M.L. Adland, H.A. Myersberg 

Cooperating Units: Nursing, Occupational Therapy Personnel on Wards 
3-East and 4-West 

Man Years: Total 18.9 

Professional 10.9 
Other 8.0 

Project Description: 

Ojjjectives The objective of these projects has been to develop a 
research program for the investigation of the behavioral, biochemical and 
physiological aspects of depressive and manic-depressive patients. 

Behavioral Objectives : Behavioral objectives include an attempt to 
delineate some of the central problems in depression. This involves an 



211 



Serial No. M-CS-Ps(C)-18, Page 2 

intensive analysis of the environmental and psychological events occurring 
prior to and during the development of depressive and manic illness. 

Biochemical and Pharmacological Objectives : Biochemical objectives in- 
volve testing the hypothesis that norepinephrine, dopamine and/or serotonin 
are decreased in depressed patients and are increased in manic patients. An 
attempt is being made to develoD methods for studying the metabolism of the 
putative neurotransmitters in humans. In part this involves the 
utilization of Dharmacological agents which affect enzymes involved in the 
synthesis and breakdown of these neurotransmitters. 

Methods Employed : 

1. Both manic-depressive and depressive patients are selected for study. 
The depressed patients demonstrate feelings of hopelessness, thoughts of 
worthlessness, preoccupation with death and dying, and difficulty sleeping, 
while the manic patients often show flight of ideas, grandiosity, inappro- 
priate and intrusive behavior and, at times, euphoria. 

2. Behavioral and biochemical data is collected on a longitudinal basis 
throughout the course of each patient's hospitalization. 

3. Behavioral data is collected by a nursing research team, the social 
worker, and ward physicians. 

a. The nursing research team is trained in systematic methods of 
observation and recording. At the end of each morning and evening shift, two 
members of the nursing team independently rate each oatient on a 15-point 
scale. The scale measures the amount of depression, anxiety, psychotic 
behavior, physical activity, somatic complaints and anger which are manifes- 
ted during the 8-hour shift. A separate scale has been developed for the 
measurement of manic symptomatology. The nurses also describe the patients' 
verbal and non-verbal behavior every eight hours. 

b. The staff physicians see each patient in individual psychotherapy 
two to four times a week. The physicians dictate information following a 
schedule after each therapy session. 

c. The social worker interviews the closest relatives of each 
patient and sees them individually on a weekly basis. 

d. Observations are made by the nurses concerning the patients' 
sleep throughout e\jery night. These observations are recorded at half- 
hour intervals. 

Biochemical Data : 24-hour urine pools are collected throughout hospitali- 
zation for the determination of urinary catecholamines and indoleamines and 
their metabolites. Cerebrospinal fluid was obtained from most patients and 
was analyzed for the metabolites of catechol- and indoleamines. Some 
patients were qiven doses of probenecid as a research procedure. Probenecid 



212 



Serial No. M-CS-Ps(C)-18, Page 3 

inhibits the active transport of acid metabolites of brain amines, 5-hydroxy- 
indoleacetic acid .(5HIAA) and homovanillic acid (HVA), the major breakdown 
products of serotonin and dopamine, respectively. The CSF levels of these 
acid metabolites are closely related to brain levels and their rate of accumu- 
lation during probenecid administration can be used as an indirect index of 
amine turnover. Blood cells and serum are also prepared for enzyme and bio- 
genic amine level measurements. 

Physiological Data : Some of the patients are monitored in terms of their 

EEG and rapid eye movement potentials throughout each night in a collaborative 

study with Dr. Frederick Snyder. Cortical evoked potentials are studied on 
most patients in collaboration with Dr. Monte Buchsbaum. 

Pharmacolo gical Studies : Active medication and placebo were adminis- 
tered double-blind in a non-random design to many of the patients, with 
placebo substitution before and after each active compound. The utilization 
of placebo substitution increased the level of confidence in the efficacy 
of a compound in an individual patient. This is important in the evaluation 
of drug effects because of the frequency of spontaneous remissions and exacer- 
bations in manic-depressive illness. 

Major Findings : The major findings in the Section during the past year 
are reviewed as follows. 

1. SEROTONIN AND BEHAVIOR: AN EVALUATION OF L-TRYPTOPHAN AS AN ANTI- 
DEPRESSANT: Evidence primarily from British studies has suggested that 
depression might be accompanied by brain serotonin depletion, since reduced 
cerebrospinal levels of 5-hydroxyindoleacetic acid has been found in depressed 
patients and several studies have reported that L-tryptophan was an effective 
antidepressant. To evaluate whether L-tryptophan was capable of significantly 
altering serotonin metabolism in man and whether its antidepressant efficacy 
could be demonstrated in a double-blind study, L-tryptophan was administered 
at an average dose of 9.6 gm/day for an average of 20 days to 16 unipolar 
depressed patients. Thirteen of these individuals showed no change or became 
worse on L-tryptophan. Only three patients showed a decrease in either 
depression or psychosis ratings. None of these three individuals showed a 
relapse when placebo was substituted. CSF and urinary 5-HIAA levels and 
platelet serotonin levels were increased in these patients during L-tryptophan 
treatment. The lack of clinical response in the majority of these patients, 
most of whom later improved with other forms of treatment, does not support 
the suggestion that L-tryptophan might be a useful antidepressant agent. 
Similarly, the lack of clinical change despite evidence of increased peripheral 
and central serotonin metabolism in response to L-tryptophan administration 
does not support the hypothesis that a functional deficiency in brain seroto- 
nin is directly involved in the pathogenesis of depressive disorders. 

2. BIOGENIC AMINES, MEMORY AND MOOD: Marked changes in verbal learning 
"capacity and memory were observed to accompany mania in the course of a 

longitudinal study of cycling manic-depressive patients. This alteration 



213 



Serial No. M-CS-Ps(C)-18, Page 4 

in learning was shown to be princioally accounted for by an increased occurr- 
ence of idiosyncratic verbal associations and an increased turnover of all 
associations, changes which appear to interfere with lonq-term memory opera- 
tions, particularly retrieval. The possibility that these cognitive changes 
may be a function of biogenic amine-related arousal is currently under 
evaluation in a series of studies of the effects of drugs which affect amines 
(L-DOPA, L-tryptonhan, alpha-methyl -para-tyrosine, lithium and antidepressant 
agents) on serial word-list learning, free random recall and word association 
functions. 

3. CELLULAR-LEVEL STUDIES OF THE EFFECTS OF PSYCHOACTIVE DRUGS ON 
ENZYME ACTIVITY AND BIOGENIC AMINE METABOLISM IN MAN: Assays to measure not 
only psychoactive drug levels but also cellular-level affects of these drugs 
in individual patients are under development. Currently in regular use in 
this Section are techniaues measuring mitochondrial monoamine oxidase (for 
MAO-inhibiting antidepressants), amine transport kinetics (for tricyclic 
antidepressants), cyclic AMP formation (for drugs with receptor-blocking 
properties) and amine levels (for drugs affecting amine storage and release). 
These techniques permit very precise comparisons of individual biochemical 
and behavioral responses to drugs. They have also led to such "incidental" 
findings as a reduced level of monoamine oxidase activity in the bipolar 
manic-depressive patient group, and the discovery of increased levels of the 
false transmitter, octopamine, in cells from patients receiving MAO-inhibitors 
and in some depressed patients with reduced MAO activity. 

4. CSF AMINE METABOLITES IN AFFECTIVE ILLNESS: PROBENECID STUDIES: 
A major focus of investigation on the 4-West Clinical Research Unit, in 
collaboration with the Unit on Clinical Biochemistry, has been the continued 
development and application of the probenecid technique for the study of amine 
turnover in the CNS. To date, 35 patients with affective illness. 10 controls 
and 7 addicts on methadone have been studied. Differences in the probenecid- 
induced accumulation in the CSF of 5-HIAA, HVA, and MHPG (the major metabolites 
of serotonin, dopamine and norepinephrine, respectively) have been shown to 
exist between diagnostic groups and in relation to different drugs, including 
L-DOPA, L-tryptophan, AMPT, PCPA, lithium and imioramine. 

5. BASELINE CSF AMINE METABOLITE LEVELS IN AFFECTIVE ILLNESS: A large 
series of depressed patients (55) has been studied under controlled conditions 
for CSF 5-HIAA and HVA. With control of the physical activity variable, we 
have been unable to demonstrate any differences in 5-HI.^A between depressed 
patients and a carefully selected control group. HVA has been found to be 
lower in depression when compared to manics or controls. Similarly, MHPG 

was found to be low in a smaller group of patients with retarded depression 
when compared to manics or controls. 

6. SIMULATED BEHAVIORAL STATES IN PSYCHOBIOLOGICAL STUDIES: EFFECTS ON 
CSF AND URINARY AMINE METABOLITES: Studies have been initiated this year on 
the 4-West Clinical Research Unit, which are designed to help clarify the 
questions concerning whether a biological abnormality identified in association 
with the behavioral state (for example, mania or deoression) is primary 



Serial No. M-CS-Ps(C)-18, Page 5 

(that is, reflecting the underlying psychopathology) or is secondary to some 
aspect of the behavioral state. Moderately depressed patients were asked to 
simulate a state of manic excitement and hyperactivity and CSF amine metabol- 
ites were studied and compared with baseline conditions. Both 5-HIAA and 
HVA in the CSF were substantially increased by this procedure, suggesting that 
the level of psychomotor activity is an important variable determining the 
level of these amine metabolites in the CSF. MHPG and cyclic-AMP in the CSF 
were not elevated by this simulated mania procedure. 

In a separate preliminary study involving a moderate exercise procedure 
in four patients (with no attempt to simulate an actual mood change) we have 
shown a large increase in urinary MHPG (100-150%) on the exercise day in three 
out of the four patients. For the group as a whole, the change was statisti- 
cally significant. 

7. COMPARISON OF THE ANTIDEPRESSANT EFFECTS OF IMIPRAMINE AND LITHIUM IN 
UNIPOLAR AND BIPOLAR DEPRESSED PATIENTS: A total of 52 patients have been 
studied under controlled conditions. Lithium has been shown to be a more 
effective antidepressant in bipolar compared to unipolar patients, whereas 

the reverse appears to be the case with the tricyclic drugs. 

8. BEHAVIORAL AND BIOCHEMICAL EFFECTS OF THC IN MAN: Tetrahydrocanna- 
binol (THC) has been administered chronically (for seven days) to a small 
group of depressed patients and a number of parameters have been evaluated. 
Behaviorally, little or no antidepressant effect was observed. Two of the 
six patients experienced clearly dysphoric reactions with increased anxiety 
and psychosis. A number of biological effects of THC are under collaborative 
investigation, including the effects of THC administration on microsomal 
enzyme systems in liver, effects of THC on the distribution of metabolism of 
labeled THC, and its effects on amine metabolism. 

9. BEHAVIORAL AND BIOCHEMICAL STUDIES OF COCAINE IN DEPRESSION: Cocaine, 
like the tricyclic antidepressants, is a powerful inhibitor of the reuptake of 
amines, potentiating the action of these neurotransmitters at critical central 
synapses; thus, theoretically, it should have antidepressant properties. An 
experimental trial of cocaine (both orally and i.v.) in depressed patients has 
been undertaken in order to further evaluate the hypothesized role of amines 

in affective illness. Preliminary results suggest that cocaine (particularly 
when administered i.v.) has definite psychoactive effects. Its effects, 
however, are not clearly antidepressant but rather that of mobilizing or 
activating a variety of affective states. The effects of cocaine on the uptake 
of infused norepinephrine is being studied by Drs. Et3ert and Kopin using 
double isotope procedures. 

10. FOLLOWUP STUDIES OF MANIC-DEPRESSIVE PATIENTS: A 200-item followup 
questionnaire has been developed; it focuses on job, family and social adjust- 
ment and on psychiatric symptomatology. To date, 60 former patients have been 
interviewed; in addition, in 50 of these cases, the spouse or significant other 
was also interviewed. Outcome over the average two-year followup period has 
been scored for each patient. In a group of 20 patients selected on the basis 

215 



Serial No. M-CS-Ps(C)-18, Page 6 

of having had a full manic episode while in the hospital, no correlation was 
found between outcome on followup and the severity of the manic episode scored 
independently during hospitalization, 

11. ASSESSMENT OF BEHAVIOR AND EGO FUNCTION IN MANIC-DEPRESSIVE PATIENTS: 
Further studies on the validation of a new milieu rating scale for manic and 
depressive behavior have been completed. Factor analysis of the scale items 
has confirmed the presence of two major subgroups of manic patients who 
manifest different behavioral patterns while manic. In another approach to 
personality assessment, data concerning eqo function and defensive patterns 

has been collected from each 4-West patient's therapist on a twice-weekly 
basis over the last year. This data is currently under analysis. 

12. SLEEP STUDIES: In collaboration with Drs . Gillen and Snyder, we 
have continued our EEC studies of sleep in depressed and manic natients, 
particularly focusing on the effect of drugs such as THC and cocaine. In 
addition, the effects of amine precursors have been evaluated, using the 
novel technigue of intravenous infusion during undisturbed sleep. I.V. L-DOPA 
was found to suppress REM sleeo and to delay the onset of the first REM period. 
Threo-DOPS and 5-HTP, precursors of norepinephrine and serotonin, respectively, 
have been studied using the same technique and no significant effects on sleep 
were observed. With longitudinal all night recordings, it was demonstrated 
that oral cocaine significantly reduces total sleeo and rapid eye movement 
(REM) sleep. Studies on the effects of chronic oral THC administration to 
depressed patients have demonstrated no sianificant sleep changes, except 
suppression of REM sleen on the first night of the drug. 

Proposed Course of the Project : Durina the next year continued emphasis 
will be given to the further development of methods for the study of amine 
function in man and their application to the study of manic depressive illness. 

Studies of the natural course of manic-depressive illness will be expan- 
ded, using follow-up studies as the major focus. An attempt will be made to 
examine psychobiological correlates of the predisposition to affective illness 
by studying patients with past histories of manic or depressive illness, and 
their first degree relatives during normal phases. 

Studies in the area of drug addiction will be given new emphasis, in 
collaboration with the Office of the Chief, LCS. These studies will involve 
the continued assessment of amine function in heroin addicts on and off 
methadone, and the effects of amine precursors and synthesis inhibitors on 
the addictive and withdrawal processes in man. 



2l6 



Serial No. M-CS-Ps(C)-18, Page 7 

HONORS AND AWARDS 

Drs. William E. Bunney, Jr., Dennis L. ^lurphy and Frederick K. Goodwin 
were chosen as First Place co-winners of the Anna-Monika Award given by the 
Anna-Monika-Stiftung, Dortmund, Germany. 

Dr. Bunney presented a paper on "Psychobiological Studies of Manic- 
Depressive Illness" in Basel, Switzerland, a paper entitled, "Studies of 
L-DOPA, L-tryptophan and alpha-methyl -para-tyrosine" to the Vth World 
Congress of Psychiatry, in Mexico City, Mexico, a paper entitled "Lack of 
clinical response to large doses of L-tryptophan: behavioral and metabolic 
studies" at the Conference on the Behavioral Effects of Changes in Level of 
Brain Serotonin, in Palo Alto, California, and a paper entitled, "CSF-MHPG 
in Affective Disorders" to the American College of Neuropsychopharmacology 
in Las Vegas, Nevada. In addition, at the 4th Annual Taylor Manor Hospital 
Scientific Symposium in Ellicott City, Maryland, he presented a paper 
entitled "Psychobiological Studies of Mania and Depression". Dr. Bunney 
will present a paper at the Annual Convention of the American Medical 
Association in June. 

Dr. Goodwin presented a paper at the Max Planck Institute, Munich, 
Germany, entitled: "Current status of amine function in affective illness", 
and at the Annual Meeting, International Group for the Study of Affective 
Disorders in Zurich, Switzerland, he presented a paper on "Amine precursors 
and synthesis inhibitors in the study of affective illness". At a Symposium 
of the American Society of Clinical Pharmacology and Therapeutics in Philadel- 
phia, he presented a paper entitled, "Psychopharmacology". He also presented 
a paper entitled "Lithium in Depression" at the V. A. -NIMH Collaborative Lithium 
Study Meeting in New Orleans. "The Psychobiology of Depression - Conceptual 
Issues" was presented at the NIMH Workshop on The Psychology of Depression in 
Arlie, Virginia, and "The Use of Probenecid for the Study of Amine Turnover 
in Man" was presented at the NIH Clinical Center Grand Rounds. 

Dr. Goodwin also presented a paper on "Lithium Response in Unipolar vs. Bipolar 
Depression" at the Vth World Congress of Psychiatry in Mexico City, and a paper 
on "Current Psychobiological Research in Affective Illness" at the Department 
of Psychiatry, Albert Einstein College of Medicine, New York. Two papers - 
"The Biology of Bipolar Affective Illness: Studies with L-DOPA and alpha-methyl- 
para- tyrosine", and "Problems in the Study of Amine Turnover in Man - The 
Probenecid Technique" were presented at the American College of Neuropsycho- 
pharmacology (ACNP), Las Vegas, Nevada. 

In addition. Dr. Goodwin will be presenting the following papers. "CSF Amine 
Metabolites in Affective Illness: Probenecid Studies", Annual Meeting, 
American Psychiatric Assn., Dallas, and "Psychopharmacology of the Affective 
Disorders", Hillside Hospital, New York. He has also been invited to present 
■a paper entitled, "Methods for the Study of Central Amine Function in Man" at 
the Annual Meeting, International Group for the Study of Affective Disorders, 
San Antonio, Texas. Dr. Goodwin participated as a co-author in several other 



217 



Serial No. M-CS-Ps(C)-"l8, Page 8 

papers presented at the World Congress of Psychiatry, the ACNP, the American 
Psychiatric Assn., the American Psychosomatic Society, the Association for the 
Psychophysiological Study of Sleep, and others. 

Dr. Murphy presented the following papers: "A Cellular Model for Studies 
of Biogenic Amine Metabolism in Mania" at the American College of Neuropsycho- 
Dharmacology in Las Vegas, Nevada; "Differential Behavior and Biochemical 
Responses to L-DOPA in Bipolar Manic-Depressive Patients" at the Vth World 
Congress of Psychiatry in Mexico City, and "Studies of Platelet and Plasma 
Serotonin in Neuromuscular Diseases" at the American Academy of Neurology in 
St. Louis, Missouri. Dr. Murphy was invited to present papers on different 
aspects of the biological and behavioral studies of affective disorders at 
Georgetown University, Johns Hopkins University, The University of California 
at Los Angeles, the University of Kentucky, the Philadelphia Naval Hospital, 
the University of Utah and Rutgers University. He will be presenting a paper, 
"Differential Excretion of Catecholamine Metabolites After L-DOPA in Depressed 
Patients" at the American Psychiatric Assn. Annual Meeting in Dallas, Texas 
in May. 

In addition. Dr. Murphy discussed the Section's studies of depression on an 
hour-long nationwide television interview on the Phil Donahue Show in Dayton, 
Ohio. 

Dr. Perez-Cruet presented the following papers. "Evidence for a Balance 
in the Basal Ganglia between Cholinergic and Dopaminergic Activity" at the 
Federation Meeting in Atlantic City; "Changes in Synthesis Rate of Serotonin, 
Dopamine and Norepinephrine after Withdrawal of Chronic Treatment with a-methyl- 
tyrosine (aF-IT) in rats" was presented at the American Federation for Clinical 
Research in Philadelphia. A paper was presented at the American Society for 
Pharmacology and Experimental Therapeutics, "Prostaglandin E] (PGEi) Induces 
"Paradoxical" Sleep, Increases Brain Acetylcholine (Ach) Levels and Serotonin 
(5HT) Turnover", in Burlington, Vermont, and a paper on "Stimulation of Sero- 
tonin Synthesis by Cecium in Rats" at the Federation Meetings in Atlantic City. 

Dr. Perez-Cruet will be presenting a paper, "Effects of Psychotropic Drugs 
on Subcellular Levels of Amino Acid Precursors and Metabolism of Monoamines 
in Brain" at the 5th International Congress on Pharmacology in San Francisco. 

Dr. Post presented a paper, "Simulated Behavior States in Psychobiological 
Research" at the American Psychosomatic Society meetings in Boston. He will 
present a paper at the American Psychiatric Assn. meetings in Dallas entitled, 
"CSF Amine Metabolites, Mood and Psychomotor Activity", and, also in Dallas, 
will present a paper to the Association for the Psychophysiological Study of 
Sleeo entitled, "Effect of Cocaine on Sleep of Depressed Patients". 

Dr. ^Kotin will present a paper at the meetings of the American Psychiatric 
Association in Dallas, entitled, "Tetrabydrocannabinol (THC) in Depressed 

Patients". 



218 



Publications: serial no. M-CS-Ps(C) -18, Page 9 

Gershon, E.S.; Bunney, W.E.,Jr. , Goodwin, F.K., Murphy, D.L., Dunner, D.L., 
and Henry, G.M. : Catecholamines and Affective Illness: Studies with L-DOPA 
and Alpha-methyl -para- tyrosine. In: Ho, B.T. & Mclsaac, W.M. (Eds.) Brain 
Chemistry and Mental Disease. Plenum Press, New York, Vol. I, pp. 135-163, 
1971. 

Carpenter, W.T.; and Bunney, W.E.,Jr.: Adrenal Cortisol activity in 
depressive illness. Amer . J_. Psychiat . 128:63-72, 1971. 

Carpenter, W.T.; and Bunney, W.E.,Jr.: Diurnal rhythm of Cortisol in mania. 
Arch. Gen. Psychiat . 25:270-273, 1971. 

Beigel, A.; Murphy, D.L., and Bunney, W.E.,Jr.: The manic-state rating 
scale: scale construction, reliability and validity. Arch . Gen . Psychiat . 
25:256-262, 1971. 

Goodwin, F.K.; and Bunney, W.E.,Jr. : Depressions following reserpine: a 
reevaluation. Seminars in Psychiatry . 3:435-448, 1971. 

Murphy, D.L.; and Bunney, W.E.,Jr.: Total body potassium changes during 
lithium treatment. J.. Nerv . Ment. Dis.. 152:381-389, 1971. 

Bunney, W.E.,Jr. : Biochemical Research in Affective Illness. In: Fieve,R.R. 
(Ed.) Depression in the 70 's. Modern Theory and Research. Excerpta Medica 
Foundation, New York, pp. 55-63, 1971. 

Bunney, W.E.,Jr. ; Goodwin, F.K. and Murphy, D.L.: Current Research on 
L-DOPA in Depression and Mania. In: Malitz, S. (Ed.) L-DOPA and Behavior. 
Raven Press, New York, 1971. 

Goodwin, F.K.; Ebert, M., and Bunney, W.E.,Jr.: Mental Effects of Reserpine 
in Man. In: Shader, R.I. (Ed.) Psychiatric Complications of Medical Drugs. 
Raven Press, New York, 1971. 

Goodwin, F.K.: Behavioral Effects of L-DOPA in Man. In: Shader, R.I. (Ed.) 
Psychiatric Complications of Medical Drugs. Raven Press, New York, 1971. 

Goodwin, F.K.; and Post, R.M.: The Use of Probenecid in High Doses for 
the Estimation of Central Serotonin Turnover in Patients. In: Barchas, J. 
and Usdin, E. (Eds.) Serotonin and Behavior. Academic Press, New York, 1972. 

Goodwin, F.K. and Bunney, W.E.,Jr.: The Biology of Bipolar Affective Illness. 
Studies with L-DOPA and Alpha-methyl-para-tyrosine. In: Gershon, S. and 
Bunney, W.E.,Jr. (Eds.) Amines and Affective Disorders. (ACNP Symposium) 
Plenum Press, New York, 1972. 

Goodwin, F.K. and Post, R.M.: Problems in the Study of Amine Turnover in Man 
- The Probenecid Technique. In: Gershon, S. & Bunney, W.E.,Jr. (Eds.) 
Amines and Affective Disorders. (ACNP Symposium) Plenum Press, New York, 1972. 



219 



Serial Mo. M-CS-Ps(C)-18, Page 10 

Borge, G.; Buchsbaum, M., Goodwin, F.K. and Murphy, D.L.: NeuroDsycholoqical 
correlates of affective disorders. Arch . Gen . Psych i at . 24:501-504, 1971. 

Dunner, D.L.; Gershon, E.S., Goodwin, F.K., Murphy, D.L. and Bunney, W.E.,Jr.: 
Excretion of 17-hydroxycorticosteroids in unipolar and bipolar depressed 
patients. Arch. Gen. Psychiat . 26:360-363, 1972. 

Buchsbaum, M.; Goodwin, F.K., Murphy, D.L. and Borge, G.: Average evoked 
responses in affective disorders . Amer . J_. Psychiat . 128:19-25, 1971. 

Henry, G.M.; Murphy, D.L., and Weinqartner, H.: Idiosyncratic oatterns of 
learning and word association during mania. Amer . J_. Psychiat . 128:564-574, 
1971. 

Beigel, A.; and Murphy, D.L.: Assessing clinical characteristics of the manic 
state. Amer . J_. Psychiat . 128:688-699, ' 1971 . 

Beigel, A.; and Murphy, D.L.: Differences in clinical characteristics 
accompanying depression in unipolar and bioolar affective illness. Arch . 
Gen . Psychiat. 24:215-220, 1971. 

Goodwin, F.K.: Psychiatric side effects of Levodopa in man. JAMA 218: 
1915, 1971. 

Dunner, D.L.; and Goodwin, F.K.: The effect of L-tryptophan on brain sero- 
tonin metabolism in depressed patients. Arch . Gen . Psychiat . 26:364-366, 
1972. 

Goodwin, F.K.; Dunner, D.L., and Gershon, E.S.: Effect of L-DOPA treatment 
on brain serotonin metabolism in depressed patients. Life Sci . 10:751, 1971. 

Gershon, E.S.; Dunner, D.L., and Goodwin, F.K.: Toward a biology of affective 
illness: genetic contributions. Arch . Gen . Psychiat . 25:1, 1971. 

Dunner,. D.L. ; Cohn, C.K., Gershon, E.S., and Goodwin, F.K.: Differential 
catechol -0-methyl -transferase activity in unipolar and bipolar affective 
illness. Arch . Gen_. Psychiat . 25:348, 1971. 

Paul, M.I.; Cramer, H., and Goodwin, F.K.: Urinary cyclic-AMP in depression 
and mania: effects of L-DOPA and lithium carbonate. Arch . Gen. Psychiat . 
24:327, 1971. 

Robinson, D.S.; Davis, J.M., Niles, A., Colburn, R.W., Davis, .i.N., Bourne, 
H.R., Bunney, W.E.,Jr., Shaw, D.M. and Coppen, A.J.: Ageina, monoamines, 
and monoamine oxidase levels. Lancet 1:290-291, 1972. 

Donnelly, E.F.; Mignone, R.J., Dent, J.K. and Murphy, D.L.: Comparison of 
temporal lobe epileptics and affective disorders on the Halstead-Rei tan 
test battery. J^. Clin . Psychol . (In press). 



220 



I 



Serial No.M-CS-Ps(C)-18, Page 11 

Lott, I.T.; Murphy> D.L. and Chase, T.N.: Down's syndrome: central mono- 
amine turnover in patients with diminished platelet serotonin. Neurol . 
(In press). 

Murphy, D.L.: Amine precursors, monoamine oxidase activity and false 
neurotransmitters in depressed patients. Amer . J^. Psych i at . (In press). 

Murphy, D.L. and Weiss, R.: Reduced monoamine oxidase activity in blood 
platelets from bipolar depressed patients. Amer . J_. Psych i at . (In press). 

Perez-Cruet, J.; Tagliamonte, A., Tagliamonte, P. and Gessa, G.L.: 
Differential effect of p-chlorophenylalanine (PCPA) on sexual behavior and 
on sleep patterns of male rabbits. Ri vista di Farmacol . e Terap . 11:27-34, 
1971. 

Tagliamonte, A.; Tagliamonte, P., Perez-Cruet, J., Stern, S. and Gessa, G.L.: 
Effects of psychotropic drugs on tryptophan concentration in the rat brain. 
J^. Phamiacol . Exp . Ther . 177:475-480, 1971. 

Tagliamonte, A.; Tagliamonte, P., Perez-Cruet, J. and Gessa, G.L.: Increase 
of brain tryptophan caused by drugs which stimulate serotonin synthesis. 
Nature - New Biology, 229:125, 1971. 

Perez-Cruet, J. ; Tagliamonte, A., Tagliamonte, P. and Gessa, G.L.: Stimula- 
tion of serotonin synthesis by lithium. J^. Pharmacol . Exp . Ther . 178:325- 
330, 1971. 

Tagliamonte, A.; Tagliamonte, P., Forn, J., Perez-Cruet, J., Krishna, G. 
and Gessa, G.L.: Stimulation of brain serotonin synthesis by dibutyryl- 
cyclic AMP in rats. J^. Neurochem . 18:1191-1196, 1971. 

Sesame, H.A.; Perez-Cruet, J., DiChiara, G., Tagliamonte, T., Tagliamonte, 
P. and Gessa, G.L.: Effect of methadone on dopamine metabolism in rat 
basal ganglia and its relation to catalepsy. Ri vista di Farmacol . e^ 
Terap . 11:99-105, 1971. 

Perez-Cruet, J.; Murphy, D.L. and Bunney, W.E.,Jr.: Changes in synthesis 
rate of serotonin, dopamine and norepinephrine after withdrawal of chronic 
treatment with a-methyl-tyrosone (aMT) in rats. Clin . Res . 19:735, 1971. 

Haubrich, D.R.; Perez-Cruet, J. and Reid, W.D.: Prostaglandin E-, induced 
paradoxical sleep and increase in brain serotonin turnover in rats. Brit . 
J^. Pharmacol . (In press). 

Perez-Cruet, J.; Tagliamonte, A., Tagliamonte, P., and Gessa, G.L.: Changes 
in brain serotonin metabolism associated with fasting and satiation in rats. 
"Life Sci. 11:31-39, 1972. 



221 



Serial No.M-CS-Ps(C)-18, Page 12 

Goodwin, F.K.; Murphy, D.L., Dunner, D.L. and Bunney, W.E.,Jr.: Lithium 
response in unipolar vs. bipolar depression. Amer . J^. Psych i at . (In press). 

Lott, I.T.; Chase, T.N. and Murphy, D.L.: Down's syndrome: transport, 
storage, and metabolism of serotonin in blood platelets. Pediatric Res . 
(In press). 

Post, R.M.; Kotin, J. and Goodwin, F.K.: The relationship between psycho- 
motor activity and cerebrospinal fluid amine metabolites in affective 
illness. Amer. J^. Psychiat . (In press). 

Goodwin, F.K.; and Ebert, M.: Lithium in Mania. In: Gershon, S. (Ed.) 
Lithium: Its Role in Psychiatric Research and Treatment. Plenum Press, 
New York, 1972 (In press). 

Goodwin, F.K.; and Bunney, W.E.,Jr. : The Current Status of Lithium as Used 
in Psychiatry and as a Research Instrument in Medicine. In: Gershon, S. 
(Ed.) Lithium: Its Role in Psychiatric Research and Treatment. Plenum 
Press, New York, 1972 (In press). 

Kotin, J.; and Goodwin, F.K.: Depression during mania: clinical observations 
and theoretical implications. Amer . J^. Psychiat . (In press). 

Bunney, W.E.,Jr.; Murphy, D.L., Goodwin, F.K. and Borge, G.F.: The "switch 
process" in manic-depressive illness. I. A systematic study of sequential 
behavioral change. Arch . Gen. Psychiat . (In press). 

Bunney, W.E.,Jr.; Goodwin, F.K., Murphy, D.L. and House, K.M. : The "switch 
process" in manic-deoressive illness. II. Relationship to catecholamines, 
REM sleep and drugs. Arch . Gen . Psychiat . (In press). 



Bunney, W.E.,Jr. ; Goodwin, F.K. and Murphy, D.L.: The "switch process" in 
manic-depressive illness. III. Theoretical implications. Arch . Gen . Psychiat . 

(In press). 

Murphy, D.L.; Baker, M., Goodwin, F.K., Kotin, J. and Bunney, W.E.,Jr.: 
Behavioral and Metabolic Effects of L-Tryptophan in Unipolar Depressed 
Patients. In: Barchas, J. & Usdin, E. (Eds.) Serotonin and Behavior. 
Academic Press, New York, 1972. (In press). 

Jacobs, L.; and Kotin, J.: Fantasies of psychiatric research. Amer . J. 
Ps^cMat. 128:1074, 1972. ~ 

Bunney, W.E., Jr.; and Murohy, D.L.: The Switch Process and Psychopathology. 
In: Mendels, J. (Ed.) Textbook of Biological Psychiatry. Academic Press, 
New York (In press) . 



222 



I 



Serial No. M-CS-Ph-5 

1. Laboratory of Clinical Science 

2. Section on Pharmacology 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Biochemistry and pharmacology of the adrenergic 
nervous system 

Previous Serial Number: None 

Principal Investigators: Roland D. Ciaranello, Joseph T. Coyle, 
G. Frederick Wooten 

Other Investigators: Julius Axelrod 

Man Years: Total 7.5 
Professional 4.5 
Others 3.0 

Project Description: 

Objectives ; To study the development of the adrenergic 
nervous system in the brain. To examine how adrenergic 
biosynthetic enzymes are transported down the axon and released. 
To examine serum dopamine- p-hydroxylase levels after disease and 
drug treatment. 

Major Findings : A sensitive method for measuring tyrosine 
hydroxylase in the brain has been developed and its distribution 
described. In studies on the development of the adrenergic 
nervous system in the rat brain it was found that all of the 
biosynthetic enzymes, tyrosine hydroxylase, dopa decarboxylase 
and dopamine- p-hydroxylase first appear 15 days after gestation, 
mainly in the cell bodies. This is followed by outgrowth of 
nerve terminal 18 days after gestation and appearance and 
storage of noradrenaline on day 20 after gestation. Both 
tyrosine hydroxylase and dopamine- p-hydroxylase move down the 
axon proximodistally by a rapid transport process. Microtubular 
elements appear to be involved in this transport. Repeated 
administration of reserpine results in an induction of tyrosine 
hydroxylase and dopamine- p-hydroxylase but no change in rate of 
transport. Studies on release process were carried out in 
collaboration with the Section on Medicine and will be described 
by Dr. Kopin. 



223 



Serial No. M-CS-Ph-5, page 2 

Serum dopamine- p-hydroxylase is reduced or absent in 
children with familial dysautonomia. In normal subjects there 
was a gradual increase in the serum enzyme from birth to 
puberty. After stress there was a rapid increase in dopamine- 
s-hydroxylase in man. 

The administration of dexamethasone results in an 
induction of a new enzyme in the sympathetic ganglia of 
newborn rats. 

Preliminary work indicates that dopaminergic cell bodies 
in the substantia nigra can be grown in organ culture. 

Significance to Biomedical Research and the Program of 
the Institute : Studies on the development of the adrenergic 
nervous system in the brain make it possible to carry out 
investigations on how these developments can be perturbed and 
the consequences. Serum dopamine- p-hydroxylase studies have 
given insight regarding the course of familial dysautonomia 
and should make possible studies of other neurological diseases, 

Proposed Course of Project : Further studies will be 
carried out to examine how specific proteins are transported 
down the axon and how they are released. The factors 
influencing dopaminergic, noradrenergic and serotonergic cell 
bodies to be maintained in organ culture will be examined. 
Changes in serum dopamine- p-hydroxylase will be studied. 
Induction and suppression of the adrenaline-forming enzyme in 
the ganglia and organ of Zuckerkandl will be examined. 

Honors and Awards : Dr. Axelrod has been invited to give 
the Harvey Lecture at Rockefeller University, the Scheuler 
Lecture at Tulane University, and the main address at the 
General Session of the Federation of American Societies for 
Experimental Biology. He also received an Honorary Sc.D. 
from New York University and from the Medical College of 
Wisconsin; the Townsend Harris Medal of The City College of 
New York, the Myrtle Wreath Award of the Hadassah Society, 
and the Man of the Year Award of the Montgomery County Chamber 
of Commerce o 

Publications : 

Axelrod, J. : Methyltransf erase enzymes in the metabolism of 
physiologically active compounds and drugs. In Brodie, B.B. 
and Gilette, J. (Eds.): Handbook of Expalmental Pharmacology . 
New York, Springer-Verlag, 1971, pp. 609-620. 



22i| 



Serial No. M-CS-Ph-5, Page 3 

Axelrod, J.: . Noradrenaline: fate and control of its 
biosynthesis. In: Les Prix Nobel . Stockholm, Impriraerieal 
Royal P. A. Norstedt & Soner, 1971, pp. 189-208. Science 173: 
598-606, 1971. 

Black, I.B., Axelrod, J., and Reis, D.J.: Hypothalmic 
regulation of the daily rhythm in hepatic tyrosine transaminase 
activity. Nature (New Biol.) 230: 185-187, 1971. 

Black, I.B. and Reis, D.J.: Central neural regulation by 
adrenergic nerves of daily rhythm in hepatic tyrosine 
transaminase activity. J. Physiol . 219: 267-280, 1971, 

Cohn, C.K. and Axelrod, J. : Effect of estradiol on catechol-0- 
methyltransf erase activity in rat liver. Life Sci . 10: 
1351-1354, 1971. 

Coyle, J.T. and Axelrod, J.: Development of the uptake and 
storage of L-['^H] norepinephrine in the rat brain. J. Neurochem . 
18: 2061-2075, 1971. 

Henry, J.P. , Stephens, P.M., Axelrod, J., and Mueller, R.A. : 
Effect of psychosocial stimulation on the enzymes involved in 
the biosynthesis and metabolism of noradrenaline and adrenaline. 
Psychosomat. Med . 33: 227-237, 1971. 

Johnson, D.G. , Thoa , N.B. , Weinshilboum, R. , Axelrod, J., and 
Kopin, I.J. : Enhanced release of dopamine- p-hydroxylase from 
sympathetic nerves by calcium and phenoxybenzamine and its 
reversal by prostaglandins. Proc. Nat. Acad. Sci . 68: 
2227-2230, 1971. 

Molinoff, P.B., Weinshilboum, R. , and Axelrod, J.: A sensitive 
enzymatic assay for dopamine- p-hydroxylase. J. Pharmacol. Exp . 
Thcr . 178: 425-431, 1971. 

Mueller, R.A. , Willard, P., and Axelrod, J.: Alterations in 
norepinephrine storage in inbred rats made hypertensive by 
triidothyronine and sodium chloride. Pharmacology 5: 
153-164, 1971. 

Weinshilboum, R. and Axelrod, J.: Reduced plasma dopamine-p- 
hydroxylase in familial dysautonomia. New Engl. J. Med . 285: 
938-942, 1971. 

Weinshilboum, R. and Axelrod, J.: Serum dopamine- p-hydroxylase 
decrease after chemical sympathectomy. Science 173: 931-934, 
1971. 



225 



Serial No. M-CS-Ph-5, Page 4 

Weinshilboum, R. , Kvetnansky, R. , Axelrod, J., and Kopin, I. J. : 
Elevation of serum dopamine- p-hydroxylase activity with forced 
immobilization. Nature 230: 287-288, 1971. 

Weinshilboum, R. , Thoa , N.B. , Johnson, D.G. , Kopin, LJ., and 
Axelrod, J. : Proportional release of norepinephrine and 
dopamine- p-hydroxylase from sympathetic nerves. Science 
174: 1349-1351, 1971. 

Cohn, C.K., Vesell, E.S., and Axelrod, J.: Studies of a 
methionine-activating enzyme. Biochem. Pharmacol . 21: 
803-809, 1972. 

Coyle, J.T. and Axelrod, J.: Dopamine- p-hydroxylase in the rat 
brain: developmental characteristics. J. Neurochem . 19: 
449-459, 1972. 

Ross, S.B., Weinshilboum, R. , Molinoff, P.B., Vesell, E.S., and 
Axelrod, J.: Electrophoretic properties of dopamine-p- 
hydroxylase in several tissues from three species. Mol . 
Pharmacol. 8: 50-58, 1972. 

Silberstein, S.D., Brimijoin, S,, Molinoff, P.B. , and 
Lemberger, L. : Induction of dopamine- p-hydroxylase in rat 
superior cervical ganglia in organ culture. J. Neurochem . 
19: 919-921, 1972. 

Thoa, N.B. , Wooten, G.F. , Axelrod, J., and Kopin, I.J.: 
Inhibition of release of dopamine- p-hydroxylase and 
norepinephrine from sympathetic nerves by colchicine, 
vinblastine, or cytochalasin-B. Proc. Nat. Acad. Sci. 69: 
520-522, 1972. 

Reis, D.J. and Molinoff, P.B. : Brain dopamine- p-hydroxylase: 
regional distribution and effects of lesions and 6-hydroxy- 
dopamine on activity. J. Neurochem. 19: 195-204, 1972. 



n 



226 



Serial No. M-CS-Ph-6 

1. Laboratory of Clinical Science 

2. Section on Pharmacology 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Tryptamine and other biogenic amines and 
psychoactive drugs 

Previous Serial Number: None 

Principal Investigators: Julius Axelrod, David S. Kreuz, 

Juan M. Saavedra (Guest Worker) 

Man Years: Total 2.5 

Professional 1.5 
Other 1.0 

Project Description: 

Objectives : To develop sensitive methods for the 
measurement of normally occurring amines and psychoactive drugs. 

Methods Employed : Biochemical, pharmacological and 
radioactive tracer techniques . 

Major Findings ; A specific and sensitive enzyme method 
for measuring tryptamine in tissues was developed. This amine 
was found to occur normally in brain and other tissues. 
Injection of C -tryptamine into the brain results in the 
formation of methyl- and dimethyltryptamine. An enzyme that 
methylates tryptamine was found in rat and human brain and an 
unidentified inhibitor was also observed. 

After its repeated administration, tetrahydrocannabinol 
was found to accumulate in the fat and to a small extent in 
the brain. 

Octopamine was found to occur rormally in human blood. 

Significance to Biomedical Research and the Program of 
the Institute! The occurrence of an enzyme that can make a 
psychotomimetic metabolite from normally occurring compounds 
(tryptamine) has implications to psychiatry. The accumulation 
of THC in the fat might be potentially harmful. 

Proposed Course of Project ; Enzyme methods for the 
development of other amines (phenylethanolamine) will be 

227 



Serial No. M-CS-Ph-6 , Page 2 

developed. The effect of drugs on tryptamine levels in tissue 
will be examined. Further studies on the tryptamine-methylating 
enzyme will be made. Blood levels of octopamine after drugs and 
various disease states will be studied. 

Honors and Awards : Dr. Axelrod has been invited to give 
the main lecture at the American College of Neuropsychopharmacology . 
He also received the Albert Einstein Achievement Award from 
Yeshiva University, and the Virchow Medal, and has been elected 
Honorary Member of the American Neurological Association and the 
American Psychopathology Association. 

Publications : 

Davis, J.M., Kopin, I.J., Lemberger, L. , and Axelrod, J: Effects 
of urinary pH on amphetamine metabolisn. Ann. N.Y. Acad. Sci . 
179: 493-501, 1971. 

Lemberger, L. , Axelrod, J., and Kopin, I.J. : Metabolism and 
disposition of delta-9-tetrahydrocannabinol in man. 
Pharmacol. Rev . 23: 371-380, 1971. 

Lemberger, L. , Axelrod, J., and Kopin, I.J.: Metabolism and 
disposition of tetrahydrocannabinols in naive subjects and 
chronic marijuana users. Ann. N.Y. Acad. Sci. 191: 142-154, 
1971. 

Lemberger, L. , Axelrod, J., and Kopin, I.J. : The disposition 
and metabolism of tryptamine in the in vivo formation of 
6-hydroxytryptamine in the rabbit. J. Pharmacol. Exp. Ther. 
177: 169-176, 1971. 

Lemberger, L. , Tamarkin, N.R., Axelrod, J., and Kopin, I.J. : 
Delta-9-tetrahydrocannabinol : metabolism and disposition in 
long-term marihuana smokers. Science 173: 72-74, 1971. 

Molinoff, P.B. and Axelrod, J.: Distribution and turnover of 
octopamine in tissues. J. Neurochem . 19: 157-163, 1972. 

Saavedra, J.M. and Axelrod, J.: Psychotomimetic N-methylated 
tryptamines : formation in brain in vivo and in vitro. Science 
175: 1356-1366, 1972. 

Silberstein, S.D„, Brimijoin, S., Molinoff, P.B. , Lemberger, L. : 
Induction of dopamine- p-hydroxylase in rat superior cervical 
ganglia in organ culture. J. Neurochem. 19: 919-921, 1972. 



228 



4 



Serial No. M-CS-Ph-7 

1. Laboratory of Clinical Science 

2. Section on Pharmacology 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 

Project Title: Biochemical and pharmacological studies on 
the pineal gland 

Previous Serial Number: None 

Principal Investigators: Takeo Deguchi (Guest Worker) 

Other Investigators: Julius Axelrod 

Man Years: Total 1.5 
Professional 1.5 
Other 

Project Description: 

Objectives : To study how the sympathetic nervous system 
transduces biochemical events in the pineal gland. 

Methods Employed : Biochemical, pharmacological and 
radioactive tracer techniques. 

Major Findings : A sensitive method was developed to 
measure the enzyme that N-acetylates serotonin in the pineal 
gland. Administration of dopa, noradrenaline, isoproterenol 
and monoamine oxidase inhibitors and theophylline caused a 
marked induction (20-fold) of the serotonin N-acetylating enzyme 
in the pineal. This elevation in enzyme activity is blocked by 
propranolol, a p-adrenergic blocking agent. When pineal gland 
is denervated, p-adrenergic agents and isoproterenol cause a 
superinduction (100-fold) of the acetylating enzyme. This 
induction is also blocked by propranolol. 

Significance to Biomedical Research and the Program of 
the Institute l None that is immediately apparent. 

Proposed Course of Project : The phenomena of denervation 
sensitivity will be further examined. The isolation of the 
p-adrenergic receptor from the pineal will be attempted. The 
molecular events in the induction of N-acetyltransf erase will 
be examined. 



229 



Serial No. M-CS-Ph-7, Page 2 

Honors and Awards : Dr, Axelrod was elected Fellow of 
the American Academy of Arts and Sciences and the National 
Academy of Sciences. He was also asked to lecture on the pineal 
gland at Howard Medical School. 

Publications: None 



230 



Serial No. M-CS-ET-1 

1. Laboratory of Clinical Science 

2. Section on Experimental Therapeutics 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Biochemistry, Pharmacology and Physiology of Cerebral Amines 

Previous Serial Number: M-CS-ET-1; M-CS-ET-2 

Principal Investigator: Thomas N. Chase 

Other Investigators: Jacob A. Brody, Cal K. Cohn, Robert W. Colbum, 
Hinrich Cramer, Edna K. Gordon, Irwin J. Kopin, 
Paul D. Maclean, Raymond Matta, Larry Keng-Yong 
Ng (Guest Worker), Elliott S. Vesell, Roger 
Weir (Guest Worker), and James L. Weiss. 

Cooperating Units: Sections on Medicine and Pharmacology and Unit on Clinical 
Biochemistry, Laboratory of Clinical Science, NIMH; 
Laboratory of Neurophysiology, NIW; Epidemiology Branch, 
NINDS; Department of Pharmacology, Pennsylvania State 
College of Medicine. 

Man Years: Total 3.0 

Professional 1.0 
Other 2.0 

Project Description: 

Objectives : 

1. To study the transport, metabolism, storage, release and 
postsynaptic interactions of monoamines and other putative central 
neurotransmi tters . 

2. To examine the functional role of monoamines and other suspected 
neurohumoral agents in the central nervous system of normal individuals 

and in patients manifesting neuropsychiatric disease. 

3. To study the mechanism of action and therapeutic efficacy of 
drugs which influence brain function. 



231 



Methods Employed : serial no. m-cs-et-i 

1. Preclinical studies utilize a) slices or homogenates of brain 
and other tissues which are incubated with radioactively labeled amines and 
related compounds, then exposed to drugs, other amines or electrical 
stimulation; b) surgically prepared laboratory animals in which the 
concentration of labeled and endogenous compounds in brain, cerebrospinal 
fluid, serum and urine are determined under various experimental conditions 
following the systemic or intracranial injection of labeled amines and 
other substances. 

2. Clinical studies are conducted in patients with 
neuropsychiatric disease and in normal volunteers. Under resting conditions 
and during the administration of drugs or procedures believed to 

influence central synaptic mechanisms, neurologic, psychiatric and psychologic 
parameters of brain function are correlated with the results of a) chemical 
assay of relevant compounds in various body fluids and tissues, b) radio- 
isotope tracer procedures and c) electrical measurement of spontaneous and 
evoked cortical potentials during waking and sleep. 

Major Findings : Studies carried out with L.K.Y. Ng, R. W. Colburn 
and I.J. Kopin indicate that 5-hydroxytryptophan enhances the release of 
dopamine and serotonin from central nervous system tissues. This action 
appeared dependent upon the decarboxylation of 5-hydroxytryptophan to 
serotonin, since it could be blocked by the addition of an inhibitor of 
L-amino acid decarboxylase. Selective destruction of catechol ami ne- 
containing neurons with 6-hydroxydopamine substantially reduced the uptake 
and release of labeled serotonin. These results suggest that dopamine 
may be released by serotonin derived from the decarboxylation of 
5-hydroxytryptophan in catechol ami nergic neurons. Conceivably, a portion 
of exogenously administered 5-hydroxytryptophan may enter central 
catechol ami nergic terminals and undergo decarboxylation to serotonin with 
resultant displacement of endogenous catecholamines from vescicular 
stores. This mechanism may explain certain of the behavioral and neurologic 
effects of 5-hydroxytryptophan loading in man. 



J 



In collaboration with L.K.Y. Ng, R.E. Gelhard and P.D. Maclean, 
attempts have been made to produce an animal model of naturally occurring 
or drug-induced dyskinetic disorders. Following unilateral intracerebral or 
intraventricular injections of 6-hydroxydopamine, monkeys displayed a 
substantially enhanced susceptibility to involuntary movement disorders 
induced by L-dopa (the precursor of dopamine) or apomorphine (a dopamine 
receptor stimulator). These observations support the hypothesis that 
denervation hypersensitivity of central catechol ami nergic receptors may 
be involved in the production of dyskinesias during L-dopa treatment of 
patients with extrapyramidal disease and suggest that 6-hydroxydopamine 
pretreated primates may provide a useful paradigm for future studies of 
the relationship between catechol amine-containing neural systems and 
spontaneous or drug-induced involuntary movement disorders in man. 



232 



Serial No. M-CS-ET-1 

In an attempt to determine the site of origin of monoamine 
metabolites in luntar cerebrospinal fluid, ventricular-lumbar infusion 
studies with radtoactively labeled substances have been carried 
out in cats with Dr. Roger Weir. Currently available data indicate that 
TOSt 5-hydroxyindoleacetic acid in lumbar spinal fluid derives from 
brain rather than spinal cord metabolism. These results provide a more certain 
rationale for the use of metabolite levels in human lumbar fluid as an index 
of cerebral monoamine metabolism. 

Recent laboratory experiments indicate that high doses of 
S-dihydro^O'phenyl serine, when given in combination with the peripheral 
decarboxylase inhibitor (MK 486), substantially elevates brain norepinephrine 
concentrations without affecting dopamine or serotonin. Since no toxic effects 
were observed, clinical trials of this drug combination are now planned in an 
attempt to discern the relationship between norepinephrine mediated neural 
transmission and disorders of motor and behavioral function. 

Studies of the probenecid-induced accumulation of monoamine 
metabolites in cerebrospinal fluid continue to yield important new information 
concerning the role of aminergic mechanisms in central nervous system 
disease. Since probenecid inhibits the active transport of homovanillic 
acid (a principal metabolite of dopamine) and 5-hydroxyindoleacetic 
acid (the major product of serotonin degradation) from the central nervous 
system, the probenecid-induced rise in these metabolites should afford an 
index to their rate of formation as well as to the central turnover of the 
parent amines. Current studies in patients with idiopathic Parkinson's 
disease indicate that basal concentrations and probenecid-induced 
accumulations of homovanillic acid are considerably below those of 
control subjects. Although steady state levels of 5-hydroxyindoleacetic 
acid did not differ from normal values, there was a substantial 
diminunition in the response of this serotonin metabolite to 
probenecid. Pretreatment severity of parkinsonian rigidity and bradykinesia, 
but not tremor, correlated inversely with the probenecid-induced rise in 
both monoamine metabolites. No apparent association was found, however, 
between the therapeutic response to L-dopa and either the severity of 
parkinsonian signs or the magnitude of the defect in monoamine 
metabolism. These results cast doubt upon the prevailing notion 
that the ability of L-dopa to ameliorate parkinsonian signs is solely 
contingent upon its conversion to dopamine in surviving dopaminergic neurons. 

In contrast to our findings in naturally incurring Parkinson's 
disease, normal or slightly elevated probenecid-induced accumulations of 
homovanillic acid were found in patients who developed parkinsonian signs 
while receiving psychotropic phenothiazines or related neuroleptic agents. 
These observations support the contention that pharmacologic parkinsonism 
may be the consequence of a drug-induced blockade of dopaminergic receptors. 

Application of the probenecid technique to the study of central 
monoaminergic function in patients with Huntington's chorea revealed a 



233 



Serial No. M-CS-ET-1 

substantial reduction in homovaninic acid formation but no abnormality 
in the turnover of 5-hydroxyindoleacetic acid. Unlike our findings in 
Parkinson's disease, however, there was no apparent correlation between the 
degree of homovanillic acid abnormality and the severity of motor or 
behavioral dysfunction. 

In a collaborative study with H. Cramer and L.K.Y. Ng, probenecid was 
found to substantially increase adenosine-3' ,5' -monophosphate (cyclic 
AMP) levels in human lumbar spinal fluid. Since experiments in the laboratory 
animal indicate that probenecid does not affect brain cyclic AMP concentrations, 
our clinical observations suggest that probenecid may act to inhibit the 
efflux of this nucleotide from the spinal fluid compartment. Use of probenecid 
to estimate central cyclic AMP turnover may thus contribute to our under- 
standing of the role of this substance in human neurotransmission. 

An improved gas-liquid chromotography method for measuring cerebro- 
spinal fluid levels of 3-methoxy-4-hydroxyphenyl glycol (MHPG), a major 
product of norepinephrine metabolism, has been applied to more than 60 patients 
with central nervous system disease in collaboration with E. K. Gordon 
and L. K. Y. Ng. MHPG concentrations were similar in ventricular and lumbar 
spinal fluid. About one-third of MHPG from either source occurred as the 
sulfate conjugate. The administration of a-methyl para tyrosine (an inhibitor of 
catecholamine biosynthesis) substantially reduced MHPG levels in all 
patients tested. Since relatively little intravenously infused, isotopically 
labelled MHPG enters spinal fluid, our results suggest that MHPG levels in 
lumbar fluid may provide an index to norepinephrine metabolism in the central 
nervous system of man. 

Various clinical studies of the effects of L-dopa on motor and 
behavioral function continue. A comparative evaluation of the therapeutic 
efficacy and toxicity of L-dopa alone and in combination with a peripheral 
decarboxylase inhibitor (MK 486) in stateside patients with Parkinson's 
disease and in Guamanians with parkinsonism-dementia (in collaboration with 
J. A. Brody) has been expanded. Currently available data from both studies 
affirm the favorable results on extrapyramidal function reported last year. 
No effect on dementia has been found in the Guamanian subjects. An 
examination of the antiparkinsonian efficacy of L-dopa in schizophrenic 
patients who have developed extrapyramidal signs while receiving long-term 
neuroleptic therapy has yielded favorable results in several patients. 

A therapeutic trial of 3-0-methyldopa in patients with Parkinson's 
disease has recently been concluded. The administration of this dopa 
metabolite, either alone or in combination with a peripheral decarboxylase 
inhibitor (MK 486), had no effect on parkinsonian signs. During treatment 
with high doses of 0-methyldopa, levels of apparent L-dopa in plasma and 
homovanillic acid in luntar spinal fluid approximated those found in 
patients receiving therapeutically effective doses of L-dopa. These 
findings raise some question about the generally assumed mechanism by 
which L-dopa exerts its antiparkinsonian action. 



23i^ 



Serial No. M-CS-ET-1 

Tests of the therapeutic efficacy of fusaric acid, a new dopamine 
3-hydroxylase inhibitor, have recently been conducted in patients with 
various extrapyramidal disorders. Use of this drug alone or together with 
a fixed dose of L-dopa failed to significantly alter parkinsonian signs 
despite markedly reduced serum dopamine g-hydroxylase levels as measured 
by R. J. Matta and C. K. Cohn. 

Parachlorophenylalanine, a potent and specific depletor of brain 
serotonin, was given to 6 patients with Idiopathic parkinsonism. Despite 
a substantial reduction in the spinal fluid content of 5-hydroxyindoleacet1c 
acid, there was no change in cardinal parkinsonian signs. These results sug- 
gest that the decrease in serotonin turnover which characteristically attends 
Parkinson's disease may be a secondary phenomenon of little consequence to 
the clinical severity of this disorder. 

A study of the effect of L-dopa on hepatic microsomal drug 
metabolizing enzymes has been conducted in collaboration with L.K.Y. Ng, 
G.T. Passananti, and E. S. Vessell. Antipyrine half-lives In plasma were 
used to detect changes In rates of drug metabolism, since the decline In 
blood antipyrine concentrations is largely dependent upon its biotransforma- 
tion In liver. Our results indicate that chronic treatment with L-dopa and 
a-methyldopahydrazine (MK 486), but not with L-dopa alone, significantly 
prolongs mean antipyrine half-life. 

The clinical effects of drugs which act relatively specifically 
on cerebral amines have been examined in patients with Huntington's 
disease. L-tryptophan, alone or in combination with a peripheral 
decarboj^lase inhibitor, failed to influence either the motor or behavioral 
aspects of this disorder. Parachlorophenylalanine in doses sufficient to 
reduce cerebrospinal fluid levels of 5-hydroxyindoleacetic acid by nearly 50%, 
was also ineffective. In view of these results as well as those obtained 
with the probenecid test, the participation of serotonergic mechanisms 
in the pathogenesis of Huntington's chorea would seem unlikely. On the other 
hand, L-dopa, the inmedlate precursor of dopamine, led to an unmlstakeable 
Increase in the severity of choreatic movements in most of the Huntington's 
chorea patients, while a-methylparatyrosine, a specific Inhibitor of 
catecholamine synthesis, tended to ameliorate hyperkinesias in these 
individuals. The effect of a-methylparatyrosine was markedly potentiated 
by the conjoint administration of haloperidol. These pharmacologic 
observations are not necessarily in conflict with the previously described 
biochemical findings suggestive of a reduction in central dopamine turnover 
in Huntington's disease. Conceivably, the small striatal nerve cells which 
are seen to degenerate in Huntington's disease are host to dopaminergic 
terminals from the nigrostriatal system, and it is the primary reduction in 
function of these striatal cells which gives rise to the involuntary 
movements characteristic of this disorder. Diminished dopamine metabolism 
in Huntington's disease might thus occur only as a secondary phenomenon. 
This functional alteration could be due to an intemeuronal feedback 
mechanism, acting in the opposite direction to that which is believed to 
occur during treatment with psychotropic phenothiazines or butyrophenone . 



235 



Serial No. M-CS-ET-1 

Significance to bioiTiedical research and the program of the Institut e; 
Biogenic amines appear to act an synaptic mediators in certain neuronal 
systems within the central nervous system of man. Alterations in these 
substances have recently been found in relation to several extrapyramidal and 
behavioral disorders and have led to discovery of drugs which reverse both 
the biochemical and clinical defect. This approach to the development of 
new pharmacologic therapies may be applicable to other disorders of brain 
function. 

Proposed Course of Project : Current studies of monoaminergic 
mechanisms in relation to naturally occurring and drug-induced neuro- 
psychiatric disease will be continued. Special emphasis will be given to 
phenothiazine-induced extrapyramidal disorders (tardive dyskinesias). 
Attempts to develop improved techniques for evaluating the metabolism of 
suspected neurotransmitters in the human central nervous system will be 
extended to include acetylcholine, y-aminobutyric acid and the 
prostaglandins. 

Honors and Awards : During the past year Dr. Chase was elected to 
the Clinical Research Committee of the NIH Medical Board and to the 
Scientific Advisory Board of the Committee to Combat Huntington's Disease. 
He was also invited to serve on an FDA advisory panel on Drug Induced 
Dyskinesias. He chaired the session on "Biogenic Amines" at the Third Annual 
Meeting of the American Society for Neurochemistry in Seattle, March 20-23 and 
the "Biochemistry Session" at the Centennial Symposium on Huntington's chorea 
in Columbus, March 26-28. In connection with the latter symposium. Dr. Chase 
served as Scientific Assistant Secretary and co-editor of the Proceedings. 
Invitational lectures and seminars were given at Einstein Medical College 
on October 14, at the University of Virginia Medical School, November 18 and 
19, and to a symposium on "Order and Disorder in Movement" at the First 
Annual Meeting of the Society for Neuroscience in Washington on October 29. 
Dr. Chase served as an invited discussant for papers entitled "The 
Association of Parkinsonism and Motor Neuron Disease", "Side Effects of 
L-dopa Related to Blood Concentration" and "The Effect of Chlorpromazine 
on Striatal Dopamine Synthesis" presented at the Twenty-Fourth Annual 
Meeting of the American Academy of Neurology in St. Louis, April 27-29. 
During the year Dr. Chase read papers before the American Society for 
Neurochemistry, American Academy of Neurology, Centennial Symposium on 
Huntington's Chorea, and the Annual Meeting of the International Society 
for Neurochemistry in Budapest, 

Publications: 

Weiss, J.L., Ng, L.K.Y. and Chase, T.N,: Long-lasting dyskinesia induced 
by Levodopa. Lancet i_:1016-1017, 1971. 

Chase, T.N,, Schnur, J. A., Brody, J. A. and Gordon, E.K.: Parkinsonism- 
dementia and Amyotrophic Lateral Sclerosis of Guam: Effect of probenecid 
on monoamine catabolite levels in cerebrospinal fluid. Arch. Neurol. 
25:9-13, 1971. 



236 



Serial No. M-CS-ET-1 

Vesell, E.S., Ng, L.K.Y., Passananti, G.T. and Chase, T.N.: Inhibition of 
drug metabolism by L-dopa in combination with a dopa decarboj^lase inhibitor. 
Lancet 2:370, 1971. 

Wyatt, R.J., Chase, T.N., Kupfer, D.J., Scott, J., Snyder, F., Sjoerdsma, A. 
and Engelman, K.: Brain catecholamines and human sleep. Nature 233 :63-65, 
1971. 

Mendel! , J.R., Chase, T.N. and Engel, W.K.: Amyotrophic Lateral Sclerosis: 
A study of central monoamine metabolism and therapeutic trial of L-dopa. 
Arch. Neurol. 2^^:320-325, 1971. 

Weiss, J.L., Cohn, C.K. and Chase, T.N.: Catechol -0-methyl transferase: 
Reduction by chronic L-dopa therapy. Nature 234:218-219, 1971. 

Chase, T.N. and Ng, L,K.Y.: Probenecid test in Parkinson's disease. 
Lancet 2:1265-1266, 1971. 

Schnur, J. A., Chase, T.N. and Brody, J. A.: Parkinsonism-dementia of Guam: 
Treatment with L-dopa. Neurology 21:236-1242, 1971. 

Mendell, J.R., Chase, T.N. and Engel, W.K.: Amyotrophic lateral sclerosis: 
Metabolism of central monoamines and treatment with L-dopa. Trans. Amer. 
Neurol. Assn. 96:284-286, 1971. 

Weiss, J.L. and Chase, T.N.: Levodopa in parkinsonism. Drugs 2:257-261, 
1971. 

Chase, T.N., Watanabe, A.M., Brodie, H.K.H., Donnelly, E.F.: Huntington's 
chorea: Effect of serotonin depletion. Arch. Neurol. 26^:282-284, 1972. 

Chase, T.N. and Watanabe, A.M.: Methyl dopahydrazi ne as an adjunct to L-dopa 
therapy in parkinsonism. Neurology. 22^:384-392, 1972. 

Chase, T.N.: Drug-induced extrapyramidal disorders. Chapter 22. In 

Res. Publ. Assn. Nerv. Ment. Pis. , Vol. 50, Williams and Wilkins, Baltimore. 

In press. 

Ng, L.K.Y., Chase, T.N., Colburn, R.W. and Kopin, I. J.: L-dopa in 
parkinsonism: A possible mechanism of action. Neurology. In press. 

Chase, T.N., Ng, L.K.Y. and Watanabe, A.M.: Parkinson's disease: 
Modification by 5-hydroxy tryptophan. Neurology. In press. 

Lott, I.T., Murphy, D.L. and Chase, T.N.: Down's syndrome: Central 
monoamine turnover in patients with diminished platelet serotonin. 
Neurology. In press. 

Cramer, H., Ng, L.K.Y. and Chase, T.N.: Effect of probenecid on cyclic 
AMP levels in human spinal fluid. J Neurochem. In press. 



237 



I 



Serial No. M-P-C-(C)-12 

1. Laboratory of Psychology 

2. Section of the Chief 

3 . Bethesda 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Studies of heredity and environment in schizophrenia. 

Previous Serial Nxunber: Same. 

Principal Investigator: David Rosenthal 

Other Investigators: Paul H. Wender, Seymour S. Kety (Harvard) , 

Shmuel Nagler (Israel) , Fini Schulsinger (Denmark) . 

Cooperating Units: None. 

Man Years : 

Total: 7.0 
Professional: 3.0 
Others: 4.0 

Project Description: 

Objectives : To understand how hereditary and environmental factors interact 
to make for schizophrenic outcomes of varying types and degrees . 

Methods Employed ; 1. A constructively critical, hypothesis-oriented anal- 
ysis of the worthwhile literature on heredity and environment in schizo- 
phrenia. 2. An intensive multidisciplinary study of a family with one-egg 
quadruplet daughters concordant as to schizophrenia but discordant as to 
severity and outcome. This study was published in book form. We are con- 
tinuing our contacts with this family to see what happens in the clinical 
course of these girls and how the course is related to earlier and current 
life experiences. 3. Studies of adoptees and their biological and adoptive 
families. 4. A study of children (of schizophrenic and control parents) 
reared in town or kibbutz in Israel. 

Major Findings : 1. The analysis of the literature has been reported in a 
series of papers and in the study of the quadruplets . A textbook which or- 
ganizes and explicates the literature on the genetics of behavioral dis- 
orders, and a modified version of this book have been piiblished. 2. Sev- 
eral papers on our adoption studies are now published. The studies indicate 
that hereditary factors contribute to the development of schizophrenia, and 
to other disorders that we include in a group called the schizophrenia 
spectrum. Several articles are in preparation and eventually a monograph 
will be written on the adoption studies. Data analysis is continuing. 
3. One hundred subjects in the Israel study have been examined, and the 

239 



Serial No. M-P-C-(C) -12, p. 2. 

research findings are currently being analyzed and evaluated. Preliminary 
findings indicate that offspring of schizophrenics have more neuropatho- 
logical signs in childhood than do controls. Two subjects have had a break- 
down and one is on the verge of breakdown. All three have a schizophrenia 
parent. 

Significance to Bio-medical Research and the Program of the Institute : We 
have resolved a chronic, critical problem in psychiatry by demonstrating 
beyond any reasonable doubt that genetic factors are importantly involved in 
the etiology of schizophrenia and related mental disorders. Moreover, the 
evidence thus far suggests that the mode of genetic transmission is polygenic 
or a dominant single gene with polygenic modifiers. 

Proposed Course of Project : We are examining additional subjects in Denmark 
with the following goals in mind: 1. to try to discriminate gene carriers 
and non-gene carriers with respect to personality and test variables; 2. to 
compare the fate of gene-carriers who are reared in the parental home as 
compared to those reared in adoptive homes; 3. to compare Ss who have a 
psychotic biological parent but who are reared by nonpsychotics with Ss 
whose biological parents are not psychotic but who are reared by a psychotic 
adoptive parent; 4. to find the incidence of schizophrenic spectrum dis- 
order in a random sample of the Danish population. In Israel, our goal is 
to prepare a volume on our findings and their theoretical implications . 
During this year we will carry out reexaminations of this unique sample of 
subjects. 

Honors and Awards : None . 

Publications : 

Rosenthal, D. : A program of research on heredity in schizophrenia. 
Behav. Sci . 16: 191-201, 1971. (Republished in abbreviated form: 
Mental Health Digest , 3[9]: 1-4, 1971.) 

Wender, P. H., Rosenthal, D. , Zahn, T. P., & Kety, S. S.: The 
psychiatric adjustment of the adopting parents of schizophrenics. Amer . 
J. Psychiat . 127: 53-58, 1971. 

Rosenthal, D.: Research patterns in assessing genetic and rearing 
factors in schizophrenia. Vestnik Akademii Meditsinskikh Nauk SSR , 
(Journal of the USSR, Academy of Medical Sciences) Meditsina (Publisher) 
#5: 42-46, 1971. 

Kety, S. S., Rosenthal, D., Wender, P. H., & Schulsinger, F.: Mental 
illness in the biological and adoptive families of adopted schizophrenics. 
Amer. J. Psychiat . 128: 302-306, 1971. 

Rosenthal, D., Wender, P. H., Kety, S. S., Welner, J., & Schulsinger, F.: 
The adopted-away offspring of schizophrenics. Amer. J. Psychiat . 128: 
307-311, 1971. 



Serial No. M-P-C- (C) -12 , p. 3. 

Rosenthal, D. : Foreword (2). In Shields, J., & Gottesman, I. I. (Eds.), 
Man, mind and heredity : Selected papers of Eliot Slater on psychiatry 
and genetics . Baltimore: The Johns Hopkins Press, 1971, pp. xix-xx. 

Rosenthal, D.: Three adoption studies of heredity in the schizophrenic 
disorders. Int. J. Men. Health 1: 63-75, 1972. 



2iH 



Serial No. M-P-C-(C)- #15 

1. Laboratory of Psychology 

2. Section of the Chief 

3. Bethesda 

PHS -HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 

Project Title: Reaction time in schizophrenia. 

Previous Serial Number: Same 

Principal Investigator: Theodore P. Zahn 

Other Investigator: Paul Fedio 

Cooperating Units : Surgical Neurology Branch, NINDS 

Section on Psychiatric Assessment, NIMH 

Man Years: .2 
Total: 

Professional: .1 

Other: .1 

Project Description: 

Objectives: To study deficits in attention in schizophrenia, particularly 
as maxilfested in difficulties in adopting axid maintaining preparatory sets. 
To study the specificity of such deficits to schizophrenia. To study 
possible organic and genetic determinants of such deficits. To determine 
the relation between such deficits and the severity of schizophrenic 
symptomatology. 

Methods Employed ; (A) A reaction time (RT) technique which puts severe 
demands on attention and which discriminates well between schizophrenic 
and non-schizophrenic subjects is being given to patients before and after 
unilateral temporal lobectomy for the relief of psychomotor epilepsy. 
This procedure and a choice technique which compared RT to monaural stimu- 
lation in each ear and responses with the same or opposite hand have also 
been used on postoperative temporal lobe followup cases and normal controls. 

(b) Acute schizophrenic and non-schizophrenic patients are being 
tested with these procedures soon after admission, on discharge from the 
Clinical Center after 3-^ months and on a followup 6 months to 1 year later. 
The results will be compared with intensive symptom ratings. 



L 



2i^3 



M-P-C-(C)- 15, page 2 

Major Findings : We continue to find that about half of the temporal 
lobe followup. cases give essentially normal performance despite some 
apparent personality disturbance. Most patients tested 10 - 15 days 
postoperatively have shown a decline from their preoperative performance 
level, suggesting a possible recovery of function over time. The followup 
cases are also slower in choice ET but further analysis of the data is 
needed to determine if this slowing is disproportionate to the simple RT 
level . 

Significance to Biomedical Research and the Program of the Institute ; 
These studies are designed in part to explore the Jjossibility of a biologi- 
cal basis for schizophrenia. Since patients with lesions in the temporal 
lobe frequently exhibit a schizophrenic-like personality picture and since 
patients with other types of brain lesions have been found to exhibit 
reaction time deficits (but of different types than those shown by schizo- 
phrenics) the reaction time performance of these patients might indicate 
if a temporal lobe disturbance is possibly involved in schizophrenia. 
The reciction time studies with schizophrenics add to our knowledge of the 
specific psychological processes involved in the disorders of set and 
attention that seem to be important aspects of the schizophrenia process. 

Proposed Course of Project ; Further collection of data on both current 
and followup temporal lobe cases. When enough data have been collected 
the effects of the side of the lesion and correlations with the amount 
of tissue removed can be determined. Further data collection on schizo- 
phrenic and non-schizophrenic patients . 

Honors and Awards : None. 

Publications: None. 



2itU 



Serial No. M-P-C-(C) - #1? 

1. Laboratory of Psychology 

2. Section of the Chief 

3. Bethesda 



PHS -HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 



Project Title: Psychophysiological Responsivity in Schizophrenia. 
Previous Serial Number: Same 

Theodore P. Zahn 

Dayid Rosenthal, William Pollin, Loren Mosher 



Principal Investigator 
Other Investigators : 
Cooperating Units : 



Section on Twin and Sibling Studies, NIMH 
Section on Technical Development, MHIRP 
Section on Psychiatric Assessment, NIMH 



Man Years: 



Total: - .5 - ■ , £ 
Professional: .2 - ■ 
Other- .3 

Project Description: 

Objectives : The general purpose of these studies is to investigate 
schizophrenic -normal differences in the relative autonomic respon- 
sivlty to various sti m uli, the relationship- of autonomic activity 
to adequacy of performance and to psychiatric condition, and possible 
genetic determinants . 

Methods Employed ; 1. ^-.Peripheral measures of autonomic functioning, namely 
GSR, heart rate, finger pulse volume, respiration and skin temperature are 
recorded during several sessions in which stimuli are presented and tasks 
are performed which vary in the demands placed on the subjects: no stimuli, 
simple auditory stimuli with no response reqiiired, the same with a "casual" 
response required, reaction time, word association, mental arithmetic, and 
cold presser. Specific and non-specific response frequencies and amplitudes, 
baseline values and baseline changes are measured. These procedures have 
been used with identical twins discordant or concordant for schizophrenia 
and their parents and with the adoptive and biological parents of schizo- 
phrenic patients in order to see if whatever genetic influence there is in 
schizophrenia is manifested in autonomic functioning. 

Currently, acute schizophrenic and non-schizophrenic patients 
are being tested on a shorter version of the above proced\ires soon after 



2i+5 



M-P-C-(C)- #17, page 2 

admission, at discharge from tne Clinical Center (3-^ months later) and at 
a 6 month to 1 year followip. 

Methods have been developed in our laboratory to analyze skin con- 
ductance, heart rate, skin temperature and finger pulse volume data 
automatically from taped analog records by means of the SEL 8lO B 
computer. 

2. A large scale exploratory correlational analysis using both uni- 
variate and multivariate (canonical) correlations of the psychophysiological 
variables with biochemical and psychiatric data collected by other 
investigators is being carried out to determine the interrelationships 
between these major classes of variables. 

3. Analyses of the genetic determinants of psychophysiological 
variables on the data from the twins is being carried out by a method of 
intra-class correlation which attempts to control for any consistent 
influence of psychopathology on the dependent variable. 

k. The variability in psychophysiological functioning is of increas- 
ing interest to investigators in this field as possibly reflecting the 
operation of regulating mechanisms. In addition to measuring the magnitude 
of spontaneous electrodermal and heart rate fluctuations, analyses of the 
frequencies of heart rate variations have been done by computing power 
spectra on the autocorrelation functions. Methods are being developed to 
compare individual subjects with respect to the patterns of frequencies 
exhibited. Since examination of the autocorrelations suggest an auto- 
regressive process, methods are being developed to fit an autoregresslve 
model to the data for individual subjects. 

5. Skin conductance data from several studies are being reanalyzed 
using a "range corrected" measure by which it is hoped to remove some of 
the extraneous variation due to anatomical factors from this measure. 

Major Findings : 1. Previously we had found that the differences between 
the schizophrenic and non-schizophrenic members of the twin pairs were simi- 
lar to the differences between unrelated schizophrenic and normal subjects 
in that: (a) despite equal autonomic responsivity to meaningless stimuli, 
the schizophrenics were significantly hyporeactive to more meaningful 
stimuli; and (b) the schizophrenics showed higher arousal levels under 
nondemanding conditions but the controls showed a greater increase in arousal 
under the mild stress of task performance. 

2. Preliminary results from the correlational analyses show un- 
expected but consistent negative correlations between electrodermal and 
heart rate indices of arousal and urinary measures of the precursors and 
metabolites of epinephrine and norepinephrine (dopamine, metanephrine, 
and normetanephrine). 



2h6 



M-P-C-(C)- #17, page 3. 

3. Premininary axialyses of the genetic determination of psycho- 
physiological variables has shown that overall autonomic arousal levels, 
variability and responsivity seem to have a significant genetic -familial 
component, while performance measures and the autonomic response to demand 
do not show appreciable genetic influence. 

h. Most subjects show significant heart rate fluctuations occuring 
at U-8 cycles per minute in addition to sinus arrhythmic (15 - 20 cycles 
per minute). Some of the twin pairs show strikingly similar spectra. 

5. Correlations among the autonomic perfonnance and behavioral 
variables suggest that schizophrenics with high resting (non-specific) 
arousal levels have poorer performance and more severe symptomatology than 
those with lower arousal levels, while the relationships of task-produced 
increments in arousal have just the opposite relationships with the behavioral 
variables. Similar, but much less marked relationships are found in controls. 

6. A review of the literature on the relationships of autonomic 
phenomena to behavior in schizophrenia has revealed much support for the 
implication from our research that there is no generalized deficit in 
autonomic reactivity in schizophrenia, but that such deficits occur speci- 
fically to meaningful or demanding stimuli such as those involved in task 
performance. It is also apparent from the literature that a simple inverted- 
U relation between autonomic arousal and performance is not well confirmed, 
and that what we have called specific and non-specific arousal might have 
different relationships to behavior in schizophrenia. 

Significance to Biomedical Research and the Program of the Institute ; The 
role of autonomic arousal and responsivity in schizophrenic deficits in 
behavior remains obscure, but it is clear from our own research and that of 
other investigators that a low arousal level is not the critical factor as 
has sometimes been postulated. Oiir evidence suggests that a high arousal 
level that is non-task-related (non-specific arousal) and low task-related 
increments in arousal or the relationship between these may be related to 
such performance deficits. Further elucidation of the autonomic concomitants 
of symptoms and behavior deficits in schizophrenia may give us an increased 
understanding of the biological aspects of this condition and therefore may 
lead to more specific therapeutic procedures . 

In view of the abundant evidence that genetic factors are of importance 
in the etiology of schizophrenia, it is reasonable to ask if a "schizophrenic 
genotype" is manifested in the autonomic nervous system. Some suggestions of 
autonomic hyperactivity in our co-twins indicate that if there is a genetic- 
ally determined autonomic pattern that predisposes individuals to 
schizophrenia it is of a markedly different nature than that shown by 
individuals who are, in fact, schizophrenic. 



I 



2iiT 



M-P-C-(C)- #17, page k. 

Proposed Course of Project: 1. Further analysis of the data from the twins 
and their families wili include (a) examining more autonomic variables such 
as vasomotor changes, and other aspects of electrodermal functioning 
based on new findings in the literature; (b) multivariate statistical 
analysis of group differences; and (c) partial correlations on selected 
subsets of the large set of variables from different investigators. 
2, The development of techniques to manipulate general arousal levels and 
specific alerting systems independently. The use of shock to reinforce 
slow reaction times and in a non-contingent fashion may be a promising 
start on "chis problem. 3- More precise measurement of cardiac responsivity 
will be attempted by means of estimation techniques based on auto-regressive 
and cross-regressive models of heart rate variation, h. Continued data 
collection on acute subjects. 

Honors and Awards : None . 

Publications: None. 



2k8 



Serial No. M-P-C-(c) - 36 

1. Laboratory of Psychology 

2. Section of the Chief 

3. Bethesda 

PHS-IiSMHA-MMH 
Indi-vidual Project Report 
Julj 1, 1971 through June 30, 1972 

Project Title: Psychological Correlates of Cortical Evoked Responses 

Previous Serial Number: Same 

Principal Investigator: Monte Buchsbaum 



Other Investigators ; 



Cooperating Units : 



Man Years: 

Total: / 

Professional: 

Other: 

Project Description: 



Lyman C. Wynne, Stephen Landau, Thomas Bittker, 
Paul Fedio, Dennis Murphy, Frederick Goodwin, 
Paul H. Wender and Robert I. Henkin. 

Adult Psychiatiy Branch, NIMH 
S\irgical Neurology Branch, NINDS, NIH 
Laboratory of Clinical Science, NIMH 
Clinical Endocrinology, NHI, NIH 



2.2 
1.2 
1.0 



Objectives : Exploration of relationships between perceptual response 
patterns, psychiatric clinical dimensions and neurophysiological measures; 
the development of improved techniques for collecting and analyzing neuro- 
physiological data collected from intact human subjects; detailed study of 
the interaction between attention, cortical area and individual differences 
in neurophysiological response. 

Methods Employed : Central nervous system function has been difficult to 
study in psychiatric patients by either conventional neuroanatomic or 
implanted electrode techniques, as the former requires a dead patient 
(or an animal model of the disease) and the latter requires a hazardous 
surgical procedure. Obviously, neither method permits long-term study 
of psychiatric episodes. With the development of average evoked response 
techniques, which allow recovery of relatively specific CNS signals from 
scalp EEG, neurophysiological attempts to study psychiatric disorders 
received new impetus. The average evoked response (AER) is a particularly 
promising tool for studying perception in the psychiatric patient because, 
unlike traditional psychophysical techniques, it does not depend upon the 
patient's report or overt performance. Thus, the importance of motivation 
or motor activity is minimized and a clearer separation of perceptual (input) 
and performance (output) factors may be achieved. 



2^+9 



Serial Wo. M-P-C-(C) - 36, page 2 

Cortical average evoked responses (AER's) are patterns of electrical 
response to sensory input which are recorded from the electroencephalogram. 
Because evoked responses are usually of extremely small amplitude (less than 
10 millionths of a volt), these patterns are completely lost in the apparently 
random fluctuation of the EEG. But we can overcome this obstacle by taking 
advantage of the fact that an evoked response is always related in time, or 
"time -locked," to a sensory stimulus, whereas the background EEG activity 
varies and bears no fixed relationship to the stimulus. By presenting the 
subject with a long series of stimuli, such as flashes of light, and summing 
the EEG for a brief time interval after each flash, an AER is produced. 

The development of computer technology has been an essential step in 
the application of AER measures to large-scale patient testing. During the 
past year a system for the collection and processing of evoked response data 
has been put into operation on the SEL 8lO B. This is a modular, multi- 
purpose system, allowing the investigator maximum flexibility in running and 
in implementing new experiments. The system is comprised of three parts. 
The first phase, EXPMAS , controls the actual running of the experiment. It 
is table driven and allows for easy implementation of new paradigms. The 
second phase, AERMAS , provides for scoring of evoked response records. The 
third phase is a package of statistical routines to perform the final 
statistical analysis. The major utility of the system is the short amount 
of time between the conception of a new experiment, its actual implementation, 
and final data analysis. Since all aspects of the experimental situation are 
under the system's control, the investigator may proceed with his design 
without a delay for experiment changes . 

Major Findings : Coping with sensory overload is perhaps the major percep- 
tual problem of 20th century urban man; individuals differ widely both in 
their relative success in meeting the challenge and in their styles of 
coping. Evoked responses to loud, repetitious, meaningless and meaningful 
stimuli have been studied in subjects attending to or trying to ignore the 
stimuli. The early discovery that some subjects paradoxically showed actual 
decreases in AER amplitude with increasing stimulus intensity led to the 
development of a perceptual style concept known as "stimulus intensity 
control", and to a variety of clinical and more basic investigations. 

1. Methodologic Issues . The apparent ability of these subjects to 
"turn down" or "turn off" is evidenced most strongly over nonspecific 
cortical areas (vertex vs. occipital cortex) and is unrelated to changes in 
pupillary diameter. When the subject's attention is directed toward the 
stimuli, the rate of increase in AER amplitude with stimulus intensity is 
correlated across visual and auditory modalities, thus supporting the concept 
of a central stimulus intensity modulating mechanism. 



2. Biochemical and Clinical Studies. AER amplitude has been found to 
increase, especially at high intensities, after infusion of L-dopa in 
patients with affective disorders in late (200 msec) components, but not in 
earlier ones (l40 msec). Amphetamine in hyperactive children has a similar 
effect. This is in contrast to phenothiazine and lithium results where the 



250 



1 



Serial No. M-P-C-(c) - 36, page 3 

earlier peak was affected. Individual differences in drug response were 
important in toth cases; patients categorized as unipolar depressive 
illnesa and children who showed worsening of hyperactivity on amphetamine 
both showed the AER augmentation; other patients and children who showed 
clinical improvement (decreasing hyperactivity) showed AER reduction. 

3. Arousal and Attention ; The effects of muscle tension, pain, and 
shifts in attention on the AER to varying intensities of light were studied 
in a series of experiments. In subjects actively discriminating light inten- 
sities, low intensity stimulus AER were as large as high intensity AER. 
This perhaps makes possible an independent neurophysiological assessment of 
attention. Muscle tension significantly decreased mean AER amplitude but 
did not alter the mean rate of change of AER amplitude with stimulus inten- 
sity. In contrast, the painful or sensory overload condition caused the 
high intensity response to diminish and the low intensity response to 
increase without altering the mean across intensities . Direction of attention 
toward the subject's body or to a diffuse task, such as searching for an 
intensity sequence, had no effect either on amplitude or amplitude-intensity 
relationships . ! 

h. Twin Studies . Data on AER, perceptual tasks, autonomic psychophysio- Ji 
logy, blood type and interview material have been collected on 60 normal twin ||, 
pairs. Data analysis will begin shortly (see Project M-AP(c) - 21-4). « 

5. Contrast, Congruence and Habituation. Anchoring or contrast effects 
were further explored using groups of individuals which either increased 
(augmenters) or decreased (reducers) their AER amplitude with increasing 
stimulus intensity. The augmenter group showed evoked responses which were 
diminished by having an intense preceding stimulus and increased by having 
a dim preceding stimulus. The reducer group, as might be expected, showed 
the reverse. They showed evoked responses which were larger when preceded 
by an intense stimulus and smaller when preceded by a dim stimulus . Thus 
in both cases an intense preceding stimulus moved the perceived intensity 
of the stimulus to a lower level and a preceding dim stimulus moved the 
perception of intensity to a higher level. This further demonstrated the 
tendency of the AER to reflect the perceived intensity of stimulation. 
This contrast effect may be closely linked to the phenomena of habitua- 
tion, and the failure to contrast to dishabituation — again both mechanisms 
for dealing with sensoiy overload. In a series of studies using complex 
stimulus sequences, pronounced individual differences were found in a 
subject's tendency to ignore minor differences as reflected in the AER. 
This tendency to ignore stimulus complexity — the "congruence illusion" — 
can be reversed by providing them with sufficient information to permit 
them to build more sophisticated and accurate interval constructs for 
their perceptual experience. 



251 



Serial No. M-P-C-(c) - 36, page k 

Significance to Bio-Medical Research and the Program of the Institute; 
This project, in helping to give a neurophysiological basis to psycho- 
logical tests, contributes to the effort to understand mechanisms of 
variation in human personality. Further, the techniques may yield 
psychological information from subjects without the need for language or 
more than passive cooperation. 

Proposed Course of Project ; This year's work has suggested potential ways 
of giving relatively specific biochemical, psychological and perhaps even 
anatomic meaning to certain AER components. Emphasis in the next two 
years will go on exploiting these new leads and developing new mathematical 
techniques. Eventually these new refinements will be applied in clinical 
directions suggested by our twin studies. 

1. Biochemical and clinical studies will continue with study of MBD 
children, patients with affective disorders and normal volunteers given 

d- and 1- amphetamine. Analysis of current data on a sample of 83 patients 
and a large group of age and sex matched normals is currently underway. 

2. Twin studies will enter a data analysis phase with emphasis both 
on determining Mz - Dz differences and using physiological and psychologi- 
cal data to predict perceptual differences in Mz pairs. 

3. Habituation. Parallels between our human AER habituation results 
and Thompson's dual process theory of habituation (based on acute spinal 
cat data) are intriguing and will be further explored in parametric studies, 

h. Studies of the interaction of attention, habituation, and stimulus 
intensity in normal subjects are planned. These studies will yield a more 
detailed understanding of the AER variation seen with shifts of attention 
and aid in the development of clinical tools for testing attentional 
deficits. Further, they will expand our battery of AER measures defining 
mechanisms for coping with sensory overload. 

5« New mathematical approaches. A package of basic mathematical 
routines required for the analysis of time series data has been completed. 
This will allow spectral, cross-spectral and covariance analysis for 
data collected on the SEL system. A group of users interested in time 
series analysis of EEG and EEG frequency conditioning will collaborate. 
It is planned to contract for additional programming necessary to utilize 
these routines in specific experimental designs. 

The combination of these techniques with beam-forming may enable 
localization and detection of individual components of the AER. The 
analysis of a subject's signal detection processes on a neurophysiological 
basis will then be investigated. 

Honors and Awards: None. 



252 



Serial No. M-P-C(c) - 36, page 5 
Publications : 

Buchsbaum, M.: Average evoked response techniques and. applications, 
Schiz. Bull . Winter, I97O. pp. IO-I8. 

Buchsbaum, M., Silvennan, J., and Henkin, R.: Contrast effects on the 
auditory evoked rec;ponse and its relation to psychophysical judg- 
ments. Percep . Psychophys . 9: 379-385, I97I. 

Buchsbaiun, M., King, C. and Henkin, R. I.: Average evoked responses and 

psychophysical performance in patients with pseudohypoparathyroidism, 
J. Neurol. Neurosurg. Psychol . In press. 

Buchsba\im, M.: Cybernetics and the cortical evoked potential. Trans. 
Amer, Cybernetic Soc. In press. 

Buchsbaum, M.: Neural events and psychophysical law. Science . 172: 502, 
1971. 

Buchsbaum, M. and Pfefferbaum, A.: Individual differences in stimulus inten- 
sity response. Psychophys iol . 8 (5): 6OO-61I, I97I. 

Buchsbaum, M., Goodwin, F. , Murphy, D., axid Borge, G. AER in affective dis- 
orders. Amer. J. Psychiat . 128: 19-25, I97I. 

Borge, G., Buchsbaum, M., Goodwin, F., Murphy, D., and Silverman, J.: 

Neuropsychological correlates of affective disorders. Arch. Gen.. Psychiat. 
2k: 501-504, 1971. 

Fedio, P., and Buchsbaum, M.: Unilateral temporal lobectomy and changes 
in evoked responses during recognition of verbal and non-verbal 
material in the left and right visual fields. Neuropsychologia 
9: 261-271, 1971. 

Gips, J., Pfefferbaum, A., and Buchsbaum, M. : Use of a small process control 
computer in a psychophysiological laboratory. Psychophysiol . 8 (h): 
538-5^2, 1971. 

Gips, J., Pfefferbaum, A. and Buchsbaum, M. : ERL - A language for implement- 
ing evoked response and psychophysiological experiments. Behav. Res . 
Meth. Instrument . 3 (4): 199-201, 1971. 

Gillin, J. C, Jacobs, L.S., Fram, D.H., Williams, R., Buchsbaum, M. and 

Snyder, F. Partial REM phase deprivation and schizophrenia: An experi- 
mental reappraisal. Arch. Gen. Psychiat . In press. 

Pfefferba-um, A., Buchsbaum, M., and Gips, J. : Enhancement of the AER to 
tone onset and cessation. Psychophysiol . 8 (3): 332-339? 1971. 

Silverman, J., Buchsbaum, M. and Stierlin, H. Sex differences in perceptual 
differentiation and stimulus intensity control. J. Pers. Soc. Psychol. 
In press. 

253 



Serial Wo. M-P-C(C) - 36, page 6 
5. 237-2i4-0, 1971. 



25^ 



serial No. M-P-C-(c)-39 

1. Laboratory of Psychology 

2. Section of the Chief 

3 . Bethesda 

PHS-HSMEIA-WIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 

Project Title: Study of heredity and environmental factors in schizophrenia. 

Previous Serial Number: Same 

Principal Investigator: Paul H. Wender 

Other Investigators: David Rosenthal, John Rainer (New York), 
Laurence Greenhill 

Cooperating Units: Research Foundation for Mental Hygiene, Inc., 
722 West 168th Street, New York, N.Y. 10032 

Man Years: 

Total: 3.1 
Professional: 2.3 
Other: .8 

Project Description: 

Objectives : To assess the role of environmental factors in the etiology of 
schizophrenia. 

Methods Employed : The strategy involves the use of adopted subjects to 
separate the roles of genetic and experiential factors. Since the biologi- 
cal parents are not the parents who rear their children, the transmitters 
of genetic factors and social experience are separated. In this study we 
evaluate the psychiatric status and cognitive function of three groups of 
parents: those who have adopted children who subsequently became schizophre- 
nic; those who reared their own schizophrenic children; and those who reared 
their own organically impaired offspring. 

Psychiatric pathology is assessed by means of structured interviews ad- 
ministered by interviewers who are blind as to the status of the parents 
interviewed. Cognitive function is assessed by means of a battery of psy- 
chological tests. 

The design permits a test of three hypotheses: (l) if psychopathology 
among the parents of schizophrenics is a cause of the disturbance in the 
offspring it should be present in both the adopting and biological parents 
of schizophrenics; (2) if psychopathology in the parents of schizophrenics 
is largely a manifestation of a genetically transmitted disorder, it should 
be present in the biological and not the adopting parents of schizophrenics; 

255 



Serial No. M-P-C-(c)-39, page 2. 

(3) if psychopathology among the parents of schizophrenics is largely re- 
active to pathology in the child, it should be present equally in the parents 
of schizophrenics and of organically impaired children. 

The present study, -which replicates an earlier study of the adopted par- 
ents of schizophrenics, has three methodological improvements: (l) it employs 
systematic sampling; (2) it employs raters who are kept blind as to the status 
of the parents interviewed; (3) it employs a comparison group of parents of 
organically impaired children (controlling for the effect of the^ child on the 
parent) . 

Ma.ior Findings : Case findings and evaluation have been completed. Fifty- 
eight couples (of the sixty proposed) have been interviewed and tested. 

Significance to Bio-medical Research and the Program of the Institute : ¥e 
are attempting to validate our earlier finding which indicated that parental 
psychopa-chology did net seem strongly related to the etiology of schizo- 
phrenia. 

Proposed Course of Project: Transcription of the Interview and test material 
should be completed by July 1972. Data analysis will begin at that time and 
should be complete -- except for the Rorschach evaluations --by the spring 
of 1973. 



256 



Serial No. M-P-C-(c)-to 

1. Laboratory of Psychology 

2. Section of the Chief 

3. Bethesda 

'■'■'■■■ PHS-HSMHA-NIMH 

Individual Project Report 
July 1, 1971 through June 30, 1972 

Project Title: Changes in neurological and psychological functioning in 

children with minimal brain dysfunction receiving d-ampheta- 
mine • , . 

Previous Serial Number: Same 

Principal Investigator: Paul H. Wender 

Other Investigators: Monte Buchsbaum 



Cooperating Units: 


None 


Man Years: 




Total: 

Professional: 

Other: 


.1 
.1 
.0 



Project Description: 

Objectives : To compare neurological and psychological functioning of 
children with minimal brain dysfunction and normal children and to eval- 
uate the changes produced in the former group following treatment with 
d -amphetamine. 

Methods Employed : The study population consists of a group of normal 
children and a group of children with minimal brain dysfunction who have 
manifested a clear-cut clinical improvement following treatment with 
d-amphetamine. 

Both groups will be evaluated to assess positions and changes along 
the following dimensions: (l) average cortical evoked response, and 
(2) field dependence. 

Children with minimal brain dysfunction are characterized by inat- 
tentiveness and stimulus boundedness, both of which appear to change fol- 
lowing successful treatment with d-amphetamine. These characteristics (and 
change in them) may be associated with performance on certain tasks; par- 
ticularly the Rod and Frame test, and the Petrie task, and in average cor- 
tical evoked response to sensory stimuli. It is the purpose of this pro- 
ject to determine if correlates exist between the clinical condition, re- 
sponse to treatment, and test performance. 



257 



Serial No. M-P-C-(c)-40, page 2. 

Ma.ior Findings : None. Data analysis has "begun. 

Significance to Bio-medical Research and the Program, of the Institute : 
Minimal brain dysfunction is an extremely common syndrome in the pre-adoles- 
cent population, occurring in perhaps 57° of that population. Its neuro- 
physiological basis is not understood and its diagnosis cannot be made with 
accuracy. This project may contribute to an understanding of its etiology 
and to more accurate diagnostic technique. 

Proposed Course of Project : To date, l6 children with minimal brain dysfunc- 
tion and 12 controls have been tested. Data analysis should be completed by 
the summer of 1972. 

Honors and Awards : None. 

Publications: None. 



258 



Serial No. M-P-C-(c)-ii3 

1. Laboratory of Psychology 

2. Section of the Chief 
3- Bethesda 



PHS-HSMHA-HIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Lithium as a therapeutic agent in hyperkinetic behavior 
disorders of childhood. 

Previous Serial Number: Same 

Principal Investigator: Paul H. Wender 

Other Investigators: Ronald 0. Rieder, James Weiss, Monte Buchsbaum, 
Theodore Zahn 

Cooperating Units: Office of the Chief, Laboratory of Clinical Science 

Man Years: 

Total: 1.2 
Professional: 1.2 
Other: 

Project Description: 

Objectives : To compare the physiological, neurological, and behavioral 
effects of lithium carbonate and dextro -amphetamine sulfate in single blind 
trials on a hospitalized population of children with the hyperkinetic syn- 
drome who have been unresponsive to amphetamines and phenothiazines. 

Methods Employed : Subjects ages 6 to 1^+ diagnosed as hyperkinetic who have 
failed to respond to conventional drugs. The subjects are admitted to the 
NIH. During their first week in the hospital, the children are screened for 
cardiac and thyroid abnormalities, have routine urinary 17-hydroxy steroid 
levels taken, and have baseline evoked potentials and autonomic reactivity 
studies completed. They are placed on a placebo at this time and baseline 
nurses' behavioral ratings and teachers' ratings at NIH are obtained. 
During the second week, the children are given dextro -amphetamine sulfate 
(not to exceed 30 mg. q.o.d., p.o.) and again, 2k hour urines, physiological 
measures, and teachers' and nurses' behavioral check lists are obtained. 
During the third and final week, the children are given lithium carbonate 
(not to exceed 1200 mg. p-o., q.o.d.), daily lithium blood levels are drawn, 
and the urines are obtained. As the child reaches the therapeutic dose 
level of between 0.8 mEq. per liter and 1.2 mEq. per liter, he is discharged 
to home and is followed on a weekly basis in the NIH Outpatient Clinic. Two 
weeks following the child's first blood level of at least or more than 



259 



Serial Uo. M-P-C-(c)-i+3, page 2. 

0.8 mEq. per liter, the third set of physiological studies are done on an 
outpatient basis. 

Because of the favorable effects of the small WLE classroom, frequent 
one to one nursing, and the strict structured environment of the ward, it 
is difficult to completely evaluate any possible improvement seen in the 
hospital. The post-hospitalization period is then used as a true single 
blind study and behavioral check lists are distributed to the child's 
teacher and the child's own parents. It is one of the major objectives of 
this project to establish both the safety and efficacy of lithium carbonate 
treatment in children outside the hospital. 

Major Findings : None. To date ten children have been treated. It appears 
that these children handle lithium very well and that safe blood levels can 
be reached and stably maintained without difficulty. Data on the effective- 
ness of lithium will not be available until a large sample has been obtained. 

Significance to Bio-medical Research and the Program of the Institute : The 
hyperkinetic syndrome of childhood is an extremely common syndrome in the 
preadolescent population, but only one-half to two-thirds of these children 
respond well to current medication. Recent reports by Annell and Dyson have 
suggested that lithium carbonate may assist some of these formerly unrespon- 
sive children. Both reports tend to stress subgroups of the hyperkinetic 
population, i.e., Dyson has worked with offspring of manic depressives and 
Annell 's success is limited to borderline psychotic adolescents. Furthermore, 
lithium carbonate treatment may be a less toxic drug than dextro-amphetamine 
sulfate when given over several years' time. 

Proposed Course of Project : Data collection has been completed. Data analy- 
sis should be completed by the spring of 1972. 

Honors and Awards : None. 

Publications: None. 



260 



Serial No. M-P-C-(c)- hk 

1. Laboratory of Psychology 

2. Section of the Chief 
3^ Bethesda 



PHS-HSMHA-NIMH 



Individual Project Report 
July 1, 1971 through June 30, 1972 

Project Title: Individual Differences in Eye Movement Search Patterns. 

Previous Serial , Number: Same 

Principal Investigator: Monte Buchsbaum 



Other Investigators : 
Cooperating Units: 



Richard Coppola, Richard Stillman, James Bryan 
and Lyman C . Wynne . 

Adult Psychiatry Branch, NIMH 

Section on Technical Development, MHERP 



Man Years: , ' 




Total:. 


2.0 


Professional: 


1.6 


Other: 


.k 



h 



Project Description: 

Objectives; ^ Development of a computer controlled, interactive, real time 
eye movement' detector; study of individual differences in eye movement with 
rega,rd to search patterns, information input and feedback; exploration of 
eye movement characteristics in normal and various psychopathologic groups . 

Methods Employed : The apparatus recently developed by this project utilizes 
a MacWorth eye movement camera stand and a television camera. The corneal 
reflection of a visible light source is transmitted through an optical 
system into a television camera. The cartesian coordinates are determined 
from the video signal by analog devices, thus yielding the eye's point of 
regard at any given time. A process control computer (lINC) is used to 
generate visual displays and record the analog record data. A data editing 
system allows calibration of the analog inputs and conversion of the data to 
the screen coordinates . The program then outputs the duration and location 
of each successive eye fixation. 

The resultant system provides for the first time an on line process 
control eye movement recorder and display system. Prior to this development 
individual difference studies have been prohibitively costly in terms of time 
required for data analysis. For instance, hand analysis of 10 seconds of eye 
movements recorded on motion picture film would require four hours to prepare 
before it could be used as computer input. This stage of data analysis is 
now completely eliminated and the average subject is run on 20 such 10-second 



261 



Serial No. M. P-C-(c) - kk, page 2 

trials. The system has been dramatically upgraded this year with the in- 
troduction of a silicon matrix vision tube with low noise levels which 
permits cleaner records and easier adjustment of subjects. In addition 
the LINC computer has been interfaced wi*-h our medium sized SEL system, 
allowing rapid statistical analysis of the eye movements. A group of 
Markov analysis programs were written and utilized in describing the data. 

Experimental Methods : Fifteen normal subjects have been tested on two 
separate occasions. Each subject viewed a computer display of the outline 
of two squares; one of which was always the same size and the other a vari- 
able size from one presentation to the next. He was given the task of 
ascertaining whether the variable square was larger or smaller than the 
standard. Sixty twin pairs (Mz and Dz) and 10 schizophrenic subjects have 
also been tested. 

Results : The reliability of individual differences in patterns of eye 
fixation during a size estimation task were studied in normal adults, 
each tested twice. The most stable measures not specifically related to 
the stimulus configuration appeared to be the number of fixations per unit 
time; measures related to dispersal of looking were unreliable. Data on 
where the subject looked, the duration of each fixation and the distance 
between fixation points appeared to follow 1st order Markov processes and 
the transitional probabilities appeared to be individual characteristics 
stable over time. 

Significance to Biomedical Research and the Program of the Institute; 

Eye movements are important indicators of information input strategies and 

may therefore reflect psychophysiological styles of information search. 

The possibility of using this and other objective, physiological measures 

to better distinguish psychiatric patients is central to psychophysiological 

research. 

Proposed Course of Project: Characterization of eye movement parameters 
as 1st and 2nd order Markov chains has suggested a conceptual model of a 
possible psychophysiological information search strategies--individuals 
with independent eye movements (o order Markov process, transitional 
probabilities independent of current state) lack any overall information 
gathering strategy or fail to change strategies after inputing relevant 
information. Further research is planned exploiting the Markov analysis 
fully. These data analysis techniques will be applied to the twin and 
schizophrenic data sample. 

Honors and Awards: None. 

Publications : 



262 



Serial No. U-F-C-{c)-h^ 

1. Laboratory of Psychology 

2. Section of the Chief 

3. Bethesda 

PHS-HSMEA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 

Project Title: The offspring of schizophrenics: markers of a schizophrenic 
disposition. 

Previous Serial Number: None 

Principal Investigator: Ronald 0. Rieder 

Other Investigators: David Rosenthal, Paul Wender 

Cooperating Units: PHS-NIH-NINDS-PRB 

Man Years: 

Total: 1.2 
Professional: .9 
Other: .3 

Project Description: 

Objectives : To discover differences between the offspring of schizophrenics 
and controls, at an early stage in life, which may represent a predisposition 
to develop schizophrenia later in life. 

Methods Employed : This study has utilized the data previously collected by 
the National Institute of Neurological Diseases and Stroke, Perinatal Re- 
search Branch, in their "Collaborative Study on Cerebral Palsy, Mental Re- 
tardation and Other Neurological and Sensory Disorders of Infancy and Child- 
hood." In that project, some 55,000 pregnancies and the offspring were 
studied, with the 7 year follow-up now being completed. About 900 of the 
mothers or fathers had had a psychiatric hospitalization, and of this group, 
we have taken 220 who were studied in the Boston area to use for our study. 
Since we are primarily interested in the offspring of schizophrenics, the 
past year has been used to gather the records of psychiatric hospitaliza- 
tions, so that we could diagnose the parents according to a set of uniform 
criteria. Since records on the children are already complete, when the 
work of diagnosis is completed, we will match a control group and compare 
the groups on such measures as the neurological examination and the Bayley 
Scale of infant behavior. 

Major Findings: None to date 



k 



263 



Serial Wo. M-P-C-(c)-i+5, page 2. 

Significance to Bio-medical Research and the Program of the Institute: This 
work follows the work of this Laboratory on the genetics of schizophrenia. 
We need to find a clinical or hehavioral marker of the predisposition to 
schizophrenia if we are to effectively intervene or do biochemical or physio- 
logical investigations of the developm.ent of schizophrenia. 

Proposed Course of the Pro.iect : Record collection and diagnosis should be 
completed by July 1972. Data analysis on the offspring will begin in the 
next year, and will probably be completed by July 1973- 

Honors and Awards: None 

Publications: None 



^ 



261+ 



Serial No. M-P-C-(C) - #^6 

1. Laboratory of Psychology 

2. Office of the Chief 
• . ' 3. Bethesda 

PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 

Project Title: Psychophysiological Changes During the Menstrual Cycle. 

Previous Serial Number : M-P-C-(c) - 17 

Principal Investigator: Theodore P. Zahn, Ph.D. 

Other Investigator: Betsy Little (Guest Worker) 

Cooperating Units: None 

Man Years : 

Total: .6 
Professional: .1 
Other: .5 

Project Description: 

Objectives : To study autonomic changes through the menstral cycle. To 
study the relationships between autonomic changes and changes in time 
estimation, reaction time, and mood throughout the menstrual cycle. 

Methods : A short experimental procedure is used every day for each subject 
for a complete cycle. Five autonomic measures are used (finger-pulse 
volume, heart-rate, respiration, skin temperature and skin resistance,) in 
three situations :- 

(i) giving the subject moderate intensity tones to listen to 
(ii) asking the subject to estimate 5-sec intervals 
(iii) giving the subject a simple reaction-time situation where 
she has to life a key as quickly as possible on hearing a 
tone. 

Both subjects and experimenter fill out a mood scale daily. A few males 
are being tested as controls. 

Major Findings: It appears that there are very striking baseline shifts 
through the cycle; tentatively it can be said that there is a much higher 
skin resistance during the premenstrual week than at other times in the 
cycle. The results with regard to other measures are still ambiguous. 

Significance to Biomedical Research and the Program of the Institute ; 
It is hoped to relate changes in autonomic fimctioning during the cycle in 
order to help elucidate the mechanisms responsible for mood fluctuations 
during the cycle, particularly "premenstrual tension". 

265 



Serial No. M-P-C-(c) #kG 

Proposed Course of Project; Further collection of data on normals and 
possitly in depressive and schizophrenic patients as well. 

Honors and Awards: None. 

Publications: None. 



266 



Serial No. M-P-C-(C) - #k'J 

1. Laboratory of Psychology 

2. Section of the Chief 

3. Bethesda 

PHS-HSMHA-NIMfi 

Individual Project Report 

July 1, 1971 through June 30, I972 

Project Title: Psychophysiological Concomitants of Minimal Brain 
Dysfunction in Children, 

Previous Serial Number: M-P-C-(c)-#17 

Principal Investigator: Theodore P. Zahn 

Other Investigators: Paul H. Wender, Betsy Little (Guest Worker) 

Cooperating Units: None 

Man Years: 

Total: 1.1 

Professional: .8 

Other: 1.1 

Project Description: 

Objectives; To compare MBD children with normal children in autonomic 
functioning. To assess the effects of drug therapy. To predict MBD 
children's response to drug therapy. 

Methods Employed; Peripheral measures of autonomic functioning, namely skin 
resistance, heart rate, respiration, skin temperature, and pupil size are 
recorded during two sessions in which children are exposed to mild auditory 
and visual stimuli, perform reaction time tests and perform a cold pressor 
procedure. Parents are given questionnaires relating to child rearing atti- 
tudes and practices, and their child's behavior. 

Subjects are children from the Washington area with a diagnosis of MBD 
under treatment by a psychiatrist. Controls are from a nearby elementary 
school and have been chosen by their teachers as not having significant 
behavior problems. The patients are tested both on and off amphetamine 
therapy . 

Comparison of autonomic base levels, responsivity to meaningless and 
meaningful stimuli and variability will be made for normal vs. MBD children 
for MBD children on and off amphetamines, and between MBD children who ' 
respond successfully to the drugs (as Judged by their psychiatrist) and 
those who do not. 

A small number of MBD patients who did not respond to amphetamines were 
given a clinical trial of lithium. Those subjects have been tested on both 
diTigs and off drugs . 

267 



Serial No. M-P-C-(c) - #14-7, page 2 

Major Findings : None, as yet. 

Significance ; Reports in the literature suggest that MBD children may be 
hypoaroused. It is of great importance to test this, since, if true, it 
would help explain the "paradoxical" effect of amphetamines. This study 
should suggest the extent of autonomic involvement in MBD, and hopefully 
will have some predictive value in determining which children will respond 
successfully to amphetamines . 

Proposed Course of Project : Continued data collection and analysis. 

Honors and Awards: None. 

Publications: None. 



268 



Serial No. M-P-C-(c)-#i+8 

1. Laboratory of Psychology 

2. Section of the Chief 

3. Bethesda _:.....•: 



PHS -HSMHA-NIMH a ■ 

Individual Project Report 
July 1, 1971 through June 30, 1972 • :' : 

Project Title: Autonomic Functioning in MZ and DZ Twins. 

Previous Serial Number: M-P-C-(c)- #17 

Principal Investigator: Theodore P. Zahn 

Other Investigators: Monte Buchsbaum, Lyman C. Wynne. 

Cooperating Units: Adult Psychiatry Branch, NIMH 

Man Years : 

Total: .6 
Professional: .3 
Other: .3 

Project Description: 

Objectives; To determine the relative importance of genetic vs . environ- 
mental factors in various aspects of autonomic functioning. To determine 
the relationships of autonomic nervous system activity to personality, 
task performance and electrocortical functioning. 

Methods Employed ; Peripheral measures of autonomic functioning, namely skin 
resistance, heart rate, finger pulse volume, respiration, and skin temper- 
ature are recorded during two sessions which include rest periods, a series 
of mild tones, a reaction time task and mental arithmetic. The subjects are 
30 MZ and 30 DZ twin pairs equally male and female. Some opposite sex DZ 
pairs have also been tested. 

Intraclass correlation will be the primary method of analysis. It \<rill 
be based on base levels, responsivity to non-demanding and demanding 
stimuli, variability and response specificity. 

Major Findings: None, as yet. 

Significance to Biomedical Research and the Program of the Institute : 
Aside from the inherent interest in the basic question of the heritability 
of autonomic indices and patterns, the data from this project will be used 
to help interpret the earlier findings from a similar study on schizo- 
phrenic MZ twins (M-P-C-(C)-#17). 



269 



Serial No. M-P-C-(c)- #i+8,page 2 

Further Course of Project ; Continued data collection and analysis. 
Correlation of autonomic data with personality, behavioral and electro- 
cortical data on the same subjects. 

Honors and Awards : None . 

Publications : None . 



270 



Serial No. M-P-D-(C)-30 

1. Laboratory of Psychology 

2. Section on Early Learning 

and Development 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Stimulus Conditions, Infant Behaviors, Caretaker-Child 

Interaction, and Social Learning in Diverse Child-Rearing 
Environments 

Previous Serial Number: Same 

Principle Investigator: Jacob L. Gewirtz, Ph.D. 

Cooperating Units: Department of Psychology, Hebrew University of Jerusalem; 
Computer Science Center at the University of Maryland 

Man Years : 

Total: 2.00 

Professional: 1.60 

Other: .40 

Project Description: 

Objectives ; In this continuing project, diverse behaviors which connote the 
quality of adaptation and social responsiveness of infants to their environ- 
ments are being related to stimulus conditions which represent opportunities 
for adaptive and social learning in early life. Within each of four child- 
rearing environments, our aims have been: (a) to describe the typical day 
for the infant, including a catalogue of caretaking schedules, the types of 
stimuli provided (primarily those provided through interaction with care- 
takers) , and the types and frequencies of behaviors of the infant; (b) to 
determine the sequential contingencies between environmental stimuli and 
infant responses insofar as they represent opportunities for learning; and 
(c) to consider specific performance issues, such as the infant's response to 
short-term separation from a caretaker to whom he has become "attached" 
(e.g., his mother), and her responses to his subsequent initiations. It is 
thought such data can provide a fruitful basis for examining the utility of 
the concepts available for conceptualizing the filiild's early experience with 
his envi r onmen t . 

Methods Employed : Subjects ( Ss ) : Samples of S^s were drawn from the infant 
population of Israel. One sample consists of 108 S^s in four age groups (8, 
16, 24, and 32 weeks) from four child-rearing environments [the Residential 
Institution, the Kibbutz , the Only-child and the (Youngest-child of) Multiple- 
child Middle-class Town family] . Each S^ was observed in his natural setting 
by a trained woman observer for two half-days, providing data to represent one 
complete day of his life. A second sample included some 700 infants in the 

271 



Serial No. M-P-D-(C)-30, Page 2 

Methods Employed (Continued) : first 18 months of life from the listed 
environments and' a day-care environment as well. Each S_ was observed once. 
His smiles, vocal, and other social responses to a woman's face presented in 
a standard way were recorded. 

A codified observation procedure was developed and used. Reliable observation 
categories and codes were devised for: (a) background events (e.g., mother 
enters, caretaker talks to visitor, caretaker attends to neighboring child); 
(b) setting (e.g., feeding, sleeping, bathing); (c) S^' s behaviors (e.g., 
smiles, vocalizes, follows, manipulates); (d) the various stimuli provided by 
(behavior of) the environment, particularly those of caretakers toward S^ 
(e.g., mother approaches, caretaker picks up S^, father tickles S^, caretaker 
smiles); (e) the sequential contingencies comprising interactions between the 
infant and his environment; (f) S^'s gross activity level (e.g., changes 
position off and on, mouths). Behaviors (but not their durations) were 
scored as they occurred during the observation period. 

Each infant's record, in successive 30-second time units, has been mounted on 
tape-reels, as have a number of the computer programs required for analyses 
of event frequencies and rates, and of selected contingencies. Programs for 
analyzing sequential details of the interaction process have recently been 
completed. These have been devised to index various aspects of interaction 
sequences that will serve as dependent variables in group comparisons between 
Ss, as well as to characterize patterns within a S^. Setting and background 
data have been summarized, as have behavior frequencies and rates and sequences 
of occurrence of the environmental stimuli provided and of the infants' 
behaviors. Comparisons within and between the different environmental and 
age groups are being made via multivariate analyses of variance employing the 
dependent variables so developed. In this process, after adjusting for time 
spent by caretakers with their infants, comparisons among environmental groups 
are being made on: (a) the types and frequencies of stimuli provided infants 
by caretaker-adults (through gross physical contact like lifting, fine 
physical contact like tickling or nuzzling, as well as talking, smiling); 
(b) the types and frequencies of infant responses to or in the presence of 
the adults (e^g., looking, smiling, vocalizing, crying, motor responding); 
and (c) the incidence and details of patterns of interaction between 
caretaker-adults and the infant. 

Major Findings : During the past year, we have concentrated on defining 
conditions prevailing in the kibbutz environment, a topic that has been of 
considerable interest in the professional literature during recent decades. 
One research tack has been to compare the kibbutz to the residential 
institution, in the time spent by caretakers with their infants and in 
behaviors by caretakers to infants and by infants to their caretakers. The 
analysis was performed separately for periods spent in ministering to their 
infants' physical needs — "caregiving" (feeding, diapering, dressing, bathing) 
and for periods when caretakers were in their infants' vicinity when not 
ministering to their infants' physical needs — "pure-social time". 

Analyses of the periods caretakers spent in their infants' vicinity showed 
that, compared to kibbutz caretakers, institution caretakers spend about 

272 



Serial No. M-P-D-(C)-30, Page 3 

Major Findings (Continued) ; twice as much time in caregi \ing, and about 
three times as much time in pure-social time. This difference appears to 
reflect the facts that kibbutz mothers do much of the caregiving during the 
first 8 months of their infants' lives — the period investigated; and that 
institution caretakers are scored as being near an infant when they minister 
to nearby children. E en so, caretaker time spent with or near infants 
represents no more than opportunities for interchanges with them. Therefore, 
differences in actual behaviors exhibited by caretakers to their infants, and 
by their infants to them, were next considered. 

An overall difference in caretaker behaviors during caregiving was found 
between kibbutz and institution caretakers. Specifically, compared to kibbutz 
caretakers, institution caretakers showed more Smiles and Fine-contact responses. 
However, in the Institution, the caretakers were the only ones who ministered 
to their charges while, in the kibbutz, caretakers shared this role with mothers. 
(In fact, kibbutz caretakers spent relatively little time caring for the 
physical needs of their infants in the early months, but took increasing 
responsibility for that care as their infants grew older.) This difference 
between caretaker behavior patterns disappeared when scores were adjusted for 
the fact that caretakers in the institution spent twice as much time ministering 
to charges than did kibbutz caretakers during this infancy period and thus had 
much more opportunity for interaction with their infants. A similar result 
pattern was found for infant behaviors _to their caretakers, while those infants 
were receiving physical care. Institution infants showed more looking at, 
smiling, and vocalizing to their caretakers. However, these differences 
between caretaker behaviors during caregiving dropped out when adjustment was 
made for differences in caregiving time (and in the differences in opportunity 
for interaction that time implies). 

Our next examination was of pure-social time caretaker behavior differences 
between institution and kibbutz, when they were not ministering to their 
infants' physical needs. The difference pattern found, which decreased with 
age, was the institution caretakers showed more Fine-contact, Talk, and 
Gross-contact behaviors than did kibbutz caretakers. However, when scores 
were adjusted for the fact that institution caretakers are in the vicinity of 
their children thrice as much as kibbutz caretakers (who share responsibilities 
with mothers) , the caretakers were found to differ only in the incidence of 
Gross-contact: compared to the kibbutz caretakers, institution caretakers 
showed more of this behavior at 2 months, the same amount at 6 months, and less 
at 8 months. No differences were found between infant group behaviors _to 
those caretakers during "pure-social" settings when caretakers were not 
ministering to their charges. This was the case whether or not account was 
taken of the fact that institution caretakers spent three times as much time 
near their infants as did kibbutz caretakers. 

An intriguing difference pattern was found when (holding age constant) we 
compared kibbutz and institution on the pattern of correlation between 
caretaker and infant behaviors within and between the caregiving and pure-social 
settings. Within those settings, the correlations between caretaker and 
infant behaviors were, overall, higher for the kibbutz than for the institution 

273 



Serial No. M-P-D-(C)-30 , Page 4 

environment. Moreover, the within-setting correlations were higher than the 
between-setting correlations for kibbutz infants, while they were not at all 
different for institution infants. Thus, kibbutz infant-caretaker pairs 
behaved differently, as a unit, in pure-social than in caregiving periods, but 
institution caretaker-infant pairs did not behave differently. That is, a dis- 
crimination between those two interaction settings was found in the kibbutz 
environment but not in the institution environment. This same overall pattern 
holds as well for infant behavior intercorrelations and for caretaker behavior 
intercorrelations. Hence, this pattern is a general one. Relative to the 
institution, it suggests a greater organization by interaction-setting in the 
kibbutz between infant and caretaker behaviors, within infant behaviors, and 
within caretaker behaviors. The possible determinants of these patterns are 
being explored further. 

Kibbutz caretakers and mothers were compared next in terms of: a) time they 
spend in the settings, b) their behaviors to th^ir infants; c) behaviors shown 
by their infants to them; and d) the correlations of their behaviors to their 
infants'. These analyses provided more direct leverage upon the role differ- 
ences between kibbutz mother and caretaker. In terms of the time spent with 
their charges, both in caregiving and pure-social settings, mothers spent more 
time than did caretakers with their infants during the first 8 months of life: 
in caregiving settings, where caretaker time remains constant through the 
eight months, mothers spend 50 times as much time at two months, and twice as 
much time at eight months; in pure-social settings, where both mothers and 
caretakers spend increasing time with their infants with age, mothers spend 
about twice as much time with their infants as do caretakers. 

When differences in mother and caretaker behaviors were examined in caregiving 
settings, mothers showed more Fine-contact and Gross-contact responses to 
their infants than did the caretakers (when adjustment was made for the greater 
amounts of time mothers spent with the infants) . During pure-social periods 
(regardless of time adjustments), mothers displayed more Smile, Fine-contact, 
Talk, and Gross-contact behaviors than did caretakers. When differences in 
infant behaviors to mothers and caretakers were examined during caregiving 
periods, infants showed more Watch, Smile, Vocal sound. Cry, and Motor act 
responses in the presence of their mothers than in the presence of caretakers. 
However, these differences tended to drop out when infant behavior scores were 
adjusted for the fact that mothers spent greater amounts of time in caregiving 
than did caretakers. A similar configuration of results was found for the 
difference in infant behaviors to mothers and caretakers during pure-social 
periods, excepting that after behavior scores were adjusted for greater pure- 
social time spent with the mother than with the caretaker, it was found that 
more Vocal sounds and Motor acts were exhibited by infants to their mothers 
than to their caretakers. 

An examination of the correlations between adult and infant behaviors within 
and between the caregiving and pure-social periods was next attempted. Holding 
age constant, the correlations within and between caregiving and pure-social 
periods were invariably of higher magnitudes between mother and infant behaviors 
than they were between caretaker and infant behaviors. This result suggests a 
better organization between the behaviors of a mother and her infant than 
between a caretaker 

27^ 



Serial No. M-P-U-(C)-30, Page 5 

and the same Infant. This Interpretation Is supported by our having found: 
a) lilgher intercorrelatlons within child behaviors in interaction with the 
mother han In those same behaviors when in interaction with the caretaker; 
and b) higher caretaker-Infant and mother-infant behavior intercorrelatlons at 
8-months than at 2-months of age. The possible determinants of these 
patterns are being explored further. 

In this context, we also compared the correlations between the behaviors of 
mothers and their Infants (within and between the caregivlng and pure-social 
periods) in the kibbutz with two other environments, that of the youngest- 
child and that of the only-child family (both urban middle-class) . The 
correlational pattern between the behaviors of a mother and her Infant was 
found to be reliably higher in magnitude In the kibbutz than in either the 
youngest- or the only-child environments. However, because Intercorrelatlons 
within infant behaviors and within mother behaviors were found to follow 
parallel patterns in this three-environment comparison, some other possible 
determinants of these patterns are being explored. In particular, contingent 
relations between the various adult and infant behaviors are being examined 
with the aim of pinpointing at a more detailed level of analysis the nature 
of the adult-infant dependencies involved. 

Finally, the three tntercorrelational analyses were examined In terms of age 
of Infant. It was found that the correlational patterns between adult and 
infant behaviors were reliably higher for older (8 months) Infants than for 
younger (2 months) Infants. Thus, the behavior organization between Infant 
and adult behaviors, and within each of those behavior sets, appears to 
Increase within the age range studied. 

In this frame of intercorrelatlons and mean differences, we have attained 
considerable empirical leverage on the difference In role between mother and 
caretaker in the kibbutz environment, between caretakers in the kibbutz and 
Institution, as well as between kibbutz and urban family mothers. 

Scientific Significance to the Program of Mental Health Research ; Watchlng- 
scanning, smiling, vocal, and similar adaptive behaviors constitute key 
human response systems, for they mediate (and hence can also index) much of 
initial adaptive and social learning and development of the Infant as well as 
his subsequent patterns of social- Interaction. A developmental picture of 
the early course of these behavior systems can be of considerable use In 
Itself, but can also provide a context for understanding the nature of the 
outcomes of different conditions of child-rearing. These conditions can be 
assumed to provide differential varieties and amounts of stimulation, and hence 
varying opportunities for social learning. At the same time, this investigation 
can provide data on an issue that has become increasingly salient in parent- 
child relations: how the child's behaviors can affect the parent's or 
caretaker's behaviors in relation to him. 

Proposed Course of the Project : It is expected that most reports for 
publication from this project will be completed during the coming year. 

Honors and Awards : None 

Publications: None ^'^ 



Serial No. M-P-D-(C)-34 

1. Laboratory of Psychology 

2. Section on Early Learning 

and Development 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH ■. 
Individual Project Report 
July 1, 1971 through June '30, 1972 

Project Title: Contextual Determinants of Stimulus Power* 

Previous Serial Number: Same 

Principal Investigator: Jacob L. Gewirtz, Ph.D. 

Other Investigators: None 

Cooperating Units : None 

Man Years : 

Total: .30 

Professional: .20 

Other: . .10 * 

Project Description: 

Objectives : A great variety of preceding or concurrent contextual conditions 
potentially exist which could determine the power of a focal stimulus in 
evoking, cueing, or reinforcing behavior. Their effects often cumulate. Our 
aim has been to survey the range of contextual factors that can q^ualify 
stimulus efficacy, to make a preliminary categorization of them, and to 
consider some underlying issues in their operation. 

Methods Employed : In the empirical portion of this program, some key 
contextual factors have been manipulated. For instance, deprivation and 
satiation conditions for a social stimulus class were effected by varying the 
availability of a social stimulus to subjects in a period immediately 
preceding a test for the effectiveness of that stimulus. A further aim has 
been to implement different maintenance patterns of prior stimulus availability. 

Major Findings : Data from diverse sources are being surveyed to identify 
classes of contextual factors. In this frame and on the basis of our earlier 
empirical studies, it was concluded that the function of a stimulus on a 
particular occasion, in evoking, cueing, or reinforcing behavior, may be 
enhanced or decreased by the manipulation of the context of stimulus 
provision. Moreover, even the direction of the effects of a stimulus on 
behavior may be determined by the stimulus context. That is, whether a given 

*Former title of project: Deprivation and Satiation of Social Stimuli as 

Determinants of their Reinforcing Efficacy 



277 



Serial No. M-P-D-CC)-34, Page 2 

Major Findings (Continued ) : stimulus evokes an approach or an avoidance 
response will often depend entirely on the context of its provision. 

Scientific Significance to the Program of Mental Health Research : The 
efficiency of human learning and performance depends on the effectiveness of 
the available stimuli in each of their roles. Hence, the identities- of 
contextual setting conditions can provide an important key for understanding 
the acquisition and performance of child behavior systems, particularly in 
natural settings. The principles identified should also bear on such 
conceptions as childhood "privation" as they suggest that effective stimulation 
depends not only on the type and number of stimuli available but also on the 
contexts of their provision as well. 

Proposed Course of the Project ; Our plan is to carry out experiments in this 
problem area when new laboratory facilities become available in 1972. 

Honors and Awards : None 

Publications: 

Gewirtz, J. L. Some contextual determinants of stimulus potency. In R. D. 
Parke (Ed.), Recent Trends in Social Learning Theory . New York: 
Academic Press, 1972. Pp. 7-33. 



278 



Serial No. M-P-I>-CC)-42 

1. Laboratory of Psychology 

2. Section on Early Learning and 

Development 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Evaluation of Concepts Employed for Early Learning and 
Development 

Previous Serial Number: None 

Principle Investigator: Jacob L. Gewirtz, Ph.D. 

Other Investigators: None 

Cooperating Units : None 

Man Years : 

Total: .30 
Professional: .20 
Other: .10 

Project Description: 

Objectives : To analyze the roles in theory and research of focal concepts 
employed in the area of early adaptive and social learning and behavioral 
development, and thereby to provide a basis for evaluating and facilitating 
researches in those sectors. Included are such concepts as development, 
critical period, environmental stimulation, drives and motivation, stimulus 
privation, deprivation, and separation, attachment and dependence, imitation 
and identification, and vicarious-reinforcement and observational learning. 

Methods Employed ; While the moment-to-moment details of the interchange 
between stimuli and responses are relevant to many process theories of 
learning and development, researches done under the aegis of such theories 
have almost routinely employed global concepts for environment and behavior 
(e.g., traits) that only summarize through lengthy time spans the occurrence 
of either stimuli or responses but not both facets of the (S-R) interchange. 
These research variables are therefore often remote from the level of analysis 
required by the process theories that have spawned them. Our approach to 
human social learning has proceeded as a detailed functional analysis of 
stimuli and responses, their interchange at a particular moment, and the 
sequences of interaction across successive moments (i.e., the stimulus-response 
chain). Thus, the conditioning concepts we have employed order environmental 
operations that effect systematic and (usually) reversible changes in 
observable behaviors. The approach employed is open to the addition of new 
concepts as required, and to the differentiation and refinement of the 
concepts in current use. 

279 



Serial No. M-P-D-(C)-42, Page 2 

Major Findings : . We moved forward during the year in the evaluation of the 
efficacy of key concepts of attachment and dependence in ordering the 
behavioral phenomena for which they were devised, and in relating them to 
what we observed in child-rearing settings. In particular, we have 
surveyed possible indices for those concepts from the viewpoint of some of 
the models advanced for their acquisition and maintenance. We considered 
indices for cases where these terms were conceived as abstractions for 
classes of functional relationships involving the positive stimulus control 
over a wide \ariety of an individual's responses by stimuli provided either 
by a class of persons (dependence) or by a particular person (attachment) . 
We surveyed indices for other cases as well, such as a) for different 
approaches to the origins of attachment and dependence, b) for different 
bases of distinctions between the concepts, and c) for diverse assumptions 
underlying cognitive-ethological and learning approaches to human attachment 
and the mother- infant relationship. As we conceive dependence and 
attachment to be gross abstractions, in different contexts many types of 
behaviors (e.g., approach, preference, approach in the context of avoidance, 
disorganization behaviors) could be used to index each concept. Considerations 
were outlined for index selection under different research strategies and 
tactics . 

Scientific Significance to the Program of Mental Health Research : Clarification 
of the purpose and utility of concepts such as those examined should lead to 
more efficient mental health research and application. Also, the role of 
response acquisition in various complex personality processes that underlie such 
concepts, and distinctions between motivation and learning concepts, can be 
delineated more explicitly and parsimoniously. On this basis, research and its 
applications in the area of the psychological development of the normal child 
should be facilitated. 

Proposed Course of the Project : The need for this project is a continuing 
one, as concepts like the ones being analyzed are in common use in the field at 
large and serve important functions in our research program. 

Honors and Awards : None 

Publications : 

Gewirtz, J. L. Attachment and dependence: Some strategies and tactics in 

the selection and use of indices for those concepts. In T. M. Alloway, 
L. Krames, and P. Pliner (Eds.), Communication and Affect . New York: 
Academic Press, 1972, in press. 



280 



Serial No. M-P-P-(c)-6 

1. Latoratoiy of Psychology 

2. Section on Personality 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 



Project Title: The Investigation of Some Formal Characteristics of Speech 

Previous Serial Number: Same 

Principal Investigator: Donald S. Boomer, Ph.D. 

Other Investigators: Allen T. Dittmann, Ph.D. 

Cooperating Units: None 
Man Years 



Total: 


2.20 


Professional: 


2.00 


Other: 


.20 



Project Description: 

Objectives: 

General: To elaborate and test a psycholinguistic theory of speech 
performance. 

Specific: To explore the psychological properties of some functional 
speech units specified by the theory. 

Methods Employed: 

1. Linguistic and phonetic analysis of natural speech utterances. 

2. Controlled experimental situations which systematically vary 
parameters of speech production and perception, and their correlates. 

Major Findings: 

An extended research program, summarized in previous annual reports has 
been incorporated into a developing theory of speech production. In bare 
outline, the theory posits a central speech planning mechanism which 
assembles motor production programs which, in turn, control the external 
articulators during actual speech production. The pre-planning aspect of 



281 



Serial No. M-P-P-(C)-6, Page 2 

this theory distinguishes it from more conventional associative theories 
which explain speech production in terms of associative bonds between 
elements: i.e., words and/or sounds. Major findings from this project, 
previously reported, include demonstrations that speech non-fluencies such as 
hesitations, repetitions, and tongue-slips are not random "noise" but occur 
lawfully with respect to the functional speech units posited in the theory. 

During the past year this research has focussed on speech perception. 
The guiding hypothesis has been that listeners, like speakers, process 
"chunks" of speech which are defined by intonational patterns. In perception 
these units, phonemic clauses, are held in short-term memory and processed as 
patterns of sound, syntax, and sense. 

The pupillographic work begun last year has continued. This work has 
been an attempt to extend Kahneman and Beatty's finding that pupillary dia- 
meter seems to be directly associated with intercurrent load on short-term 
memory. We have hypothesized that as a subject listens to speech a gradient 
of pupillary dilatation would occur over the co\jrse of a phonemic clause, 
while it is being loaded into short-term memory. 

Since the pupil is richly and complexly innervated and a variety of 
processes are affecting its moment-to-moment diameter, signal averaging 
techniques are required in order to separate out the hypothesized psycho- 
linguistic effect from "noise," 

The course of the project this year has involved repeated attempts to 
match a set of experimental stimuli to a Line computer program in such a 
fashion as to be able to test the pupil diameter hypothesis. A number of 
difficult problems have been solved; some still remain. These attempts 
will continue during the next year. 

Scientific Significance to Mental Health Research Program: 

Behavioral and medical research involving speech fvmction, studies of 
psychotherapy and aphasia, for example, are hampered by the lack of appro- 
priate psychological theories of speech production. Most current linguistic 
theories are inappropriate in that they aim to describe abstract language 
structures without reference to the live users of the language, thus failing 
to link with theories and data in psychology and neurophysiology. The theory 
underlying the present program is broadly psycholinguistic in scope and can 
thus accommodate data and observations from other relevant disciplines. Of 
more direct benefit to the field of neurophysiology is the fact that this 
work provides a detailed, structured analysis of the output of an important 
motoric system. Such analysis will be necessary as neurophysiology increas- 
ingly attempts to deal with complex sequential behavior. 



282 



Serial No. M-P-P-(c)-6, Page 3 
Proposed Course of Project: 

A number of lines of investigation will be pursued in the coming year. 

1. A continued attempt to separate the processes of word- finding 

and syntactic framing — the so-called paradigmatic-syntagmatic distinction 
proposed by Jakob son. 

2. The pupillographic work will continue. The LINC signal averaging 
program for pupil data has been rewritten and tried 3 times in the past year, 
and is still unsatisfactory. These electronic and data handling difficulties 
are being worked on with assistance from James Bryan and his staff. 

Honors and Awards : None 

Publications: 

Boomer, D. S. : Review of Rhythms of Speech by Jaffe and Feldstein. 
Contemporaiy Psychology . l6: 530-531, 1971- 

Boomer, D. S. and Laver, J. Slips of the tongue. Brit. Jour. Disord. 
Commun . 3: 2-11, 1968. Reprinted in V. A. Frofflkin (Ed.): Speech 
Errors as Linguistic Evidence . Mouton (in press). 



283 



Serial No. M-P-P-(c)-22 

1. Laboratory of Psychology 

2 . Section on Personality 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 

Project Title: Development of Potentially Creative Scientists: Personality 
Characteristics Associated with Creative Performances 

Previous Serial Ninnber: Same 

Principal Investigator: Kenneth Burgdorf, Ph.D. 

Other Investigators: Morris B. Parloff, Ph.D. 

Cooperating Units: None 

Man Years 

Total: _ .20 
Professional: .10 
Other: . .10 . 

Project Description: 

Objectives : " 

To conduct a longitudinal study to assess the nature, degree and cor- 
relates of personality change evidenced by highly selected samples of male 
subjects judgedto be highly creative, as well as those judged to be less 
creative. This aspect of the study covers a five year period following high 
school graduation. 

Methods Employed : 

In accordance with the plans for this longitudinal study, a battery of 
tests was readministered in 1970-1971 to a sample of approximately itOO sub- 
jects (Beta Sample) who had been previously identified and tested in I965 
and 1966. The Personality, Social Adjustment and Performance measures 
employed are identical to those administered to another sample of approxi- 
mately 500 students (Alpha Sample) who had been studied by these investi- 
gators in 1963, 196^1 and I969. The Battery included the California Psycho- 
logical Inventory, four scales from the MMPI, a specially devised Social 
History Questionnaire, and other instruments related to achievement, 
recognition, and creativity. 



285 



Serial No. M-P-P-{C)-22, Page 2 
M ajor Findings: 

1. Followup personality data from the Beta sample were found comparatle 
to the data from the Alpha sample, 

2. Individual differences in personality changes over time were found 
strongly related to individual differences in psychiatric help seeking be- 
havior. These relationships have been described elsewhere (see project 

Wo. M-P-P-(c)-it2). 

3. Followup personality variables differentiated high and low creativity 
subjects much less strongly than high school personality variables had been 
found to do. 

k. This finding (No. 3) was found to be largely an artifact resulting 
from sample attrition. The nature of this artifact was rather interesting. 
No differences were found on high school personality measures between the 
total group of subjects who returned followup data and the overall group of 
non-respondents. A number of interactions were found, however, between 
creativity and foUowup response status on high school personality measures. 
Specifically, low creative non-respondents were much lower than low creative 
respondents on measures of ego-strength, adjustment, sense of well-being, 
responsibility, and similar traits, while the differences on these measures 
between high creative respondents and high creative non-respondents were 
also large but in the opposite direction. 

5. It appears that those members of the high creativity group who were 
especially well-functioning during high school and those members of the low 
creativity group who were least integrated during high school were the ones 
who did not return followup data five years later. This explains the attenu- 
ation of creativity group differences in the followup sample. It also sug- 
gests that two rather different kinds of people may fail to return question- 
naires dealing with achievements, accomplishments, etc.: those who have few 
accomplishments to report and those who feel too busy to waste' their time 
responding to questionnaires which have no direct bearing on their lives. 

Scientific Significance to Mental Health Research Programs : 

Factors which influence personality development and motivation are 
known to facilitate or impede the full use of one's capacities. While this 
issue is of significance in affecting the development of all individuals, it 
is of particular iuportance in aiding us to understand the impact of social 
and cultural influences on uniquely gifted individuals who demonstrated 
"creative" abilities at an early age. 



286 



Serial No. M-P-P-(c)-22, Page 3 

Proposed Course of Project : 

These findings -will be prepared for publication. 

Honors and Awards : None 

Publications: 

Parloff , M. B. : Creativity research program: A review. In 
Taylor, C. W. (Ed.): Climate for Creativity . Elmsford, New York, 
Pergamon Press. In press. 



287 



Serial No. M-P-P-(c)-i+0 



1. Laboratory of Psychology 

2. Section on Personality 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 



Project Title: Body Movement as Expression of Change in Psychological 
Tension States 

Previous Serial Number: Same 

Principal Investigator: Allen T. Dittmann, Ph.D. 

Other Investigators: Donald S. Boomer, Ph.D. 

Cooperating Units : None 

DISCONTINUED. 



289 



Serial No. M-P-P-(C)-Ul 

1. Laboratoiy of Psychology 

2. Section on Personality 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 



Project Title: Survey of Literature on Emotional Communication 

Previous Serial Number: Same 

Principal Investigator: Allen T. Dittmann, Ph.D. 

Other Investigators: None 

Cooperating Units : None 

Man Years 



Total: 


.k6 


Professional: 


.25 


Other: 


.21 



Project Description: 

Objectives : To provide a conceptual framework within which existing 
research on emotional communication may he evaluated and new research 
designed; and to test the concepts of that theory in the context of various 
specific research areas. 

Methods Employed : Standard library research methods for the development 

of the theory and for some of its applications; research methods appropriate 

to the study for other applications. 

Ma j or Findings : The monograph , Interpersonal Messages of Emotion , the 
general theoretical statement, is now in press. Two studies of specific 
applications are published. 

Scientific Significance to Mental Health Research Program : The sort of 
general theorizing with which this project began has turned out to be 
useful in examining two quite disparate problems in language behavior, 
a topic related to, but in certain respects not central to the original 
theory itself. The theory thus appears to have useful generality, and 
will no doubt find application in other research areas. 



291 



Serial Wo. M-P-P-(C)-l4l, Page 2 



Proposed Course of Project: Project completed. 

Honors and Awards : None 

Publications : 

Dittmann, A. T. : The body and movement-speech rhythm relationship 
as a cue to speech encoding. In Siegman, A. W. and Pope, B. (Eds.): 
Studies in Dyadic Communication. Elmsford, New York: Pergamon Press, 
1972, pp. 135-151. 

Dittmann, A. T. : Review article on Kinesics and Context by Ray L. 
Birdwhistell. Psychiati-y , 3^: 33^-3^2, 1971. 

Dittmann, A. T. : I nterpersonal Messages of Emotion . New York, 
Springer Publishing Co. In press. 



Serial No. M-P-P-(C)-U2 

1. Laboratoiy of Psychology 

2. Section on Personality 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Precocious Science Students in Psychiatric Treatment: 
A Longitudinal Study 

Previous Serial Number: Same 

Principal Investigator: Kenneth Burgdorf, Ph.D. 

Other Investigators: Morris B. Parloff, Ph.D. 

Cooperating Units : None 

Man Years 

Total: 2.08 

Professional: -70 
Other: 1>38 

Project Description: 

Objectives : 

1. To describe the pre-college, college, and post-college characteristics 
and experiences of a group of precocious science students who enter psychiatric 
treatment during college. 

2. To describe the type and magnitude of treatment-related change ex- 
hibited by the patient group. 

3. To examine relations between treatment-related change and (a) para- 
meters of treatment; (b) pre-college characteristics; and (c) college 
experiences . 

Methods Employed : 

1. A wide variety of measures, including indices of personality traits, 
parent-child relationships, interests, activities, achievements, etc., were 
collected on a nationwide sample of 756 precocious science students at each 
of three points in time: (a) senior year of high school; (b) freshman year 
of college; and (3) first year of graduate school (i.e. , 5 years after high 
school) . 



293 



Serial No. M-P-P-(cLl|2, Page 2 

2. The post-college followup contained a series of items in which sub- 
jects were asked whether' or not they had sought professional assistance for 
emotional problems while at college and, if so, to describe the assistance 
which they had received. Initial analyses involved comparisons between 
students who reported receiving 5 or more sessions of individual or group 
therapy (W = 95) and students who reported that they had neither entered nor 
ever seriously considered entering treatment (N = k26) . 

Major Findings: 

1. In this sample, the number of students who expressed concern about 
emotional well-being at college was remarkably high. Nearly half of the 
sample reported that they had seriously considered entering treatment at 
some time during college, and 23^ of the sample (i.e., half of those who 
considered entering treatment) actually did so. The prevalence of psychiatric 
help-seeking among college students in general is about 6%. 

2. Specific problems of adjustment at college appeared to be the primary 
source of motivation for help-seeking. Students who reported feeling "out 

of place" at college or who received low grades, for example, were much more 
likely to seek assistance than those who did not experience such problems. 

3. Treatment-related change tended to be negative in direction and non- 
specific in type. That is, a decline in quality of functioning was evident 
for students who had received psychiatric treatment on measures of change 
(post-college data being compared to pre-college data) in personality, self- 
esteem, family relations, academic and extracurricular achievement, social 
and career development, etc. The extent of change was strongly related both 
to Intensiveness ' and to duration of treatment. Thus, students who received 
more than 20 sessions of individual psychotherapy exhibited the greatest 
negative change, while those who received fewer than five sessions of voca- 
tional counseling changed in a positive direction on most measures. The 
quality of functioning of untreated students tended to improve over time. 

k. In attempting to explain help-seeking (and the decline in fionctioning 
associated with it) in terms of pre-college characteristics and college ex- 
periences, it was found useful to distinguish help-seekers who gave evidence 
of psychiatric problems during high school from those who did not give such 
evidence. Approximately two thirds of the help-seekers were of the latter 
type: their emotional problems did not antedate college. The basic relation- 
ships were: (a) students who evidenced psychiatric problems during high school 
and attended extremely selective, competitive colleges were very likely to 
experience adjustment problems, to enter treatment, and to become increasingly 
impaired; (b) impaired students who attended less selective colleges tended 
not to experience adjustment problems, not to enter treatment, and to improve 
over time; and (c) among students who appeared psychiatrically unimpaired 
during high school, those who were most talented, forceful, and autonomous 
were the ones most likely to feel frustrated at college, to enter treatment, 
and to become psychiatrically impaired. 



29^^ 



Serial No. M-P-P-(C)-U2, Page 3 

5. It appears that a substantial number of students who enter college 
with highly developed sliills and interests in science react to college by- 
developing adjustment problems and by entering psychiatric treatment. It 
is also apparent that the assistance which such students receive is typically 
ineffective either at producing an amelioration of problems or at preventing 
a continued deterioration of functioning. 

Scientific Significance to Mental Health Research Programs: 

Recognizing that some students react adversely to stresses in the college 
environment and that others possess long-standing emotional problems which 
limit their ability to function productively, many colleges and universities 
have instituted programs to meet the mental health needs of their students. 
Very little is known at present about the kinds of students who seek help 
at college mental health facilities or about the effectiveness of the assist- 
ance which they receive. At the very least, the results of this study 
demonstrate that current methods of psychiatric intervention are not adeq^uate 
to meet the mental health needs of all college students . Distinguishing 
students who are likely to respond well to current methods of intervention 
from those who are not, and devising more effective modes of treatment for 
the latter group should become high priority topics for future research in 
this area. 

Proposed Course of the Project: 

Data analyses have been completed. A monograph length report of 
this research is being prepared for publication. 

Honors and Awards : None 

Publications : None 



295 



Serial No. M-P-P(c)-ii3 



1. Laboratory of Psychology 

2. Section on Personality 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 
Individual Project Eeport 
July 1, 1971 through June 30, 1972 



Project Title: Test and Performance Measures of Creativity in Science 

Previous Serial Niiunber: Same 

Principal Investigator: Kenneth Burgdorf, Ph.D. 

Other Investigators: Morris B. Parloff, Ph.D. 

Cooperating Units : None 

Man Years 

Total: . .58 '■ 
Professional: .20 
Other: .38 

Project Description: 

Objectives : 

1. To examine the construct validities (meaningfulness ) of two per- 
formance meas\ares of individual differences in scientific creativity in a 
highly select group of adolescents. 

2. To examine the construct validities of six -well-known paper-and- 
pencil tests alleged to measure creative ability in science. 

3. To examine the construct validity of a paper-and-pencil test of 
creativity developed by the senior investigator from theories which conceptu- 
alize creativity as a personality trait rather than as an ability trait. 

k. To assess the relative advantages of the approaches to test and 
performance measurement represented in the study. 

Methods Employed : 

1. Subjects were 131 male high school seniors who: (a) had indicated a 
strong desire to pursue careers in science; (b) had demonstrated an exception- 
ally high degree of familarity with basic facts, principles, and methods in 
science; and (c) had produced at least one major independent research project 
in a field of science. High levels of scientific knowledge, motivation for 



297 



Serial Wo. M-P-P-(C)-l+3, Page 2 

research, and effort to actually do research are regarded as necessary pre- 
conditions for the demonstration of creativity in science. 

2. Subjects' research projects were classified by field of science 
(mathematics, biochemistry, etc.) and were rated for creativity by two 
eminent scientists whose expertise was in that field. Reasoning that sci- 
entific research is an intrinsically creative activity and that any indication 
of research quality might be a useful index of extent of creativity in this 
sample, a second performance measure was formed by determining the level of 
recognition in science which each subject had attained (national vs. less 
than national). 

3. The construct validities of the test and performance measures were 
assessed by examining the pattern of correlates which each produced with a 
set of reference variables. In addition, it was predicted that each of the 
tests (if valid) would be found associated with at least one of the two per- 
formance measures. 

Ma j or Findings : 

1. Of the two performance measures, recognition was found to possess the 
superior construct validity. As compared to the project evaluation measure, 
it was more strongly related to indices of achievement in science and in 
other creative fields, to self-ratings of creativity, to personality traits 
theoretically allied to the concept of creativity, etc. As hypothesized, 
both performance measures were found unrelated to indices of academic aptitude 
and achievement. 

2. The evidence of construct validity for the creative ability tests was 
nil. None was associated in the expected manner with other ability tests, 
with either of the performance measures, with the test developed by the in- 
vestigators, or with any of the reference variables. The personality test, 
on the other hajid, was found to possess a remarkably high degree of construct 
validity. " It was associated with the recognition measure of performance and 
its pattern of correlates with reference variables was completely in accord 
with expectation (i.e., nearly identical to that produced by the recognition 
measure) . 

3. The conclusions are: (a) When major creativity-irrelevant determinants 
of behavior are controlled, recognition measiires provide useful and meaningful 
indices of individual differences in creative performance; (b ) All of the 
ability tests investigated are invalid measures of scientific creativity and 
should not be used as operational definitions of the constnict in future 
research; and (c) For purposes of theory development, it may prove more use- 
ful to conceptualize creativity as a personality trait than as an ability 
trait . 



Serial No. M-P-P-(C)-i+3, Page 3 

Scientific Significance to Mental Health Research Programs: 

Creativity has become the topic of a great deal of speciolation in 
recent years, much of which involves mental health matters. It has been 
claimed, for example, that certain forms of psychotherapy enhance creativity, 
that mental illness impairs creativity, and that creative individuals develop 
psychiatric problems when exposed to certain kinds of educational environ- 
ments. Before such speciilations can be verified or disproven, an understand- 
ing of the nature of creativity must be attained and valid measures of the 
trait must be found. This project is felt to contribute to this end by 
demonstrating that several popular tests of creativity are not valid and by 
suggesting an approach which may prove more fruitful. 

Proposed Course of Project: 

The findings are currently being prepared for publication. 

Honors and Awards: None 

Publications : None 



299 



Serial No. M-P-P-(C)-ltlt 

1. Laboratory of Psychology 

2. Section on Personality 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

Jiily 1, 1971 through June 30, 1972 



Project Title: Psychodynamic and Instrimiental Learning Models: 

Implications for Personality Theory and Psychotherapy. 

Previous Serial Number : Same 

Principal Investigator: Stanley I. Greenspaji, M.D. 

Other Investigator: None 

Cooperating Units: School and Residence — Hillcrest Children's Center 
Children's Hospital, Washington, D. C. 



Man Years 




Total: 


1.20 


Professional: 


1.00 


Other : 


.20 



Project Description: 
Objectives : 

1. To develop an internally consistent model of personality (development 
and organization) based on instrumental learning theory and psychodynamic 
theories. 

2. To develop a psychoanalytic learning model. 

3. To test the utility of the integrated model as an aid to: (a) pro- 
viding a conceptual basis for examining change in psychotherapy; (b) 
facilitating differential diagnosis and treatment of children and adoles- 
cents ; (c) designing an effective classroom milieu in a traditional school 
setting; (d) aiding psychotherapy in a residential child treatment setting; 
(e) aiding psychoanalytic conceptualizations of the role of external reality 
in personality development and in treatment; and (f) aiding behavioral 
approaches in using psychoanalytic concepts to enrich -cheir techniques. 



301 



Serial No. M-P-P-(C )-Ui+, Page 2 

Methods Employed : Formulation of an integrated model representing critical 
variables affecting human behavior. Utilizing these concepts in establish- 
ing a therapeutic milieu in the treatment center, and an environment con- 
ducive to learning in a classroom. Formulation of a psychoanalytic learning 
model as an addition to current psychoanalytic theory. Pilot studies of the 
clinical and educational effectiveness of this approach were conducted with 
the aid of a psychotherapy team and of ' educators . 

Major Findings : Ho firm conclusions are warranted in this time regarding 
the effectiveness of the derived techniques; however, the applicability of 
the model to the educational and treatment setting has been demonstrated. 
The model was translatable into operational terms and was successfully com- 
municated to the staffs of the two centers. The treatment plan, derived 
from the integrated model, appeared to be effective in aiding the treatment 
of a child and an adult who had previously been described as "resistant to 
treatment." 

The consideration of this model together with educators suggests that it is 
useful in the joint conceptualization of educational and mental health aspects 
of the school setting. Specific recommendations for research projects on 
classroom structure to test this and other models are being considered. 
A monograph integrating learning variables into psychoanalytic theory has 
been completed. It provides a framework for studying the effect of environ- 
mental variables in early personality development and analytic therapy. 

Scientific Significance to Mental Health Research Program: Theories which 
focus on intrapsychic determinants of behavior have each made important 
contributions to our understanding of personality development, organization, 
psychopathology, and treatment. A more unified model allows conceptualiza- 
tion of both these sets of variables within one model and thereby affords a 
fuller understanding of these important areas. 

Proposed Course of Project : Further development of the more lonified model 
with special emphasis on its practical applications. 

Honors and Awards : None 

Publications: None 



302 



Serial No. M-P-P-(C)-lt5 

1. Laboratory of Psychology 

2. Section on Personality 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 



Project Title: Developmental Factors in Conversational Behavior 

Previous Serial Number: M-P-C-(c)-35 

Principal Investigator: Allen T. Dittmann, Ph.D. 

Other Investigator: Donald S. Boomer, Ph.D. 

Cooperating Units: Green Acres School, Bethesda, Maryland. 

Man Years: 

Total: l.i+li 
Professional: .75 
Other: .69 

Project Description: 

Objectives : To compare language-like listener responses ("M-hmm," head 
nods, and the like) in children of different ages with those of adolescents 
and adults, with special reference to the situations in which they occur, 
the events which stimulate them, and their functions, both for the listener 
as a direct consequence of his speech decoding efforts, and for the speaker 
as social feedback. 

Methods Employed : Systematic observations of children in a school (but not 
an instructional) situation, and more controlled observational sessions in 
the laboratory. School observations were taken at Green Acres School of 
kindergarten, 1st, 2nd, 3rd, and 5th grades, with the most complete obser- 
vations in 1st, 3rd, and 5th grade classes. The situation was a free-time 
period of 30 minutes in each class , when pupils chose their own activities , 
including reading and studying, drawing, playing games, talking quietly. 
Most of the time included conversation, but its importance to the rest of 
the activity varied widely. Three observers watched small groups of 
children in interactions ranging from brief exchanges to periods lasting 
10 minutes. Notes were later judged for the degree to which the social 
situation "pulled" listener responses (structured games had low piill, inter- 
current conversation while drawing had medium pull, while straight conversa- 
tion and instructing another in a game had high pull). 



303 



Serial Wo. M-P-P-(C)-^5, Page 2 

The situations in, the laboratory have been exploratory. Since this area of 
research is new, there is no body of knowledge to draw upon in designing an 
experiment. We have learned from the school observations and from initial 
laboratory observations that we must systematically vary the situation by a 
number of factors: (l) differences between conversational partners along 
variables of age, sex, acquaintance, status, and the like; (2) the purpose 
of the interaction, such as instruction compared with social conversation; 
(3) the content of the conversation, such as emotional, personal, focused, 
"weather talk," and others; {h) the physical structure of the conversational 
environment, such as spatial arrangements between the conversationalists. 
All sessions are recorded on video tape and audio tape, and a few have also 
used the head, movement transducers from earlier studies to record precise 
timing of the responses. 

Analysis of the laboratory observations begins with segmenting the type- 
script of the speaker's speech into what are called phonemic sentences, a 
unit derived from the Trager-Smith phonemic clause. Then the visible and 
audible responses are entered into the typescript. Rates of listener 
response per phonemic sentence are then computed for comparisons. 

Ma j or Findings : In the school situation h'J children were observed for a 
total of 111 minutes. Twenty-nine listener responses were observed and 
these were all contributed by 8 of the children. The responses came almost 
exclusively in high pull conditions. The exceptions came in medium pull 
conditions , but there was some question as to whether they should be classi- 
fied as listener responses; their function appeared to be not so much letting 
the speaker know that he was being understood as to initiate a turn in the 
conversation. The striking occurrences were those where the observers judged 
the situation to be high pull conditions and yet where no responses were 
emitted. And of course 29 responses in 111 minutes (.26 responses /minute) of 
conversational time is a very low rate in comparison with results from the 
previous project conducted here with college students: in a total of ko 
minutes, these subjects produced 538 responses (l3.^5 responses /minute ) . The 
two studies are not directly comparable, because the college-age subjects 
were observed under more controlled conditions, but that difference can 
probably not account for the 50-1 difference in rates. 

In the laboratory observations we have closer comparisons, despite the fact 
that the experimental situation is still being developed. Four subjects 
younger than adolescent, and h adolescent and young adults have been recorded, 
half of each sex in both groups. The rate of response per phonemic sentence 
differs significantly on both the age and sex, with no interaction between 
the two. The fact that large individual differences occur for both groups 
(earlier research on other aspects of conversational behavior led us to ex- 
pect this) did not obscure these group differences. These results must of 
course be regarded as most preliminary. 



304 



Serial No. M-P-P-(C)-li5, Page 3 

Some qualitative observations of the responses of the children are of con- 
siderable interest: (l) many of the responses are very slight (a head 
movement of such small extent that it is visible only on repeated viewings 
of video tape, for example) and seem not to function as communications to 
the speaker; (2) many responses of the yoiinger children are late in compar- 
ison to those of adults, so that they overlap the speaker's next words. 

Scientific Significance to Mental Health Research Program: Finding a 
lajiguage-like response to be learned late (or used late if it is learned 
earlier) opens a number of research and practical possibilities ranging 
from basic research about language learning to educational and diagnostic 
applications. From the standpoint of language learning, the responses seem 
to fimction partly as an offshoot of the person's mastery of the decoding 
process, as has been studied here before. One hypothesis from the first 
results of the present research is that few responses mean meager under- 
standing, and that study of these responses may provide a new research tool 
for problems in language learning — and the acquisition, or reliable use, 
of these responses appears to come at a stage in life far later than that 
which most language-learning research these days is concentrating on. It 
is, in fact, the age when reading is being learned, and some recent theorizing 
relates reading readiness to listening skills. Hence the educational possi- 
bilities in this research. 

The other aspect of the listening response is the more obvious one: it is a 
social response, one which provides the speaker with feedback on his progress 
— the cue to whether he is getting his points across successfully. Seen in 
this light the development of the response corresponds to social development, 
to how well the child is becoming aware of how the other person (the speaker) 
feels about his own progress, or how much the young child is really listening 
to the speaker, as Piaget questioned many years ago. From this standpoint, 
the listener response may have possibilities for the study of social develop- 
ment, and eventually for developmental diagnosis. 

Proposed Course of Project: To pursue the parameters of this finding in 
depth, developing more precise methods for observation. This will require 
cooperative work with schools, since the individual differences are so large 
that many subjects must be used. In addition, new conceptualizations must be 
developed to account for these differences so that they can be examined in 
fvirther studies . 

Honors and Awards : None 

Publications : None 



305 



I 



Serial No. M-P-P-(C)-it6 

1. Laboratory of Psychology 

2. Section on Personality 

3. Bethesda, Maryland 

PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 

Project Title: Stimulus Intensity Modification: Ueurophysiologic and 
Psychoanalytic Relationships. 

Previous Serial Number: None 

Principal Investigator: Stanley I. Greenspan, M.D. 

Other Investigators: Monte Buchshaum, M.D. 

Cooperating Units: Unit on Psychophysiology, Laboratory of Psychology, 
NIMH. 

Man Years 

Total: .68 
Professional: .50 
Other; .18 

Project Description: 

Objectives : 

1) To develop a psychoanalytic model of defense organization based on 
defense patterns established early in life which would provide a psycholo- 
gical parallel to the augmenting vs. reducing average evoked response measure. 

2) To test first the possibility of a relationship between this model 
and the augmenting and reducing measures by using it to make blind predictions 
of the rank order distribution of augmenting and reducing in a small group of 
normal young adults who were previously measured along the augmenting-reducing 
dimens ion . 

3) To refine the model and to develop a replicable scoring system and 
test it on a large sample of young adults. 

3) To do the same for a group of young children. 

Methods Employed: 

Groups of normal volunteers , ages 18-30 , were studied on whom both 
Rorschach and neurophysiological data were already available. The augment- 
ing-reducing average evoked response procedures is described elsewhere 



307 



Serial No. M-P-P-(C)-1|6, Page 2 

(see M-P-P-(C)-36, 19Tl). The Rorschach records were rated according to the 
appearance of predefined defense patterns and from these ratings with rank 
order distribution of augmenting and reducing was predicted. 

Ma,i or Findings : 

Part one of this project has heen accomplished. A model of defense 
organization hypothesizing two defense patterns was developed. One pattern 
was the internalization of stimuli or stimulus deprivation which is related 
to the development ally early defenses incorporation withdrawal and identifi- 
cation of stimuli or stimulus deprivation which is related to the develop- 
mentally early defenses incorporation withdrawal and identification. The 
second defense pattern was the externalization of stimuli or stimulus enrich- 
ment related to the developmentally early defenses projection acting out and 
active avoidance. Rank order predictions of augmenting and reducing were 
made on two groups of eight subjects. The model and scoring procedure was 
refined between the first and second group. The predictions for the second 
group were significant (rho = .97, -.01). This finding supports the pro- 
posed model of defense organization as a parallel to augmenting and reducing. 
It supports the further development of the model and scoring procedures for 
the next steps in the project. 

Scientific Significance to Mental Health Research Programs : 

There are a number of implications from this project. The suggested 
relationship between constructs from two separate disciplines can aid in 
cross-validating each construct and in giving each construct added meaning. 
If our proposal model is correct, the neurophysiologic constructs of augment- 
ing and reducing can be related to both individual and groups of defenses. 
The psychoanalytic meaning of defense mechanism can be expanded to include 
basic neurophysiologic mechanisms. An easily replicable way to measure 
complex psychological processes can be developed. 

In addition, identifying neurophysiologic and concomitant psychological 
differences in homogeneous diagnostic groups would further the development 
of an effective nosology with implications for prevention and treatment. 

Further documentation of the relationship of augmenting and reducing to 
specific psychological mechanisms may provide a model and a technology to 
observe the early predisposition toward specific character styles as well 
as pathologic formations. 

Proposed Course of Project: 

Further development of this model, as mentioned, and a study of its 
implications for models of psychopathology and personality development. 

Honors and Awards : None 

Publications: None 



Serial No. M-F-A-I6 

1. Laboratory of Psychology 

2. Section on Higher Thought 

Processes 

3. Bethesda 



PHS-BBMHA-NIMH 

Individual Project Report 
July 1, 1971 through June 30, 1972 

Project Title: A Study of the Means-end Thought Processes in Hiiman Subjects. 

Previous Serial Number: Same 

Prlnci^l Investigator: ildward A. Jerome 

Other Investigators: None 

Cooperating Units: Technical Development Section, NIMH, Computer Systems 
Laboratory, DCRT 



-Man Years: 




!E6tal:'' 


4.00 


Proifefisioilal: 


1.00 


Other-: - "' 


3.00 



Project Description: ■ • ^ 

Objectives; It is the purpose of this project to investigate the mental 
activities that are responsible for resolving problematic situations that 
occur in the course of the individual's interaction with his environment. 
Problems often resxilt from imperfect knowledge of the operational regular- 
ities' of the escternal systems, and resolution of the difficulty is achieved 
by cdBipetent inquiry into these regularities. In order to be effective, the 
inquiries must be guj.ded or controlled by a set of cognitive principles 
collectively called heuristic processes.' This project has the following 
objectives: to describe the distribution of heuristic capabilities in 
various cross- sections of the population, to discover meajis of facilitating 
the acquisition of heuristic principles, to find ways of improving the 
ability to apply such principles, and to participate in the development of 
a hormative thepry of effective heuristic structures. 

Methods Employed ; Standard tests of mental ability are administered for com- 
parison with performances on a variety of computer- controlled system analysis 
problems developed for this project. A set of ik related classes of prob- 
lems called HEPP has been described in previous reports. Two sets of new 
problems were developed last year for the new SEL 81OB real-time computer 



309 



Serial No. M-P-A-I6, Page 2 

configuration. The new problems ^ called ATSEL and ATREC, monitor improved 
procedures for the selection and reception paradigms of experiments on 
concept formation. All of these programs implement special controls that 
were impossible (prohibitively expensive and/or cumbersome) without the 
support of a high speed process- control computer. 

An investigation designed to evaluate the difficulty of two types 
of means-end thinking is in progress. It is concerned with those numerous 
situations in which uncertainty results from not knowing which subset of a 
given set of factors is relevant to a desired outcome. When the given set 
is known to include all possibly relevant factors, two types of Information 
about any particiilar factor is possible: one implies that the factor is 
relevant, the other implies that it is irrelevant. Sufficient information 
to control outcomes may be a mixture, in various proportions, of these two 
types of implications, i.e., the set of factors implied to be relevant may 
not, in itself, be sufficient, and the set of factors implied. to be 
irrelevant may not, in itself, be sufficient, but the sum of these two 
sets of implications may suffice to yield the desired control. 

The experiment in progress provides data on the relative efficiency 
with which people use information (a) that implies relevance for a sufficient 
set of factors, (b) that implies irrelevance for a sufficient set of factors, 
or (c) that implies the relevance of some factors and the irrelevance of 
others so that the simi of information is just sufficient to support a 
solution. The evaluations will be derived from a factorial design in which 
comparisons will be made within individuals (i.e., each S will serve as his 
own control) . 

Major Findings : 

Acquisition and Interpretation of Information . From an analysis of data 
obtained in an experiment described in last year's report, new perspectives 
on the analysis of data obtained from attribute identification paradigms 
have been formulated. It was foiond advantageous to replace the traditional 
analysis of "total trials (errors, time) to solve" by separate analyses of 
trials that occur before and after the trial on which sufficient infor- 
mation (tSI) for a solution becomes available. Most of the earlier trials 
are necessary to elicit information that has not been disclosed, whereas 
all of the later trials are redundant, but apparently required to assist 
in the process of interpretation. Moreoever, the number of pre-TSI trials 
is largely determined by objective characteristics of the problem space and 
it shows little within- or between- subject variability, whereas post-TSI 
trials, being associated with the difficulty of interpreting information," 
reflect the psychologically interesting components of performance and ac- 
count for most of the within- and between- subject variability. 



310 



Serial No. M-P-A-I6, Page 3 

It is, of course, possible for the processes of acquisition and 
interpretation to function concurrently; in this case the problem is solved 
on the TSI. The present analyses demonstrate — and all prior data suggest — 
that the two processes usually proceed in a serial, or possibly overlapping 
sequence. Some people learn — for a particular problem area, at least — to 
interpret information as it is acquired, but this appears to be a somewhat 
special cognitive skill that other people do not manifest during practice 
sessions that are not arbitrarily long. In any case, it is important to 
study acquisition and interpretation of information as conceptually separable 
processes. 

Attribute Identification System. A computer program that " solves" attribute 
identification problems by heuristics specified in a variety of current 
theories has been developed as sm experimental device for performing suf- 
ficiency tests on any explicit and reasonably concise hypothesis about the 
heuristics used by human subjects in their efforts to solve this type of 
problem. 

Thus far the simple "hypothesis" theory and the "local consistency" 
theory with memories of length 1, 2 and 3j with and without a heuristic 
that concentrates on the more informative type of instance (positive in- 
stances are more informative then negative instances in conjunction problems, 
and the reverse is the case in disjvmction problems) have been implemented. 
A device that is driven by a random mechanism under "local consistency" 
constraints with a memory for two events and a knowledge of the more in- 
formative type of instance does as well as a human subject on all classes 
of problems in a binary valued universe of four dimensions regardless of 
the logical connective that governs the classification rule . Systems with 
progressively fewer constraints on the random driver perform progressively 
less efficiently. 

Although simulators are, of course, important instruments for 
checking and developing theories, their greatest value may be found to 
derive from the care and attention to detail that they force upon their 
designers. The present effort has directed attention to several formal 
characteristics of the traditional attribute Identification paradigm that 
have important technical implications suggesting that a new type of problem, 
having a less constrained uncertainty structure, is needed in the current 
stage of development of this research area. 



h 



311 



Serial No. M-P-A-I6, Page k 

Scientific Significance to the Program of Mental Health Research : On the 
hypothesis that one of the most important determiners of mental health in 
a normal person is his ability to think effectively in the variety of 
puzzling situations that challenge him daily, the primary goal selected for 
this project is the development of theory and the acquisition of data on the 
quality of means-end thinking in the population as a whole and in selected 
sub- samples thereof. More specifically it is directed toward the detection 
of heuristic or thinking deficits and toward the development of methods for 
avoiding or repairing such deficits in otherwise normal people. To acquire 
the understanding necessary to achieve this goal present theory and knowledge 
of the processes that support this mental activity need to be extended by 
intensive research. 

Proposed Course of the Project : Experiments will be developed to evaluate 
the ability of people to discover what kinds of regularity exist in events 
(rule identification), and a study of how this ability can be improved will 
be undertaken. In the direction of training, an effort will be made to 
design a computer implemented version of the WFF 'N PROOF games, which 
purport to be enjoyable lessons in logic. 

The work on simulators will be extended in the direction of discovering 
what kinds of amendments to existing theories seem to be required in order 
to increase their ability to predict problem solving behavior. 

Honors and Awards: None 

Publications: Jerome, E. A., and Young, M. L.: Means-end thinking of 

schizophrenics. Psych . Reports 29: 855-862, I97I. 

Young, M. L.: Age and sex differences in problem solving. 

J. Geront . 26: 330-336, 1971. 



^ 



312 



Serial No. M-P-B-2 

1. Laboratory of Psychology 

2. Section on Neuropsychology 
•? - 3. Bethesda 

PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 

Project Title: Analysis of the relationship between problem-solving behavior 
and certain cortical and subcortical structures in the sub- 
human primate brain. 

Previous Serial Number: Same. 

Principal Investigators: H. Enger Rosvold, Mortimer Mishkin, Patricia 

Goldman 

Other Investigators: Lajos Vereczkei (International Research and Exchanges 
Board, Foreign Exchange Scholar, University Medical 
School, Pecs, Hungary) 
,, , Roger Buddington (NIMH Postdoctoral Fellow) 

Cooperating Units: None 

Man Years: 

i. Total: 5 3/5 
.^Professional: 3 
.- Other: 2 3/5 

Project Description: 

Project : To identify the brain structures that are essential for problem- 
solving behavior. 

Objectives : To determine the neural system or systems serving problem-solving 
behavior as exemplified in delayed-response, discrimination, learning set, 
etc., and to describe the nature of the behavioral deficits which follow 
damage, to the structures comprising these systems. 

Methods : (1) A variety of behavioral tests are used to define the functions 
which are specific to the prefrontal lobes as a whole, or to various of its 
parts. The current emphasis is to analyze the frontal-lobe deficit in terms 
of its participation in spatially directed responses and the utilization of 
interoceptive and exteroceptive cues. (2) Lesions are placed in subcortical 
structures (caudate nucleus, centrum medlanum, medialis dorsalis hypothalamus) 
and the effects compared with those following selective frontal lesions. 



313 



Serial No. M-P-B-2, Page 2 

Major Findings : (1) Earlier work had suggested that the deficit in monkeys 
following dorsolateral prefrontal lesions is due to a disturbance in the 
utilization of response-produced cues elicited by spatial responses in a test. 
To assess this view, monkeys with dorsolateral prefrontal lesions and normal 
controls were trained to run to one side of a T-Maze under two conditions of 
illumination - dimly lit and well lit. When the maze is dimly lit, learning 
the spatial response should rely heavily on response-induced or proprio- 
ceptive cues and frontal monkeys should be impaired. In fact, the results 
did not confirm the prediction. While the data from "critical" trials inter- 
polated between regular training trials indicated that the monkeys did indeed 
learn the task on the basis of proprioception, the frontal monkeys neverthe- 
less performed as well, if not better, than the controls. In the well lit 
condition, by contrast, frontal monkeys were impaired and there was evidence 
to indicate that they attended to and were perhaps confused by the visual- 
spatial cues available in that situation. This study is the first of its 
kind to dissociate between sensory (response-produced or proprioceptive) and 
"gnostic" modes of spatial learning in frontal monkeys and to call into 
question the proprioceptive basis of the frontal disorder. (2) Earlier work 
had demonstrated that those functions which are differentially affected by 
dorsolateral and orbital cortical lesions are also differentially affected by 
lesions in subcortical structures which receive anatomical projections selec- 
tively from the dorsolateral or orbital frontal cortex. One of these sub- 
cortical structures is the medial dorsal thalamic nucleus. It has been a 
long-standing puzzle in neuropsychology that lesions in this nucleus do not 
result in "frontal" deficits despite the intimacy of its anatomical connec- 
tions with the frontal cortex. Nevertheless, since the anatomical relation- 
ships are so compelling, we undertook to investigate this problem again with 
slightly different procedures. The results clearly indicate that lesions in 
this nucleus can result in profound deficits on these tasks. Current efforts 
are being directed toward determining which of the factors introduced into 
the new study is critical in producing these deficits , Another of these sub- 
cortical structures having close anatomical relationships with the prefrontal 
cortex, is the hypothalamus. While many studies have demonstrated similari- 
ties between the frontal cortex and the hypothalamus in the emotional and 
motivational functions which they subserve, none has considered whether or 
not there are also similarities in cognitive functions . Our recent work has 
shown >;hat large lesions involving different divisions of the hypothalamus 
result in a pattern of deficits on cognitive problems which are characteristic 
of damage to the orbital frontal cortex. Smaller, selectively placed lesions, 
though resulting in impairments, did not yield a pattern of deficits unequi- 
vocally characteristic of one or the other of the frontal-lobe systems. 

Scientific Significance to Mental Health : The results of this project have 
revealed that the prefrontal cortex in monkeys is functionally heterogeneous 
with dorsal and ventral areas participating in problem-solving behavior in two 
quite different ways; even within these areas there is evidence of further 
specialization of function. Furthermore, each of these frontal areas appears 
to be but one component of a larger cortical-subcortical system. Specifica- 



314 



Serial No. M-P-B-2, Page 3 

tion of the types of cortical contributions to problem-solving, and delineation 
of the two cortical-subcortical systems, should help to resolve the long- 
standing puzzle regarding the functions of the frontal lobes. 

Proposed Course of Project : No major shift in emphasis is anticipated. 

Honors and Awards: None 

Publications: 

Goldman, P. S., Rosvold, H. E. , Vest, B. and Galkin, T. W. Analysis of the 
delayed-alternation deficit produced by dorsolateral prefrontal lesions in 
the Rhesus monkey. J. Comp. Physiol. Psychol ., 77: 212-220, 1971. 

In Press: 

Rosvold, H. E. The frontal lobe system: cortical-subcortical interrelation- 
ships. Acta Neurobiologiae Experimentalis (In Press). 



315 



Serial No. M-P-B-5 
1. Laboratory of Psychology 
■ - 2 . Section on Neuropsychology 

3. Bethesda 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Neural mechanisms in vision. 

Previous Serial Number: Same 

Principal Investigator: Mortimer Mishkin 

Other Investigators: Lillian Blake (Consultant Part-time) 
Charlene Jarvis (NIMH Staff Fellow) 

Jean Delacour (NIMH Guest Worker from College de France, 
Paris) 

Cooperating Units: Charles Gross, Princeton University, Cambridge 
Frederick J. Manning, WRAIR, Washington, D. C. 
Marvin Sr5"'^=er (NEI, Research Psychology) 

Man Years: 
Total: 4 3/5 
Professional: 1 3/5 
' Other: 3 , 

Project Description: 

Project : Behavioral, anatomical, and electrophysiological analysis of neural 
mechanisms in vision. 

Objectives : To define the role in vision of neural structures outside the 
primary visual projection system. 

Methods: (1) Monkeys are prepared at NIMH with various lesions to the visual 
system, and they are then studied electrophysiologically at Princeton Univer- 
sity by Gross and his colleagues to determine whether or not the receptive 
field properties of inferotemporal units have been altered in a manner pre- 
dicted by our theory of cortico-cortical transmission. (2) Monkeys are 
trained before and after tectal or pulvinar lesions on a spatial or a diffi- 
cult non-spatial visual discrimination task as a step toward determining 
whether the tecto - pulvinar - extrastriate cortical projection might be 
concerned with spatial as opposed to object or pattern vision. (3) Monkeys 
are trained after various lesions of the limbic system on visual associative 
learning tasks as a step toward determining whether direct interaction between 
the visual and limbic systems might be the mechanism whereby visual stimuli 
gain emotional/motivational significance for the animal. 



317 



Serial No. M-P-B-5, Page 2 

Major Findings : (1) In accord with predictions, left striate cortex ablation 
restricts the receptive zones of inf erotemporal units in both hemispheres to 
the left visual field, while forebrain commisurotomy limits the receptive 
zones of inf erotemporal units to the visual field contralateral to the 
hemisphere being recorded from (i.e., the left field for right inf erotemporal 
units, and the right field for left). Pulvinar lesions do not eliminate 
any visual inputs. (2) Tectal lesions impair performance on visual spatial 
but not on nonspatial discriminations, supporting the conception that the 
"second" visual system is concerned with spatial rather than object vision. 
(3) Both orbital frontal and temporal pole plus amygdala lesions (but not 
hlppocampal lesions) impaired object reversal learning, suggesting that 
anatomical interconnections between the visual system and these two parts of 
the limbic system may indeed participate critically in the formation of 
stimulus-reward associations. 

Scientific Significance to Mental 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 
stimulus reception at the cortex and the observed response. The demonstration 
that damage to the inferior convexity of the temporal lobes in monkeys produces 
impairment in visually-guided behavior has opened up the hitherto inaccessible 
area of the intracerebral processes in vision, i.e., neural activity related 
to vision hut beyond the level of the striate cortex. Unravelling these 
mechanisms in vision should 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 : (1) Monkeys with bimacular striate and prestriate 
lesions are currently being added to the electrophysiological study in order 
to test the theoretical neural model in greater detail. (2) Animals are 
being trained on the visual spatial tasks preliminary to electrocoagulation of 
the pulvinar. (3) Animals with temporal pole plus amygdala lesions and animals 
with anterior inf erotemporal lesions will be compared on associative learning 
and on visual memory tasks . 

Honors and Awards: None 

Publications : 

Mishkin, M. Cortical visual areas and their interactions. In A. G. Karczmar 
& J. C. Eccles (eds) : The Brain and Human Behavior , Springer-Verlag, 1972, 
pp. 187-208. 

Snyder, M. The evolution of mammalian visual mechanisms. In R. Jung (ed) : 
A Handbook of Sensory Physiology , Springer-Verlag. In Press. 



318 



Serial No. M-P-B-5, Page 3 

Jones, B. and Mishkin, M. Limbic lesions and the problem of stimulus-rein- 
forcement associations. Experimental Neurology . In Press. 



319 



Serial No. M-P-B-7 

1. Laboratory of Psychology 

2 . Section on Neuropsychology 

3. Bethesda 

PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 

Project Title: Histological analysis of cerebral lesions and Intracerebral 
connections in primates . 

Previous Serial Number: Same 

Principal Investigator: H. E. Rosvold, M. Mishkin, Patricia S. Goldman 

Other Investigators: T. N. Johnson (Consultant Part-time) 

Marvin Snyder (NEI Research Psychologist) 

Cooperating Units: None 

Man Years: 
Total: 2 2/5 
Professional: 4/5 
Other: 2 2/5 

Project Description: 

Project : Verification of lesions in chronic experimental animals, and 
analysis of intracerebral connections in acute preparations . 

Objectives : The objective of the first part of this project is to delineate 
the loci of the lesions which produce specific behavioral effects, and of 
the second, to determine whether or not loci yielding similar effects are 
anatomically interconnected. 

Methods : When the behavioral testing of chronic experimental animals is 
completed, their brains are embedded in either celloidin (large specimens) 
or paraffin (smaller specimens), sectioned, stained for cells and fibers, 
examined microscopically, and the lesions reconstructed. In the second 
part of the project, animals are prepared with selective lesions purely 
for anatomical investigation. The animals are sacrificed within a few days 
after surgery and their brains examined microscopically to determine the 
locus, extent and course of degenerating fibers. Special staining procedures 
and fiber-size determinations are used to study stage of myelinization. 

Major Findings : Specimens completely processed and examined include 70 monkey 
brains. This material has been examined for the purpose of verifying the 
loci of the cortical and subcortical lesions in animals used for behavioral 
studies. Twenty others have been studied to determine intracerebral 



321 



Serial No. M-P-B-7, Page 2 

interconnections . 

In previous studies it had been demonstrated that there is a topographic 
projection of fibers from various parts of the prefrontal cortex to the head 
of the caudate nucleus and putamen. We have now completed a study demon- 
strating that this topographic arrangement is maintained in the efferent 
projections of the caudate to the globus pallidus, fibers from the dorso- 
lateral caudate taking a lateral position in the pallidum, and fibers from 
the ventrolateral caudate taking a medial position in the pallidum. Current 
work is intended to show that, in turn, the efferents from the lateral palli- 
dum and from the medial pallidum are dissociable, each taking separate 
trajectories into the thalamus and subthalamus. Another study concerned with 
the connections between frontal cortex and caudate nucleus deals with the 
question of when in ontogeny these connections are established. So far, 
infant animals at various stages of development have been prepared with 
lesions in different parts of the cortex and their brains have been processed 
for study of degenerating fibers. 

lu an anatomical study concerned with interrelationships in the visual 
system, lesions were placed in the superior colliculus of monkeys to deter- 
mine whether the secondary visual pathway present in the rat, cat, tree 
shrew, and squirrel is also present in higher primates. Utilizing both the 
Fink-Heimer and Voneida silver-impregnation techniques we have demonstrated 
that the superior colliculus sends a heavy projection to the inferior 
portion of the pulvinar, a connection which appears to be homologous to that 
reported in non-primate animals. In addition the colliculus sends a rela- 
tively heavy projection to the nucleus centralis lateralis. Animals have 
now been prepared with lesions placed either superficially or deep in the 
superior colliculus to determine if these two pathways can be dissociated. 
Preliminary results from another study indicate that the pretectim, also 
involved in vision, projects to the parietal cortex through the lateral 
posterior nucleus, suggesting still another visual pathway. 

Scientific Significance to Mental Health Research : Sufficient evidence has 
been accumulated in behavioral studies with brain damaged animals to suggest 
that widely separated cell aggregates in cortex and subcortex may be combined 
into a complex system; and it is the functioning of such neural systems, rather 
than the functioning of the particular elements of which they are composed, 
that seems most directly relevant to an understanding of the organization 
and disorganization of behavior. The significance of this project lies in 
the fact that it can provide detailed information on the composition of these 
neural systems; systems which through electric and chemical manipulation 
have been related to mental health and disease. 

Proposed Course of Project : The studies involving localization of function, 
anatomical substrate of the frontal systems, and anatomical substrate of the 
visual systems will continue. Their will be an increased emphasis on the 



322 



Serial No. M-P-B-7, Page 3 

ontogeny of the development of the connections in the frontal system and, 
as well, the anatomical basis of the potential for cerebral reorganization 
in the infant brain. Electronmicroscopic and autoradiographic techniques 
as well as traditional techniques will be used for this purpose. 

Honors and Awards: None 

Publications : 

Johnson, T. N. , and Rosvold, H. E.: Topographic projections on the globus 
pallidus and the substantia nigra of selectively placed lesions in the 
precommissural caudate nucleus and putamen in the monkey. Experimental 
Neurology , 33: 584-596, 1971 



323 



Serial No. M-P-B-14 

1. Laboratory of Psychology 

2. Section on Neuropsychology 

3. Bethesda 

PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 

Project title: The neural regulation of appetitive behavior. 

Previous Serial Number: Same 

Principal Investigator: H. Enger Rosvold 

Other Investigator: Douglas Bowden (University of Washington, Seattle) 

Cooperating Units: None 

Man Years: 

Total: of NIMH; only of other investigator 
Professional: 
Other: 

Project Description: 

Project : To identify the brain structures which are involved in food-oriented 
social behavior. 

Objectives : The objective is first to identify structures in the brain which 
are related to food and water oriented behavior, then to obtain an under- 
standing of how food regulating mechanisms in the brain function. 

Methods : The brain is first explored with roving electrodes for sites which 
regulate drinking behavior when stimulated while the animal is restrained. 
When such structures are located, the effect of stimulation in these areas 
was examined with respect to various degrees of thirst motivation and the 
reliability of the effects over length of time of stimulation. Four monkeys 
were implanted with a total of 80 chronic electrodes in brain areas where 
electrical stimulation elicits drinking. All of the histological analysis has 
been completed and the behavioral data has been analyzed. The material is now 
being prepared for publication. 

Major Findings : The effect of stimulation in areas which elicit drinking was 
examined with respect to the various degrees of thirst motivation and the 
reliability of the effects over length of time of stimulation. It was found 
that some animals drink to brain stimulation, others do not, even though the 
same brain areas are stimulated. In those animals that drink to stimulation, 
the volume of the brain system mediating the response increased during the 
six weeks of stimulation for drinking points; i.e., a greater proportion of 
sites gave rise to the response as the exploration for sites proceeded. In 

325 



Serial No. M-P-B-14, Page 2 

non-drinkers, the anatomical system from which drinking could be elicited 
became smaller. Within animals, the relationship between self-stimulation 
and drinking elicited from selected points was consistent from point-to-point, 
but the kind of relationship differed for the two animals which were studied 
in this regard. The interpretation being placed on these data is that activi- 
ty in at least some cells of the hypothalamus motivates behavior only in a 
general sense until physiological and/or environmental conditions are such as 
to shape specific behavior patterns. Furthermore, these cells can be com- 
mitted to other functions should the conditions change. 

Scientific Significance to Mental Health Research : Understanding the motiva- 
tion of behavior is fundamental to an understanding of both normal and ab- 
normal behavior. It is anticipated that this study will contribute to an 
understanding of the brain's participation in motivation. 

Proposed Course of Project : Project will terminate with publication of re- 
sults. No further research on this project is possible due to reduction in 
staff. 

Honors and Awards: None 

Publications: None 



326 



Serial No. M-P-B-16 

1. Laboratory of Psychology 

2. Section on Neuropsychology 

3. Bethesda 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Cerebral mechanisms underlying functional plasticity in the 
developing organism. 

Previous Serial No.: Part of M-P-B-2 

Principal Investigator: Patricia S. Goldman 

Other Investigators: H. Enger Rosvpld 

Epp Milder (NIMH Postdoctoral Fellow) 

Cooperating Units : None _, . 

Man Years: . 

Total: 4 2/5 ' 

Professional: 1 4/5 
Other: 2 3/5 

Project Description: 

Project : To determine the cerebral mechanisms underlying functional plasti- 
city in the developing organism. 

Objectives : Behavioral deficits following cortical injury are commonly less 
severe the earlier in life the injury is sustained. The major purpose of 
this research is to understand the mechanisms by which recovery is accom- 
plished following brain damage in infancy and to determine whether or not 
similar mechanisms could be enhanced or induced when such damage is sustained 
later in life 

Methods : The studies involve the comparison of identical lesions in infants 
and juveniles. The infants are usually operated when they are 2-months of 
age; the juveniles between 11/2 and 2 years old. Both groups are allowed 
a 10-month postoperative recovery. Thus, the infants are 1-year of age and 
the juveniles 28-34 months old when formal testing of their cognitive 
abilities is begun. Unoperated monkeys of the same ages (that have also 
resided in the laboratory for ten preceding months) are tested as well. The 
studies have involved the following lesions: prefrontal lobectomies; dorso- 
lateral prefrontal and orbital prefrontal resections; caudate nucleus 
lesions; combined prefrontal lobectomies and caudate lesions; and ablation 
of the dorsomedial nucleus of the thalamus. The behavioral tests utilized 



327 



Serial No. M-P-B-16, Page 2 

are designed to measure specific and dissociable functions of the prefrontal 
cortex. The same tests are given in the same order to infants and juveniles 
alike. Upon completion of the testing, which may require a year or longer, 
the monkeys are sacrificed and their brains processed for histological 
examination. 

Major Findings ; (1) Recovery of function is not an immutable consequence of 
early brain damage as the literature would imply. Lesions of the orbital 
cortex in infants, unlike those in other regions of the cortical mantle, 
produce impairments in behavior comparable to those produced by identical 
lesions in adults. (2) These impairments are equally severe whether the 
lesions are induced at 3 days, 1 week, 4 weeks, 8 weeks, or 130 weeks of age. 
(3) The capacity for recovery is directly related to the age of the animal 
at surgery but the relationship is almost the opposite of what might be ex- 
pected. It might be supposed that the less mature the cortical area is when 
damaged, the greater the chance of recovery. Actually, if a lesion is made 
in an area such as the orbital cortex that develops early in ontogeny, there 
will ultimately be greater recovery than if a lesion is made in the dorso- 
lateral cortex which develops later in ontogeny. We have proposed a theo- 
retical frame work for interpreting these somewhat paradoxical phenomena, 
stressing the relative maturity of functionally related areas which are 
spared by the early injury. (4) Both the expression of deficits attributable 
to early brain damage as well as compensatory readjustments to such injury 
may be delayed until the brain approaches full maturity. Thus, monkeys given 
dorsolateral lesions in infancy appear to behave as well as normal controls 
at early stages in development but later in ontogeny there emerges a picture 
of retarded development. In the case of monkeys given orbital lesions in 
infancy, the adultlike deficits which are evident when testing is conducted 
in the first year and a half of life, tend to disappear when the monkeys 
reach two years of age. (5) Recovery mechanisms are not necessarily reci- 
procal. Our evidence suggests that the dorsolateral cortex may compensate 
for the loss of orbital cortex since monkeys given orbital lesions as infants 
recover at about the time the dorsolateral cortex approaches functional 
maturity. Monkeys given dorsolateral lesions, on the other hand, do not 
recover despite the integrity of the orbital cortex. (6) Subcortical functions 
may be more vulnerable to early injury than are cortical mechanisms. Lesions 
of the caudate nucleus and the dorsomedial nucleus of the thalamus in infants 
result in severe impairments irrespective of age at surgery. (7) Monkeys 
given caudate lesions as infants are impaired on just those tasks and at just 
those ages that the monkeys with dorsolateral lesions are not. This finding 
suggests that in the course of normal development, subcortical structures 
may be primarily responsible for mediating many of the functions that the 
cortex will ultimately assume. 

Scientific Significance to Mental Health Research : By understanding mechanisms 
for recovery of function following neonatal injury, we may be in a better 
position to correct errors of normal development as well as approach the 
problem of recovery in the adult-brain injured. 



328 



Serial No. M-P-B-16, Page 3 

Proposed Course of Project ; So far our studies have been neuropsychological 
in emphasis. Many questions remain concerning the behavioral effects of 
early lesions within the frontal-lobe system and our current efforts are 
designed to confront these questions in neurobehavioral terms . At the same 
time, our accumulated knowledge about the functions of the frontal lobes 
justifies directing our efforts to another level of analysis, namely the 
neuroanatomical. Two types of neuroanatomical questions arise within the 
context of developmental research. The first has to do with the normal 
development of the nervous system. We are seeking to determine when in 
ontogeny the dorsolateral cortex establishes connections with the caudate 
nucleus. Monkeys will receive selective cortical lesions at various stages 
of developm.ent and silver impregnation techniques will be used to determine 
the status of cortical-subcortical pathways . The information from such 
studies will be valuable in their own right since little is known about the 
structural development of the nervous system but they will also bear directly 
on the theoretical analysis of our behavioral findings. The second major 
question which we wish to approach anatomically concerns the presumptive re- 
organization of the nervous system upon early injury. To this end, monkeys 
who have been given orbital prefrontal lesions as infants, for example, will 
be allowed to mature and behavioral data will be collected at maturity to in- 
sure that functional recovery has been realized. At this time, unilateral 
cortical lesions will be placed in the area suspected of mediating the re- 
covery and silver impregnation techniques will be used to determine if there 
has been any alteration or elaboration of normally existing pathways which 
could mediate the behavioral recovery. Ultimately we would like to combine 
the neuroanatomical, behavioral, and neurochemical approaches to obtain as 
complete a picture as possible of the normal development of the brain and its 
decreasing potential for plasticity with age. 

Honors and Awards: None 

Publications: 

Bowden, D. M. , Goldman, Patricia S., Rosvold, H. E. and Greenstreet, R. L. 
Free behavior of Rhesus monkeys following lesions of the dorsolateral and 
orbital prefrontal cortex in infancy. Experimental Brain Research , 12: 
265-274, (1971). 

Goldman, Patricia S. Functional development of the prefrontal cortex in early 
life and the problem of neuronal plasticity. Experimental Neurology , 32: 
366-387, (1971). 

Goldman, Patricia S. Developmental determinants of cortical plasticity. Acta 
Neurobiologiae Experimentalis (In Press). 



329 



Serial No. M-P-B-16, Page 4 

Goldman, Patricia S. and Rosvold, H. E. The effects of selective caudate 
lesions in infant and juvenile Rhesus monkeys. Brain Research . (In Press), 



330 



Serial Wo. M-P-L-5 

1. Laboratory of Psychology 

2. Section on Perception 

3. Bathe sda 



PHS-HSMHA-imffl 

Individual Project Report 

July 1, 1971 through June 30, 1972 

Project Title: Individual Differences in Normal Perceptual Processes 

Previous Serial Number: Same 

Principal Investigator: V. R. Carlson 

Other Investigators: Harry Blum, Francine Frome 

Cooperating Units: DCRT; University of Maryland 

Man Years 

Total: 

Professional: 
Others : 

Project Description: 

Objectives : (l) To obtain normal control data for standardizing procedures 
and apparatus in the measurement of perceptual variables , and to obtain 
comparison data for evaluating the effects of abnormal and other special 
conditions. (2) To develop a general specification of perceptual response 
in terms of the parameters of the immediate stimulus-situation, past 
experience, generalized perceptual- cognitive attitudes, and the subject's 
motivational reaction to the situation. 

A general difficulty hampering the investigation of form perception has 
been the lack of a psychologically adequate method for specifying form. 
Concepts based on the Euclidean geometry of contours have so fax not resulted 
in a coherent set of parameters in terms of which perceptual responses to 
shapes and patterns can be ordered. A biologically-oriented geometry of 
form has recently been developed by Harry Blum, DCRT, -which provides a more 
efficient set of principles for generating the kinds of shapes occurring in 
the natural environments of organisms. The initial objective of the present 
research was to see whether differential response could be demonstrated to 
variation in a parameter, the symmetric axis, postulated to be a primary 
aspect of form generation. 

Methods Employed : It is well-established that the perception of the 
orientation of oblique lines is less accurate than the perception of 
horizontal and vertical lines. Accuracy is also dependent upon line 



k 



331 



Serial No. M-P-L-5, Page 2 

length. Subjects judged the orientations of a series of ellipses with 
varying lengths of major diameter, focal axis, and symmetric axis. The 
relationship between length and orientation accuracy was determined for 
each of these parameters. 

Major Findings : Judged orientation of the ellipses followed a function 
similar to that for straight lines, and the precision of perceived 
orientation was significantly related to the length of the symmetric axis 
but not to the lengths of the conventional geometrical properties of the 
ellipse, major diameter and focal axis. The theoretical Implication is 
that the perceptual information presented by the ellipse is contained in 
the symmetric axis. 

Scientific Significance to Mental Health Research Program : The geometry 
tested may prove to be an invaluable tool in dealing with biological shape 
and growth processes in general. The present test indicates that it may 
have important specific application to developmental and physiological 
processes underlying visual perception. 

Proposed Course of Project : The present experiment was a preliminary test 
in one particular area. Tests in other aspects of form perception are 
planned. If these indicate that the principles involved have sufficient 
generality, application to development ally related problems will be explored. 

Honors and Awards : Appointment to Board of Editors, Perception & 
Psychophysics . 

Publications: None 




332 



Serial No. M-P-L-7 

1. Laboratory of Psychology 

2. Section on Perception 

3. Bethesda ■ 



PHS-HSMHA-m]y[H 

Individual Project Report 

July 1, 1971 through June 30, 1972 



Project Title: Perceptual Adaptation 

Previous Serial Number: Same 

Principal Investigator: V. R. Carlson 

Other Investigators: Irwin Feinherg, Eugene Tassone 

Cooperating Units: VA Hospital, S^ Francisco 

Man Years • ■ ■^ . 

Total: 

Professional: 

Others: 

Project Description: 

Objectives : To investigate,, the characteristics of perceptual adaptation,. -.. 
both when the adaptation occurs in a single limited period of persistent 
stimulation and when it is cumulative in a series of stimulations over 
relatively long periods of time. 

A basic problem in the investigation of perceptual adaptation is the 
role of the perception of time itself, whether changes in time sense are a 
cause or an effect of adaptational change. The predominant view is that the 
subjective rate of the passage of time is dependent upon the events and 
factors determining the state of the organism at any given time. Changes in 
such factors as body temperature, metabolic rate, and neural activity of the 
brain associated with the circadian cycle have figured most prominently in 
theories of the basis of the time sense. The eAridence upon which the apparent 
lability of time perception rests, however, has depended upon time judgments 
which may be affected by motivational, emotional, and attitudinal factors 
whether or not the fundamental ability to discriminate time is also affected. 
We have sought to develop a method of measurement less susceptible to the 
influence of extraneous factors and to apply this method to conditions 
purported to produce changes in time perception. 

Methods Employed : The essential difference between the method and 
conventional methods is that we obtain a measure of the slopes of the 
response x time functions generated by three different procedures and 
determine whether variations in these slopes are mutually consistent among 

333 



Serial BTo. M-P-L-7, Page 2 

the procedures. Data to date have heen obtained -under conditions of extended 
repeated testing over periods of waking activity and over periods of normal 
nighttime sleep during which EEG activity was continuously monitored. 

Major Findings : Unlike the inconsistencies generally found with conventional 
measures, changes in the slopes of the response functions were highly 
consistent for the different procedures and indicate a moderate slowing in 
the subjective rate of the passage of time at reduced levels of arousal. 
Interpretation in terms of variation in the rates of body processes is not 
justified, however, because a similar slowing occurred over periods of 
testing during normal waking activity. The effect appears rather to be in 
the nature of an habituative or adaptational shift with repeated exposure 
to constant external stimulus conditions. 

Scientific Significance to Mental Health Research Program : Abnormal behavior 
is often accompanied by disorientation with respect to time, and even normally 
one may be disoriented for awhile when aroused out of deep sleep. A 
perplexing question is whether such disorientation depends upon a disordered 
capacity to discriminate time or whether aberrant time judgments are the 
result of generally confused thought processes. The present research 
indicates that the perception of time is a stable psychological capacity 
in spite of gross variations in physiological activity and state of arousal. 
If time perception is involved in a behavior disorder, however, it may well 
be as a basic causal factor rather than as a symptomatic aspect of the 
disorder. 

Proposed Course of Project : An evaluation of the effect of more purely 
psychological alterations on time perception is planned utilizing THC 
intoxication as a means of altering psychological state. 

Honors and Awards: None 

Publications: None 



33^ 



Serial No. M-P-L-9 

1. Laboratory of Psychology 

2. Section on Perception 

3. Bethesda 



PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through June 30, 1972 



Project Title: Discriminative and Conceptual Behavior in Preschool Children 

Previous Serial Number: Same 

Principal Investigator: Albert J. Caron 

Other Investigators: None 

Cooperating Units: Private and Cooperative Nursery Schools in Montgomery 
County and the District of Columbia 

Man Years: None 

This project was temporarily suspended and is being held in abeyance 

Honors and Awards: None 
Publications: None 




335 



Serial Wo. M-P-L-10 

1. Laboratory of Psychology 

2. Section on Perception 

3. Bethesda 



PHS-HSMHA-KIMH 

Individual Project Report 

Jioly 1, 1971 through June 30, 1972 



Project Title: Discriminative and Conceptual Behavior in Infancy 

Previous Serial Number: Same 

Principal Investigator: Albert J. Caron 

Other Investigators: Rose F. Caron 

Cooperating Unit: Eye Research Foundation 

Man Years: 



Total: 


1.50 


Professional: 


1.00 


Others 


.50 



Project Description: 

Objectives : To assess the perceptual- cognitive capacities of human infants 
during the first year of life and to investigate the antecedent environmental 
conditions promoting early perceptual and intellective development. 

Study I : The specific aim of a study just completed was to determine 
which features (eyes, nose/mouth, contour) predominate in the four-month-old's 
perception of the human face and to what extent these are seen as isolated 
elements or as structured configurations. 

Methods Employed : Fixation time to a regular schematic face was compared for 
sixteen groups of infants (7 boys and 7 girls per group) following prolonged 
exposure to a distorted version of the schematic face, under the assumption 
that the greater the perceived difference between the regular face and the 
previously exposed distortion, the longer the looking time to the former. 
The groups differed only in terms of the facial distortion presented for 
prior exposure. The distortions were applied independently to four facial 
areas — eyes, nose/mouth, contour, and all features combined — and were of four 
general types: (a) elimination of feature, (b) scrambling, (c) positional 
displacement, and (d) orientation change. A control group was given prior 
exposure to the regular face. 

Major Findings : The data are now being analyzed but preliminary indications 
are that in the four-month-old's perception of the human face (l) the eyes are 

337 



Serial No. M-P-L-10, Pa^e 2 

more salient than the nose/mouth, (2) the orientation of the contour is more 
critical than the orientation of the features, and (3) the horizontal 
arrangement of the eyes is more important than their precise orientation. 

Study II: The purpose of a study now in progress is to determine whether 
the three-month-old has already achieved perceptual object constancy, i.e., 
whether objects retain their identity despite shifts in perspective. 

Methods Employed : A number of three-month-old infants are being given 
discriminative operant training to the point where they will emit responses 
(l8° head-turns to the left or right) in the presence of a rectangle and not 
emit responses in the presence of a trapezoid. Following conditioning, the 
infants will be shown, together with the original stimuli, two critical test 
stimuli: (l) a backward tilted rectangle (which projects retinally as a 
trapezoid) and a forward tilted trapezoid (which projects retinally as a 
rectangle) . The extent of responding in the presence of these stimuli will 
provide an indication of whether the infant perceives retinally or objectively, 
and hence whether he has learned to use visual distance cues such as binocular 
parallax and motion parallax to preserve object constancy. 

Major Findings : This study actually involves two phases: (l) bringing yovmg 
infants under precise discriminative control (not yet successfully accomplished 
in any infant laboratory) and (2) testing for generalization to the critical 
transfer stimuli. The first phase has involved a number of knotty technical 
problems such as (a) putting together an optimal reinforcement package to 
prevent satiation and loss of interest prior to the establishment of 
discriminative control, (b) preventing infants from becoming emotionally 
upset during extinction periods, (c) insuring attention to the discriminative 
stimuli, and (d) establishing precise control by the form dimension. During 
the past year we have successfu ll y negotiated the first two of these problems 
and are currently on the threshold of solving the third and fourth. We expect 
within the next two months to bring a number of infants under rectangle- 
trapezoid control, which in itself will constitute a contribution to the 
infant experimental literature. Once this is achieved we should be able to 
answer our primary question concerning object constancy. 

Study III : The purpose of a third study for which equipment is now under 
construction is to determine whether differential responding and/or differen- 
tial consequences are necessary for infants to learn to discriminate between 
stimuli (or whether they can learn by simple exposure to the stimuli and 
without the occurrence of correlated consequences) . 

Methods Employed : Groups of infants will receive different types of 
discriminative training over a four week period in the home. One group will 
be required to make differential responses (e.g., head turn vs. no head turn) 
to two stimuli (e.g., circle and triangle) which in turn lead, to differential 
rewards (visual and auditory events vs. no consequence). A second group will 
not be required to emit differential responses but will receive visual and 
auditory events in the presence of the circle and no such event in the presence 

338 



Serial No. M-P-L-10, Page 3 

of the triangle. A third group (a simple exposure group) will not he 
required to emit differential responses nor will it experience differential 
consequences in the presence of the circle and triangle. Appropriate control 
groups to assess the independent contributions of responding, reinforcement, 
and operant training will be employed. Apparatus is currently being 
constructed which will allow for automatic presentation and recording of 
these various types of contingencies. 

Major Findings ; There are no findings at this time. 

Scientific Significance to Mental Health Research Program : The three studies, 
taken together, will give us some insight into the yoiing infant's perceptual 
capabilities and, what is more important, into the environmental arrangements 
which helped foster these attainments. Once we have learned how the environ- 
ment impresses itself on the maturing organism to produce a stable perceptual 
world, then we are in a position to manipulate the sensory input to infants 
to promote optimal perceptual and intellective development. 

Proposed Course of Project : This project is an indefinitely continuing one 
in pursuance of the general objectives stated above. 

Honors and Awards: Elected Fellow, American Psychological Association (Div. 7). 

Publicatioias: 

Caron, R. F., Caron, A. J., and Caldwell, R. : Satiation of visual 
reinforcement in young infants. Developmental Psychology , _5(2): 
279-289, 1971. 



339 



Serial No. M-P-L-12 

1. Laboratory of Psychology 

2. Section on Perception 

3 . Bethesda 

PHS-HSMHA-NIMH 

Individual Project Report 

July 1, 1971 through Juae 30, 1972 

Project Title: Cortical Mechanisms in Somesthesis 

Previous Serial Number: M-P-B-12 

Principal Investigator: Josephine Serames 

Other Investigators: Mary Randolph (NIMH Special Fellow) 

Louis Porter (NIMH Predoctoral Fellow) 

Cooperating Units: None 

Man Years 

Total: k 

Professional: 2 

Other : 2 

Project Description: 

Objectives : The general aim is to identify in monkeys the neural mechanisms 
crucially concerned in various forms of somesthetic perception. Our recent 
experimentation has focus sed on the sensorimotor cortex contralateral to the 
hand trained on a series of manual discrimination tasks. The immediate pur- 
pose is to define more precisely the contributions made by the various sub- 
divisions of this general region. Behavioral tests are needed in order to 
confirm or deny hypotheses derived from electrophysiological and anatomical 
studies concerning the functional organization of the region and its relation 
to other parts of the cortex. 

Methods: Rhesus monkeys are trained to make somesthetic discriminations in 
a situation requiring them to reach with one hand into an opaque box and 
select one of two stimulus objects, indicating his choice by pulling it 
toward him. Discrimination tasks involving consistency, shape, size, rough- 
ness, and temperature have been employed, and for the last three, repeated 
determinations of thresholds are made. In these tasks, the monkey subject 
has to discover the differential cue by active palpation. A passive testing 
situation has also been used: the monkey is restrained in an opaque box with 
the hand to be tested extending through an aperture and held flat on a plat- 
form by straps. An instrumental response, pushing open a hinged door when 
the animal detects the positive stimulus, is performed with the free hand. 
The threshold of sensitivity to light touch, as determined by a series of 
graded nylon filaments , is determined in this manner . 



3iH 



Serial No. M-P-L-12 p. 2. 

Ablations of cortical areas are made by aspiration of grey matter, with 
aseptic technique and barbiturate anesthesia. The postoperative recovery 
period is usually four weeks, after which training or retraining is begun. 
Following completion of the behavioral observations and the formal diserimin- 
ination tests, the monkeys are given a lethal dose of barbiturate, and their 
brains are prepared for histological examination. The actual limits of the 
cortical lesion and the consequent thalamic degeneration are then determined. 
Special attention is given -to unintended sparing of tissue within the limits 
of the planned ablation and to unintended damage outside these limits . 

Major Findings : Previous research in this unit has established that either 
anterior or posterior lesions of the precentral gyrus (the classical motor 
cortex) have no adverse effects whatever on performance of any of the soma- 
tosensory discrimination tasks, despite a substantial projection to this 
gyrus from the main thalamic somatosensory nucleus (ventralis posterolatera- 
lis). In contrast to these negative findings, lesions of the immediately 
adjacent postcentral gyrus (the classical somatosensory cortex), which also 
receives input from this nucleus, produce marked decrements in performance, 
an effect which was much more severe in our experiments than in those reported 
in the literature. The anterior postcentral lesion we made was followed by 
severe deficit on all tests, which amounted in many instances to complete 
inability to learn to discriminate grossly different stimulus objects. The 
posterior postcentral removal produced a selective deficit on difficult 
shape discriminations. These two impairments (the general after the anterior,- 
and the selective after the posterior postcentral lesion) provided the 
starting-point for investigations designed to discover the most important 
parts of the original lesions in the production of the deficits, and to 
illuminate the nature of each of them. 

With respect to the anterior postcentral lesion, we have found that the 
part in the posterior bank of the central sulcus is far more crucial than 
the part on the crown of the gyrus. Since it has been discovered by others 
that the more crucial area is characterized by slowly-adapting neurons repre- 
senting the entire hand, whereas the less crucial one is characterized by 
quickly-adapting units likewise representing the entire hand, our behavioral 
findings provide an important tie-in to electrophysiological data. Turning 
now to the nature of the deficit, we have found that monkeys, following the 
anterior postcentral lesion, either retain or quickly recover normal sensi- 
tivity to simple punctate tactile stimuli, thus showing that their severe 
deficits on other tasks cannot be ascribed to cutaneous hypesthesia. This 
finding led us to look more closely at our testing procedures that had 
revealed the deficits. We investigated the possible ameliorative effects 
of intensive preoperative training on all tasks, or of a postoperative re- 
covery period of six months (the latter in order to allow the ataxia commonly 
found after postcentral removals ample time to disappear). Neither of these 
procedural modifications proved to ameliorate the deficit, however. Thus, 
although we have ruled out certain hypotheses as to the nature of the anterior 
postcentral deficit, we have yet to establish in positive terms how it 
should be interpreted. 



3^2 



Serial No. M-P-L-12 p. 3- 

With respect to the posterior postcentral lesions, we have \mdertaken 
analogous experiments with the aims of more precisely localizing the subarea 
responsible for the deficit and of exploring further the nature of the 
selective impairment in difficult shape discriminations. The former objec- 
tive is being pursued by comparing the effects of lesions of the posterior 
crown of the postcentral gyrus with those of the anterior bank of the intra- 
parietal sulcus, since both these subareas were included in the original 
lesion. As to the second objective, we have already shown that animals with 
this lesion, like those with the more anterior removal, exhibit normal sensi- 
tivity to simple light tactile stimuli. Procedural modifications such as 
those described above will also be tried in order to see if the severity of 
the deficit can be influenced by these means. A further question of interest 
is how the postcentral deficit is shape discrimination compares in severity 
and quality with that described by others as following lesions of the parietal 
"association" area behind the postcentral gyrus. 

A kind of somesthetic discrimination not previously studied in this 
laboratory, namely, temperature, is being explored by Mr. Porter for his 
doctoral dissertation. A new way of teaching monkey to discriminate tempera- 
tures, which results in far more rapid learning than do the procedures pre- 
viously employed by other investigators, has been worked out. The major 
finding of Mr. Porter's experiment is that manual temperature discrimination, 
like simple touch, is extremely resistant to disturbance by cortical lesions, 
even those which include the entire somatosensory cortex of both hemispheres. 
It is true that learning times may be prolonged, both with regard to gross 
and to fine temperature discriminations, but eventually all animals are able 
to respond consistently and appropriately to differences of 2° C or less. 
With regard to the most important part of the somatosensory cortex for such 
discrimination, he has shown that bilateral destruction of the postcentral 
gyrus is necessary, but not sufficient, to produce the prolonged learning 
times mentioned above. 

Scientific Significance to Bio-Medical Research : The finding of a difference 
in the degree of the cortical contribution to light touch and temperature, on 
the one hand, and to the appreciation of consistency, shape, size, and rough- 
ness, on the other, is not wholly unexpected but has never before been 
clearly established by objective tests on animals with verified cortical 
lesions. The finding may be related to the classical distinction between the 
kinds of sensation mediated by the lemniscal vs. the anterolateral ("spino- 
thalamic") tracts in the spinal cord, but it has not heretofore been suggested 
that this particular kind of distinction might also apply to the cortical 
level. Our experiments are also the first to demonstrate a sharp functional 
distinction between the precentral and postcentral gyri, and to relate the 
deficit found after postcentral lesions to the slowly-adapting rather than 
the quickly-adapting population of postcentral neurons. It is further 
expected that the outcome of our study of the postcentral vs. the posterior 
parietal deficits in shape discrimination may clarify the functions of the 
parasensory "association" cortex. These contributions to basic knowledge of 
cortical organization in somesthesis will, it is hoped, lead to rational re- 
habjlitative procedures for patients with losses in sensation occasioned by 
cerebral disease or injury. 

3^3 



Serial Wo. M-P-L-12 p. h. 

Proposed Course of Project : Studies designed to localize more precisely the 
lesions within the sensory cortex which are responsible for deficits, and to 
examine the nature of those deficits, will be pursued. The first of these 
objectives leads to further investigations designed to determine what connect- 
ions of the crucial area give it its special function. The second leads to 
experiments with additional tests and modified procedures which attempt to 
resolve ambiguities in interpretation of deficits obtained. 

Honors and Awards : 1. Membership, Experimental Psychology Study Section, 
DRG, 1969-1973. 



2. Editorship, CORTEX , I968- 



Publications; 



Schwartzman, R. J. and Semmes, J.: The sensory cortex and tactile sensitivity. 
Exptl. Neurol ., 1971, 33: 1^7 - 158. 

Semmes, J.: Soraesthetic effects of damage to the central nervous system. In 
Jung, R. (Ed.): Handbook of Sensory Physiology . New York, Springer- 
Verlag, in press. 

Semmes, J. and Porter, L. : A Comparison of Precentral and Postcentral Cortical 
Lesions on Somatosensory Discrimination in the Monkey. Cortex , 1972, in 
press . 

Semmes, J., Porter, L. , and Randolph, M. C: Further Studies of Anterior 
Postcentral Lesions in the Monkey. Cortex , 1972, in press. 



3hk 



Serial No. M-S-C-11 



1. Socio- environmental Studies 

2. Office of the Chief 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 



Project Title: Social Psychological Correlates of Occupational Position 

Previous Serial Number: Same 

Principal Investigators: Melvin L. Kohn and Carmi Schooler 

Other Investigators: Lindsley Williams (guest worker, on assignment from 
the Career Development Program in Global Community 
Health, HSMHA) 

Cooperating Units: None 

Person Years 

Total: 4 5/6 
Professional: 1 1/3 
Other: 3 1/2 

Project Description: 

Objectives : To ascertain the relationship of some principal dimensions of 
job, occupation, and career to relevant aspects of men's values, 
social orientation, self-conception, and off-the-job behavior. 

Methods Employed : Structured interviews with a sample of 3100 men, represent- 
ative of all men employed in civilian occupations in the United 
States. 

Major Findings : A. Occupational Experience and Psychological Functioning . 
The issue of principal concern in this year's analyses is whether 
occupation affects or only reflects personality. Our key to dealing 
with this problem is to focus on dimensions of occupation, in con- 
trast to the traditional approach of studying some one occupation. 
We attempt to disentangle the many intercorrelated dimensions of 
occupation by securing a large sample of men who work in many occu- 
pations, inventorying their job conditions, and differentiating the 
psychological concomitants of each facet of occupation by statistical 
analysis. There are serious limitations to securing occupational 
data by interviewing a representative sample of men. For example, 
many men have only limited inforraation about some facets of their 



3^5 



Serial No. M-S-C-11, page 2 

jobs; moreover, a sample of men scattered across many occupations 
and many work places does not contain enough people in any occupation 
or any workplace to trace out interpersonal networks and belief 
systems. But the method is highly satisfactory for studying the 
immediate conditions of the man's own job--what he does, who deter- 
mines how he does it, in what physical and social circumstances, 
and subject to what risks and rewards. 

As noted in last year's report, virtually all of the many 
occupational conditions we have examined are significantly related 
to one or another of the facets of psychological functioning included 
in our study. But relatively few occupational conditions- -thirteen 
in all--are significantly related to more than one facet of 
psychological functioning, independently of education and of all the 
other pertinent dimensions of occupation. Although few in number, 
these occupational conditions are sufficient to define the structural 
imperatives of the job. The thirteen occupational ^conditions can be 
grouped into four clusters--( 1) organizational locus [ownership, 
bureaucracy, position in the supervisory hierarchy]; (2) occupational 
self -direction [closeness of supervision, routinization, substantive 
complexity]; (3) job pressures [time pressure, overtime, heaviness 
of the work, dirtiness]; and (4) uncertainties [the likelihood of a 
dramatic change in the man's situation, the frequency with which men 
in his position are held responsible for things outside of their 
control, the risk of loss of job or business]. 

Our preferred explanation of the linkages between these 
occupational conditions and psychological functioning is that job 
conditions affect men's orientations to, and behavior in, both occu- 
pational and nonoccupational realms of life. But there are other 
possible interpretations. The two most important are that our findings 
reflect a tendency for men to mold their conditions of work to meet 
their needs and values, and that men are selectively recruited and 
retained in jobs to which they are well suited. 

Job molding . Several lines of evidence suggest that job- 
molding processes take place within rather narrow structural limita- 
tions--too narrow to provide an adequate explanation of the relation- 
ships between occupational conditions and psychological functioning. 

In particular, occupational conditions are structurally 
interrelated. Thus, a man who does substantively complex work stands 
a greater risk of being held responsible for things outside of his 
control than does a man who works at simpler tasks: the correlation 
of substantive complexity with such a risk is 0.32. The risk in- 
creases if the job is not only substantively complex but also time- 
pressured (the multiple correlation being 0.36), and increases further 
if the man stands high on the supervisory ladder or is an owner 
(r = 0.40). From this perspective, an increased risk of being held 



3h6 



Serial No. M-S-C-11, page 3 

responsible for things outside of one's control is the price one 
pays for holding an interesting and responsible job. Each of the 
other occupational conditions cem also be seen as part of an inter- 
locking network. It is not as if one could make a series of independent 
decisions--to be self-directed, not to be under great time-pressure, 
to work in a non-bureaucratic firm; their structural interrelatedness 
means that one has to accept some occupational conditions as the 
price for securing others. 

Other findings- -from analyses of men's job preferences, from 
comparisons of men who do and who do not have much control over 
their occupational conditions, and from analyses of those occupational 
conditions that may be especially subject to workers' control --buttress 
our conclusion. The evidence consistently suggests that, although men 
undoubtedly do mold their jobs to fit their personal requirements, 
these processes do not provide anything like a complete explanation 
of the relationships between occupational conditions and psychological 
functioning. 

Occupational self-selection . The issue here is whether occu- 
pation is related to personality mainly because employers hire men 
they think are qualified, because men search out jobs that meet 
their needs and desires, and because men drop out of jobs for which 
thoy are ill-suited or which they find intolerable. Our method of 
analysis is based on a reconstruction of each man's job history, with 
emphasis on one pivotal facet of occupation, the substantive complexity 
of men's jobs been affected by their psychological characteristics, 
and to what extent have their psychological characteristics been 
affected by the substantive complexity of their jobs? 

Since we do not have measures of psychological functioning 
from times before the men entered their present, and each of their 
previous jobs, we must estimate. To do this, we provisionally make 
an assumption directly contrary to our major thesis: we assume that 
men's levels of psychological functioning are essentially established 
before their occupational careers begin. If so, indices based on 
performance at the present time would provide reasonably accurate 
estimates of what the men's level of functioning had been at earlier 
times. Such indices enable us to assess the maximum possible effect 
of psycholgical functioning on occupational recruitment and retention. 

Our analyses show that psychological functioning plays, at 
most, a small part in determining the substantive complexity of men's 
past and present jobs. Moreover, no matter which aspect of psycholog- 
ical functioning we examine, it is more affected by, than a determinant 
of, the substantive complexity of the job. Occupational self- 
selection undoubtedly does take place, but it does not provide the 
major explanation of our findings. There must be some continuing 
interplay, throughout men's careers, between man affecting job and 
job affecting man. 

3^7 



Serial No. M-S-C-11, page 4 

There are several implications of these findings. First 
and most generally, these findings contribute to the growing sense, 
in social science as in society at large, that we have for too long 
fixated on the importance of early, especially childhood, experience 
in the shaping of personality. The potentiality for change exists 
well into adulthood; our findings suggest that this potentiality 
persists throughout men's occupational careers. 

Second, these findings should help reshape sociological con- 
ceptions about what is important in occupational experience. The 
variables that have been at the center of interest in the study of 
occupations--status, interpersonal relationships, organizational 
structure- -prove to be less pertinent for psychological functioning 
than do the immediate realities of men's jobs. 

Third, these findings bear directly on the issue of whether 
men similarly located in the structure of society come to share 
beliefs and values because of their similar experiences or because of 
some process of value-transmission. Marx and the structuralists 
would have us believe that the former is basic, theorists as diverse 
as the "human relations in industry" and "culture of poverty" schools 
stress the latter. Our data come down solidly on the side of the 
structuralists. Men come to value self -direction, for example, not 
because they live in an atmosphere where others value it, but because 
they work under conditions where they can and must exercise it. Men 
learn from their own experience. Social structure matters because 
it shapes this experience. 

Fourth, our findings provide some insight into the processes 
by which occupational experience affects psychological functioning. 
These findings argue for a learning- generalization model, as opposed 
to a reaction-formation or compensatory model. That is, the specific 
linkages between particular facets of occupational experience and 
particular facets of psychological functioning suggest that men learn 
to cope with the realities of their job and they generalize these 
lessons to non-occupational realities. Men whose jobs require intel- 
lectual flexibility, for example, come not only to exercise their 
intellectual prowess on the job but also to engage in intellectually 
demanding leisure-time activities. Nowhere in these data is there 
evidence that men turn their occupational f rustrations loose on the 
nonoccupational world or try to find compensation in nonoccupational 
realities for occupational lacks and grievances. 

B. Community and Psychological Functioning . Lindsley 
Williams has pursued his interest in a topic that links three domains: 
the psychological functioning of individuals, their social charac- 
teristics, and the social characteristics of the communities in which 
they reside. In this work he is utilizing 1600 respondents to the 
national survey, melding these data with data which characterize the 
41 urbanized areas in which the sample was drawn. 

3U8 



Serial No. M-S-C-11, page 5 

This research is directed at several objectives. The first 
is to demonstrate that human values and orientations differ from 
one urban setting to another. The second objective is to interpret 
these variations in terms of the social dimensions that underlie 
the communities in which they reside and in which these values operate. 
The third objective is to explore variations in individual orienta- 
tion to self and others in terms of the social consonnance (or 
dissonance) of the individual's characteristics with those of the 
community in which he lives, that is, an analysis of the social 
context in which the individual finds himself. 

All of the data excepting those which characterize communities 
were drawn from the Occupations Study; they represent a subset of the 
original 3100 obseirvations, namely those persons living within the 
perimeter for urbanized areas as defined by the U. S. Bureau of the 
Census. The social characteristics of the communities themselves were 
drawn from data published by the Census for "Urbanized Areas." These 
include the size of the population; density per square mile; rate of 
growth; the composition of the community in terms of marital status, 
housing stock, ethnicity, racial groups; age distribution; and 
indicators of collective social status including education, family 
income, occupation and a composite index. 

The overall inquiry is being carried out in several steps. The 
first is a confirmation that human values and social orientations do 
vary from one community to the next. The second step is an exajnination 
of the social characteristics of the communities themselves, this 
being in preparation to the second analysis in which variation from 
community to community is considered from the vantage point of the 
underlying dimensions of urban social structure (a logic which 
parallels that of the analysis of occupations). The third step con- 
siders the juxtaposition of the social characteristics of the individ- 
ual and his community where dimensional counterparts exist; it 
addresses questions such as the following: Does an individual's own 
education make more or less of a difference to, say, his level of 
anxiety, depending upon the general level of education in the community? 

Work has proceeded to the point where some findings may be 
reported. First, variation exists in the psychological functioning 
of residents of different urbanized areas. These variations exist 
both in the outlook a person has to others as well as to himself. 

Second, there are a number of social dimensions or "factors" 
that underlie community. These social factors include urbanicity, 
the distribution of households and housing, the composition of the 
population with respect to social minorities, and a factor of socio- 
economic status. Each of these factors, as reflected in its constituent 
elements, apparently influences, though hardly determines, the 
psychological functioning of community residents. It was expected 
that many dimensions would operate at the level of the community in 

3^9 



Serial No. M-S-C-11. page 6 

the same direction as did their "counterpart" at the level of the 
individual. For example, persons of more education are generally 
more composed, less anxious. It was expected that anxiety would 
operate in the same way for communities as a whole, i.e., residents of 
more highly educated communities would reveal less anxiety. In this 
case the hypothesis was supported. In other instances the community 
characteristic was of significance, but in an opposing direction-- 
suggesting an provocative conflict in individual versus collective 
characteristics: while more highly educated persons are less self- 
deprecating (more self -approving) , residents of more highly educated 
communities, controlling on their own education, are more self- 
deprecating. Finally, a number of instances of a second order rela- 
tionship appear in which residents of urbanized areas at the extremes 
differ from residents of more typical communities. Residents of the 
more highly educated communities together with those from less highly 
educated ones are less willing to accept change than those who are 
resident in communities in the midst of the collective distribution. 

Scientific Significance : In industrial society, occupational role is of 

central importance in shaping men's conceptions of self and of social 
reality. This research is addressed to a systematic appraisal of 
precisely which aspects of occupation affect which facets of man's 
social psychological functioning. 

Proposed Course of Project : The analyses on which we are embarked will 

continue for some time: the data are rich and the scientific payoff 
has thus far been considerable, but the analytic problems are 
exceedingly difficult and it would be foolhardy to expect them to be 
solved quickly. 

Honors and Awards: None 

Publications: 

Kohn, M. L. : Bureaucratic man: a portrait and an interpretation. 
American Sociological Review 36: 461-474, 1971. 

Kohn, M. L. : Class, family, and schizophrenia: a reformulation. 
Social Forces , in press. 

Schooler, C. : Childhood family structure and adult characteristics. 
Sociometry , in press. 

Schooler, C. : Psychological antecedents of the modem adult. 
American Journal of Sociology , in press. 

Schooler, C. : Birth order effects: not here, not nowl Psychological 
Bulletin , in press. — 



350 



Serial No. M-S-D-10 



1. Socio- environmental Studies 

2. Developmental Psychology 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 



Project Title: Research on the Processes of Internalization of Rules, 
Standards, and Values 

Previous Serial Number: Same 

Principal Investigator: Roger V. Burton 

Other Investigators: None 

Cooperating Units: None 

Person Years 

Total : 2 

Professional: 1 
Other: 1 

Project Description: 

Objectives : This project entails research on conditions leading to self- 
control during temptation. The primary study of focus this year 
was designed to investigate how a mother's presence and her specific 
childraaring practices are related to her child's behavior in a 
cheating test. The issue of generality of the child's behavior and 
of the effects of the mother's actions on the child were also analyzed. 
The two aspects of consistency in the child that could be explored 
were (1) a comparison of the same measures of his honesty under two 
different conditions, and (2) how related were the two facets of 
conscience of observing rules in a game and of telling the truth. 
The mother's behavior was assessed both for its immediate Impact on 
the child and for its more long-term effect on the inculcation of 
honesty when the child performed alone. 

It is felt that in our society an especially worthwhile 
temptation to investigate is one in which the values of honesty and 
successful achievement are in conflict. Research on conscience 
development and achievement motivation, and the social learning 
theory of the Investigator indicated that the rearing areas of warmth, 
rejection, dominance, harmony, and achievement orientation would be 
most likely to demonstrate the kinds of interactions leading o honesty 
or cheating in an achievement arousing temptation test. 

351 



Serial No. M-S-D-10. page 2 

Methods Employed : To analyze the relations between the mother's rearing 
and the child's self-control requires a measure of the child's 
resistance to temptation when by himself. For the rearing measures 
to be immediately relevant for assessing how honesty is trained, 
mother-child interactions obtained in a temptation test setting are 
needed. Therefore, the child's honesty was measured twice: when 
alone and when the mother was present, with all other condi tiors held 
constant. The rearing measures were based on the interactions during 
this second test. 

The child's performance on a bean bag game provided the 
measures of his behavior during temptation. Deviation from the simple 
rules were necessary to achieve a good score. All children were 
first tested alone. A week later, their mothers were asked to be 
with them while they were retested. The interactions were scored by 
direct observation from behind one-way mirrors. An interview with 
the mother immediately following the test explained the purposes of 
the study and obtained information on what she thought the study was 
about and what we were measuring, and on her judgments of how "normal" 
her behavior was during the test compared to her behavior at home, 
especially on the major dimensions of child rearing that were scored. 

Major Findings : The analysis of consistency of the children's behavior 

showed that the control group of children retested alone under identi- 
cal conditions were very stable in either cheating or being honest. 
By comparison, a significant number of the children changed in their 
observance of the rules with their mothers present, the tendency being 
stronger in changing from having been honest to cheating. The mother's 
presence influenced some of the children, who had demonstrated inter- 
nalized self-control in the first test, to cheat, and in some cases 
this influence was shown quite directly in that the mother told the 
child to ignore the rules. The reluctance of these children to cheat 
was reflected in their cheating later and less extensively than 
either ihe experimental or control groups of consistent cheaters. 
The effect of the mother's presence, however, is more complex in 
that, besides tending to increase the number of cheaters, it also 
inhibited cheating among those who had already cheated by themselves 
even though they again cheated with the mother. The inhibitory 
effect in these consistent cheaters was shown in their cheating later 
and to a lesser extent than they had when alone. This contrasts 
significantly with the behavior of the consistent cheaters in the 
control group who cheated earlier and more extensively in the second 
test. There is no support here for what has been described as 
"externalization of conscience" or "transfer of the superego" which 
has been hypothesized to occur when the presence of an adult (espec- 
ially the parent) permits the child to shift responsibility for con- 
trol from himself to the adult. On the contrary, the evidence 
indicates the presence of the mother inhibited cheating even more 
than when the child was alone and yet her actions kept him engaged in 
the g£ime and eventually elicited some deviation, 

352 



Serial No. M-S-D-10, page 3 

The child's portrayal of the rules were scored for truth- 
fulness (or lying). This lying score was significantly correlated 
with cheating when alone, with the mother, and most strongly with 
consistency of cheating. The magnitudes of the correlations (.35 to 
.50) are larger than has generally been reported and is likely due 
to the commonness of the situation for the scores. Nevertheless, 
these findings provide rather substantial evidence that under such 
conditions there is more generality across these response dimensions 
of honesty than would be expected from a strictly specificity position. 

It is often concluded from reviews of research on conscience 
development that parental warmth is positively associated with early 
and high conscience development. The finding for this study was the 
opposite: A measure of overall warmth was related to cheating in the 
mother's presence and to cheating consistently. Further analyses that 
separated the expressions of warmth contingent on the child's behavior 
in the game from noncontingent warmth provided a clearer understanding 
of the processes involved. The noncontingent warmth, a measure 
similar to "general warmth" as usually used, was unrelated to any of 
the measures of the child's behavior, whereas the measure of contingent 
warmth showed significant relations to cheating with the mother 
present, to consistent cheating across both conditions, and to cheat- 
ing alone, though in this last case for girls only. These findings 
challenge the interpretation that "warmth" is related to high conscience 
and suggest that the broad notion of warmth that has served as the 
basis for assessing the nurturant relationship provided the child 
is misleading. These findings indicate that warmth may be more 
adequately conceptualized as a specific resource that is manipulated 
rather than as a general quality of a relationship. These data do 
fit predictions from social learning principles that requiring 
successful achievement for showing warmth or reacting to poor per- 
formance by withholding or withdrawing emotional support by the 
mother would lead to cheating rather than to honesty, 

A measure of the mother's relationship to the child during 
the test period compared to her usual expressions of warmth was 
obtained in the post-test interview. This interview measure of 
warmth was unrelated to the child's cheating. It was also unrelated 
to the observed measures of the mother's warmth. Even though 
obtained in the same setting, this self-report measure and the 
observed measures of expressed warmth were certainly not equivalent 
nor even seemed to assess the same underlying dimension. In a factor 
analysis of the mothers' scores, this self -report measure of warmth 
loaded highest on a factor that combined the self -reports of more 
warmth, less tension, and less directing with the behavioral measures 
of noncompliance, and depriving-ignoring-rejecting. Thus the mothers 
seem to perceive their nonintrusive though calmly (cooly) controlling 
behavior during the test period as a reflection of warmth rather than 
as more like what would be rated from the observations as rejection. 



353 



Serial No. M-S-D-10, page 4 

For those observed measures of rejection that loaded on 
this factor with self -reported warmth, noncompliance and depriving- 
ignoring-rejecting were associated with honesty for girls (unrelated 
for boys). These findings suggest that the lack of overt and direct 
attempts to control the child's behavior (such as scolding or 
physically restraining or punishing the child) is perceived by the 
mother as warmth, and there is the further possibility that some of 
the association between the self -reported warmth and the child's 
conscience development found in previous studies is based on inter- 
actions that would be scored toward the cold end of the warmth 
continuum. 

In addition to warmth and rejection, the other domains of 
childrearlng assessed were dominance, harmony, and achievement 
orientation. The specific findings from each of these sets of 
observational measures rather consistently fit the interpretation 
that the more the mother focused her own attention on the child's 
successful achievement and attempted to direct and restrict the 
child's behavior to performance of the game, the more likely the 
child was to violate the rules. Findings from the self -report 
measures generally were not consistent with their observational 
counterparts. For example, the observational measure of directing 
and restricting related to cheating whereas the self-report measure 
of directing related to honesty. The implication is that the mothers 
reacted to quite different aspects of the situation than were scored 
by observing her behavior. Rather than indicate that only one type 
of measure is worthwhile, the evidence indicates the value of obtain- 
ing both kinds of information for providing a fuller understanding 
of the processes involved in personality development. 

To achieve a parsimonious picture of the underlying dimensions 
in the mothers' behavior, a factor analysis was done and the factor 
scores correlated with the child measures. The first rotated factor 
accounted for most of the common variance and correlated strongly 
with the consistency score (cheating in both sessions) and especially 
with cheating in the mother's presence. The rearing measures that 
defined this factor were initiations, game related statements, con- 
tingent warmth, negative evaluations, pushing, directions and 
restrictions, and the self-report measure of tension. This factor, 
labelled "Intrusive, Dominant Achievement Orientation," is composed 
of measures from all five of the domains of childrearlng hypothesized 
as determinants of moral conduct. It is unlikely that this factor 
is a basic dimension of childrearlng but rather represents those 
various techniques commonly brought to bear in a mother's Immediate 
attempts to produce successful achievement in her child. A different 
pattern was primarily related to the measures representing the child's 
internalization of moral standards. Though no factor related 
significantly for boys' self-control, two independent factors related 
to the performance of girls when alone. The first factor, "Interest 



35^ 



Serial No. M-S-D-10. page 5 

with Indirect Control," indicated that a blend of active interest in 
the child's activity with noncompliance and unresponsiveness to 
unwanted behavior as the means of setting limits related to the 
inculcation of honesty. The mother's conscious avoidance of directing 
the child's behavior toward achievement and behaviorally not exerting 
direct control was related to her daughter's low self-control. 

These findings indicate the dilemma confronting parents in 
their attempts to inculcate a balance in their children of standards 
of moral conduct and of excellence in achievement. The indications 
are that some rearing techniques develop achievement at the expense 
of honesty, and conversely. An awareness of the possibility of over- 
emphasizing one value seems desirable for the parent to achieve a 
desired balance. 

Scientific Significance : These studies will contribute to an understanding 
of socialization process, particularly to the inculcation of moral 
standards involved during temptation to cheat in an achievement 
situation. This information will add important empirical data 
necessary to the building of a comprehensive theory of socialization 
and of the development of conscience. 

Proposed Course of Project : A paper is being prepared for submission to 
scientific publications. 

Honors and Awards : None 

Publications: 

Burton, R. V. : Cross-sex identity in Barbados. Developmental 
Psychology 6, 1972, 365-374. 



i 



355 



Serial No. M-S-D-L6 



1. Socio- environmental Studies 

2. Developmental Psychology 

3. Bethesda, Maryland 



I 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 



Project Title: Occupational Experiences of Muscians 

Previous Serial Number: Same 

Principal Investigator: Roger V. Burton 

Other Investigators: None 

Cooperating Units: None 

Person Years 

Total: 
Professional : 
Other: 

Project Description: 

Objectives : This study explores how adult coping mechanisms and personality 
measures determine and, in turn, are modified by reactions to 
naturally occurring stress in the occupational sphere of a group of 
highly competent, intensively trained persons who were strongly 
dedicated and committed to their professions. The sample is a select 
group of professional musicians, most of whom had been under contract 
to a motion picture studio. These men, whom this investigator had 
previously studied while under contract and when there was no indica- 
tion of the future stress, suddenly became part of the large number 
of "free-lance" musicians competing for the diminishing demands for 
their skills. The precipitating event was the termination of all 
musicians' contracts in all studios. 

Methods Employed : The main instrument in the earlier study had been the 
Guilf ord-Zimmerman Temperament Scale, a standardized, objective 
personality inventory. This test is again being used in order to 
have objective measures of changes which might have occurred since 
the loss of definite steady employment. Two other objective instru- 
ments are used- -Rosenberg ' s Self -Esteem and Faith-in-People Scales-- 
together with a semi -structured interview for information on the 
musician's background, musical training, reactions to the loss of a 
contract, and his current overall circumstances. 



357 



Serial No. M-S-D-16, page 2 

Major Findings : This project has continued to be inactive this year 
because of other" commitments. Broadly speaking, the findings 
already cited for previous reports indicate that the large majority 
of these successful musicians have stable and desirable personalities. 
Furthermore, the increased pressure from decreasing work appears to 
have eliminated those with unstable characteristics and to have 
changed those who coped well toward being more competitive and 
indifferent about the plight of their colleagues. 

Scientific Significance : Capitalizing on a previous study of these 

musicians, this project uses an unfortunate but naturally occurring 
event (contract termination) to investigate reactions to occupational 
stress. Stability of personality, predictability of individual 
ability to cope with occupational stress, and modification of per- 
sonality through adaptation to major problems in life are some of 
the issues considered in this investigation. 

Proposed Course of Project : Some analyses have already been performed 
though many still need to be done. 

Honors and Awards : None 

Publications: None 



358 



Serial No. M-S-D-23 



1. Socio-environmental Studies 

2. Developmental Psychology 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 



Project Title: Observational Learning from Nurturant and Nonnurturant 
Models 

Previous Serial Number: Same 

Principal Investigators: Marian Radke Yarrow, Carolyn Zahn Waxier, and 

Phyllis M. Scott 

Other Investigators: None 

Cooperating Units: None 

Person Years 

Total: 1 1/2 
Professional : 1 
Other: 1/2 

Project Description: 

Objectives : To investigate the effects of nurturant and nonnurturant 

adult models on children's behavior, with particular interest in 
(a) observing influences over a wide range of behaviors, and (b) 
examining the impact of varying kinds of modeling input: symbolic 
and live modeling, didactic and incidental modeling. 

Methods Employed : Experimental socialization environments were created 
in which the models had caretaker roles, either nurturant or non- 
nurturant. As meaningful persons in the children's experience, 
the experimenters modeled a diversity of behaviors: (a) a variety 
of isolated responses, including neutral acts and acts of positive 
and negative affect; and (b) behaviors that represented more inherent 
qualities of the adult--her preferences, her motivations, a self- 
involved response, namely altruism. 

The children were 130 nursery school children. The details 
of procedure have been described in previous reports. The experi- 
ment was replicated; also, the intactness of the experimental effects 
were examined six months later. 



359 



Serial No. M-S-D-23. page 2 

Major Findings : Selected parts of the analyses have been described in 

previous annual reports. As a final report of the completed project, 
the major conclusions are summarized. 

These conclusions regarding modeling effects on child behavior 
should be interpreted within the following conditions: (a) The 
models are women who have meaningful caretaker functions in the 
children's experiences, (b) The children are of preschool age, 
(c) The model's nurturance is a high schedule of reinforcement, not 
for imitation. The model's nonnurturance is not of high intensity; 
it is nonreinforcement and mild reproof, 

1, When easy-to-perform actions are modeled repeatedly by the 
adult, and relatively obtrusively, the majority of children match 
some of the adult's behavior. Although the majority adopt some of 
the adult's behaviors, at least on a temporary basis, the amount of 
imitation is very often small. The frequency of matching is in- 
creased when the child's imitation of the adult receives approval by 
the adult. 

2, When matching occurs in the presence of the model, or in 
close proximity in time to the adult's modeling, it is likely to be 
equally frequent whether the model-child relationship has involved 
nurturance or nonnurturance, 

3, When the adult's modeling has been relatively didactic, as 
in a demonstration to which the child's attention has been directed, 
variables of nurturance again do not affect the children's performance. 

4, The social responses by the adult when modeled in 
symbolic or play form were imitated and generalized in a similar 
play form, but there was no generalization of these responses into 
real behavior. 

5, Children are selective in what they imitate. Regardless 
of the model-child relationship, specific aggressive acts are more 
readily selected out of the adults' repertoires than are specific 

acts of positive, friendly affect. (The models' friendly and aggressive 
actions were observed in dramatic play. ) However, when themes of 
aggression and of friendliness are considered in relation to each 
other, and the individual child is his own control, there is signifi- 
cant over- emphasis on aggressive themes when the model has been 
nonnurturant to the children; whereas the emphasis is reversed, toward 
imitation of friendly themes, when the models have been nurturant to 
the children. 

6, Nurturant adults are significantly more effective as 
models than are nonnurturant adults under the following circumstances: 



360 



Serial No. M-StD-23, page 3 

(a) when the adult's modeling is incidental, her behaviors occurring 
in natural and meaningful social interactions, as opposed to test 
situations with demand-characteristics; (b) when the learning of the 
child is measured after a passage of time; (c) when the child's 
imitations involve his own idiosyncratic adaptations of the adult's 
responses; and (d) when the child is confronted later with situations 
in which his newly- learned behaviors are appropriate. Under these 
circumstances, meaningful patterns of adult behavior- -hobby prefer- 
ences and sympathetic helping of others in circumstances of distress- - 
were adopted significantly more frequently by children of nurturant 
models than by children of nonnurturant models. 

Scientific Significance : The focus in these projects on the dimensions of 

nurturance and nonnurturance in the rearing agent was prompted by the 
considerable inconsistency in existing research evidence regarding 
the effects of these variables on learning, particularly learning 
through observing the adult. Research on nurturance is hampered by 
conceptual ambiguities, and by inadequate manipulations of nurturance 
in experimental work. These studies have been directed to these 
issues. Further, one set of experiments in this series contributes 
data to the understanding of the origins and development of a 
socially valued behavior, namely the development of altruism or 
concern for the welfare of others. 

Proposed Course of Project : The project has been completed, with the 
findings published or in press. 

Honors and Awards: Invited symposium on The Development of Altruism: 

Theory, Research, and Social Import. Divisions 7 and 8, American 
Psychological Association, Honolulu, Hawaii, August, 1972. 

Publications: 

Yarrow, M. R, and Scott, P. M. : Imitation of nurturant and non- 
nurturant models. Journal of Personality and Social Psychology , 
in press. 

Yarrow, M. R. , Waxier, C. Z. , and Scott, P. M. : Child effects on 
adult behavior. Developmental Psychology 5: 300-311, 1971. 



361 



Serial No. M-S-D-26 

1. Socio- environmental Studies 

2. Developmental Psychology 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 



Project Title: An Observational Study of Maternal Models 

Previous Serial Number: Same 

Principal Investigators: Carolyn Zahn Waxier and Marian Radke Yarrow 

Other Investigators: None 

Cooperating Units: National Institute of Child Health and Human 
Development 

Person Years 

Total: 3/4 
Prof es s ional : 1/2 
Other: 1/4 

Project Description: 

Objectives : To examine interactions between mothers and their 20-month- 
old children in relation to patterns of maternal behavior that 
influence imitative responding, and in relation to theoretical form- 
ulations regarding the origins of imitation. In particular, to 
examine sequences of behavior in terms of a reinforcement theory 
of generalized imitation, and to identify characteristics of 
parental models associated with imitative responding in their chil- 
dren. This study extends investigation to a much younger age than 
that of the usual subjects in experimental work on imitation. 

Methods Employed : Thirty-five black mothers from middle and low economic 
classes were observed with their children in a planned series of 
settings which permitted natural and semi-natural interaction. 
Mother and child were observed in a laboratory trailer during a 
brief waiting period, in play, in teaching situations, and in a 
planned modeling session. Later, an experimenter repeated the 
mother's modeling. On another occasion, the children were given 
the Bayley Developmental Test. Interactions were observed, with the 
mothers' knowledge, from behind a one-way screen. Observer re- 
liabilities on exact matching of sequential behavior units range 
from 68% to 87%. 



363 



Serial No. M-S-D-26. page 2 

Major Findings : Analyses to date have dealt only with the settings that 
preceded the planned modeling session; in other words, the mother 
was not aware of the research intent. Every child imitated at least 
a few of the mother's manipulations of the teaching and play 
materials; however, there was an appreciable range of matching be- 
haviors. What might account for differing frequencies? Prominent 
in theory and experimental research is the theme that consistent 
rewards for imitating, early in the child's developmental history, 
are the important determinants. In the ongoing interactions ob- 
served, consistent schedules of reward were not common. Over one- 
fourth of the children were never rewarded for imitation, and less 
than one-fourth received over 50% reinforcement (average rate of 
reward was 28%). These relatively "lean" schedules occurred in 
settings when the mothers are most free to be sensitive and responsive 
to children's actions. 

Within the range of reinforcement observed, is there evidence 
of an association between maternal rewards and child imitations? 
Children who received a relatively high rate of reinforcement for 
imitation did not imitate more frequently than did children who 
had received little reinforcement. Children were no more likely 
to respond readily with another imitation after reward than after 
nonreward. Both analyses lead to the same conclusion: that imitation 
is not under the control of specific reinforcements for such actions. 
Further, neither mothers' general rewardingness nor their level of 
punitiveness was related to children's imitation. Characteristics 
of the mother's rewardingness, other than frequency, are being 
explored--e.g, , explicitness, appropriateness, and timing in a 
given situation. Similarly, maternal behaviors relating specifically 
to modeling have yet to be analyzed- -enthusiasm and enjoyment, 
clarity of manipulations, verbal accompaniments that highlight actions, 
manner of encouraging child participation, etc. 

Imitation was related to the children's affective states. 
Children who expressed a great deal of enjoyment, who laughed and 
smiled frequently, were the same children who were highly imitative. 
Conversely, in a separate measure of negative affect (crying, 
sulking, whining), the children who were unhappy showed infrequent 
imitation. Child dependency was not predictive of imitation, 
contrary to theories in which imitation is associated with attention- 
seeking. 

Scientific Significance : Observed interactions of mothers and children 
under field conditions can (a) test principles formulated from 
laboratory research, (b) raise questions about these formulations, 
and (c) provide new evidence that will further understanding of 
the processes involved. 



36k 



Serial No. M-S-D-26, page 3 

Proposed Course of Project : A small amount of staff time has been 

assigned to this project. Work will continue on it through this 
year. 

Honors and Awards: None 

Publications: None 



365 



Serial No. M-S-D-28 



1, Socio- environmental Studies 

2, Developmental Psychology 

3, Bethesda, Maryland 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 



Project Title: A Comparison of Methods of Obtaining Data on Parent and 
Child Behavior 

Previous Serial Number: None 

Principal Investigators: Marian Radke Yarrow and Carolyn Zahn Waxier 

Other Investigators: Thomas A. Padrick 

Cooperating Units: None 

Person Years 

Total; 2 7/12 
Professional: 1/2 
Other: 2 1/12 

Project Description: 

Objectives : To compare information concerning child rearing and child 

behavior obtained by different and accepted methods of assessment, 
and to examine particular problems associated with different data- 
gathering procedures. 

Methods Employed : Sixty preschool children and sixty families were the 

subjects. From an interview with the mother, summary assessments of 
her rearing practices and her child's behavior were obtained. In 
the following two weeks, there were four hours of observations in 
the home. Observations were in the form of sequential accounts of 
mother and child behavior. Ratings of mother and child behavior in 
the home were also made, based on the same periods of observation. 
At the close of the second session in the home, the mother was inter- 
viewed about the behavior that had occurred during that session. 

Behaviors were assessed in the following dimensions: mother's 
warmth, coldness, demonstrativeness, rewarding, and punishing of 
the child's dependency; child's compliance or dependaicy, "conscience," 
and aggression. In coding the interviews and in making the observa- 
tional ratings, the same categories and scales were used. In coding 
the observations, the indicators for each variable were as similar as 

367 



Serial No. M-S-D-28, page 2 

possible to those used in the interviews. The observational records 
were time-marked in 30-second intervals. Based on the proportion of 
time units in which the variaU e occurred, subjects were assigned 
decile scores on each variable. 

The interviewer and the observer of a given subject were 
never the same person. All interviews were coded independently by two 
coders; intercoder reliabilities ranged from r' s of .51 to .93. Dual 
observations carried out in the nursery school were the basis of an 
estimate of observer reliability in the home. Correlations ranged 
from r's of .50 to .89. Variable observer agreement on different 
behavioral dimensions was one of the interests in the analysis. 

Analyses are directed to examining the congruence of assess- 
ments (a) of the same variable across methods, and (b) of relation - 
ships between variables--both within the same method and across 
methods. There are eight maternal variables and six child variables 
in four within-method comparisons, and in six across-methods com- 
parisons. 

Associations between variables across data sets and within 
data sets were analyzed using Pearson correlations and Kendall's 
Tau coefficients. 

Major Findings : 1. One should expect in assessing the same parents and 

children, on the same dimensions, at very nearly the same time, that 
the levels of association (i.e., the similarity of scores on the 
four instruments) would be statistically significant and high. This 
is not generally the case, however. 

(a) Four hours of observation in the home and the typical 
child rearing interview do not, by and large, result in similar ratings 
of mother and child. Tau coefficients range from -.16 to +.48; 
correlations from -.17 to +.57. Most associations do not reach the 

5% level of significance, 

(b) Of considerable methodological significance is the com- 
parison of two sets of observational assessments. These were made 
by the same observers, and with reference to the same four hours of 
observed interaction in the home. One set is in the form of 5-point 
ratings made shortly after the observations; the other set is sequential 
accounts of interaction, from subsequent coding of which the fre- 
quencies of specific behaviors could be ascertained. Associations 
between these two data sets range from a tau of -.16 on measures of 
warmth to a tau of +.29 on reward and praise. 

(c) Closest agreement was obtained between observer's ratings 
and ratings by mother when both were referring to the specific period 
of home observation. Associations were significant (r's from .25 to 



368 



I 



Serial No, M-S-D-28, page 3 

.53) on all but one variable (use of praise and reward, r = .13). 
When the sequential observation records (rather than the observer's 
ratings) and the mother's ratings of the same period in the home are 
compared, all associations are nonsignificant (Taus -.08 to +.13). 

(d) Directional differences between observers and mothers 
occur on four child variables; each time the mothers are "harder" in 
their judgments of the child. Directional differences occur on four 
mother variables; each time the mothers are "easier" in their judg- 
ments of themselves than are the observers, 

2. Relations between maternal and child behaviors based on 
one method of assessment are not identical to the relations based on 
another assessment. For example, based on interview data, maternal 
warmth is associated with the child's ability to abide by the mother's 
rules (Tau = +.31, p < .08); whereas, based on observational data, 
the tau is -.02. 

Scientific Significance : Preceding work in this program of research has been 
concerned with methods of investigating child and parent behaviors 
through the use of verbal reports. In those studies, major and dis- 
tressing inconsistencies were frequently found in the empirical data 
deriving from different measuring techniques. The present project 
extends the investigation to methods using direct observations. An 
appraisal of observational data, along with verbal report information, 
is important to the understanding of the methods upon which research 
and theory rely. 

Proposed Course of Project : The data have been analyzed and the writing of 
a scientific report is in progress. 

Honors and Awards : None 

Publications: 

Yarrow, M. R. : Research on child rearing as a basis for practice. 
Journal of Child Welfare , in press. 



369 



Serial No. M-S-P(C)-23 



1. Socio- environmental Studies 

2. Personality and Environment 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 



Project Title: Cultural and Psychodynamic Factors in the Occurrence and 
Treatment of Psychiatric Illnesses in Japan, Taiwan, and 
the United States 

Previous Serial Number: Same 

Principal Investigator: Carmi Schooler 

Other Investigators: William Caudill, Hsien Rin 

Cooperating Units: Department of Psychiatry, National Taiwan University, 
Taipei , Taiwan 



Person Years 




Total: 


1 1/12 


Professional: 


1/3 


Other: 


3/4 



Project Description: 

Objectives : (1) To identify and describe the types and symptom patterns 

of psychiatric illnesses in Japan and Taiwan. (2) To determine the 
relationship of these types of illnesses to social, cultural, £Uid 
psychological variables in Japanese and Chinese cultures, (3) To 
compare the results obtained with results from similar data on 
psychiatric patients in the United States, 

Methods Employed : Methods have been described in detail in previous annual 
reports. Currently we are working with two samples obtained by use 
of the same schedule in interviews with patients and their families: 
(1) all admissions to five psychiatric hospitals in Tokyo during a 
twelve-month period in 1963-64 for a total of 994 patients; (2) all 
admissions to three psychiatric hospitals in Taipei during a two- 
year period, 1967-68, for a total of 1,009 patients. 

Major Findings : This year saw the completion of the data coding and of the 
first stage of the data analysis--the factor analysis of patient 
symptomatology. Factor analyses were carried out for the cross- 
cultural sample as a whole, and separately for each culture, and also 



371 



Serial No. M-S-P(C)-23, page 2 

within each culture separately by sex. Although there were minor 
differences, a fairly similar factor structure emerged in each of the 
different samples so that factor scores based on the factor analyses 
of the total population seem to accurately index the pathology of 
individuals of both races and sexes. 

The eight factors which emerged from the analysis of the 
total population are (1) hostility, (2) apathy and retardation, 
(3) depression, (4) reality break (delusions, hallucinations), (5) 
bizarre hebephrenic behavior, (6) headaches and bodily concerns, 
(7) physical somatization (sleeping, eating, and gastrointestinal 
problems), and shinkeishitsu (a combination of phobia, obsessiveness, 
and tense interpersonal relations which was found and described 
in our earlier work on Japan). 

We have also been able to do some preliminary analysis of 
cultural differences. These analyses were done through the use of 
multiple regression techniques which permit the control of the back- 
ground variables of the patient's age, sex, rurality, and his father's 
social class and size of place of work. These analyses reveal that 
the Taiwanese are generally more inclined than the Japanese to show 
hostility, breaks with reality, and bodily concerns and headaches. 
The Japanese of both sexes are more likely to show shinkeishitsu and 
depression, and Japanese women exhibit more apathy, bizarre hebe- 
phrenic behavior, and somatization than do Taiwanese women. 

Scientific Significance : Our preliminary findings suggest that Japan and 

Taiwan are quite similar in their pattern of psychiatric symptomatology 
and that this pattern, in all likelihood, is not very dissimilar from 
that of the United States. Some of the details of the above analyses 
may well be modified as more sophisticated methods are undertaken. 
However, very meaningful differences between the two cultures do 
exist. The magnitude of some of these differences strongly suggests 
that a central finding which will almost certainly persist is the 
difference between the two cultures in the direction in which 
psychiatric patients express negative affect: inwardly in Japan 
through shinkeishitsu and depression, and outwardly in Taiwan through 
hostile aggressive behavior. 

groposed Course of Project : Analysis of the data will continue, both in 

terms of cross-cultural comparisons and in the investigation of the 
relation between social structural variables, likelihood of hospital- 
ization, and symptom patterns within cultures. 

Since the symptomatology of the Taiwanese patients has also 
been rated on a rating form (IMPS) which is in standard use in the 
United States, it is hoped that it will be possible to make com- 
parisons between these two cultures, as well. 



372 




Serial No. M-S-P(C)-23., page 3 

Honors and Awards: Dr. Carmi Schooler was awarded a Japanese Government 
Research Award for Foreign Specialists. This award was sponsored 
by the Japanese National Institute of Mental Health, and permitted 
Dr. Schooler to carry out research in Japan during the period May 1. 
1971 to November 30, 1971. 

Publications: None 



373 



Serial No. M-S-P(C)-27 



1. Socio -environmental Studies 

2. Personality and Environment 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 



Project Title: Parental Care and Child Behavior in Japan and the United 
States 

Previous Serial Number: Same 

Principal Investigator: William Caudill 

Other Investigators: Carmi Schooler 

Cooperating Units: None 

Person Years 



Total : 


4 


Professional: 


1 1/6 


Other: 


2 5/6 



Project Description: 

Objectives : (1) To identify and describe patterns of parental care and 

child behavior in Japanese and American families. (2) To determine 
the relationship of these patterns of behavior to personality 
development, psychopathology, culture, and social structure in the 
two countries. 

Methods Employed : The basic design of the study and methods used have been 
described in detail in previous reports. Briefly, this is a longi- 
tudinal observational study of the behavior of parents and children 
in the home over the first six years of life in Japan and the United 
States. During 1961-64, 30 Japanese and 30 American middle-class 
mother-infant pairs were selected for observation. The infants were 
first-born, normal babies, and were three-to-four months of age at 
the time of observation. The first 20 Japanese and the first 20 
American cases were selected for follow-up study at 2^ years of age, 
and observations in the home were completed during 1963-1967. These 
same children were studied for a third and final time at 6 years of 
age during 1967-70, and all observations have been completed. 

Major Findings : The great bulk of the time during the current year has been 
spent in the detailed task of coding the data from the observations 



375 



Serial No. M-S-P(C)-27, page 2 

at 6 years of age. Preliminary data analyses were also performed 
on the data gathered when the subjects were 2% years of age. The 
preliminary analysis of the data gathered when the subjects were 
2% years old gives a striking indication of the general continuity 
of the cultural differences in the behavior of both the children 
and their caretakers. Just as they were at three months, both 
American children and parents were more vocal than were Japanese 
children and parents. Furthermore, a higher proportion of the 
American vocal behavior was aimed at cognitive communication, 
whereas Japanese mothers were more likely to make lulling, or 
cognitively noncommunicative, and emotionally expressive sounds 
than were American mothers. 

The earlier greater level of physical activity of both American 
children and their caretakers also continues at this later date. 
Additionally, this greater activity on the part of the American 
children is linked to signs of increased independence. The Japanese 
caretaker is likely to assist the children in performing these 
functions over 80% of the time, while in America this occurs only 
about 50% of the time. Another continuity in cultural differences 
is in the emotional sphere. Japanese children at 3 months were more 
likely to vocalize unhappily than were American children. This 
same tendency continues at 3 years of age. 

Scientific Significance : This research permits us to empirically examine 
some of the most important processes through which culture affects 
personality. It does this by providing precise measures of parental 
care and of infant and child behavior in two cultures. The longitudinal 
nature of the design maikes it possible to study both cultural differ- 
ences in childrearing practices, and children's reactions to such 
differences from birth to six years of age. Furthermore, the exis- 
tence of such data permits us to examine cross-culturally the con- 
sistency of an individual's behavior patterns from infancy through 
young childhood. The similar behaviors of both caretaker and child, 
(e.g., the greater level of physical and verbal behavior and the more 
open expression of hostility on the part of the Americans) strongly 
suggest that the differences between the behavior of the children in 
the two cultures can be explained on the bases of learning and 
modeling. Such an explanation seems especially likely since the 
work reported last year showing essential similarities in the 
behavior of 2% month old Japanese-American and Caucasian-American 
babies would make a genetic explanation of the cross-cultural 
differences unlikely. The preliminary results we now have clearly 
indicate that the differences in both the pattern of childrearing 
and children's behavior in the two cultures, particularly the greater 
stress on independence among the Americans, are congruent with fre- 
quently reported differences between the two cultures. 

Proposed Course of Project : To the great shock of those of us who knew 
him, Dr. William Caudill died on March 24, 1972. Since that time 

376 



Sen. al No. M-S-P(C)-27. page 3 

we have been able to ascertain that his data were in such good 
condition that it should be possible to carry out the main thrust 
of his investigation: the longitudinal cross-cultural examination 
of continuities and discontinuities in childrearing practices and 
child behavior. Of course, the final product, whatever its level 
of statistical sophistication, will lack the clinical and anthro- 
pological insights which only Dr. Caudill could have provided. 

Honors and Awards: None 

Publications: 

Caudill, W. : Tiny dramas: vocal communication between mother and 
infant in Japanese and American families. In Lebra, W. P. (Ed.): 
Mental Health Research in Asia and the Pacific, Volume Two . 
Honolulu, East-West Center Press, in press, 

Caudill, W. : A comparison of maternal care and infant behavior in 
Japanese-American, American, and Japanese families. In Lebra, 
W. P. (Ed.): Mental Health Research in Asia and the Pacific , 
Volume Three . Honolulu, East-West Center Press, in press. 



I 



377 



Serial No. M-S-P(C)-38 



1. Socio- environmental Studies 

2. Personality and Environment 

3. Bethesda, Maryland 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 



Project Title: The Interrelationships between Social Interaction, 

Psychological Functions, Perceptual Style, Physiological 
Arousal and Personal History Factors Among Schizophrenics 

Previous Serial Number: Same 

Principal Investigator: Carmi Schooler 

Other Investigators: Monte S. Buchsbaum 

Cooperating Units: Laboratory of Psychology, NIMH; Saint Elizabeths 
Hospital; DCRT 

Person Years 

Total: 11/12 
Professional: 1/6 
Other: 3/4 

Project Description: 

Objectives : The objective of this series of studies remains the attempt to 
explain the variance found in earlier experiments with schizophrenics 
by discovering the interrelationships among those variables which 
these earlier studies indicate are central to an understanding of 
schizophrenia: task performance, physiological arousal, perceptual 
style, social behavior, symptomatology and psychiatric history, 

^ethods Employed : Several approaches are presently being followed. (1) 

The level of physiological arousal and task performance under different 
social conditions of both schizophrenics and nonschizophrenics have 
been measured and related to variations in perceptual style and 
personal history. (2) A major study has been initiated which involves 
the interrelating of measures of evoked response, perceptual style, 
skin temperature (a measure of physiological arousal) and symptom- 
atology. (3) In order to facilitate the continuance of both of the 
above types of study, an attempt is being made to develop a generalized 
computer program to simplify the analysis of measure of physiological 
arousal and to relate these measures to each other and to other 
aspects of the experimental situations. 



379 



Serial No. M-S-P(C)-38. page 2 

Major Findings : This year there are no new findings; the year has been 

devoted primarily to the collection of data both at Saint Elizabeths 
Hospital and at the National Institutes of Health for the above- 
mentioned study of the interrelationships between evoked response, 
perceptual style, skin temperature, and symptomatology, and to the 
continued development of the general computer program to analyze 
physiological measures of arousal. 

Scientific Significance : Since clinicians had long noted that social with- 
drawal appeared to be a marked feature of schizophrenia, and exper- 
iments by Schooler and others had demonstrated that the greater the 
degree of social contact the greater the decrement in the schizo- 
phrenic's functioning, it seemed reasonable to initiate a series of 
studies seeking the key to the schizophrenic's malfunctioning in 
his reactions to his social environment. In one of these studies. 
Schooler and his co-workers were able to establish through direct 
observation of ward behavior that lack of social interaction is, 
indeed, one of the characteristics which differentiates schizophrenics 
from other hospitalized mental patients. Furthermore, the results of 
another study indicate that this lack of interaction is mirrored by 
an expressed preference for avoiding entanglements with others. 
Additional studies in the series have shown how the schizophrenic's 
performance in standard psychological experiments is affected by 
orientations which are at least partially the results of his past 
social experiences. Thus, one study indicates that the effect of 
positive or negative evaluation on verbal -paired associate learning 
is a function of the subject's self-esteem; subjects with low self- 
esteem doing especially poorly on tasks requiring novel associations 
after being given positive evaluations of their performance which 
are dissonant with their negative self-image. 

Several other studies point to the possibility that society's 
general norms as to sex roles have differentially affected male and 
female schizophrenics' willingness to show or receive signs of positive 
or negative feelings. Their findings are congruent with the supposi- 
tion that in our culture the expression of emotion, and particularly 
of affection, is an area of conflict for men, while for women a major 
area of concern is fear of evoking the hostility of others. The 
possibility that social psychological factors can even affect 
psychophysiological relationships is indicated by the findings of 
another study which show that the social nature of the situation 
can affect the direction of the relationship between physiological 
arousal and task performance. 

The interaction between the social situation, the schizo- 
phrenic's functioning, and his physiological reactivity pointed to a 
general weakness in the way this series of studies had been carried 
out. It had been conducted primarily from one research perspective 
and was concerned with only a liitited area of the individual's 



Serial No, M-S-P(C)-38, page 3 



functioning. Although the findings were significant they had not been 
very powerful, possibly because differences in the nature of physio- 
logical reactivity of different subgroups of schizophrenics may 
have produced contrasting, or at least differing, results. 

A. review of the literature revealed that the general concentra- 
tion on one aspect of the individual which had marked these social 
■psychologically oriented studies was at least as pronounced in 

, studies in other areas. It was therefore not at all surprising that 
the weak results which marked the series of social psychological 
studies were at least as powerful as the results of studies approaching 
the problem of schizophrenia from other directions. Thus, for example 
.years of search for biochemical differences between schizophrenics 

- and others have resulted in no reliably replicable findings. The 
effects of genetics appear to be less and less powerful, the better 
controlled the study. Putative social class differences between 
schizophrenics and others do not seem to exist under all conditions 
and where they do exist it is far from clear whether such differences 
are related to the cause of the disease or its effects. Those theor- 
etically based systems of classifying patients into subgroups which 
have been investigated have not produced consistent findings and, 
in fact, the most highly touted mode of classification- -pre-morbid 
adjustment-.proved totally unable to pass the test of controlled 
replication. 

The lack of findings has certainly not been due to any lack 
of theories or hypotheses. Hypotheses have been brought forth with 
the ease of the proverbial blind men describing the elephant, e g 
those studying tails describing the elephant as long, thin and " 
floppy; those studying problem- solving seeing the essence of schizo- 
phrenia in thought disorder. 

Two courses seem to be presently open. One can keep on making 
hypotheses from limited bodies of data, hoping to achieve the flash 
of insight which will permit us to see from our limited point of view 
what the elephant is really like, or one can go ahead with the duller 
task of trying to do studies which attempt to coordinate data from 
many vantage points in order to get enough information to make meaning- 
ful hypotheses possible. The present series of studies represents 
an attempt to follow the second of these courses with the aid of modern 
multivariate techniques and computer technology. It thus involves 
the interrelation of five different types of variables which seem to 
be the most promising in terms of their possible etiological significance, 
their consistency in predicting schizophrenic responses, and their 
amenability to experimental manipulation. These five classes of data 
are (1) perceptual functioning, (2) central and autonomic nervous 
system arousal, (3) task performance, (4) social interaction, (5) 
psychiatric symptomatology and history. 



381 



Serial No. M-S-P(C)-38, page 4 

Studies were undertaken which involved the replication and 
evaluation of earlier studies of schizophrenia in these five areas 
in a way which would permit the examination of their interrelation- 
ships among different schizophrenic subgroups. These studies of the 
investigator and his collaborators are now starting to show that many 
of the previously contradictory findings in the area of schizophrenia 
research have been due to an incomplete comprehension of the com- 
plexity of the interrelationships between psychiatric sjmiptomatology, 
patterns of physiological arousal, and perceptual and social function- 
ing among different types of patients. 

Proposed Course of Project : Data collection will be continued and analyses 
of already collected data will be continued and the results prepared 
for publication in a scientific journal. 

Honors and Awards: None 

Publications: None 



382 



Serial No. M-S-PS-1 



1, Soclo-environinental Studies 

2, Personality and Stress 

3, Bethesda, Maryland 



PHS-HSMHA-NIMH 
Individual Project Report 
July 1, 1971 through June 30, 1972 



Project Title: Health Orientations of Parents and Children 

Previous Serial Number: Same 

Principal Investigator: John D. Campbell 

Other Investigators: Iris Posner, Margaret F. Luther 

Cooperating Units: Children's Hospital, Washington, D. C. 

Person Years 

Total: 2 1/4 

Professional: 1 
Other: 1 1/4 

Project Description: 

Objectives: To study health orientations of family members. Specifically, 
the goals of the study are, first, to describe systematically the 
patterns of variation in family members' attitudes, values, beliefs, 
perceptions, and behavior concerning phenomena of illness and health; 
and second, to examine ways in which selected personal and situational 
factors relate to health orientations. Relev£int to the attainment 
of these objectives are the following three assumptions basic to the 
study: (a) an individual's orientation to health and illness is 
embedded in interactive processes; (b) such orientations are at 
least in part learned; and (c) to a considerable extent such learning 
takes place as an aspect of routine family relationships. 

Methods Employed : Information on 264 hospitalized children and their 

mothers was obtained by use of focused interviews, questionnaires, 
and rating scales. Interviews with children and mothers, and 
questionnaires completed by the mothers provide data on (a) aspects 
of their definitions of illness, (b) reports of their own and other 
family members' feelings and actions when ill, (c) their attitudes 
and beliefs about illness prevention and treatment, (d) their values 
in selected areas not directly relevant to health, and (e) views 
about appropriate standards of behavior: what should or should not 
be done in circumstances pertaining to illness and health. Ratings, 



383 



Serial No. M-S-PS-1, page 2 

made by .nurses in the hospital setting, appraise children's emotional 
dependence and anxiety. 

Major Findings : During the past year data analyses have dealt primarily 
with three different facets of mothers' and children's views of 
illness: (a) variations in definitional sophistication of illness 
concepts, (b) variations in circumstances perceived as pivotal in 
labeling a person as sick, and (c) variations in the extent to which 
a series of specific signs and sjmiptoms is viewed as indicative of 
illness. 

Comparison of mothers' and children's thematic emphases in 
their definitions of illness has shown that as social development 
progresses persons typically adopt a broader, more psychosocial ly 
oriented, more precise, and more subtle configuration of themes in 
their illness concepts. These appraisals have led to a composite 
measure of definitional sophistication, an index permitting further 
exploration of the development and intergenerational transmission of 
illness concepts. As expected, sophistication of children's illness 
definitions was clearly related to age. Yet with age statistically 
controlled, the negligible correlation between mothers' and children's 
sophistication scores provided little support for the logical possi- 
bility that, in defining illness, the child adopts a conceptual 
style similar to that of his mother. Moreover, parent-child corre- 
spondence on this dimension of qualitative variation was not enhanced 
by certain favorable mother-child relationships. To a considerable 
extent, then, children's illness concepts may be acquired, not by 
adoption, but by independent formulation growing out of their own 
experiences. In addition to and independent of the effect of the 
child's age, several aspects of family composition showed a cumulative 
impact on sophistication of definition: If a child's mother was older 
than the average, if he had a relatively large number of younger 
siblings, and if his mother was not employed outside the home, that 
child was more likely than others to define illness in a conceptually 
sophisticated fashion. 

There is a difference between knowing what illness is and 
knowing when one is ill- -the difference between the definition of a 
state and the specification of pivotal circumstances labeling the 
onset of that state. This is evident when one considers critical 
illness-defining circumstances: For children the relevant circumstances 
are in some respects markedly different from those of adults. Parents 
serve as gatekeepers for the child, legitimizing his illness or 
imposing a label of illness on him. Children were nearly ten times 
more likely than mothers to state that a pivotal circumstance in 
defining illness was the intervention of some other family member, 
and younger children were more than one and one-half times more 
likely than older. Moreover, after