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MYRNA M. WEISSMAN

Interviewed by Thomas A. Ban

Waikoloa, Hawaii, December 12, 2001

TB: This will be an interview with Dr. Myrna Weissman for the Archives of the AmericanCollege of Neuropsychopharmacology. We are at the 40th anniversary of the college in Waikoloa, Hawaii. It is December 12, 2001. I am Thomas Ban. Could you tell us where you were born, brought up, your early interests, education and so on?

MW: I was born in Boston, Massachusetts and was an only child. My father had a small business and my mother stayed home. I went to BrandeisUniversity and graduated when I was about twenty. The fields women were shunted into were nursing, social work or teaching. I did social work, got married and had four children. I didn’t like social work.

TB: Where are we time wise?

MW: In the late 1960's.

TB: Late 1960's.

MW: Right. In 1970 I entered graduate school at Yale for a PhD. My four children were age six and under, I was thirty and decided I had to do something with the rest of my life. Fortunately that was the beginning of the women’s movement, because otherwise, they wouldn’t have let me into graduate school, especially at Yale. My first plan had been to develop real estate. We lived in Bethesda, Maryland, my husband was a scientist at NIH, and real estate in the area was rapidly developing. I saw an opportunity to do something creative that was also very lucrative. So, I took out my real estate license but then my husband accepted a job at Yale. We arrived in New Haven and I realized it was not a place for real estate development, so I’d better find something else. I got the most interesting job of my life with Gerry Klerman, working two days a week on a study of the maintenance treatment of depression to prevent relapse and recurrence. I was the social worker with no experience and small children who didn’t want to work more than two days a week or an academic career. I wanted something fun and this seemed like an important project. I was hired to help get started until they found an experienced fulltime social worker to run the project, travel and do psychotherapy. It was difficult to work with young children. My first day of work, the baby sitter didn’t show up. I remember Gerry saying, “Well, bring them along”. My 18-month old and I arrived and the meeting was about life events. Gene Paykel was there with Gerry gearing up for the maintenance study and they had just obtained their first data on life events. It showed more life events in six months prior to onset of depression compared to controls in the same time period. Life event exits seemed more important than entrances.

TB: You had your degree in social work but no prior experience?

MW: I was quite inexperienced but I knew this was an important study. It was interesting and I didn’t want to spend my time doing something boring.

TB: So you found the people stimulating?

MW: Oh, they were so interesting. There were no guidelines on what to do and they had a hard time finding this super social worker to run the project. Gerry didn’t like to waste time and gave me Aaron Beck’s hand written manual on cognitive therapy, about a hundred pages long. He told me to design the psychotherapy component and specify the procedures for the depressed patients, mostly women. I was the perfect person to do that because I had no pre-existing ideologies. I started reading. I read Bowlby & Rutter, the life events literature and Parsons and Bales, working very closely with Gerry. I suggested we should define the dose of the psychotherapy like a drug, then the duration, quality, and who does it. That was easy. Then we started to get into the tough part. What’s important in depression with depressed middle-aged women who have children? I knew something about children. I remember saying, these patients should know they have depression; it shouldn’t be a mystery. So, we began by going through a diagnostic procedure with the patient explaining what depression is, its symptoms and its course. Then we needed to figure out how it started. We developed the idea of an interpersonal inventory enquiring what was going on, and who, were the important people in the patient’s life. While depression is a biological disorder what’s happening in life, probably triggers it. We developed a draft manual and Gerry used to say, “You have to be specific, you can’t just say, be supportive. You have to specify what you do to be supportive, write scripts”. I was working two days a week, but most of this was done on the other days at home. I only had the obligation to go in to work two days a week, which freed me up.

TB: So, you did some of your work at home?

MW: I did most of it at home. Finally, we had a manual, maybe 50 pages. Then Gerry said to me and to Gene Paykel, “Now you have to define the outcome. Social function should be the outcome of psychotherapy. We expect that drugs will help symptoms, make people sleep better and eat better, feel less hopeless, but psychotherapy will have effects of how people function, so define the social functioning”. I remember going home with a stack of papers, all the articles I could find on social functioning. After that, at Gerry’s request, I wrote a review for the FDA on Social Functioning Scales, which was one of my first publications.

TB: When was that?

MW: It was in the early seventies. Gerry had left for Harvard but he called and said, “The FDA needs a review of social adjustment scales, could you do it, and make it like a consumer report”? I did, and we published it in Archives. As a review it was quoted a lot. The scales fell into two categories: Those designed for studies of schizophrenia, where functioning was assessed at a low level. For example, do you brush your teeth and take your own bath? Our patients were depressed women, living at home taking care of families, so these scales were not appropriate. The other scales were for college students and assessed dating. Again, our patients were married and had children. Barry Gurland had a scale that he’d been working on for years that had many items appropriate for us, but it didn’t cover children and extended family, so, working with him, we developed the Social Adjustment Scale. Now that we had the scale and a manual, we were ready to begin the study but Gerry pointed out we had to validate the scale. Not having studied psychometrics I wasn’t sure what was needed. With the help of Jerry Myers in New Haven, who worked with Hollingshead and Redlich, we identified an appropriate normal sample. This led to a book, The Depressed Woman, a Study of Social Relationships, published in 1974 by the University of Chicago Press. After Gerry left for Harvard and Gene returned to England I went to graduate school. I completed graduate school very quickly because Brig Prusoff and I were running the remaining studies left at Yale. Gerry was the Principal Investigator and subcontracted the studies to us.

TB: So your book was published before your graduation?

MW: It came out in 1974, the year I got my degree.

TB: Did you use it for your dissertation?

MW: No, they wouldn’t let me because the writing began before I started graduate school.

TB: What did you do for your dissertation?

MW: My dissertation was much less interesting than the book. It was the follow-up of the maintenance study.

TB: Could you use the data from that study for your dissertation?

MW: I could, because I had been heavily involved in the study. I designed the psychotherapy and the major outcome measure and had been involved in data collection and supervising the staff. I didn’t do it alone and could never have done it without Gerry, Gene Paykel and Brig Prusoff.

TB: Could you tell us something about the results?

MW: One hundred and fifty depressed women received either drugs or high contact psychotherapy with placebo or no pill. First, they received an open trial of amitriptyline. If they responded, they were then randomized into the six cell factorial design. The major finding was that amitriptyline, over eight months, prevented relapse compared to placebo or no pill. Psychotherapy had no effect on preventing relapse but had an effect on social functioning. Since patients had problems in both areas, those who had both medication and psychotherapy had the best outcome. This was the first evidence for the efficacy of combined treatment. Gerry and Gene were very dubious about the efficacy of psychotherapy. No one had ever shown a psychotherapy effect so they were surprised to find one.

TB: Were you also involved in the “life events” studies?

MW: No. That was Gene and Gerry’s work.

TB: I see.

MW: My one involvement in life events came from a graduate school course. I was learning new statistical approaches and concepts in a class on relative and attributable risks. I suggested to Gene this might be useful in presenting life events data. So he did that and published a paper which showed that attributable-risks were much higher for depression than other disorders. So, we collaborated closely, even from afar.

TB: And, then, Gerry and Gene left?

MW: Right. When Gerry and then Gene left Yale, I finished the follow up of the maintenance study. Then we wrote another grant on acute treatment with drugs and interpersonal therapy. Mason DeLaverne was hired as the treating physician. He was a semi-retired internist, a very nice man, who took care of the patients. One morning I arrived to find a waiting room full of patients and no Mason.

I called his wife and learned he’d had a heart attack and stroke and died that night on the stage, while performing on the violin. So there we were Brig and I, no doctorate degree between us, and patients. That was trial by fire. We hired another doctor and just continued. We were off campus at a little house on Park Street so we didn’t cost the University anything. In fact, we brought in money from overhead on the grants so nobody paid much attention to us. We did what we wanted and had a great deal of fun.

TB: When did you finish your dissertation?

MW: I finished up my dissertation in 1974. Then we wrote a collaborative grant with Gerry as the principal investigator at Harvard while I was the principal investigator at Yale, now I had my PhD. This was an acute treatment study, because we argued that psychotherapy would have more of an effect from the beginning, not just after patients responded to medication. It was much easier to do a 16-week acute treatment trial, using amitriptyline and what we had now named high contact, Interpersonal Psychotherapy (IPT). Bruce Rounsville and Eve Chevron began to work with us and we put together a comprehensive manual, which was published in 1984. Gerry and I did not want to train people in IPT when it had never been used outside of Yale and Harvard. We wanted to wait until there was more evidence for efficacy.

TB: Did you work full time by then?

MW: After I got my degree in 1974 I went full time.

TB: I suppose by then the children were in school all day?

MW: They were still young, but I worked at home a lot, so I never worked nine till five. I would go to work very early after the children went to school and I was always back when they got home. I would work in the evenings and on weekends, but we were a working family. We all worked. If I had any major writing to do, I would stay home. I was very close to home, so if I wanted to go to the children’s performance or help at the school, I did. I had no bosses.

TB: Did you have your own projects?

MW: I had several grants, because it wasn’t difficult to get funded if you had ideas. I was also involved in research with Herb Kleber at the Drug Abuse Unit. We were outside the main stream in psychiatry, the Department was very psychoanalytic. Herb was next door in the same complex a couple of blocks from the medical school. He had a big government contract to study methadone for heroin addicts and invited Brig and I to do the part on depression. Brig and I had a weekend to get the project written. I knew nothing about methadone but Brig’s husband was a very prominent pharmacologist, so we decided she should take the methadone part and I would write the depression part. We wrote that portion of the grant on the effects of methadone on mood using the assessments from our clinical trial. We only needed an additional section on the pharmacology of methadone and its effect on mood. The grant was funded and, suddenly, I was studying drug abuse. There were two other grants that came soon after. One was a very large grant to study co-morbidity in drug addicts and the other was to do psychotherapy, IPT, added to a standard program for drug addicts to see if it improved the outcome of methadone treatment.. This was in collaboration with Bruce Rounsaville at Yale. ITP didn’t have an effect and it was also negative in another sample of drug addicts. That, to us, was reassuring. If you have something that works for everything, you probably don’t have anything.

TB: Were you on the faculty by that time?

MW: I was an Assistant Professor and I had the maintenance study follow up, the acute treatment study, the methadone depression study, the co-morbidity study and psychotherapy opiate studies. It was a big operation.

TB: You moved ahead fast on the academic ladder.

MW: I got promoted to Associate Professor and I can’t remember when I was made full Professor, but I was the first woman to get tenure in the Department of Psychiatry at Yale and I was a PhD. Interest in research became salient and Boris Astrachan, head of Community Mental Health, was a supporter and really pushed for my tenure.

TB: Is your PhD in Epidemiology?

MW: It’s in Chronic Disease Epidemiology.

TB: You had joint appointments in psychiatry and epidemiology?

MW: Yes.

TB: How long did you stay at Yale?

MW: Well, I stayed with Yale until 1987.

TB: 1987?

MW: Yes, a long time. I liked Yale. I was very happy there, but, by that time, Gerry and I were married, living in different cities and I did not like that. My career was not as important as having a real life and my children were older. I was going to move to Boston, but there was no tenure job with Harvard. I was afraid to move to a non-tenured position. Gerry was willing to move to Yale, but they didn’t have anything for him. Then we got these great job offers in New York.

TB: So, you moved to New York?

MW: Gerry moved to New York in 1985 and I moved in 1987. Gerry was working at Cornell and it was easy, because he worked a couple of days in Westchester and we lived in Woodbridge, a forty-minute trip. We wanted to be in the same city, so we moved.

TB: Did you work together or did you have your own projects?

MW: We worked together, but also had different projects. When I was at Yale, in the 1980s, we had the Epidemiologic Catchment Area (ECA) study. We obtained the first rates for psychiatric disorders in the community, using modern diagnostic criteria. That was like a dream for someone who was an epidemiologist. Jerry Myers, who was a sociologist, had done major work on community surveys, using the older techniques measuring symptoms, not diagnoses. Together we wrote the first application to do the ECA and got the first grant. That was followed later by sites in St. Louis, Baltimore, North Carolina, and California.

TB: Could you tell us about the study?

MW: The ECA surveyed eighteen thousand people in five US communities, using the Diagnostic Interview Schedule, which became DSM-III. It was developed by Lee Robins, PhD. and could be used by lay interviewers, because it was highly structured but generated the diagnoses used in clinical psychiatry. In the New Haven site, we surveyed eight thousand people with an over sample of the elderly and Black Americans. North Carolina had a rural sample. People developed their careers from that study. Marty Bruce, who is here at the ACNP, was my post-doc and she got interested in geriatric psychiatry. She took over a follow-up sample and wrote her own grant. So, there was a lot going on. We still had funding from the ECA. Gerry wasn’t involved in that. But while Gerry and I sometimes did separate studies, he had some on HIV we always talked with each other about what we were doing.

TB: What did you find in the ECA?

MW: In the ECA, we found that the rates of depression were fairly high, the rates of schizophrenia were what we had expected, about one percent, and so were the bipolar rates. Sex differences in depression were what we expected; about two to three fold greater in women than men. The major surprise was that most of these disorders begin in the young. We thought of depression, bipolar and the anxiety disorders as conditions of middle aged people. What we found, consistently, across all the sites was that these disorders begin often in adolescence, and certainly, by young adulthood. That didn’t mean that older people didn’t get depressed, but these were usually recurrences. So, the biggest contribution of the ECA was turning the focus on young people and their high rates of psychiatric disorders. There have been similar findings in subsequent studies like the National Comorbidity Survey (NCS). I then got interested in Genetic Epidemiology and started to do family studies of depression and panic disorder. These continue and I still am studying the grandchildren of our sample from New Haven. Now we are doing Magnetic Resonance Imaging (MRI) studies of three generations at high and low risk for major depression (MDD).We presented the first findings from the three generations study at this meeting.