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December 18, 1998
The National Alliance for Research on Schizophrenia and Depression (NARSAD) has honored scientists for research that may help clinicians prevent the recurrence of depression and help pharmacologists design treatments targeting the most fundamental processes underlying schizophrenia and other disorders. NARSAD also honored journalist Mike Wallace and his wife for their role in raising awareness of the nature and treatability of depression.
The awards were conferred in October at NARSAD's annual gala in New York City. NARSAD awarded George Aghajanian, M.D., and Sarnoff Mednick, Ph.D., the 1998 Lieber Prize for Outstanding Achievement in Schizophrenia Research. NARSAD's 1998 Lieber Prize for Outstanding Achievement in Depression Research went to Julien Mendlewicz, M.D., Ph.D., and Martin Keller, M.D. The Lieber prizes include a $50,000 payment for each award, the largest prizes awarded in psychiatry, according to NARSAD.
NARSAD granted its 1998 Humanitarian Award to Mike and Mary Wallace for "their pivotal role in helping to bring to millions the understanding of psychiatric disorders." Mike Wallace, best known for his role as coeditor of CBS television's "60 Minutes" since its inception in 1968, has spoken publicly and testified before Congress about his own struggle with and recovery from depression. His wife Mary was honored for her role in promoting awareness of the need to recognize and treat depression. In 1994, she started a support group for families struggling to cope effectively with depression. Both the Wallaces have been involved in efforts to destigmatize depression and raise public awareness that it is a treatable illness.
Mike Wallace, one of the mostly highly esteemed journalists working today, told a Congressional committee last year that his self-esteem plummeted when he was depressed. The depression "takes over your life. . . . Your self-esteem drops to zero, and you're trying to hide it, which makes it more difficult," he said.
In accepting the NARSAD award, Mary Wallace recalled her guilt feelings in trying to deal with Mike's depression. She felt guilty "not because he was depressed, but because I couldn't make him feel better," she said. "I didn't know what to do. I thought it was my fault." The stigma of depression today is much like that once associated with cancer, she observed. "When I was a little girl, one didn't say the word cancer; you might whisper it. If someone died of cancer, another reason was given for it. That's how I think depression is now."
Aghajanian, co-recipient of the Lieber Prize for Outstanding Achievement in Schizophrenia Research, is associate professor of psychiatry and pharmacology at Yale University School of Medicine. Mednick, the other co-recipient, is professor of psychology at the University of Southern California. The two have not formally collaborated in their research.
Aghajanian's work has elucidated some of the fundamental mechanisms surrounding the functions of neurotransmitters and neurons within the brain, without which other research on schizophrenia would have been difficult. Mednick's research has focused more specifically on the theory and epidemiology of schizophrenia.
In his acceptance speech, Aghajanian noted that because he does basic science research, he rarely attends meetings on schizophrenia. But he added that "the idea that schizophrenia is a problem that can be approached scientifically is very, very important." Recalling his recent attendance at the first scientific conference on schizophrenia to be organized by the Nobel Foundation, Aghajanian observed that the Nobel Foundation's recognition that schizophrenia is a medical problem "akin to any other medical problem, that it can be approached scientifically," was important not only for its scientific implications, but also because it helped counter the stigma attached to the disease.
Aghajanian explained that his research has helped explain the way in which glutamate, which is the brain's most abundant excitatory neurotransmitter, modulates the excitatory messages of the neurotransmitters dopamine and serotonin. There is reason to believe that "the psychotic state may be ultimately a result of a disorder in glutamate transmission," he noted. From a practical perspective, such research may help define a role for existing and yet-to-be-developed drugs that modulate glutamate transmission.
Mednick summarized the thrust of 40 years of work that led to his receipt of the Lieber award. His research has focused on the relationship between maternal influenza infection during the second trimester of pregnancy and the subsequent development of schizophrenia as a result of fetal exposure to influenza during the second trimester. Mednick later found that affective disorders were also more likely following second trimester fetal exposure to influenza. He then analyzed the data and was able to narrow the period of maximum risk for subsequent development of schizophrenia to in-utero exposure during the sixth month of pregnancy.
"We interpret all of these findings as suggesting that there is a disturbance in the development of the brain, which occurs as a function of this maternal influenza infection," said Mednick. The findings "suggest that there exist periods of fetal neural development during which a teratogen, such as an influenza infection. . . may increase the risk specifically for brain areas related to schizophrenia." If, however, the teratogen strikes during a different period of neural development that involves a region of the brain related to another disorder, then the risk for that disorder will be increased. By further clarifying how this process works, scientists may ultimately be able to design targeted treatments to prevent or counter the development deficits incurred during fetal development.
Mendlewicz, co-recipient of the Lieber Prize for Outstanding Achievement in Depression Research, is professor of psychiatry at the faculties of medicine, psychology, and law at the University of Brussels. Keller, the other co-recipient, is chair of the department of psychiatry at Brown University.
Mendlewicz was honored for his work elucidating the biochemical, neuroendocrinological, physiological, and genetic mechanisms that underlie the pathophysiology of unipolar and bipolar depression. In his remarks at the NARSAD conference, Mendlewicz discussed his research on the genetics of bipolar and unipolar depression.
He noted that through studies of twins and familial pedigrees, he has been able to find a concordance between genotype and occurrence of affective illness. For example, family studies have revealed that the risk of getting unipolar or bipolar depression is more than 10 times greater in some families than in the general population. He and colleagues have concluded that "multiple genes with small variance seem to operate in conjunction with the environment" to cause bipolar and unipolar depression. There are some methodological problems with research based on familial pedigrees, since the inclusion of very large families with many affected people is not representative of what's happening in the general population, Mendlewicz noted. For that reason, he has employed other genetic methods, including association and case-controlled population studies, to buttress his research.
Through a program called the European Program for Molecular Genetics in Affective Disorder, he has been able to collect clinical, genetic, psychological, and social data on more than 1,600 people, including 600 bipolar, manic, or depressed patients.
Keller's work has focused on characterizing the long-term course of bipolar and unipolar affective disorders and on clarifying the best pharmacological approaches for treating and preventing episodes of affective and anxiety disorders. He received APA's 1997 Award for Research in Psychiatry for that work.
Keller and colleagues conducted a series of studies in which they systematically followed patients suffering from a recurrent affective disorder. After building up a systematic database on the longitudinal characteristics of these disorders, Keller followed up with a series of controlled clinical trials that demonstrated the benefits of drugs in the acute and long-term treatment of affective disorders.
In his acceptance speech, Keller offered some examples of his research. In the 1980s, he explained, he and colleagues "looked at adults with bipolar disorder and found that standard doses of lithium were four times more effective in preventing relapse than lower doses." The interest in lower doses related to concern-prevalent at that time-that lithium was causing long-term liver and kidney damage. In the area of unipolar depression, said Keller, he and colleagues have drawn on the results of nine separate studies to clarify optimal treatment duration for all major antidepressant drugs. Keller stressed that his research shows that it is best to keep patients on antidepressant therapy "for a period of at least six to 12 months after" their symptoms remit. Although there is "some variability in the [success] rates, I think that's very hard evidence." In another study, said Keller, he found that people kept on imipramine have only a 20 percent chance of recurrence after three years compared with an 80 percent chance of recurrence if drug therapy is discontinued.