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Psychiatric Times. Vol. 13 No. 10
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The Cutting Edge of Sadness

By Leon Cytryn, M.D.
| October 1, 1996
Dr. Cytryn is clinical professor at George Washington University Medical School. He collaborated with Donald H. McKnew Jr., M.D., on Why Isn't Johnny Crying (1983) and, in 1996, Growing Up Sad: Childhood Depression and Its Treatment, available from W. W. Norton & Co.

Gene Linkage

In the 1980s, linkage analysis studies aimed at the disclosure of the location of a gene on a particular chromosome used biological characteristics as genetic markers, linking their occurrence to patients with a mental disorder (Rieder and Gershon). The hope was that knowledge of the genetic locus of such a physical characteristic would eventually lead to the identification of the genetic locus for the disorder under study (Cytryn and colleagues).

The modern techniques in molecular genetics spurred a new generation of linkage analysis studies. As it became possible to study specific DNA fragments, scientists realized that such fragments could be used as genetic markers if they showed deviations from the normal DNA sequence. In the last decade many such polymorphic DNA fragments have been isolated and identified on the human genome.

The eminently successful and almost unceasing identification of genes for numerous physical disorders serves as a powerful stimulus for comparable studies aimed at identification and localization of genes responsible for mental illness, including the affective disorders.

While the hereditary contribution to affective disorders has been amply demonstrated by the numerous twin and adoption studies carried out in the last half-century, the exact identification of such genetic factors still remains elusive. The field of genetic inquiry of mental illness is replete with skeletons of highly publicized discoveries of genetic linkage of mental disorders that enjoyed a quick meteoric rise and an even quicker demise when the results failed to be duplicated. It is said that the euphoria of such startling discoveries gives way soon to the dysphoria of disappointment. The difficulty may possibly be related to the polygenic mode of inheritance in mental disorders (Plomin and colleagues; Reiss and colleagues).

Other explanations focus on the interplay between inborn genetic factors and environmental influences on normal and abnormal behavior. The primacy of environmental influences in American psychiatry and psychology lasted well into the middle of this century. However, the advent of adoption and twin studies, coupled with the amazing progress in molecular genetics, led to a fascination by behavioral scientists and even the general public, which is fed an almost daily "diet" of news about important genetic discoveries in the media. Only within the last few weeks did we learn about the spectacular achievement of the team in the Institute for Genome Research led by J. Craig Venter, M.D., inventor of the gene sequencing method. In a matter of six months, researchers were able to identify the entire genome (1,700 genes) of archea, a form of life whose existence was only postulated a few years ago.

Such recognition of hereditary factors by scientists and the general public represents, of course, a positive and long overdue development. However, this intense interest in the genetic etiology of disease has led behavioral scientists to downplay the environmental influences on human behavior. Robert Plomin, M.D., one of our eminent behavioral scientists, states it succinctly:

"Genetic research provides the best evidence for the importance of nonheritable factors. As convincing as twin and adoption studies are, the genetic factors do not account for more than about half of the variance for behavioral disorders"and most of the disorders"show as much nonheritable as heritable influences"The current enthusiasm for genetics should not obscure the important nonheritable factors, even though they are much more difficult to investigate."

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