Weighing the causes of severe depression.

Scientists have taken an intial step toward identifying the ways in which genes and specific personal experiences jointly act to produce severe depression in women.

Although genes assume a high profile in much recent research on mental illness, the new study finds they exert "a substantial but not overwhelming" influence on episodes of severe depression, assert Kenneth S. Kendler, a psychiatrist at the Medical College of Virginia in Richmond, and his co-workers. Stressful personal events, such as getting divorced, losing a job, or developing a serious illness act as the strongest instigators of depression, the researchers contend.

Their results appear in the August American Journal of Psychiatry.

Kendler and his colleagues have moved the field ahead by taking the time and care to study a large sample with prospective measurement of several putative risk factors [for depression]," writes C. Robert Cloninger, a psychiatrist at Washington University School of Medicine in St. Louis, in an accompanying editorial.

Kendler's team studied 416 identical and 264 fraternal female twin pairs located through a state twin registry in Virginia. Both members of each pair had lived in the same household through age 16. Participants averaged about 30 years of age.

At an initial assessment, each twin filled out questionnaires on the warmth and support offered by her parents, traumas she had endured during her life (such as sexual assault and life-threatening injury), neuroticism (a measure of anxiety and the quality of life), social support (from family, friends, and others), and prior bouts of severe depression lasting two weeks or more.

At follow-up interviews conducted about 14 months later, each woman reported any instances of depression in the previous year, childhood separations from parents of more than one year, recent interpersonal, financial, and health difficulties, and stressful events in the past three months. Around 17 months later, the women again were asked to cite new episodes of depression and recent stressful events.

Nearly one-third of the sample reported an instance of severe depression at some time in their lives. In the more than two years of follow-up, about 16 percent of the women cited one or more new episodes of severe depression.

New instances of depression occurred more often among both identical twins, who share the same genes, than among both fraternal twins, who share about half the same genes. A woman's genetic risk for depression, signaled by a history of depression in a twin sibling, more strongly predicted future instances of depression than did the genetic risk combined with other factors studied.

This finding indicates that genes boosting the likelihood of getting depressed may largely do so through a direct effect on the brain that remains active during adulthood, rather than by fostering personality traits or behavioral tendencies that lead to depression, the researchers argue.

Recent stressful events showed the strongest direct association with new cases of severe depression. Genes may, to a small degree, influence personality characteristics that cause some people to encounter more traumatic events, according to Kendler and his co-workers.

Taken together, the various risk factors in the study accounted for half of each twin's susceptibility to severe depression, they conclude.

Further research must consider other possible influences, such as marital status and history of other mental disorders, the researchers maintain.

Untested assumptions by the researchers about cause and effect still muddy the meaning of the new data, Cloninger adds. For example, some recent stressful life events may result from, rather than contribute to, depression.