Reich is the principal investigator for the St. Louis site of the 10-center study, which involves researchers in the United States and Europe. Washington University is the only center in the United States that is recruiting study participants. Originally hoping to recruit people from 120 families in which some members suffer from depression and others do not, Reich now hopes to identify about 240.

"Our productivity has been so good during the first two years of this study that we have been asked to find more subjects," Reich said. "We are especially interested in families where two siblings have had to battle depression and another has not. Because those siblings were raised in the same home environment and would presumably have had similar experiences, we would expect that genetic differences may help explain why one becomes depressed and another does not."

Study volunteers provide detailed family histories and also give a blood sample that can be used for DNA analysis. In the next few months, the project expects to begin DNA analysis on the first 400 affected sibling pairs.

Researchers hope that the international study, sponsored by British pharmaceutical company GlaxoSmithKline, will provide new insights into the genetic and environmental factors associated with unipolar depression.

Also referred to as clinical depression or major depression, unipolar depression causes patients to slip into states of extreme sadness, hopelessness and lethargy. As they work to locate the genes related to unipolar depression, Reich and the other investigators will take advantage of new information from the DNA sequence provided by the Human Genome Project.

"We will use the genome map as we try to determine why some people in a family develop depression while others do not," Reich said. "If we can identify the genes that make people susceptible, it will revolutionize our understanding of the disease and guide the design of new drugs to prevent or treat this extremely debilitating disorder."

Depression affects up to 12 percent of people in the Western world, and although about 70 percent of patients respond to treatment, three-fourths of those patients experience a recurrence of their illness within 10 years.

In addition, an estimated 60 percent of depressed people remain undiagnosed and untreated. The World Health Organization estimates that by the year 2020, depression will be the second leading cause of "lost years of healthy life."

Reich and colleagues are recruiting volunteers for the study. All required study visits, examinations, evaluations and laboratory procedures will be provided free of charge. Those who qualify also will receive a small cash stipend.