Search begins for genes behind manic depression Hopkins scientists join 3-year project


WASHINGTON -- Six years after the demons of manic depression convinced him he was God and commanded him to leap from a window, presidential health reform adviser Robert Boorstin still wonders "why I have this illness and my fraternal twin doesn't."

He may find out when scientists at the Johns Hopkins Medical Institutions and two other institutions complete a three-year, $2.5 million project to identify the genes believed to be responsible for most manic-depressive illness.

Fifty families, including several living in Maryland, will be the focus of the project, which was announced yesterday by the sponsoring Charles A. Dana Foundation, a health and education philanthropy.

If it is successful, doctors eventually would be able to test people for the gene, enhancing diagnosis and treatment.

"I think it's really the frontiers of science," said Dr. Kay Redfield Jamison, a Hopkins professor of psychiatry, who will participate in the project.

Mr. Boorstin joined a panel of scientists to discuss the project, putting a human face on an incurable, but treatable problem that afflicts 2.5 million people -- roughly 1 percent of the population -- and is a leading cause of suicide.

Several prominent Americans, including cable TV mogul Ted Turner and Lear's magazine founder Frances Lear, have come forward in recent years to describe the effects of an illness that often goes undiagnosed or is kept secret by those who have it.

A sufferer may experience signs of major depressive illness such as apathy, lethargy, a sense of hopelessness, disturbed sleep and faulty concentration. But those with manic depression also go through periods of mania marked by vastly increased activity and energy, frenetic thought patterns and moods that may be paranoid and irritable, or elevated and expansive.

Thoughts of suicide are common. Some people may attempt dangerous actions that could harm themselves.

Mr. Boorstin, who is 34, vividly recalls his first psychotic episode, in July 1987, when he was working as a reporter for the New York Times. It ended in hospitalization.

"In the midst of my delusional episode it became apparent to me that not only was I the son of God, but also that I could fly," he said. "And I was locked into what was euphemistically called the quiet room, a room with a mattress and nothing else. . . . And I attempted to jump out of the window because I thought I could fly."

Mr. Boorstin had endured bouts of depression since 1983, but it took four years for a doctor to diagnose manic-depressive illness. Delays in diagnosis are common and pose a major obstacle to treatment, which has advanced considerably in the past two decades through the use of medications such as lithium, which Mr. Boorstin takes.

But medication isn't a panacea. Frances Lear takes lithium but is "still plagued by thoughts of self-destruction," she wrote in a letter that was read aloud at the news conference. Unlike Mr. Boorstin, she has tried to kill herself -- six times.

Yet, as terrible as the illness is, one of its mysteries is a link with artistic achievement. Dr. Jamison, the Hopkins professor, recently published a book on the subject, "Touched with Fire: Manic Depressive Illness and the Artistic Temperament." The writers Herman Melville and Virginia Woolf are among those noted in the book.

But as Dr. J. Raymond DePaulo Jr., a professor of psychiatry at Hopkins, observed, artistic creativity may come at too high a price for those with MDI. "If it goes over a certain line, it tends to be very destructive."

Researchers have amassed evidence of the genetic origins of the disease, which runs in families, and believe that more than one gene is responsible. By pooling the resources of three institutions -- Hopkins in Baltimore, Stanford in California and the Cold Spring Harbor Laboratory in New York -- scientists are confident they can pinpoint the culprits.

Finding the right families to study is essential. A Hopkins team led by Dr. DePaulo has already found 30 appropriate families but needs 20 more who fit the criteria. To qualify, a family must have at least three affected siblings and either the mother's family or father's family must have members with MDI. Families interested in participating should call Hopkins at 955-5212.

Using blood samples from the families, Stanford scientists led by Dr. David Botstein will look for genetic evidence of MDI, with assistance from Dr. James D. Watson and others at Cold Spring Harbor. Dr. Watson shared a 1962 Nobel Prize for discovering the structure of DNA.

Even if they aren't able to identify particular genes, the scientists say they hope their work will advance knowledge of treatment of manic-depressive illness.

If they do succeed, there is the possibility some people would use gene screening to decide whether to have children. But neither the scientists nor Mr. Boorstin said they believe people would have abortions if they knew a child might be born with genetic susceptibility to the illness.

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