Medicine: Is Mental Illness Inherited?

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It is rare to find a chatterbox among the Amish of Lancaster County, Pa. Rarer still is a flamboyant personality, a braggart, a show-off or, at the other extreme, someone who is deeply depressed or suicidal. In this community of quiet-spoken, humble pacifists, such behavior "really stands out against the social landscape," observes Medical Sociologist Janice Egeland, who has spent more than 25 years among the Old Order Amish, as the group is formally known. When it does occur, the Amish often have an explanation: "Siss im blut," they say; the peculiar behavior is "in the blood."

Last week Egeland, who is from the University of Miami School of Medicine, and a group of scientists at Yale and M.I.T. confirmed that traditional Amish explanation. By employing the tools of molecular biology along with the handwritten genealogical records of Amish families, they showed that the mental disorder known as manic depression is indeed at least partly a matter of bloodlines. Their report, published in the journal Nature, conclusively linked cases of manic depression in an Amish family to genes in a specific region of human chromosome 11. "This is the first demonstration of a possible genetic basis for one of the major mental disorders," says Dr. Darrel Regier, director of the division of clinical research at the National Institute of Mental Health (NIMH). "The study ushers in a new era of psychiatric research."

Usually beginning somewhere between the ages of 15 and 35, manic depression afflicts about 1 in every 100 people. Because it causes its victims to oscillate between two extreme emotional states, it is also known to psychiatrists as bipolar affective disorder. In the manic phase, victims become expansive and extravagant, are often unable to sleep or eat, and may talk incessantly. Some assume airs of grandeur. The depressive phase plunges them into hopelessness, loneliness and boundless guilt, feelings that sometimes lead to suicide.

Researchers have long suspected that heredity plays a role in some if not all cases, and the Amish present an ideal setting in which to test that hypothesis. Not only does bipolar behavior contrast sharply with the community's quiet ways, making it easy to diagnose, but a number of confounding factors that might contribute to such behavior are absent: alcoholism, drug abuse, unemployment, divorce and violence are extremely rare. In addition, the Amish have large families (seven children on average) and keep genealogical records worthy of Mendel. Best of all, they represent a closed genetic pool. All 12,500 Amish in Lancaster County are descended from 20 or 30 couples who emigrated from Europe in the early 1700s, and only a handful of outsiders have ever married in.

Though manic depression is no more common among the Amish than other groups, Egeland's research turned up 32 active cases. All proved to have family histories of the disease going back several generations. Curiously, all of the 26 suicides documented in the community since 1880 occurred in just four of these families.