The first strong proof that psychiatric illnesses can be inherited has emerged from a decade-long study, and the discovery could be a major advance in the detection and treatment of mental illness, scientists are reporting today.
In a report published in Nature magazine, a leading British science journal, researchers from three U.S. centers said they have found a genetic marker that is associated with manic-depressive illness, a condition that causes as many as 2 million Americans to experience radical mood swings between extreme elation and dark depression.
"It's a very important step toward defining the biological basis of a major mental illness," said geneticist Elliot S. Gershon of the National Institute of Mental Health.
The finding comes only a week after scientists in Boston reported using the same genetic engineering technique to identify a gene associated with Alzheimer's disease, a general mental deterioration associated with aging. The Boston scientists had previously used the technique to identify a gene associated with Huntington's disease, which causes memory and speech loss, trembling and death.
"We're making very good progress mapping (human genes) and will probably soon find genes for many other (mental) disorders," said psychologist Theodore Reich of Washington University School of Medicine in St. Louis.
The study reported in Nature was conducted among the 12,000 members of the Old Order Amish community in Lancaster County, Pa. All are descended from 30 immigrants from Europe in the early 18th Century.
Psychiatrist Janice A. Egeland of the University of Miami School of Medicine has been studying the Amish community for 25 years, but the specific work on manic depression began in 1976. A number of epidemiological studies had already shown that the illness runs in families.
Manic-depressive illness is no more common in the Amish than in the general population, Egeland said in a press conference Wednesday in Washington, D.C. But the large family size, clearly established paternity, and social and religious prohibitions against drug and alcohol use in the community make it an ideal place to study hereditary factors in psychiatric disorders, she said.
Egeland and her fellow researchers at the Massachusetts Institute of Technology and the Yale University School of Medicine first identified a family of 81 members, 19 of whom suffer from manic-depressive illness.
They then studied cells from these individuals, using sophisticated genetic engineering techniques that can identify even very small differences between nearly similar stretches of DNA, or deoxyribonucleic acid, which encodes genetic information.
They found that all 19 affected individuals had an identical stretch of DNA on the short end of chromosome 11, one of the 46 chromosomes (23 pairs) in which all genetic information is concentrated. They have not yet identified a specific gene that causes the illness, biologist David E. Housman of MIT said in a telephone interview.
But they have shown that it is located very close to the gene for insulin and to a normally benign gene called H- ras that can become a cancer gene, and these genes served as markers for identifying the location of the hypothetical manic-depressive gene, he said.
The researchers also found the gene in three of the family members who did not have manic-depressive illness. This indicates, Housman said, that not everyone who has the gene will develop the illness, and that environmental factors are also important.
The next step, he said, "is to try to nail down the location and identity of the chromosome 11 gene, and we have a candidate gene in mind to check out first."
That gene, which scientists already knew is on chromosome 11, codes for the production of an enzyme called tyrosine hydroxylase. The enzyme plays a key role in the production of dopamine, epinephrine and other chemicals that play a key role in thought processes.
Many scientists have speculated that abnormal levels of dopamine in particular play a key role in the genesis of manic-depressive illness and other psychiatric disorders.
But Housman cautioned that manic-depressive illness is so widespread in the general population that more than one gene may be associated with a predisposition to it, "just as there are a number of genes that predispose to heart attacks. Other people may not have this gene."
In fact, two other papers in the same issue of Nature indicate that this is the case. A team headed by psychiatrist Hugh Gurling of the University of London failed to find a link to the insulin or H- ras genes in a family in Iceland with a history of manic-depression. A second team headed by Gershon failed to find such a linkage in three similar U.S. families.
But that does not mean that the finding in the Amish is wrong, Gershon emphasized in a telephone interview. "I am sure that sooner or later we or another group will replicate the Amish finding," he said. "We simply may not have studied enough cases, or our group may have a different genetic link."
Any application of the new findings lies several years in the future, Housman said. "There won't be (a test for the illness) until very detailed studies of large numbers of families are carried out to accurately identify all the genes that are involved."
Could Prevent Suffering
"If we can identify those genes," said psychologist Allen Gruenberg of the Institute of Pennsylvania Hospital in Philadelphia, "we might be able to identify manifestations of illness before they interfere with people's lives. We will be able to begin effective treatment earlier and prevent a great deal of suffering."
But perhaps the greatest immediate benefit, Housman said, is that it may remove some of the stigma from mental illness.