Genetic susceptibility to schizophrenia found Hopkins study indicates afflicted family members may share genetic marker

September 01, 1998|By Jonathan Bor | Jonathan Bor,SUN STAFF

A 15-year study of families touched by schizophrenia has turned up strong evidence of a genetic susceptibility to the mental disorder, according to scientists from the Johns Hopkins School of Medicine.

The scientists, who studied more than 100 families, said they have found a genetic marker that many schizophrenic patients shared with family members afflicted with the disease. This, they say, lends weight to the long-held belief that genetics is at least partly responsible for the disease.

Led by Dr. Ann Pulver of Johns Hopkins, an international team of researchers found a stretch of DNA where the gene apparently resides -- but not the gene itself. This is somewhat akin to finding a city but not the house where someone lives, she said.

The discovery, reported in the September issue of the journal Nature Genetics, clears up only a small part of the mystery behind a disease that afflicts about 1 percent of the world population.

The gene is probably one of several that work in various combinations to predispose people to the disorder. Even then, an environmental "trigger" is probably needed for the disease to occur.

"The assumption is that genes aren't acting alone," said Dr. Gerald Nestadt, a Hopkins psychiatrist who worked on the study. "There are environmental factors -- perhaps injuries during pregnancy."

Other possibilities are infections, drugs, stress and trauma.

This separates schizophrenia from such diseases as Huntington's, a neurological affliction caused by a single gene.

Among the most devastating of mental disorders, schizophrenia causes distorted and often paranoid thinking. Patients can hallucinate, hear voices or become fixated on single ideas -- such as a belief that they are a historical figure or the target of a worldwide conspiracy.

It often strikes as victims are entering adulthood, and can cause them to withdraw from friends and family. Medications can reduce symptoms, helping patients to function better in society. There is no cure.

In the study, scientists identified more than 100 people who had been diagnosed with schizophrenia. They took blood samples from the patients -- and from afflicted and unafflicted family members. A genetic analysis was done on 1,000 people.

Scientists looked for genetic sequences that were shared by schizophrenic relatives but rarely turn up in the general population. Such patterns mark the approximate location of genes that play some role in disease.

The discovery was a stretch of DNA along chromosome 13 that was shared by 40 percent of afflicted siblings.

The odds against these patterns turning up by chance was extremely remote -- about 1 in 50,000, Pulver said.

L Eventually, the scientists hope to identify the gene itself.

"Once we find that gene, the next step is to understand its function -- what the gene is actually doing, how it affects the chemistry and physiology of the brain," Nestadt said.

That, in turn, could lead to new medications that would counteract whatever the gene is doing.

Also, doctors could turn their attention to identifying people who carry the same susceptibility genes as their schizophrenic relatives -- and to treating them early.

Dr. Irving I. Gottesman, a University of Virginia professor who has written extensively on the genetics of schizophrenia, cautioned that scientific teams have reported eight similar findings over the past decade. In each case, the "discovery" fizzled when other groups were unable to replicate the results.

"Predisposition plays a strong role, there's no doubt about it," Gottesman said. Schizophrenia, he said, may turn out to be like hypercholesterolemia, a predisposition to high cholesterol in which 17 genes are implicated.

The Johns Hopkins team expressed confidence in its discovery, saying the genetic region was shared by a much larger percentage of research subjects than others cited in the past.

Dr. E. Fuller Torrey, a Washington psychiatrist who, with Gottesman, has studied schizophrenia through identical twins, said the environmental triggers may be more important than the genes in understanding schizophrenia.

Torrey, who is studying a hypothesis that viruses trigger the disease, said genes might work by giving viruses a direct route to a sensitive part of the brain.

"At minimum, genes play a role as predisposing factors, but you could say practically the same about other chronic diseases," Torrey said.

Pub Date: 9/01/98

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