Study Ties Schizophrenia to Genetic Flaw

An international team of researchers today reported “the first concrete evidence” that schizophrenia can be caused by a genetic defect.

Studying seven Icelandic and British families in which 39 of 104 family members were schizophrenic, the researchers found that all the affected individuals shared a specific segment of deoxyribonucleic acid (DNA) that they believe contains the abnormal gene.

Schizophrenia is a severe mental illness that affects one in every 100 people. Its symptoms include hallucinations and delusions, severely inappropriate emotional responses, erratic behavior, and problems in thinking and concentrating.

The discovery, reported by a team that included researchers from the University of London and UC Irvine in the British journal Nature, promises to make possible identification of individuals who are susceptible to the disorder. Such individuals could then be monitored so that therapy is initiated when the first symptoms develop, a factor that is known to improve the outcome of therapy. The finding could also eventually lead to prenatal screening for at least some forms of schizophrenia.

But researchers believe that schizophrenia may take subtly different forms and that different genetic defects could cause the disorder in other families. American and Swedish researchers also reported today in Nature that they could not find the same gene abnormality in a Swedish family with a high incidence of schizophrenia.

“We know there must be other genes (in this family),” said psychiatrist Kenneth K. Kidd of the Yale School of Medicine, who headed the study of the Swedish family.

Nevertheless, said psychiatrist Charles Schulz of the National Institute of Mental Health, “Our feeling is that this is a significant and historic piece of work. It’s the very first report identifying a single gene abnormality in schizophrenia. It (the gene) may be relevant only for some patients, but the discovery is something that textbooks will note in the future.”

The new study represents the second time in two years that researchers have found an abnormal gene linked to mental illness. In February, 1987, U.S. researchers reported the discovery of a similar DNA segment associated with manic-depressive illness in an Amish community in Pennsylvania. That condition causes sharp swings in mood in an estimated 2 million Americans.

“These studies are confirming what many of us have always thought, that all mental illness has a biological basis,” said psychologist Theodore Reich of the Washington University School of Medicine in St. Louis.

During the last three decades, epidemiological studies have indicated that schizophrenia runs in families. Although the incidence of schizophrenia in the total population is 1%, it is 10% among close family members of a schizophrenic and 50% among the identical twins of schizophrenics.

Studies have also shown a 16% incidence of the disorder in children of schizophrenic mothers placed for adoption shortly after birth. Conversely, the incidence among children adopted by women who were subsequently diagnosed as schizophrenic is near 1%. Such discoveries placed in serious doubt the once-prevalent theory that schizophrenia was a result of the way children were reared.

In studying the genetic material in the blood of the subjects, the University of London team, headed by psychiatrist Hugh Gurling, linked schizophrenia to a specific DNA segment of chromosome number five. Kidd’s group did not.

Kidd’s failure to find the defective segment on chromosome five “does not minimize the importance of the finding that Gurling and his collaborators have made,” said psychiatrist Carlos Pato of NIMH. The apparently contradictory results simply indicate that more than one gene can cause schizophrenia, he said.

In a telephone interview, Gurling said it “would be technically feasible now” to begin genetic counseling of families with a history of schizophrenia, “but it wouldn’t be very accurate until we have identified the other genes that are involved” in specific families.

Gurling and others also said that the gene confers only a predisposition to schizophrenia, and that other physical and environmental factors, such as viral infections during pregnancy and trauma during birth may also be necessary for development of the disorder.