HEALTH

The roots of insanity

New data show a genetic role in schizophrenia

MARK NICHOLS November 28 1988
HEALTH

The roots of insanity

New data show a genetic role in schizophrenia

MARK NICHOLS November 28 1988

The roots of insanity

HEALTH

New data show a genetic role in schizophrenia

Ever since it was first identified as a disease about 100 years ago, schizophrenia has defied doctors’ search for a cure. During the 1960s, psychiatrists speculated that domineering mothers or other psychological influences might be responsible for causing the debilitating illness that is characterized by hallucinations, disordered thinking and irrational behavior (the idea that schizophrenia involves dual, or “split,” personalities, is a popular misconception). More recently, a theory has grown that at least some types of schizophrenia may have a physical cause and can be passed on by parents to their children. Now a team of international researchers has reported new evidence of a genetic basis for schizophrenia after following up a tantalizing clue uncovered last year by a Canadian researcher. Writing in the Nov. 10 issue of the British scientific weekly Nature, team members, under Dr. Hugh Gurling, head of the molecular psychiatry laboratory at the University of London, reported that after studying schizophrenia in seven families in Britain and Iceland, they had uncovered “the first strong evidence for the involvement of a single gene in the causation of schizophrenia.”

The breakthrough by the Britishled team took place after its researchers tested samples of deoxyribonucleic acid (DNA)—the substance inside human cells that contains coded genetic information—from 104 members of the five Icelandic and two British faiftilies, which all had histories of schizophrenia. The results in each case showed a link between schizophrenia and the fifth of the 23 pairs of gene-bearing chromosomes that everyone inherits from his parents. Scientists cautioned that the finding did not mean that all schizophrenia is related to a genetic flaw on the fifth chromosome. Still, the discovery marked an important step forward in finally understanding the disorder. “I think it can be done,” said Dr. James Kennedy, a Canadian researcher who is studying schizophrenia at Yale University in New Haven, Conn., “if enough money and manpower are involved.”

Gurling’s team launched its research on the strength of an almost accidental discovery by Dr. Anne Bassett, a Vancouver-born psychia-

trist who is now studying at the New York State Psychiatric Institute in New York City. In the spring of 1986, when Bassett was attached to the University of British Columbia’s Health Sciences Centre in Vancouver, she became interested in the case of a 20-year-old schizophrenic. Her curiosity was aroused by the facts that the young man’s uncle also had the disor-

der and that the two men shared certain physical characteristics—including unusually short fourth toes. When Dr. Tapio Pantzar, a University of British Columbia geneticist, examined DNA from the two men, he found that both had an extra copy of the fifth chromosome inside their first chromosome.

When Bassett described that finding at a meeting of the American Psychiatric Association in May, 1987, it created excitement among scientists studying schizophrenia. Said

Dr. Robin Sherrington, the British researcher who carried out the laboratory work for Gurling’s group: “We thought it was one of the best clues we had seen for the possible genetic locus for schizophrenia.” While the British group began studying schizophrenic families in Britain and Iceland to see if their illness was linked to the fifth chromosome, a team of scientists under Yale University geneticist Kenneth Kidd launched a similar study of a large family with a history of schizophrenia in northern Sweden.

In a report that was also published in the Nov. 10 issue of Nature, Kidd’s team reported that it found no link between the disorder in the Swedish family and the fifth chromosome. Still, Kennedy, who played a leading role in the Yale study, said that the group’s findings did not invalidate the discovery by Gurling’s group. “It’s more useful information,” he said. “Now we know that there’s a gene on chromosome five that is involved in some cases of schizophrenia, but not in others.” Indeed, many scientists say that they now expect that a number of different genes may be involved in causing the symptoms associated with schizophrenia.

Meanwhile, a series of other studies triggered by Bassett’s Vancouver discovery may soon shed further light on the disease. She, along with other Canadian and American scientists, is studying several families in Eastern Canada with schizophrenic histories to see if their illness is linked to the fifth chromosome. As well, Gurling’s group is collaborating with scientists in Italy and Bulgaria to test schizophrenic families in those countries. And at least four other U.S. teams are testing groups of schizophrenics and manicdepressives in a wide-ranging search for the underlying genetic causes of those mental illnesses. In London, Gurling’s group now plans to use genetic engineering techniques to narrow their study of DNA from the British and Icelandic families in an attempt to determine which of the hundreds of genes on the family members’ fifth chromosome is involved in schizophrenia.

When the gene itself is isolated, doctors will be able to determine what role it plays in causing the illness in some people. That, in turn, could lead to improved drugs for treating schizophrenics and—perhaps in the distant future—ways of replacing defective genes in unborn babies with healthy ones. For her part, Bassett said that, ultimately, schizophrenia may turn out to be an illness caused by the complex interplay of genetic and environmental factors. But, she added, the work of Gurling’s group has demonstrated that “we now have a hope—and a realistic hope” of understanding one of mankind’s cruellest afflictions.

MARK NICHOLS