German researchers joined a conspicuous club Monday when they announced they had discovered a gene that might be responsible for causing a rare form of schizophrenia.
While they are not the first to declare progress in finding a gene for mental illness, they are fully aware that so far, each other team that declared victory has had its work debunked.
No area of genetics has been as rife with disappointment as the search for the genes of mental illness. And several experts were quick to challenge the German discovery, saying the evidence tying the gene to the disease is weak. Even a leader of the discovery team says the finding is only tentative.
The long hunt for a gene that could trigger schizophrenia--finding genes is the requisite first step for developing a genetic therapy--shows how elusive the answers are. Hundreds of researchers around the world have joined the hunt because the need is so compelling, and the promise of genetic therapies is tremendous. But it remains just promise.
The recent tsunami of triumph over completion of the Human Genome Project has overshadowed the fact that despite decades of taxpayer-supported research, not a single gene responsible for mental illness has been found.
Mental illness is the leading cause of disability in developed nations, and each sickness is polygenic--involving many genes interacting with the environment. The worst disease--schizophrenia--costs the U.S. an estimated $45 billion a year.
More than 2 million Americans are schizophrenics, and only one in five recovers completely. Families are shattered when the disease seems to strike without warning. Half the victims can't accept that they have it, and even though the most severe symptoms often can be controlled by drugs, four out of 10 still attempt suicide to escape its horrors.
The first signs--which typically emerge in young people--are hallucinations, delusions, disordered thinking, unusual speech and behavior, and social withdrawal, which destroy the ability to interact with others.
Now regarded as a biological disorder rather than a psychological one, schizophrenia seems to run in families, and researchers face tremendous pressures to come up with genes that predispose for it, or cause it, or could be targeted by drugs.
However, the quest has been shattered by the debunking of highly visible reports localizing genes for schizophrenia. Similar fates met discoveries of genes for manic-depression, alcoholism, homosexuality--there even was a report of a gene for bed-wetting--causing gene researchers to vow to be more careful. Indeed, the team that published the possible discovery of the gene was careful not to overstate its importance.
"We have no definitive proof," said Klaus-Peter Lesch, a professor of psychiatry and neurosciences at the University of Wuerzburg in Germany. "But as the data stand now, mutations in this gene appear to be associated with the disease."
But to experts such as Ken Kendler, professor of psychiatry and human genetics at Virginia Commonwealth University, the results of the study are unconvincing and could simply be due to chance. The University of Toronto's Anne S. Bassett and her collaborator, Linda Brzustowicz of Rutgers University, called the results "only suggestive."
Nonetheless, the journal Molecular Psychiatry, in which the study appears, stands by its decision to promote the finding as pivotal.
Molecular Psychiatry, although a young journal, is respected and often cited by researchers. It is regarded as more daring than the parent Nature Genetics, the most cited journal in the field.
"I'm on the editorial board of Molecular Psychiatry and I respect the editor," said Elliot Gershon, a leading schizophrenia gene researcher and chairman of psychiatry at the University of Chicago. "I just disagree with him about this study. I think it poses problems that we researchers will have to work out.
"The field has had a lot of false starts and overhyped findings that turn out to be wrong."
According to Gershon, the chromosomes in which linkage to the disease has been reported at least once, with some corroboration from other studies, include Chromosomes l, 5, 6, 8, 10, 13, 15 and 22.
"If it turns out that this new mutation is seen in a very large series of patients, then these guys spotted it first," he said. "But that has to be shown."
The editor of Molecular Psychiatry seems to believe a new approach is crucial.
"The flaw with most other studies is that schizophrenia is probably a collection of diseases with similar symptoms," said Editor Julio Licinio, a professor of psychiatry at the University of California at Los Angeles. "When you group patients in a study, which everybody does, you can't discover anything because they'll have a series of genetic defects.
"The beauty of this study is Lesch focused on one family with a very distinctive syndrome and was able to find the gene that causes schizophrenia in that family."