Schizophrenia Linked to Rare, Often Unique Genetic Glitches

By Rick Weiss
Washington Post Staff Writer
Friday, March 28, 2008

Patients with schizophrenia are three to four times as likely as healthy people to harbor large mutations in genes that control brain development, and many of those glitches are unique to each patient, researchers reported yesterday.

The findings are forcing scientists to rethink the reigning model of how genes and environment conspire to cause the debilitating disease, which affects about 1 percent of the population worldwide.

In part, scientists said, the new view is daunting because it suggests that many people with schizophrenia have their own particular genetic underpinnings.

At the same time, the study shows that new screening techniques can find and differentiate among those various mutations. In the long run that could help doctors choose the best medications for individual schizophrenics and speed the development of drugs tailored to certain patients' needs.

"If the genetics tells us that schizophrenia is really 10 different disorders, then let's have 10 treatments that optimize the outcomes for everyone and not just use the same drugs for everybody," said Thomas Insel, director of the National Institute of Mental Health, which helped fund and conduct the study.

The work also offers evidence that autism shares some genetic roots with schizophrenia.

"Take away schizophrenia's hallucinations and delusions," said Jon McClellan, a child psychiatrist at the University of Washington and a leader of the study, published in yesterday's online issue of the journal Science, "and the symptoms that remain, the lack of social interest and withdrawal, are what we call autism. There is clearly an intersection of the brain systems involved."

"It's not that we're now going to be able to solve schizophrenia tomorrow," said Samuel Barondes, director of the center for neurobiology and psychiatry at the University of California at San Francisco, who was not involved in the work. "But it does present a new way of figuring this puzzle out."

Schizophrenia is a disease of disordered thinking and behavior. Patients have trouble organizing their thoughts or communicating sensibly, and many have auditory or visual hallucinations.

The disease, which typically emerges in early adulthood, used to be blamed on "bad mothering" but has since come to be recognized as having genetic roots.

Yet environmental factors also contribute. Pregnant women who experience famine are at increased risk of giving birth to children who will get schizophrenia. Childhood infections may also add to the risk. Further muddying the picture, most schizophrenics have no family history of the disease. That suggests that, to the extent the disease is genetic, the mutations often arise spontaneously either at conception or during fetal development, perhaps after having inherited a general propensity to get such mutations.

Those and other details led scientists to conclude that the mutations contributing to schizophrenia are probably common in the population but have little impact individually, and that only when several occur together is a critical mass of neurological trouble achieved.

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