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Schizophrenia study offers clue

Researchers discover a possible link to an infectious agent in the human genome.

March 20, 2007|From Newsday

MELVILLE, N.Y. — A team of Long Island scientists has scanned the entire human genome for evidence of genes that play a role in schizophrenia and has discovered a hot spot near two genes that regulate the immune system.

Dr. Anil Malhotra and Todd Lencz of the Zucker Hillside Hospital campus of the Feinstein Institute for Medical Research in Glen Oaks, N.Y., found that certain markers within these genes were more common in patients with schizophrenia than in those without a history of the mental illness. Their study will appear today in the journal Molecular Psychiatry.

A small group of scientists has long proposed that infectious agents might play a role in schizophrenia.

A finding supported by multiple studies is that toxoplasma, a cat parasite, is two times more common among patients than normal volunteers. One percent of the population suffers from schizophrenia, a serious mental illness that can cause hallucinations, delusions, apathy, dulled emotion and cognitive problems.

The Hillside study looked at genes from 178 chronic schizophrenia patients and 144 volunteers. For computer analysis, they put the DNA from each individual onto a gene chip that has 500,000 markers, numbers along the entire stretch of the human genome.

When they found markers overrepresented in the patient population studied, they looked for genes at or near the marker. The two closest genes they identified are both involved with immune function and are activated when the body is responding to an infection.

The genes are on the male Y chromosome and the female X chromosome, although the genes don't have a specific sex-linked role, Malhotra said. Some of the markers were seen in as many as 30% of the schizophrenia patients, compared with 10% of healthy controls.

The scientists studied another group of 71 schizophrenia patients, and the markers pointed to the same two genes.

"There are a number of common and rare polymorphisms [varieties] that are overrepresented in patients with schizophrenia," Malhotra said.

He suspects that cytokines, substances produced by the immune system, might play a role as a genetic switch that puts certain people at risk.

"It's interesting work," said Dr. Robert Yolken, a professor of pediatrics and director of the Stanley Laboratory of Developmental Neurovirology at Johns Hopkins University School of Medicine. "It fits with the prediction that Dr. [E.] Fuller Torrey and I made that genes discovered in schizophrenia will be associated with an immune response.

"It would make sense that some of the genes are determinants of the response to infection."

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