Genetic underpinnings of schizophrenia revealed

By Will Dunham

WASHINGTON (Reuters) - The devastating mental illness schizophrenia may be caused by many different mutations in many different genes that disrupt biological pathways vital to normal brain development, scientists said on Thursday.

Schizophrenia is a complex disorder marked by delusions, hallucinations and disordered thinking that appears in about 1 percent of all adults. Experts long have struggled to grasp its causes and the role of genetics and environmental factors.

Two teams of researchers published new genetic insights in the journal Science. Their findings suggest that instead of one crucial gene or a handful, a myriad of different glitches in many genes could be responsible for schizophrenia.

DNA deletions and duplications that disrupt genes are far more common in schizophrenics, the researchers found.

These disrupted genes often are related to pathways critical for brain development. They involve creating the infrastructure in which neurons communicate, as well as such functions as neuronal growth and migration and cell death.

"You're basically screwing up the way that the regulation of brain growth occurs," said Dr. Jon McClellan of the University of Washington in Seattle, one of the researchers.

Researchers at the University of Washington and Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, looked at DNA from 150 schizophrenics and from 268 healthy people. These genetic deletions and duplications were present in 15 percent of schizophrenics and only 5 percent of healthy people.

A team of researchers from the U.S. National Institutes of Health came up with similar results looking at another group of schizophrenics who developed the disease as children. The tiny genetic glitches were seen in about 20 percent of them.

Schizophrenia that begins in childhood, as opposed to adulthood, is believed to be a more profound and genetically driven version of the disease.

The findings could inspire new drugs aimed at stabilizing brain pathways disrupted by the genetic anomalies, the researchers said.

"Identifying genes prone to harboring these mutations in brain development pathways holds promise for treatment and prevention of schizophrenia, as well as a wide range of other neurodevelopmental brain disorders," Dr. Thomas Insel, head of the National Institute of Mental Health, said in a statement.

Treating schizophrenia has been a tricky business. Many medicines are available. They often work in the short term to improve symptoms such as hallucinations and delusions, but they generally are less effective over the long term. Also, the drugs treat symptoms and do not cure the underlying disorder.

"It's absolutely true that the genetic causes have been elusive. There's always been recognition that it likely has multiple causes, it's complex and it probably has interactions between both genes and environment," McClellan said.

"If anything, our findings may indicate that it's even more complex than what we suspected because there may be literally thousands and thousands of different mutations in many different number of genes," McClellan said.

(Editing by Mohammad Zargham)

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