Genetic Link May Explain Some Schizophrenia Symptoms

A genetic defect that makes it hard for the brain to screen out background noise may underlie some symptoms of schizophrenia, including hallucinations and hearing voices, researchers report in today's Proceedings of the National Academy of Sciences. The study is the first to find a genetic link to a specific symptom of schizophrenia, an illness estimated to affect more than 2 million Americans.

Based on evidence that some schizophrenia patients have difficulty filtering out background noise and other sensory stimuli, a team led by Robert Freedman, a professor of psychiatry at the University of Colorado School of Medicine and the Veterans Affairs Medical Center in Denver, studied 104 members of nine families, each with at least two cases of schizophrenia. They tested the subjects' brain response to two noises spaced a half-second apart. In most healthy people, the brain screens out the second noise, responding only weakly. But in 35 of 36 schizophrenia patients tested, and in 22 healthy family members, the response to the second noise was as strong as the first.

The researchers then searched for a genetic "marker"--a tag that pinpoints a specific region of DNA consistently inherited by family members who have the abnormality but not by others. Such an inheritance pattern may suggest that a mutation responsible for the abnormality lies close to the marker. They found a candidate region on chromosome 15, which includes a gene for a brain protein called alpha7-nicotinic cholinergic receptor. This receptor responds to the neurotransmitter acetylcholine and other chemicals, including nicotine.

Freedman and his colleagues speculate that a genetic defect in the receptor may lie behind the abnormality, although they have not found a specific mutation. In addition, he says, smoking may temporarily relieve the symptom by flooding the brain with nicotine and stimulating the defective receptor. This may explain why the vast majority of schizophrenia patients smoke, Freedman says.

Other experts say the work is a promising step forward, but caution that the study must be replicated in more families. The method of identifying a trait and then looking for a gene is a good approach, says Ann Pulver, a schizophrenia researcher at Johns Hopkins University. Still, the paper does not prove a link between the gene and the disease, says Steven Moldin, chief of the genetics research program at the National Institute of Mental Health's schizophrenia branch. "In this field, we have had a long history of [statistically promising results] that unravel," he says. "We need a confirming study."

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