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Mental Health Channel
Reported February 8, 2011

Schizophrenia Gene Mutation Found

(Ivanhoe Newswire) -- In a major advance for schizophrenia research, scientists identified a gene mutation linked to the severe brain disorder and a signaling pathway that could be treatable with existing methods.

"In some ways, this is the kind of gene that the pharmaceutical industry has been waiting for," Jonathan Sebat, PhD, assistant professor of psychiatry and cellular and molecular medicine at the University of California, San Diego School of Medicine, was quoted as saying.” Its activity can be modulated by synthetic peptides; and some have already been created."

Schizophrenia is a chronic, severe and disabling brain disorder, characterized by hallucinations, delusions, and thought disorders. It is believed to be caused by environmental and genetic factors. 

For this study, researchers scanned for copy number variants (CNVs)- a type of genetic variation in which the number of copies of a gene differs between people- in 8,290 individuals with diagnosed schizophrenia and 7,431 healthy controls. “We found very strong links to multiple sites in the genome," said Sebat. "Some had been picked up before in earlier studies, but we uncovered a very important new finding: duplications at the tip of chromosome 7q were detected in individuals with schizophrenia at a rate14 times higher than in healthy individuals. These CNVs impact a gene that is important for brain development – the neuropeptide receptor VIPR2."

Formally known as the Vasoactive Intestinal Peptide Receptor 2, VIPR2 is expressed in the nervous system, including in the brain, blood vessels and gastrointestinal tract. Previous studies have shown that VIPR2 helps to regulate the formation and activity of neurons in the brain. In mice, VIPR2 also has been found to play important roles in behavioral processes, including learning and timing of daily activity.

Sebat and colleagues measured expression of the VIPR2 gene in blood cells from the patients, and they found that individuals with mutations had greater expression of VIPR2 and greater activity of the receptor. "We concluded that the effect of the causal mutations is to raise the volume on the VIP signaling pathway," said Sebat.

"This discovery might be the best target yet to come out of genetic studies of mental illness." said Sebat. "This is what genomic medicine is all about, finding the relevant genes and using this genetic information to come up with a possible strategy for treatment."

Sebat said the next step will be to test whether compounds like these have beneficial effects in mice and in cultured human cells that carry the VIPR2 gene mutation.

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SOURCE: Nature, published online February 3, 2011


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