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Rare gene glitch may hold clues for schizophrenia -- NIH-funded study
Date:2/24/2011

as R. Insel, M.D. "This new finding with VIPR2 suggests a series of important follow up studies, even in people without the mutation."

Schizophrenia is known to have a strong genetic component -- having a parent or sibling with the disorder increases one's risk tenfold. Yet, genetic studies have so far explained relatively few cases of the illness. As hopes wane that common genetic variations might account for many cases, evidence is mounting that patients harbor disproportionately large numbers of individually rare copy number variations (CNVs) some shared in families, but many apparently unique to one individual.

The VIPR2 CNV is among the first to implicate a specific gene and neurobiological pathway in schizophrenia. CNVs previously identified, spanning dozens of genes, were too large to yield such clues. In the new genome-wide scan, Sebat and colleagues found the mutation in 29 of 8290 patients (.35 percent) compared to only 2 of 7431 healthy controls. A few other schizophrenia-linked CNVs seen in previous studies were also detected.

VIP and its receptor are known to play a role in regulating the growth of neurons and in learning and memory. They are also expressed in the immune and cardiovascular systems and in the gut hence its name.

When VIP binds to the VIPR2 receptor on a neuron, it triggers a key relay chemical within the cell, called cyclic AMP. The researchers found that both VIP and cyclic AMP were overactive in blood cells of patients with the VIPR2 mutations.

"It's likely that cyclic AMP signaling is disturbed in a larger fraction of patients, so it's possible that a treatment that targets VIPR2 might have benefits even for people who don't have mutations in the VIPR2 gene," said Sebat. "It looks like the volume is turned-up in the whole VIP signaling pathway."

Since the mutations lead to an overexpression of VIPR2, agents that block the receptor, which already exist, might hold pot
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Contact: Jules Asher
NIMHpress@nih.gov
301-443-4536
NIH/National Institute of Mental Health
Source:Eurekalert  

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