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Common gene version optimizes thinking -- but with a possible downside

Most people inherit a version of a gene that optimizes their brain's thinking circuitry, yet also appears to increase risk for schizophrenia, a severe mental illness marked by impaired thinking, scientists at the National Institutes of Health's (NIH) National Institute of Mental Health (NIMH) have discovered. The seeming paradox emerged from the first study to explore the effects of variation in the human gene for a brain master switch, DARPP-32.

The researchers identified a common version of the gene and showed how it impacts the way two key brain regions exchange information, affecting a range of functions from general intelligence to attention.

Three fourths of subjects studied had at least one copy of the version that results in more efficient filtering of information processed by the brain's executive hub, the prefrontal cortex. However, the same version was also more prevalent among people who developed schizophrenia, a severe mental illness marked by delusions, hallucinations and impaired emotion that affects one percent of the population.

"We have found that DARPP-32 shapes and controls a circuit coursing between the human striatum and prefrontal cortex that affects key brain functions implicated in schizophrenia, such as motivation, working memory and reward related learning," explained Andreas Meyer-Lindenberg, M.D.

"Our results raise the question of whether a gene variant favored by evolution, that would normally confer advantage, may translate into a disadvantage if the prefrontal cortex is impaired, as in schizophrenia," added Daniel Weinberger, M.D. "Normally, enhanced cortex connectivity with the striatum would provide increased flexibility, working memory capacity and executive control. But if other genes and environmental events conspire to render the cortex incapable of handling such information, it could backfire -- resulting in the neural equivalent of a superhighway to a dead-end."

Meyer-
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Contact: Jules Asher
NIMHpress@nih.gov
301-443-4536
NIH/National Institute of Mental Health
8-Feb-2007


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