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Feb 9, 2007

Gene Variant that Optimizes Thinking but Increases Risk of Schizophrenia Identified by NIMH

  • Scientists at the NIMH discovered that most people inherit a version of a gene that optimizes their brain's thinking circuitry, yet also appears to increase risk for schizophrenia. The researchers report that their discovery emerged from the first study to explore the effects of variation in the DARPP-32 gene.

    "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," explains Andreas Meyer-Lindenberg, M.D.

    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. Of all the subjects studied, 75% had at least one copy of the version that results in more efficient filtering of information processed by the prefrontal cortex. However, the same version was also more prevalent among people who developed schizophrenia.

    "Our results raise the question of whether a gene variant favored by evolution that would normally confer an advantage may translate in a disadvantage if the prefrontal cortex is impaired, as in schizophrenia," adds 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-Lindenberg, Weinberger, and colleagues in the NIMH Genes, Cognition, and Psychosis program report their results in the February 9, 2007 issue of the Journal of Clinical Investigation.



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