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A Signal Deficit in Schizophrenia?

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Science  08 Aug 2003:
Vol. 301, Issue 5634, pp. 737
DOI: 10.1126/science.301.5634.737c

Schizophrenia, a form of mental illness that affects about 1% of the population, is believed to depend on a complex interplay of genetic and environmental factors. Two related articles provide evidence suggesting that alterations in pathways involving the serine-threonine phosphatase calcineurin may contribute to the pathogenesis of this severe and disabling disease.

Miyakawa et al. examined a strain of mutant mice that lacked forebrain calcineurin and observed a spectrum of behavioral abnormalities reminiscent of those found in individuals with schizophrenia. In addition to previously noted deficits in working memory in these mice, the authors describe decreased social interaction, impaired attention, and impaired nesting behavior. The mice also displayed increased hyperactivity, which is characteristic of other animal models of schizophrenia, and enhanced susceptibility to N-methyl-D-aspartate receptor blockade.

In an accompanying article, Gerber et al. demonstrate that the PPP3CC gene, which encodes the calcineurin γ catalytic subunit, maps to a chromosomal locus previously associated with susceptibility to schizophrenia and displays a polymorphism that resulted in a nonconservative change in amino acid sequence. Genetic analysis of families affected with schizophrenia suggested that variations in PPP3CC could increase susceptibility to the disease. — EMA

Proc. Natl. Acad. Sci. U.S.A. 100, 8987; 8993 (2003).

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