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  • Title: Effect of catechol O-methyltransferase val(158)met polymorphism on the p50 gating endophenotype in schizophrenia.
    Author: Lu BY, Martin KE, Edgar JC, Smith AK, Lewis SF, Escamilla MA, Miller GA, Cañive JM.
    Journal: Biol Psychiatry; 2007 Oct 01; 62(7):822-5. PubMed ID: 17448448.
    Abstract:
    BACKGROUND: Studies have implicated prefrontal dopamine in cortical information filtering. Deficit in stimulus filtering, an endophenotype of schizophrenia, can be demonstrated using the auditory P50 paired-click gating paradigm. The role of prefrontal dopamine on P50 gating was investigated, using catechol-O-methyltransferase (COMT) valine (val)(158)methionine (met) polymorphism as a predictor of prefrontal dopamine activity. METHODS: Twenty-five comparison and 42 schizophrenia subjects underwent P50 gating measurement and COMT genotyping. RESULTS: In the combined sample, COMT polymorphism accounted for a unique 10% of gating variance (p = .02), after variance due to diagnosis, smoking status, and antipsychotic use was removed. Valine homozygous individuals exhibited the greatest gating deficit. CONCLUSIONS: Valine homozygous individuals are more likely to have gating deficits, supporting COMT as a genetic determinant of the P50 endophenotype, as well as a role for prefrontal dopamine in auditory filtering.
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