Effect of Catechol O-Methyltransferase Val158Met Polymorphism on the P50 Gating Endophenotype in Schizophrenia

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)158methionine (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.