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.