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Biol Psychiatry. 2007 Oct 1;62(7):822-5. Epub 2007 Apr 19.

Effect of catechol O-methyltransferase val(158)met polymorphism on the p50 gating endophenotype in schizophrenia.

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  • 1Department of Psychiatry, University of New Mexico, Albuquerque, New Mexico 87108, USA. brettlu@yahoo.com

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.

PMID:
17448448
[PubMed - indexed for MEDLINE]
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