Journal
BIOLOGICAL PSYCHIATRY
Volume 62, Issue 7, Pages 822-825Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2006.11.030
Keywords
auditory gating; dopamine; electrophysiology; genetics; schizophrenia
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Funding
- NIMH NIH HHS [MH-65304] Funding Source: Medline
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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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