Catechol-O-methyltransferase val 108/158met genotype predicts working memory response to antipsychotic medications

Thomas W. Weickert, Terry E. Goldberg, Aaron Mishara, Jose A. Apud, Bhaskar S. Kolachana, Michael F. Egan, Daniel R. Weinberger

Research output: Contribution to journalArticlepeer-review

Abstract

The gene encoding catechol-O-methyltransferase (COMT), an enzyme that regulates prefrontal cortex dopamine, contains a common functional polymorphism (val 108/158met) that influences prefrontal cortex function in an allelic dose-dependent manner. A recent study reported that the COMT val 108/158met polymorphism influences cognitive- and physiologic-related prefrontal cortex responses to antipsychotic treatment. The present study tested the effects of several COMT polymorphisms on the cognitive response to antipsychotic medication in patients with schizophrenia. Twenty inpatients with schizophrenia or schizoaffective disorder (5 with the val-val genotype, 11 with val-met, and 4 with met-met) were administered cognitive tests at two time points: once after 4 weeks of treatment with antipsychotic medication and once after 4 weeks of placebo administration, according to a counterbalanced, double-blind, within-subject study design. Patients homozygous for the COMT met allele displayed significant improvement on the working memory task after treatment. Patients homozygous for the COMT val allele did not show working memory improvement with treatment. Other COMT polymorphisms were not associated with significant differences between treatment and placebo conditions. These results support other data suggesting that the COMT val 108/158met polymorphism might be an important factor in the cognitive response to antipsychotic medication.

Original languageEnglish (US)
Pages (from-to)677-682
Number of pages6
JournalBiological psychiatry
Volume56
Issue number9
DOIs
StatePublished - Nov 1 2004
Externally publishedYes

Keywords

  • Catechol-O-methyltransferase
  • antipsychotics
  • dopamine
  • prefrontal cortex
  • schizophrenia
  • working memory

ASJC Scopus subject areas

  • Biological Psychiatry

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