The catechol-O-methyltransferase polymorphism

Relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes

Robert M. Bilder, Jan Volavka, Herbert M. Lachman, Anthony A. Grace

Research output: Contribution to journalArticle

560 Citations (Scopus)

Abstract

Diverse phenotypic associations with the catechol-O-methyltransferase (COMT) Val158Met polymorphism have been reported. We suggest that some of the complex effects of this polymorphism be understood from the perspective of the tonic-phasic dopamine (DA) hypothesis. We hypothesize that the COMT Met allele (associated with low enzyme activity) results in increased levels of tonic DA and reciprocal reductions in phasic DA in subcortical regions and increased D1 transmission cortically. This pattern of effects is hypothesized to yield increased stability but decreased flexibility of neural network activation states that underlie important aspects of working memory and executive functions; these effects may be beneficial or detrimental depending on the phenotype, a range of endogenous factors, and environmental exigencies. The literature on phenotypic associations of the COMT Val158Met polymorphism is reviewed, highlighting areas where this hypothesis may have explanatory value, and pointing to possible directions for refinement of relevant phenotypes and experimental evaluation of this hypothesis.

Original languageEnglish (US)
Pages (from-to)1943-1961
Number of pages19
JournalNeuropsychopharmacology
Volume29
Issue number11
DOIs
StatePublished - Nov 2004

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Catechol O-Methyltransferase
Dopamine
Phenotype
Executive Function
Short-Term Memory
Alleles
Enzymes

Keywords

  • Aggression
  • Alcoholism
  • Bipolar disorder
  • Cognition
  • COMT
  • Dopamine
  • Obsessive-compulsive disorder
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology

Cite this

The catechol-O-methyltransferase polymorphism : Relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes. / Bilder, Robert M.; Volavka, Jan; Lachman, Herbert M.; Grace, Anthony A.

In: Neuropsychopharmacology, Vol. 29, No. 11, 11.2004, p. 1943-1961.

Research output: Contribution to journalArticle

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