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- Title
The catechol-O-methyltransferase polymorphism: relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes.
- Authors
Bilder, Robert M; Volavka, Jan; Lachman, Herbert M; Grace, Anthony A
- 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.
- Publication
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2004, Vol 29, Issue 11, p1943
- ISSN
0893-133X
- Publication type
Journal Article
- DOI
10.1038/sj.npp.1300542