The DOI matches its Crossref record; 168 of the 173 references it cites were found in a registry or an index.
The Catechol-O-Methyltransferase Polymorphism: Relations to the Tonic–Phasic Dopamine Hypothesis and Neuropsychiatric Phenotypes
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.
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“Animal studies show that the catechol-O-methyl transferase (COMT) enzyme, which breaks down dopamine, is closely involved in dopamine regulation in both subcortical and prefrontal areas, and plays a major role in the dopaminergic signalling exchange between these areas 87, 88.”
From Resilience in mental health: linking psychological and neurobiological perspectives. (2013) · cites this paper as [87]
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Inverted-U–Shaped Dopamine Actions on Human Working Memory and Cognitive Control
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Metadata
- Authors
- Bilder, R. M., Volavka, J., Lachman, H. M., & Grace, A. A.
- Affiliations
- University of California, Los Angeles (US)
- Nathan Kline Institute for Psychiatric Research (US)
- Albert Einstein College of Medicine (US)
- University of Pittsburgh (US)
- Corresponding author
- Bilder, Robert M
- Venue
- Neuropsychopharmacology
- Published
- 2004-08-11
- Volume
- 29
- Issue
- 11
- Pages
- 1943-1961
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W1997343027
- Cited by
- 769
- References
- 173
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 16 · 2023: 20 · 2022: 21 · 2021: 45 · 2020: 20 · 2019: 23 · 2018: 32 · 2017: 34 · 2016: 36 · 2015: 42 · 2014: 57 · 2013: 60 · 2012: 64
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- catechol-O-methyltransferase, COMT Val158Met polymorphism, tonic dopamine, phasic dopamine, dopamine D1 receptor, working memory, executive function, neuropsychiatric phenotypes
- MeSH terms
- Animals, Mental Disorders, Catechol O-Methyltransferase, Dopamine, Humans, Phenotype, Polymorphism, Genetic
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