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Cited by 216Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorPharmacogenetics and Drug Metabolism

The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: evidence and lessons

Craddock, N, Owen, M J, O'Donovan, M C·2006·Molecular Psychiatry
DOI 10.1038/sj.mp.4001808
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Abstract

The enzyme catechol-O-methyl transferase (COMT), identified in the 1950s, is involved in catabolism of monoamines that are influenced by psychotropic medications, including neuroleptics and antidepressants. The COMT gene lies in a chromosomal region of interest for psychosis and bipolar spectrum disorder and a common polymorphism within the gene alters the activity of the enzyme. As a consequence, COMT has been one of the most studied genes for psychosis. On the basis of prior probabilities it would seem surprising if functional variation at COMT did not have some influence either on susceptibility to psychiatric phenotypes, modification of the course of illness or moderation of response to treatment. There is now robust evidence that variation at COMT influences frontal lobe function. However, despite considerable research effort, it has not proved straightforward to demonstrate and characterise a clear relationship between genetic variation at COMT and psychiatric phenotypes. It is of course, possible that COMT will turn out to be an unusually intractable case but it seems more likely that the experiences with this gene will provide a foretaste of the complexity of genotype-phenotype relationships that will be found for psychiatric traits. In this review, we consider the current state of evidence and the implications both for further studies of COMT and more generally for studies of other genes.

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  • The COMT enzyme breaks down dopamine, is involved in dopamine regulation in both subcortical and prefrontal areas, and plays a major role in dopaminergic signalling exchange between these areas.

    “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 [88]

  • The COMT enzyme mediates the degradation of catecholamines, in particular dopamine.

    “The gene coding for the catechol-O-methyltransferase (COMT) enzyme, which mediates the degradation of catecholamines, in particular dopamine, has attracted considerable attention as a promising candidate gene for studying variance in cognitive function and mental illness (1,2).”

    From Influence of the COMT genotype on working memory and brain activity changes during development (2011) · cites this paper as [1]

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Authors
Craddock, N., Owen, M. J., & O'Donovan, M. C.
Affiliations
Cardiff University (GB)
Corresponding author
Craddock, N
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2006-02-28
Volume
11
Issue
5
Pages
446-458
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/sj.mp.4001808
OpenAlex
W1996330474
Cited by
216
References
123
Citations by year
2026: 1 · 2025: 3 · 2024: 4 · 2023: 9 · 2022: 10 · 2021: 5 · 2020: 6 · 2019: 1 · 2018: 2 · 2017: 5 · 2016: 7 · 2015: 8 · 2014: 2 · 2013: 10 · 2012: 15
FWCI
4.29
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Molecular Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
Funders
  • Wellcome Trust
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
catechol-O-methyltransferase, COMT gene, COMT gene polymorphism, psychosis, bipolar spectrum disorders, psychiatric phenotypes, frontal lobe function, genotype-phenotype correlation, genetic susceptibility, treatment response, antipsychotic drugs, antidepressants
MeSH terms
Bipolar Disorder, Catechol O-Methyltransferase, Chromosomes, Human, Pair 22, Frontal Lobe, Humans, Phenotype, Psychotic Disorders, Genetic Predisposition to Disease

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