Effects of the catechol-O-methyltransferase Val158Met polymorphism on executive function: A meta-analysis of the Wisconsin Card Sort Test in schizophrenia and healthy controls
Abstract
The catechol-O-methyltransferase (COMT) Val(158)Met polymorphism is hypothesized to affect executive function in patient and control populations. Studies inconsistently report better performance on the Wisconsin Card Sort Test (WCST) in individuals with one or more Met alleles. We conducted a meta-analysis of studies published until August 2006 that reported WCST perseverative errors from healthy volunteers or patients with schizophrenia-spectrum disorders. Twelve studies met inclusion criteria (total n=1910) providing 10 samples each of patients and controls. In healthy controls, individuals with the Met/Met genotype performed better than those with the Val/Val genotype (d=0.29; 95% confidence interval (CI) 0.02-0.55; P=0.03), but this was not supported in the patient sample (d=-0.07; 95% CI -0.40 to 0.26; P=0.68). Post hoc analyses suggested that Val and Met alleles are codominant in their effects on cognition. Effect size was greater in studies published at an earlier date and may also be larger in non-Caucasian samples. Gender did not affect the results. There was no evidence of publication bias. We conclude that there is small but significant relationship between Val(158)Met genotype and executive function in healthy individuals but not in schizophrenia.
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The Met allele is associated with fewer perseverative errors in healthy individuals.
“Better working memory (WM) performance (e.g. in N-back tasks), fewer perseverative errors, and higher IQ tend to be associated with the Met allele in healthy individuals (9-11), although some studies have failed to replicate these effects (see 10).”
From Influence of the COMT genotype on working memory and brain activity changes during development (2011) · cites this paper as [9]
The Met allele is associated with better working memory performance in healthy individuals.
“Better working memory (WM) performance (e.g. in N-back tasks), fewer perseverative errors, and higher IQ tend to be associated with the Met allele in healthy individuals (9-11), although some studies have failed to replicate these effects (see 10).”
From Influence of the COMT genotype on working memory and brain activity changes during development (2011) · cites this paper as [9]
The Met allele is associated with higher IQ in healthy individuals.
“Better working memory (WM) performance (e.g. in N-back tasks), fewer perseverative errors, and higher IQ tend to be associated with the Met allele in healthy individuals (9-11), although some studies have failed to replicate these effects (see 10).”
From Influence of the COMT genotype on working memory and brain activity changes during development (2011) · cites this paper as [9]
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- Authors
- Barnett, J. H., Jones, P. B., Robbins, T. W., & Müller, U.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Barnett, J H
- Venue
- Molecular Psychiatry
- Published
- 2007-02-27
- Volume
- 12
- Issue
- 5
- Pages
- 502-509
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W1982342057
- Cited by
- 274
- References
- 65
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 8 · 2023: 2 · 2022: 8 · 2021: 7 · 2020: 8 · 2019: 11 · 2018: 10 · 2017: 11 · 2016: 14 · 2015: 17 · 2014: 18 · 2013: 26 · 2012: 23
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Stanley Medical Research Institute
- 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 Val158Met polymorphism, executive function, Wisconsin Card Sorting Test, perseverative errors, schizophrenia, schizophrenia spectrum disorders, genetic association, cognitive performance, healthy controls
- MeSH terms
- Catechol O-Methyltransferase, Cognition, Female, Gene Frequency, Humans, Male, Neuropsychological Tests, Problem Solving, Reaction Time, Reference Values, Schizophrenia, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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