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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

Molecular Psychiatry volume 12, pages 502–509 (2007)Cite this article

Abstract

The catechol-O-methyltransferase (COMT) Val158Met 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 Val158Met genotype and executive function in healthy individuals but not in schizophrenia.

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Acknowledgements

We thank Dr Tim Croudace for statistical, and Professor David C Rubinsztein for genetic, advice. We are grateful to all the researchers who made extra data available to us to enable its inclusion in the meta-analysis. This study was in part completed at the Cambridge Behavioural and Clinical Neuroscience Institute, jointly funded by Medical Research Council (MRC) and Wellcome Trust. JHB is supported by the Stanley Medical Research Institute and UM by a MRC Pathfinder award.

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  1. Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK

    J H Barnett & P B Jones

  2. Department of Experimental Psychology, University of Cambridge Behavioural and Clinical Neuroscience Institute, Downing Site, Cambridge, UK

    T W Robbins & U Müller

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  1. J H Barnett
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Correspondence to J H Barnett.

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Barnett, J., Jones, P., Robbins, T. et al. 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. Mol Psychiatry 12, 502–509 (2007). https://doi.org/10.1038/sj.mp.4001973

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