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COMT Val158Met modulates the effect of childhood adverse experiences on the risk of alcohol dependence

Authors

  • Arnt F. A. Schellekens,

    Corresponding author
    1. Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, The Netherlands
    2. Nijmegen Institute for Science Practitioners in Addiction, Radboud University Nijmegen, The Netherlands
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  • Barbara Franke,

    1. Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Department of Human Genetics, Radboud University Nijmegen Medical Centre, The Netherlands
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  • Bart Ellenbroek,

    1. Wellington University, School of Psychology, Wellington, New Zealand
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  • Alexander Cools,

    1. Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, The Netherlands
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  • Cor A. J. de Jong,

    1. Nijmegen Institute for Science Practitioners in Addiction, Radboud University Nijmegen, The Netherlands
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  • Jan K. Buitelaar,

    1. Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, The Netherlands
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  • Robbert-Jan Verkes

    1. Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour Pompestichting Nijmegen, Radboud University Nijmegen Medical Centre, The Netherlands
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Arnt F. A. Schellekens, Radboud University Nijmegen Medical Centre, Department of Psychiatry, 966, PO Box 9101, Reinier Postlaan 10, 6500 HB Nijmegen, the Netherlands. E-mail: a.f.a.schellekens@psy.umcn.nl

ABSTRACT

Genetic factors and childhood adverse experiences contribute to the vulnerability to alcohol dependence. However, empirical data on the interplay between specific genes and adverse experiences are few. The COMT Val158Met and DRD2/ANKK1 Taq1A genotypes have been suggested to affect both stress sensitivity and the risk for alcohol dependence. This study tested the hypothesis that genetic variation in COMT Val158Met and DRD2/ANKK1 Taq1A interacts with childhood adverse experiences to predict alcohol dependence. Male abstinent alcohol-dependent patients (n = 110) and age-matched healthy male controls (n = 99) were genotyped for the COMT Val158Met and the DRD2/ANKK1 Taq1A genotypes. Childhood adverse events were measured using three self-report questionnaires. Alcohol dependence severity, age of onset and duration of alcohol dependence were analyzed as secondary outcome measures. Statistical analysis involved logistic regression analysis and analysis of variance. Alcohol-dependent patients reported increased childhood adversity. The interaction between childhood adversity and the COMT Val158Met genotype added significantly to the prediction model. This gene–environment interaction was confirmed in the analysis of the secondary outcome measures, i.e. alcohol dependence severity, age of onset and duration of alcohol dependence. The DRD2/ANKK1 Taq1A genotype was not related to alcohol dependence, nor did it interact with childhood adversity in predicting alcohol dependence. This study provides evidence for a gene–environment interaction in alcohol dependence, in which an individual's sensitivity to childhood adverse experience is moderated by the COMT genotype. Exposed carriers of a low-activity Met allele have a higher risk to develop severe alcohol dependence than individuals homozygous for the Val allele.

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