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Genes Brain Behav. 2016 Jun;15(5):503-13. doi: 10.1111/gbb.12296.

COMT Val(158) Met genotype is associated with reward learning: a replication study and meta-analysis.

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Psychiatry Department, Washington University in St. Louis, St. Louis, MO, USA.
BRAIN Laboratory, Department of Psychology, Washington University in St. Louis, St. Louis, MO, USA.
Center For Depression, Anxiety and Stress Research and Neuroimaging Center, McLean Hospital and Harvard Medical School, Belmont, MA, USA.
Nipissing University, North Bay, Ontario, Canada.
Centre for Addiction and Mental Health Toronto, Ontario, Canada.
Massachusetts General Hospital and Harvard Medical School, Cambridge, MA, USA.
Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, USA.
23 and Me.
Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.
Department of Psychiatry Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Laboratory of NeuroGenetics, Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO, USA.


Identifying mechanisms through which individual differences in reward learning emerge offers an opportunity to understand both a fundamental form of adaptive responding as well as etiological pathways through which aberrant reward learning may contribute to maladaptive behaviors and psychopathology. One candidate mechanism through which individual differences in reward learning may emerge is variability in dopaminergic reinforcement signaling. A common functional polymorphism within the catechol-O-methyl transferase gene (COMT; rs4680, Val(158) Met) has been linked to reward learning, where homozygosity for the Met allele (linked to heightened prefrontal dopamine function and decreased dopamine synthesis in the midbrain) has been associated with relatively increased reward learning. Here, we used a probabilistic reward learning task to asses response bias, a behavioral form of reward learning, across three separate samples that were combined for analyses (age: 21.80 ± 3.95; n = 392; 268 female; European-American: n = 208). We replicate prior reports that COMT rs4680 Met allele homozygosity is associated with increased reward learning in European-American participants (β = 0.20, t = 2.75, P < 0.01; ΔR(2) = 0.04). Moreover, a meta-analysis of 4 studies, including the current one, confirmed the association between COMT rs4680 genotype and reward learning (95% CI -0.11 to -0.03; z = 3.2; P < 0.01). These results suggest that variability in dopamine signaling associated with COMT rs4680 influences individual differences in reward which may potentially contribute to psychopathology characterized by reward dysfunction.


Anhedonia; COMT; dopamine; meta-analysis; response bias; reward

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