title: Replication study implicates COMT val158met polymorphism as a modulator of probabilistic reward learning.
abstract: Previous studies suggest that a single nucleotide polymorphism in the catechol-O-methyltransferase (COMT) gene (val158met) may modulate reward-guided decision making in healthy individuals. The polymorphism affects dopamine catabolism and thus modulates prefrontal dopamine levels, which may lead to variation in individual responses to risk and reward. We previously showed, using tasks that index reward responsiveness (measured by responses bias towards reinforced stimuli) and risk taking (measured by the Balloon Analogue Risk Task), that COMT met homozygotes had increased reward responsiveness and, thus, an increased propensity to seek reward. In this study, we sought to replicate these effects in a larger, independent cohort of Caucasian UK university students and staff with similar demographic characteristics (n = 101; 54 females, mean age: 22.2 years). Similarly to our previous study, we observed a significant trial × COMT genotype interaction (P = 0.047; η(2) = 0.052), which was driven by a significant effect of COMT on the incremental acquisition of response bias [response bias at block 3 - block 1 (met/met > val/val: P = 0.028) and block 3 - block 2 (met/met > val/val: P = 0.007)], suggesting that COMT met homozygotes demonstrated higher levels of reward responsiveness by the end of the task. However, we failed to see main effects of COMT genotype on overall response bias or risk-seeking behaviour. These results provide additional evidence that prefrontal dopaminergic variation may have a role in reward responsiveness, but not risk-seeking behaviour. Our findings may have implications for neuropsychiatric disorders characterized by clinical deficits in reward processing such as anhedonia.
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.
authors.forename: T M
authors.initials: TM
authors.lastname: Lancaster
authors.affiliation: School of Psychology, Bangor University, Bangor, UK.
authors.forename: E A
authors.initials: EA
authors.lastname: Heerey
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.|MRC Centre for Neuropsychiatric Genetics & Genomics, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: K
authors.initials: K
authors.lastname: Mantripragada
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.|MRC Centre for Neuropsychiatric Genetics & Genomics, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: D E J
authors.initials: DE
authors.lastname: Linden
mesh_terms: D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003657:Decision Making; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011337:Probability Learning; D012201:Reward; D012309:Risk-Taking; D055815:Young Adult
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D004298:Dopamine
keywords: Anhedonia; BART; COMT; dopamine; genetics; prefrontal; reward responsiveness; reward seeking; signal detection; val158met