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

Abstract

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.

Keywords: Anhedonia; COMT; dopamine; meta-analysis; response bias; reward.

Figure 1. Schematic diagram of the reward learning task

Participants are instructed to press a button on the keyboard to indicate whether a long or short mouth is presented (100 ms) within a schematic face. Following some, but not all correct responses, participants received a monetary reward of 5 cents. One stimulus (rich) was rewarded 3 times more than the other (lean). Figure adapted from (Pizzagalli et al., 2005).

Figure 2. COMT genotype associated with differences in total response bias in the probabilistic reward task

A. In the European-American sample Met/Met participants (n = 55) demonstrated significantly greater total response bias than Val carriers (n = 153) (β=.20, t=2.75, p<.01; ΔR²= .04). Data points are jittered to allow for distribution visualization.

Figure 3. Forest plot of the pooled effect of COMT genotype on total response bias

Size of square is proportional to sample size. CI: confidence interval; df: degrees of freedom; IV: Inverse Variance (statistical method). Lancaster et al., 2015 report a significant COMT rs4680 genotype x block interaction; here we depict the effect for the main effect of COMT rs4680 genotype on response bias.