In a first analysis, win-stay, lose-shift, and perseveration rates were mean-corrected and entered in a repeated-measures GLM to assess any differential effects of the polymorphisms

on these three measures. Learning criterion attainment and gender were included as fixed factors of no interest, and age and education were included as covariates of no-interest. The Huyn-Feldt correction was used when significant nonsphericity was detected. After significant interactions CB-839 price of SERT and DAT1 with these behavioral measures were established, further analyses were used to determine the nature of these effects. Lose-shift and win-stay rates were entered as dependent variables in univariate ANOVA, with genotype for each polymorphism, learning criterion attainment (supplement) and gender as fixed effects, including all pairwise interactions. Age and education were included as covariates of no-interest. For significant

effects (p < 0.05) post hoc pairwise t tests of the different genotypes were conducted Regorafenib molecular weight to establish the nature of the genotype effects. Again, for significant effects, we then assessed the specificity with respect to the phase of the experiment (acquisition versus reversal) and the feedback validity, in two mixed repeated-measures ANOVAs with the same factors (DAT1, SERT, learning criterion attainment). For feedback validity, trials were divided into valid trials (win on a correct response, or loss on an incorrect response) and invalid trials. For task phase, trials were divided into acquisition and reversal phases of the task. Due to the small total number of trials it was Idoxuridine not possible to perform this analysis in a single 2 × 2 factorial analysis. The effect of genotype on the perseverative error rate was assessed using a hierarchical regression analysis with three sets of regressors: (1) regressors of no interest: sex, age, and education; (2) main effects: DAT1 and SERT genotype and acquisition score; and (3) interactions: DAT1 × acquisition score, SERT × acquisition score, and DAT1 × SERT. The same analysis was repeated for chance errors to establish the selectivity of the effect. We confirmed

any gene-dose effects using a robust regression on the perseverative error rates versus acquisition scores for each genotype (Cauchy weighting, implemented in MATLAB 2011A). To ascertain that any observed effects on perseveration could not be explained by differences in acquisition, we assessed genotype effects on two basic measures of learning: (1) proportion of subjects passing a strict learning criterion of eight consecutive correct responses, using a χ2 test, and (2) acquisition score, using an ANOVA. To understand the effects of DAT1 on perseveration in the context of reinforcement learning, we used an augmented version of a standard Rescorla-Wagner model of learning. The key feature of this model is learning that is weighted by an experience weight.