increased dopamine levels above an optimum level in met/met individuals and thus negatively impacted cortical function. In contrast, in val/val individuals, amphetamine increased the lower pre-drug dopamine levels so that they were closer to optimal and thus enhanced function. The WCST also showed genotypic effects, with val/val subjects improving following amphetamine administration and met/met individuals performing worse. Taken together, the results of this study suggest that an optimum level of dopamine in the prefrontal cortex is necessary for efficient prefrontal cortex function, and that this efficiency is in part mediated by val158-met genotype. Another study (Hamidovic et al. 2010b) evaluated the effect of val158-met on a processing speed task (Digit Symbol Substitution Test; Wechsler 1958) and a reaction time test measuring attention lapses (Deviation from the Mode; de Wit 2009) and reported that when compared to placebo, amphetamine improved DSST performance in val homozygotes and heterozygotes, but not in met homozygotes. However, val homozygotes and heterozygotes exhibited more lapses in attention under placebo conditions, suggesting that the drug improved a preexisting deficit in one genotypic group. Taken together, these findings suggest that individuals with the met allele are less sensitive to the cognitive enhancing effects of stimulant drugs.
