School of Medicine

In order to guide amphetamine's effective use as a treatment, it would be helpful to identify biomarkers that predict its clinical effects. It has been shown in previous studies that there are interindividual differences in amphetamine's effects on working memory. Expanding on a genetic target implicated in the literature, this experiment tested the hypothesis that the COMT val¹⁵⁸met polymorphism contributes to differences in sensitivity to the effects of d-amphetamine on working memory. 69 healthy subjects completed the MATRICS Consensus Cognitive Battery (MCCB) to test their neurocognitive performance after ingesting placebo or d-amphetamine (20 mg). Before and after order effect was corrected, amphetamine's effect on t-scores was inversely proportional to baseline scores in a significant manner on both the letter-number span (R=-0.411, p<0.0001) and the spatial span tasks (R=-0.430, p<0.0001) the lower the score on the placebo day, the more that amphetamine improved scores, and vice versa. Otherwise, there were no significant differences between genotypes or sex and MCCB t-scores. Permutation analyses could not rule out regression to the mean as a potential confound. In conclusion, this experiment was unable to support the hypothesis that COMT genotype is significantly associated with amphetamine's different effects on working memory. Other sample characteristics such as ethnicity may be complicating this relationship and can be examined in future studies.