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.

Background

Prepulse inhibition (PPI) of startle, an operational measure of sensorimotor gating, is used to study normal and pathological brain function. From 2001 to 2016, we screened healthy subjects (HS) to establish their suitability for tests of drug effects on PPI. Because of the size and systematic characterization of this sample across variables of relevance to PPI, we now report these screening results.

Methods

Acoustic startle and PPI were assessed in HS to identify those eligible for studies of drug effects on PPI from 2001 to 2016, yielding 457 "eligible" subjects.

Results

Data confirmed the consistency of PPI across this 15-year period, and supported the role of several variables previously reported to moderate either startle or PPI.

Conclusions

Startle and PPI are robust physiological measures that are predictably moderated by specific physiological variables in healthy adults. As such, these measures serve as robust markers of neurobiological processes in healthy and patient populations.