Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine.
Level 3 - non-randomized controlled study
Non-randomized pharmacogenetic challenge study stratified by genotype.
PubMed 12716966 · doi:10.1073/pnas.0931309100
What was done
Authors investigated the effect of the catechol O-methyltransferase (COMT) val158-met functional polymorphism on prefrontal cortex responses to amphetamine. Brain activation was measured using functional MRI during a working memory task across varying levels of difficulty in subjects with the high-enzyme-activity val/val genotype versus the low-activity met/met genotype.
What was found
No numerical values, p-values, or sample sizes were reported in the abstract. Amphetamine enhanced prefrontal cortex efficiency during working memory across all task difficulty levels in val/val subjects. In met/met subjects, amphetamine had no effect on cortical efficiency at low-to-moderate working memory loads and caused deterioration at high working memory loads.
Why it matters
These findings provide human neuroimaging evidence supporting an inverted-U dopamine response curve in the prefrontal cortex and demonstrate that COMT genotype moderates individual cognitive and adverse responses to amphetamine.
Limits
The abstract does not state the sample size, participant demographics, dosing, or quantitative metrics. Details regarding placebo control, blinding, or whether a crossover design was used are omitted, and data for heterozygous (val/met) carriers are not described.
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