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Related Experiment Video

Updated: May 16, 2026

The 5-Choice Serial Reaction Time Task: A Task of Attention and Impulse Control for Rodents
09:43

The 5-Choice Serial Reaction Time Task: A Task of Attention and Impulse Control for Rodents

Published on: August 10, 2014

Does COMT genotype influence the effects of d-amphetamine on executive functioning?

M C Wardle1, A B Hart, A A Palmer

  • 1Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.

Genes, Brain, and Behavior
|December 13, 2012
PubMed
Summary

This study found that amphetamine did not impact executive functions like working memory, regardless of COMT genotype. Previous findings of amphetamine affecting executive functioning based on COMT genotype were not replicated in this larger sample.

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Last Updated: May 16, 2026

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07:30

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Published on: November 21, 2012

Area of Science:

  • Neuroscience
  • Pharmacogenetics
  • Cognitive Psychology

Background:

  • The catechol-O-methyltransferase (COMT) val158met polymorphism influences dopamine regulation.
  • A prior study suggested amphetamine's effects on executive functioning interact with COMT genotype.

Purpose of the Study:

  • To replicate and extend findings on the interaction between amphetamine and COMT genotype on executive functioning.
  • To investigate the impact of varying d-amphetamine doses on cognitive performance in relation to COMT genotype.

Main Methods:

  • A double-blind, placebo-controlled study with 200 healthy adults.
  • Administration of placebo, d-amphetamine (5, 10, 20 mg), and assessment of executive functioning using the Wisconsin Card Sorting Task and N-Back test.
  • Analysis of COMT val158met genotype in relation to cognitive performance.

Main Results:

  • Amphetamine administration did not significantly alter executive functioning performance.
  • No interaction was observed between COMT genotype (val/val, val/met, met/met) and amphetamine treatment effects on executive functioning.
  • Amphetamine did affect blood pressure and processing speed as expected.

Conclusions:

  • The behavioral interaction between COMT genotype and amphetamine on executive functioning reported previously was not replicated.
  • Findings suggest caution in using COMT genotyping to predict individual responses to dopaminergic drugs.
  • The utility of intermediate phenotypes in genetic research warrants further investigation.