Skip to main content

Interactive Effects of Tolcapone and Catechol-O-methyltransferase (COMT) Val158Met Polymorphism on Neural Circuits Underlying Emotion Processing

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • N.D. Fogleman
  • C.J. Li
  • R. Rasetti
  • B. Kolachana
  • Q. Chen
  • K.F. Berman
  • D.R. Weinberger
  • V.S. Mattay
  • J.A. Apud


Functional magnetic resonance imaging studies have identified neural networks involved in emotion processing. However, few studies have investigated the interaction of dopaminergic drugs with the COMT val158met polymorphism on emotion regulation. In this study, we explored effects of tolcapone, a drug known to increase cortical dopamine levels via COMT enzyme inhibition, on neural circuits underlying emotion processing. Forty-six normal controls (NCS), matched for age, gender, IQ, race, and drug starting condition, were stratified by COMT genotype and enrolled in a double-blinded, cross-over, placebo controlled trial. Subjects underwent BOLD fMRI while performing an emotion processing task (Faces Task). We found that tolcapone significantly modulated neural activity in the right prefrontal cortex and left amygdala during the Faces task by decreasing BOLD signal in met/met NCS compared to placebo. Tolcapone also increased connectivity from the left amygdala to the anterior cingulate cortex in met/met NCS while decreasing connectivity in val/val NCS compared to placebo. These results (pFWE<0.05) suggest that tolcapone is able to modulate the neural activity underlying emotion processing. Furthermore, differences in the val158met polymorphism seem to influence an inverse relationship for activation and connectivity of the left amygdala. Further analysis using effective connectivity to determine direction of modulation is underway.

back to top