Interactive effects of tolcapone and catechol-o-methyltransferase (COMT) on anxiety in healthy volunteers

Tuesday, September 23, 2014 — Poster Session III
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NIMH	PHARM-2

Authors

• D.N. Pratt
• N.D. Fogleman
• K.F. Berman
• D.D. Dickinson
• J.A. Apud

Abstract

Catechol-O-methyltransferase (COMT) is an enzyme that catabolizes dopamine (DA) in the prefrontal cortex (PFC). A functional single nucleotide polymorphism (SNP) in the gene, resulting in a valine (Val) to methionine (Met) amino acid substitution, accounts for a three- to four-fold decrease in COMT activity. Therefore, Met allele carriers show increased DA levels in the PFC compared to Val allele homozygotes (Val-Val). Tolcapone is a blood-brain barrier penetrating drug that inhibits COMT enzyme activity, leading to increased DA levels in PFC. Studies have shown better cognitive performance and increased risk sensitivity with COMT inhibition. We hypothesized that Tolcapone treatment might increase anxiety in healthy individuals. Seventy-one healthy adults (31 Val-Val genotype; 40 Met-Met genotype) participated in a blinded, placebo-controlled Tolcapone trial, following a within group, counter-balanced study design. The second arm of the study was performed after a one-week wash-out period following the first arm. Each subject completed the Hamilton Anxiety Scale (HAM-A) on the seventh day of each study arm. The main effect of Tolcapone did not differ between Val-Val and Met-Met individuals. Contrary to hypotheses, Tolcapone decreased anxious mood (P=0.044) and insomnia (P=0.051), but did not affect other anxiety variables or the total score on the HAM-A.

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