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Publication Abstract Display
Type: Poster
Title: COMT Val158Met Val/Val genotype may mitigate methamphetamine related executive dysfunction.
Authors: Cherner M, Minassian A, Ellis R, Heaton R, Suarez P, Bousman C, Grant I , and the TMARC Group
Date: 02-04-2015
Abstract:OBJECTIVE: Catechol-O-methyltransferase (COMT) is responsible for dopamine (DA) clearance in prefrontal cortex. The COMT Val158Met genetic polymorphism has been linked to differences in executive function. COMT Val alleles confer a high rate of dopamine catabolism, whereas Met alleles result in slower clearance. Met/Met homozygotes typically show advantages on tests of executive function, perhaps resulting from greater bioavailability of DA. Methamphetamine (METH) use causes large releases of DA. This, in turn, is associated with injury to brain tissues. Heavy METH users show a number of cognitive deficits, including executive problems. We hypothesized that, contrary to its effect in non-METH-using populations, faster DA clearance conferred by the Val/Val genotype will be associated with better executive function in METH users. PARTICIPANTS & METHOD: COMT Val158Met genotype was obtained for 85 methamphetamine dependent (METH+) and 62 healthy comparison (METH-) Caucasian men. Val/Met heterozygotes were excluded, resulting in 16 METH- Met/Met, 18 METH- Val/Val, 20 METH+ Met/Met and 16 METH+ Val/Val. Within each METH group, genotype groups had comparable background characteristics. All received the Wisconsin Card Sorting Test 64-item-computerized version as part of a larger battery. Number of perseverative responses was transformed into a demographically adjusted T-score and used as the dependent variable in a multiple regression analysis with METH group, COMT genotype, and their interaction as predictors. RESULTS: There was a significant COMT x METH interaction (p=.0096). Among METH-, those with Met/Met genotype outperformed those with Val/Val [Mean(SD) = 51(11) vs. 44(13)], while among METH+, Val/Val outperformed Met/Met [46(12) vs. 39(8)] and performed comparably to METH-. CONCLUSIONS: Val/Val genotype may confer protection against METH-related executive dysfunction, possibly as a result of greater inactivation of DA in prefrontal cortex, suggesting genetically influenced differences in vulnerability to METH effects.

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