학술논문

Adverse effect of catechol-O-methyltransferase (COMT) Val158Met met/met genotype in methamphetamine-related executive dysfunction
Document Type
article
Source
Subject
Biological Psychology
Psychology
Neurosciences
Substance Misuse
Methamphetamine
Genetics
Good Health and Well Being
Adolescent
Adult
Aged
Amphetamine-Related Disorders
Catechol O-Methyltransferase
Dopamine
Executive Function
Genetic Predisposition to Disease
Genotype
Humans
Male
Middle Aged
Polymorphism
Single Nucleotide
Prefrontal Cortex
Stroop Test
Trail Making Test
Wisconsin Card Sorting Test
Young Adult
COMT Val158Met
Executive function
Cognition
TMARC Group
Public Health and Health Services
Substance Abuse
Public health
Biological psychology
Clinical and health psychology
Language
Abstract
IntroductionThe Val allele of the Val158Met single-nucleotide polymorphism of the catechol-o-methyltransferase gene (COMT) confers greater catabolism of dopamine (DA) in the prefrontal cortex (PFC) than the Met allele. Met/Met homozygotes typically outperform Val-carriers on tests of executive function (EF), perhaps resulting from increased DA bioavailability. Methamphetamine (METH) causes large releases of DA, which is associated with neurotoxicity and executive dysfunction in chronic METH users. We hypothesized that, contrary to its effect in non-METH-using populations, slower DA clearance conferred by Met/Met will relate to worse EF in METH users.Methods149 non-Hispanic White men, stratified by METH dependence (METH+/-) and COMT (Val/Val, Val/Met, Met/Met), completed three tests of EF: Wisconsin Card Sorting Test (WCST), Stroop Color-Word Test (Stroop), and Trail Making Test Part B (Trails B). Demographically-adjusted test scores were averaged to create an EF composite T-score. We examined the interaction of METH and COMT on the EF composite and individual test T-scores, controlling for premorbid functioning and alcohol use.ResultsMETH group differences in EF were evident only among Met/Met carriers (beta = -9.36, p