Adverse effect of catechol-O-methyltransferase (COMT) Val158Met met/met genotype in methamphetamine-related executive dysfunction

The 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), pe...

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Bibliographic Details
Published in:Addictive behaviors 2019-11, Vol.98, p.106023-106023, Article 106023
Main Authors: Cherner, Mariana, Watson, Caitlin W.-M., Saloner, Rowan, Halpin, Laura E., Minassian, Arpi, Murray, Sarah S., Vaida, Florin, Bousman, Chad, Everall, Ian
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Amphetamine-Related Disorders - genetics
Amphetamine-Related Disorders - physiopathology
Amphetamine-Related Disorders - psychology
Catechol O-Methyltransferase - genetics
Cognition
COMT Val158Met
Dopamine
Dopamine - metabolism
Executive function
Executive Function - physiology
Genetic Predisposition to Disease
Genotype
Humans
Male
Methamphetamine
Middle Aged
Polymorphism, Single Nucleotide
Prefrontal Cortex
Stroop Test
Trail Making Test
Wisconsin Card Sorting Test
Young Adult
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Summary:The 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. 149 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. METH group differences in EF were evident only among Met/Met carriers (beta = −9.36, p 
ISSN:0306-4603
1873-6327
DOI:10.1016/j.addbeh.2019.06.012