Adverse effect of catechol-O-methyltransferase (COMT) Val158Met met/met genotype in methamphetamine-related executive dysfunction.
Adolescent
Adult
Aged
Amphetamine-Related Disorders
/ genetics
Catechol O-Methyltransferase
/ genetics
Dopamine
/ metabolism
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
COMT Val158Met
Cognition
Dopamine
Executive function
Methamphetamine
Journal
Addictive behaviors
ISSN: 1873-6327
Titre abrégé: Addict Behav
Pays: England
ID NLM: 7603486
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
07
09
2018
revised:
03
06
2019
accepted:
10
06
2019
pubmed:
14
7
2019
medline:
29
10
2020
entrez:
14
7
2019
Statut:
ppublish
Résumé
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 < .001) but not among Val carriers: Val/Met (beta = -1.38, p = .44) and Val/Val (beta = -4.34, p = .10). These effects were most salient on the WCST. In the pre-frontal hyperdopaminergic state triggered by methamphetamine, greater DA inactivation conferred by the Val allele may protect against METH-related executive dysfunction, suggesting genetically-driven differences in vulnerability to METH.
Identifiants
pubmed: 31301644
pii: S0306-4603(18)31006-2
doi: 10.1016/j.addbeh.2019.06.012
pmc: PMC6733518
mid: NIHMS1534151
pii:
doi:
Substances chimiques
Methamphetamine
44RAL3456C
COMT protein, human
EC 2.1.1.6
Catechol O-Methyltransferase
EC 2.1.1.6
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
106023Subventions
Organisme : NIDA NIH HHS
ID : R01 DA026334
Pays : United States
Organisme : NIDA NIH HHS
ID : T32 DA031098
Pays : United States
Organisme : NIMH NIH HHS
ID : P30 MH062512
Pays : United States
Organisme : NIA NIH HHS
ID : F31 AG064989
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI036214
Pays : United States
Organisme : NIDA NIH HHS
ID : P50 DA026306
Pays : United States
Organisme : NIDA NIH HHS
ID : K24 DA040550
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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