title: COMT val158met and 5-HTTLPR genetic polymorphisms moderate executive control in cannabis users.
abstract: The adverse effects of cannabis use on executive functions are still controversial, fostering the need for novel biomarkers able to unveil individual differences in the cognitive impact of cannabis consumption. Two common genetic polymorphisms have been linked to the neuroadaptive impact of Δ9-tetrahydrocannabinol (THC) exposure and to executive functions in animals: the catechol-O-methyltransferase (COMT) gene val158met polymorphism and the SLC6A4 gene 5-HTTLPR polymorphism. We aimed to test if these polymorphisms moderate the harmful effects of cannabis use on executive function in young cannabis users. We recruited 144 participants: 86 cannabis users and 58 non-drug user controls. Both groups were genotyped and matched for genetic makeup, sex, age, education, and IQ. We used a computerized neuropsychological battery to assess different aspects of executive functions: sustained attention (CANTAB Rapid Visual Information Processing Test, RVIP), working memory (N-back), monitoring/shifting (CANTAB ID/ED set shifting), planning (CANTAB Stockings of Cambridge, SOC), and decision-making (Iowa Gambling Task, IGT). We used general linear model-based analyses to test performance differences between cannabis users and controls as a function of genotypes. We found that: (i) daily cannabis use is not associated with executive function deficits; and (ii) COMT val158met and 5-HTTLPR polymorphisms moderate the link between cannabis use and executive performance. Cannabis users carrying the COMT val/val genotype exhibited lower accuracy of sustained attention, associated with a more strict response bias, than val/val non-users. Cannabis users carrying the COMT val allele also committed more monitoring/shifting errors than cannabis users carrying the met/met genotype. Finally, cannabis users carrying the 5-HTTLPR s/s genotype had worse IGT performance than s/s non-users. COMT and SLC6A4 genes moderate the impact of cannabis use on executive functions.
authors: School of Psychology and Psychiatry, Monash University, Melbourne, VIC, Australia. antonio.verdejo@monash.edu
authors: Antonio
authors: A
authors: Verdejo-García
authors: Ana Beatriz
authors: AB
authors: Fagundo
authors: Aida
authors: A
authors: Cuenca
authors: Joan
authors: J
authors: Rodriguez
authors: Elisabet
authors: E
authors: Cuyás
authors: Klaus
authors: K
authors: Langohr
authors: Susana
authors: S
authors: de Sola Llopis
authors: Ester
authors: E
authors: Civit
authors: Magí
authors: M
authors: Farré
authors: Jordi
authors: J
authors: Peña-Casanova
authors: Rafael
authors: R
authors: de la Torre
mesh_terms: D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000235:genetics* / Q000523:psychology; D008715:Methionine / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011597:Psychomotor Performance / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D014633:Valine / Q000235:genetics; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine