title: CHRNA5 variants moderate the effect of nicotine deprivation on a neural index of cognitive control.
abstract: Individuals with reduced attention and memory cognitive control-related processes may be motivated to smoke as a result of the cognitive enhancing effects of nicotine. Further, nicotine deprivation-induced reductions in cognitive control may negatively reinforce smoking. Minor allele carriers at rs16969968 in the nicotinic acetylcholine receptor α5 subunit gene (CHRNA5) have been shown to exhibit both reduced cognitive control and greater nicotine dependence. It is therefore of interest to see if variants in this gene moderate the influence of nicotine deprivation on cognitive control. P3b and P3a components of the event-related brain potential waveform evoked by a three-stimulus visual oddball task are widely viewed as positive indices of cognitive control-related processes. We tested the hypothesis that individuals possessing at least one minor allele at rs16969968 in CHRNA5 would show greater nicotine deprivation-induced reductions in P3b and P3a amplitude. The sample included 72 non-Hispanic, Caucasian heavy smokers (54 men and 18 women) with a mean age of 36.11 years (SD = 11.57). Participants completed the visual oddball task during counterbalanced nicotine and placebo smoking sessions. Findings indicated that rs16969968 status did not moderate nicotine effects on P3b or P3a, whereas variation in other CHRNA5 polymorphisms, which are not as well characterized and are not in linkage disequilibrium with rs16969968, predicted nicotine deprivation-induced reduction of P3a amplitude: rs588765 (F1,68 = 7.74, P = 0.007) and rs17408276 (F1,67 = 7.34, P = 0.009). Findings are interpreted in the context of vulnerability alleles that may predict nicotine effects on cognitive control.
authors.affiliation: Department of Health Outcomes and Behavior, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA; Department of Oncologic Sciences, University of South Florida, Tampa, FL, USA; Department of Psychology, University of South Florida, Tampa, FL, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Evans
authors.forename: D A
authors.initials: DA
authors.lastname: MacQueen
authors.forename: K G
authors.initials: KG
authors.lastname: Jentink
authors.forename: J Y
authors.initials: JY
authors.lastname: Park
authors.forename: H-Y
authors.initials: HY
authors.lastname: Lin
authors.forename: D J
authors.initials: DJ
authors.lastname: Drobes
mesh_terms: D000328:Adult; D001288:Attention; D003071:Cognition; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009538:Nicotine / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D013375:Substance Withdrawal Syndrome / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics
chemical_list: C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; D009538:Nicotine
keywords: CHRNA5; ERP; P300; P3a; P3b; cognitive control; genetics; nicotine; nicotinic acetylcholine; rs16969968; rs588765; smoking