Evans D E, MacQueen D A, Jentink K G, Park J Y, Lin H-Y, Drobes D J
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.
Genes Brain Behav. 2014 Sep;13(7):626-32. doi: 10.1111/gbb.12151. Epub 2014 Jul 23.
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.
注意力和记忆认知控制相关过程减弱的个体，可能会因尼古丁的认知增强作用而产生吸烟的动机。此外，尼古丁剥夺引起的认知控制能力下降可能会对吸烟起到负强化作用。已证实，烟碱型乙酰胆碱受体α5亚基基因（CHRNA5）中rs16969968位点的次要等位基因携带者，认知控制能力下降且尼古丁依赖性更强。因此，研究该基因中的变异是否会调节尼古丁剥夺对认知控制的影响具有重要意义。由三刺激视觉Oddball任务诱发的事件相关脑电位波形中的P3b和P3a成分，被广泛视为认知控制相关过程的积极指标。我们检验了这样一个假设：CHRNA5基因中rs16969968位点至少携带一个次要等位基因的个体，尼古丁剥夺引起的P3b和P3a波幅下降会更明显。样本包括72名非西班牙裔白人重度吸烟者（54名男性和18名女性），平均年龄为36.11岁（标准差 = 11.57）。参与者在尼古丁和安慰剂吸烟阶段相互平衡的情况下完成视觉Oddball任务。研究结果表明，rs16969968位点状态并未调节尼古丁对P3b或P3a的影响，而其他CHRNA5多态性的变异（其特征不明确且与rs16969968不存在连锁不平衡）则预测了尼古丁剥夺引起的P3a波幅下降：rs588765（F1,68 = 7.74，P = 0.007）和rs17408276（F1,67 = 7.34，P = 0.009）。研究结果是在可能预测尼古丁对认知控制影响的脆弱等位基因背景下进行解释的。
