McLean Hospital & Harvard Medical School, Boston, MA, USA.
Black Dog Institute, University of New South Wales, Sydney, NSW, Australia.
Nicotine Tob Res. 2021 Aug 29;23(10):1779-1786. doi: 10.1093/ntr/ntab072.
Rates of light smoking have increased in recent years and are associated with adverse health outcomes. Reducing light smoking is a challenge because it is unclear why some but not others, progress to heavier smoking. Nicotine has profound effects on brain reward systems and individual differences in nicotine's reward-enhancing effects may drive variability in smoking trajectories. Therefore, we examined whether a genetic risk factor and personality traits known to moderate reward processing, also moderate the reward-enhancing effects of nicotine.
Light smokers (n = 116) performed a Probabilistic Reward Task to assess reward responsiveness after receiving nicotine or placebo (order counterbalanced). Individuals were classified as nicotine dependence 'risk' allele carriers (rs16969968 A-allele carriers) or non-carriers (non-A-allele carriers), and self-reported negative affective traits were also measured.
Across the sample, reward responsiveness was greater following nicotine compared to placebo (p = 0.045). For Caucasian A-allele carriers but not non-A-allele carriers, nicotine enhanced reward responsiveness compared to placebo for those who received placebo first (p = 0.010). Furthermore, for A-allele carriers but not non-A-allele carriers who received nicotine first, the enhanced reward responsiveness in the nicotine condition carried over to the placebo condition (p < 0.001). Depressive traits also moderated the reward-enhancing effects of nicotine (p = 0.010) and were associated with blunted reward responsiveness following placebo but enhanced reward responsiveness following nicotine.
These findings suggest that individual differences in a genetic risk factor and depressive traits alter nicotine's effect on reward responsiveness in light smokers and may be important factors underpinning variability in smoking trajectories in this growing population.
Individuals carrying genetic risk factors associated with nicotine dependence(rs16969968 A-allele carriers) and those with higher levels of depressive personality traits, showmore pronounced increases in reward learning following acute nicotine exposure. These findingssuggest that genetic and personality factors may drive individual differences in smoking trajectoriesin young light smokers by altering the degree to which nicotine enhances reward processing.
NCT02129387 (pre-registered hypothesis: www.clinicaltrials.gov).
近年来，轻度吸烟的比例有所增加，并且与不良健康结果相关。减少轻度吸烟是一个挑战，因为不清楚为什么有些人而不是其他人会发展为更严重的吸烟。尼古丁对大脑奖励系统有深远的影响，而个体对尼古丁奖励增强作用的差异可能会导致吸烟轨迹的变化。因此，我们研究了一个已知调节奖励处理的遗传风险因素和人格特质是否也调节尼古丁的奖励增强作用。
轻度吸烟者（n = 116）接受尼古丁或安慰剂（顺序随机）后进行概率奖励任务，以评估奖励反应能力。个体被分为尼古丁依赖“风险”等位基因携带者（rs16969968 A 等位基因携带者）或非携带者（非 A 等位基因携带者），并报告负面情感特质。
在整个样本中，与安慰剂相比，尼古丁组的奖励反应能力更高（p = 0.045）。对于白种人 A 等位基因携带者，但不是非 A 等位基因携带者，与安慰剂相比，首次接受安慰剂的个体，尼古丁增强了奖励反应能力（p = 0.010）。此外，对于首次接受尼古丁的 A 等位基因携带者，但不是非 A 等位基因携带者，在尼古丁条件下增强的奖励反应能力延续到安慰剂条件（p < 0.001）。抑郁特质也调节了尼古丁的奖励增强作用（p = 0.010），并与安慰剂后奖励反应能力下降相关，而尼古丁后奖励反应能力增强相关。
这些发现表明，遗传风险因素和抑郁特质的个体差异改变了轻度吸烟者中尼古丁对奖励反应能力的影响，并且可能是该人群中吸烟轨迹变化的重要因素。
携带与尼古丁依赖相关的遗传风险因素（rs16969968 A 等位基因携带者）的个体和具有较高抑郁人格特质的个体，在急性尼古丁暴露后，奖励学习的增加更为明显。这些发现表明，遗传和人格因素可能通过改变尼古丁增强奖励处理的程度，驱动年轻轻度吸烟者吸烟轨迹的个体差异。
NCT02129387（预先注册假设：www.clinicaltrials.gov）。
