Genetic and Depressive Traits Moderate the Reward-Enhancing Effects of Acute Nicotine in Young Light Smokers

Introduction: 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. Methods: Light smokers (n = 116) performed a Probabilistic RewardTask 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. Results: 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. Conclusion: 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. Implications: Individuals carrying genetic risk factors associated with nicotine dependence (rs16969968 A-allele carriers) and those with higher levels of depressive personality traits, show more pronounced increases in reward learning following acute nicotine exposure.These findings suggest that genetic and personality factors may drive individual differences in smoking trajectories in young light smokers by altering the degree to which nicotine enhances reward processing. Clinical trial registration: NCT02129387 (pre-registered hypothesis: www.clinicaltrials.gov)