Carey Caitlin E, Knodt Annchen R, Conley Emily Drabant, Hariri Ahmad R, Bogdan Ryan
Washington University in St. Louis, Department of Psychological and Brain Sciences, St. Louis, Missouri, USA.
Duke University, Department of Psychology and Neuroscience, Durham, NC, USA.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2017 Mar;2(2):180-187. doi: 10.1016/j.bpsc.2016.10.003.
Problematic alcohol use in adolescence and adulthood is a common and often debilitating correlate of childhood attention-deficit/hyperactivity disorder (ADHD). Converging evidence suggests that ADHD and problematic alcohol use share a common additive genetic basis, which may be mechanistically related to reward-related brain function. In the current study, we examined whether polygenic risk for childhood ADHD is linked to problematic alcohol use in young adulthood through alterations in reward-related activity of the ventral striatum, a neural hub supporting appetitive behaviors and reinforcement learning.
Genomic, neuroimaging, and self-report data were available for 404 non-Hispanic European-American participants who completed the ongoing Duke Neurogenetics Study. Polygenic risk scores for childhood ADHD were calculated based on a genome-wide association study meta-analysis conducted by the Psychiatric Genomics Consortium and tested for association with reward-related ventral striatum activity, measured using a number-guessing functional magnetic resonance imaging paradigm, and self-reported problematic alcohol use. A mediational model tested whether ventral striatum activity indirectly links polygenic risk for ADHD to problematic alcohol use.
Despite having no main effect on problematic alcohol use, polygenic risk for childhood ADHD was indirectly associated with problematic alcohol use through increased reward-related ventral striatum activity.
Individual differences in reward-related brain function may, at least in part, mechanistically link polygenic risk for childhood ADHD to problematic alcohol use.
青少年期和成年期的酒精使用问题是儿童注意力缺陷多动障碍（ADHD）常见且往往使人衰弱的相关因素。越来越多的证据表明，ADHD和酒精使用问题具有共同的加性遗传基础，这可能在机制上与奖励相关的脑功能有关。在本研究中，我们考察了儿童ADHD的多基因风险是否通过腹侧纹状体（一个支持食欲行为和强化学习的神经中枢）奖励相关活动的改变，与青年期的酒精使用问题相关联。
404名完成正在进行的杜克神经遗传学研究的非西班牙裔欧美参与者提供了基因组、神经影像学和自我报告数据。儿童ADHD的多基因风险评分基于精神病基因组学联盟进行的全基因组关联研究荟萃分析计算得出，并测试其与奖励相关的腹侧纹状体活动（使用数字猜测功能磁共振成像范式测量）以及自我报告的酒精使用问题之间的关联。一个中介模型测试了腹侧纹状体活动是否间接将ADHD的多基因风险与酒精使用问题联系起来。
尽管对酒精使用问题没有直接影响，但儿童ADHD的多基因风险通过增加奖励相关的腹侧纹状体活动，与酒精使用问题间接相关。
奖励相关脑功能的个体差异可能至少部分地在机制上将儿童ADHD的多基因风险与酒精使用问题联系起来。
