Neural mechanisms of maturing out of problem alcohol use

摘要 在酗酒后的25岁左右，问题酒精的使用会自然减少， 大量饮酒的高峰期，这一过程被称为“成熟”。虽然大多数年轻人成熟的问题使用， 亚组坚持或升级在他们的饮酒;这些人是在一生的斗争与酒精使用的风险 紊乱什么区别那些成熟的问题饮酒与那些谁不完全是 明白大脑的发育变化被假设在酒精的作用中起着核心作用。 消费的变化，定义成熟期，因为神经成熟是不完全完成，直到中期， 20先令此外，青年期是一个关键的神经发育时期， 奖励相关和皮层认知控制区域成熟，伴随着执行能力的改善， 冲动和寻求刺激的能力下降。尽管假设神经成熟 风险行为（如酗酒）的减少，没有研究直接测试 神经生物学过程和轨迹的酒精使用在年轻的成年。 在这项研究中，我们将招募400名年龄在21岁至25岁之间的人（50%为女性），他们至少报告 在过去的3个月里，每个月都有一次酗酒事件， 共振和功能成像扫描（认知控制，情绪调节，酒精提示反应， 静息状态）。还将收集详细的神经心理学和心理社会测量结果。 随访评估将包括：1）自我报告的酒精使用情况，扫描后每3个月在线测量一次， 检查使用轨迹，2）神经心理学和心理社会测量，在线收集 每年扫描后。参与者将在1-3年级招募。将收集随访评估 直到研究结束，最大限度地延长数据收集期，并允许较大的随访年龄范围 （25-29岁）。我们将使用基线成像数据作为标记， 区分或预测坚持或停止使用的参与者。这种设计将使我们能够1）确定 认知控制、情绪调节和奖励/提示的神经和行为机制 反应预测饮酒轨迹，和2）检查问题饮酒对这些过程的影响。作为 认知控制、情绪和奖励发展方面的性别差异可能会导致酒精使用的变异性， 3)我们还将描述预测酒精使用轨迹的性别差异。作为探索性分析， 我们将使用多模态（结构，静息状态，任务）来研究成熟的神经生物学预测因子。 MRI数据分析。

ABSTRACT There is a normative decrease in problem alcohol use that naturally occurs in the mid-20s after binge and heavy drinking peak, a process called “maturing out”. While most young adults mature out of problem use, a subset persist or escalate in their drinking; these individuals are at risk for lifetime struggles with alcohol use disorders. What differentiates those who mature out of problem drinking versus those who do not is not fully understood. Developmental changes in the brain are hypothesized to play a central role in the alcohol consumption shifts that define the maturing out period, as neural maturation is not fully complete until the mid- 20s. Furthermore, young adulthood is a critical neurodevelopmental period when subcortical emotion and reward-related and cortical cognitive control regions mature, concomitant with improvements in executive control and declines in impulsivity and sensation-seeking. Despite the presumed effect that neural maturation has on decreases in risky behavior (like heavy alcohol use), no study has directly tested associations between neurobiological processes and trajectories of alcohol use in young adulthood. For this study, we will recruit 400 individuals between the ages of 21 and 25 (50% female) who report at least one binge drinking episode a month for the past 3 months to undergo high-resolution structural magnetic resonance and functional imaging scans (cognitive control, emotion regulation, alcohol cue reactivity, and resting state) at baseline. Detailed neuropsychological and psychosocial measurements will also be collected. Follow-up assessments will consist of 1) self-report alcohol use, measured online every 3 months post-scan to examine trajectories of use, and 2) neuropsychological and psychosocial measurements, collected online every year post-scan. Participants will be recruited during Years 1–3. Follow-up assessments will be collected until the end of the study, maximizing the data collection period and allowing for a large follow-up age range (25–29 years). We will model alcohol use trajectories across time, using baseline imaging data as a marker to differentiate or predict participants who persist or desist in use. This design will allow us to 1) determine the extent to which neural and behavioral mechanisms of cognitive control, emotion regulation, and reward/cue reactivity predict drinking trajectories, and 2) examine the effect of problem drinking on these processes. As sex differences in cognitive control, emotion, and reward development likely introduce variability in alcohol use, 3) we will also characterize sex differences predictive of alcohol use trajectories. As an exploratory analysis, we will investigate neurobiological predictors of maturing out using multimodal (structure, resting state, task) MRI data analysis.