Circadian rhythms, sleep, and substance use risk during adolescence: Observational, experimental, and longitudinal studies

项目总结 物质使用(SU)和物质使用障碍(SUDS)广泛流行，并对健康造成毁灭性的影响， 金融和社会成本。CARRS中心的主要目标是了解睡眠和昼夜节律 青春期的节律特征和环境破坏导致对物质的易感性增加 虐待。我们的进一步目标是测试青春期对睡眠和昼夜节律因素的操纵是否会改变 与SU风险增加相关的因素。SU和SUDS的发病率在整个青春期都会增加， 使这一敏感的发展时期既是高风险时期，也是高风险时期 预防和干预。然而，为了开发有效的干预措施，我们需要确定新的和可修改的 系统性红斑狼疮的危险因素和机制。CARRS的项目2(P2)将测试个体差异 青春期的睡眠和昼夜节律特征与自我报告、行为和神经有关 奖励功能和认知控制的指标，这反过来又与SU风险增加有关。 此外，P2测试了一种操纵睡眠和昼夜节律的实验干预，以直接检查 它对奖励功能的影响。P2将研究150名青少年(年龄13-15岁)，其中早期(n=50)和晚期(n=100) 睡眠时间。所有参与者将完成为期两周的家庭睡眠监测，然后是过夜实验室 访问以评估认知控制和奖励功能的自我报告、行为和神经成像(FMRI)任务， 以及通过唾液褪黑激素的昼夜节律和通过毛囊的分子节律。晚到的小组将 继续实验研究，每个参与者被随机分为两周的操作或注意控制 条件(n=50)。最后，我们包括对所有人的睡眠和SU进行重复6个月的跟踪评估 在P1和P2中的参与者检查纵向关联。目标1是比较早睡者和晚睡者 睡眠/昼夜节律因素和神经行为标记物。因变量包括昼夜节律、睡眠 持续时间和昼夜节律失调，以及认知控制的自我报告、行为和神经测量 和奖励功能。目的2探讨实验性睡眠提前和延长对睡眠的急性影响 和昼夜节律，以及对睡眠迟缓青少年神经行为标记物的影响 计时(n=100)。我们的合作目标(P1/P2)是检查睡眠/昼夜因素、认知控制、 奖励函数使用自我报告、行为和神经测量来预测后续的SU， 以及多变量机器学习方法(核心C)。P2将直接利用核心A的资源： 管理，核心B：表型和生物库，核心C：数据管理和统计。发现 来自P2的将补充来自P1的关于昼夜节律和动态平衡睡眠驱动的研究结果，并将提供 关于操纵睡眠/昼夜节律如何改变认知控制、奖赏功能和 SU在人类中的风险，这可能反过来为新的睡眠和基于昼夜节律的干预提供信息，以降低这种风险。

PROJECT SUMMARY Substance Use (SU) and substance use disorders (SUDs) are widely prevalent and pose devastating health, financial and societal costs. The primary goal of the CARRS Center is to understand how sleep and circadian rhythm traits and environmental disruptions during adolescence lead to increased vulnerability for substance abuse. We further aim to test whether manipulation of sleep and circadian factors during adolescence will alter factors associated with increased risk for SU. The incidence of SU and SUDs increases across adolescence, making this sensitive developmental period one of both heightened risk—and heightened opportunity for prevention and intervention. However, to develop effective interventions, we need to identify novel and modifiable risk factors and mechanisms for SUD. Project 2 (P2) of CARRS will test the hypothesis that individual differences in sleep and circadian characteristics during adolescence are associated with self-report, behavioral, and neural indicators of reward function and cognitive control, which in turn are associated with increased risk for SU. Further, P2 tests an experimental intervention that manipulates sleep and circadian rhythms to directly examine its impact on reward function. P2 will study 150 adolescents (age 13–15) with early (n=50) and late (n=100) sleep timing. All participants will complete 2 weeks of home sleep monitoring, followed by an overnight laboratory visit to assess self-report, behavioral, and neuroimaging (fMRI) tasks of cognitive control and reward function, as well as circadian phase via salivary melatonin and molecular rhythms via hair follicles. The Late group will continue to the experimental study, each participant randomized to 2-week manipulation or attentional control conditions (n=50 each). Finally, we include repeated 6-month follow-up assessments of sleep and SU for all participants in P1 and P2 to examine longitudinal associations. Aim 1 is to compare Early versus Late sleepers on sleep/circadian factors and neurobehavioral markers. Dependent variables include circadian phase, sleep duration, and circadian misalignment, as well as self-report, behavioral, and neural measures of cognitive control and reward function. Aim 2 is to probe the acute effects of experimental sleep advance and extension on sleep and circadian rhythms, as well as effects on neurobehavioral markers of SUD risk, in adolescents with late sleep timing (n=100). Our Collaborative Aim (P1/P2) is to examine whether sleep/circadian factors, cognitive control, and reward function predict subsequent SU across follow-up using self-report, behavioral, and neural measures, as well multivariable machine learning approaches (Core C). P2 will draw directly on resources of Core A: Administration, Core B: Phenotyping and Biobanking, and Core C: Data Management and Statistics. Findings from P2 will complement findings on circadian rhythmicity and homeostatic sleep drive from P1 and will provide definitive findings on how manipulation of sleep/circadian rhythms alters cognitive control, reward function, and SU risk in humans, which may, in turn, inform novel sleep and circadian-based interventions to reduce this risk.