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

项目摘要 物质使用（SU）和物质使用障碍（SUD）广泛流行，并造成破坏性的健康， 经济和社会成本。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脆弱性增加 虐待我们进一步的目标是测试在青春期对睡眠和昼夜因素的操纵是否会改变 与SU风险增加相关的因素。SU和SUD的发生率在青春期增加， 使这一敏感的发展时期既有更高的风险，也有更大的机会， 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 SUD的风险因素和机制。CARRS的项目2（P2）将检验个体差异 青春期的睡眠和昼夜节律特征与自我报告、行为和神经系统有关。 奖励功能和认知控制的指标，这反过来又与SU的风险增加有关。 此外，P2测试了一种实验性干预，该干预操纵睡眠和昼夜节律，以直接检查 对奖励功能的影响。P2将研究150名青少年（13-15岁），早期（n=50）和晚期（n=100） 睡眠时间所有参与者将完成2周的家庭睡眠监测，然后进行通宵实验室检查。 访视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。后期组将 继续实验研究，每个参与者随机分为2周的操作或注意控制 条件下（各n=50）。最后，我们对所有受试者进行了为期6个月的睡眠和SU重复随访评估。 P1和P2的参与者检查纵向关联。目的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志物。因变量包括昼夜节律、睡眠 持续时间和昼夜节律失调，以及自我报告，行为和认知控制的神经测量 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SUD风险的神经行为标志物的影响， 定时（n=100）。我们的合作目标（P1/P2）是检查睡眠/昼夜因素，认知控制， 和奖励功能预测后续SU使用自我报告，行为和神经措施， 以及多变量机器学习方法（Core C）。项目2将直接利用核心A的资源： 管理，核心B：表型分析和生物库，核心C：数据管理和统计。结果 将补充P1的昼夜节律和稳态睡眠驱动的发现，并将提供 关于睡眠/昼夜节律的操纵如何改变认知控制、奖励功能和 人类的SU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.