Circadian rhythms and homeostatic sleep regulation during adolescence: Implications for reward, cognitive control, and substance use risk

项目摘要项目1(P1) 物质使用障碍(SUD)广泛流行，造成毁灭性的健康、经济和社会成本。 SU的发病率在整个青春期都在增加，使这一敏感的发育期成为 风险增加，预防和干预机会增加。然而，要想开发出有效的 通过干预，我们需要确定新的、可改变的SUD危险因素和机制。昼夜节律 睡眠障碍与SU风险有很强的联系，并且它们对SU风险的中介标记物的影响 青春期--奖赏和抑制控制系统--提供了一种看似合理的机械底物。该中心的 概念模型假设青少年的发展与增强的奖励功能有关。 认知控制，内源性昼夜节律的相位延迟，以及较低的稳态睡眠动力。 环境和社会因素与这些发育过程相互作用，通常会导致迟睡。 计时、睡眠时间短和昼夜节律失调--每一种都与物质的增加有关 在青少年和年轻人中使用。P1将利用恒定的例行公事范例严格地描述昼夜节律 通过控制体力活动，姿势，饮食， 以及光线的强度。我们将考察它们在奖赏和认知方面的单独和综合影响。 控制，并结合P2，关于物质使用的发展，以测试潜在的机制 参与CARRS概念模型。小一将招收96名年龄在13-15岁(50%为女性)的青少年，按年龄分组 习惯性睡眠时间(早、中、晚，N=32)。参与者将在家中监测睡眠模式， 活动记录和睡眠日记，然后完成奖励和认知控制的fMRI测量，以及60小时的实验室 会议。实验室课程包括两个晚上的多导睡眠图(PSG)睡眠研究，间隔36小时 睡眠不足。在第一次PSG之后，参与者将在接下来的24小时内遵循固定的程序 清醒的卧床休息；半卧姿；持续昏暗的灯光；以及每小时补充一次营养。24小时后， 参与者将保持清醒，但不限于卧床。生理昼夜节律测量包括唾液 褪黑素；核心体温；毛囊细胞的分子节律(在P3中检查)。生理学 睡眠平衡测量包括唤醒脑电波强度。36小时后的增量睡眠脑电反应 清醒的感觉。行为测试索引有无奖赏调制的认知控制性能 此外，每2小时还会收集一次情绪和困倦的自我报告。最后，在线调查将编制索引 每6个月用药一次，直至研究结束。P1将直接利用由 中心核心。CARR和P1将创新性地促进对不同的昼夜节律和睡眠的理解 动态平衡对青少年SU奖赏认知控制功能和发育的影响。

PROJECT SUMMARY PROJECT 1 (P1) Substance use disorders (SUD) are widely prevalent and pose devastating health, financial, and societal costs. The incidence of SU 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. Circadian rhythm and sleep disturbances have strong ties to SU risk, and their effects on intermediary markers of SU risk in adolescence—reward and inhibitory control systems—provides a plausible mechanistic substrate. The Center’s conceptual model posits that adolescent development is associated with enhanced reward function relative to cognitive control, phase delay in endogenous circadian rhythms, and lower homeostatic sleep drive. Environmental and social factors interact with these developmental processes, often resulting in late sleep timing, short sleep duration, and circadian misalignment—each of which is associated with increased substance use in teens and young adults. P1 will utilize the constant routine paradigm to rigorously characterize circadian rhythms and homeostatic sleep drive by controlling for masking influences of physical activity, posture, meals, and light levels. We will examine their individual and combined effects on measures of reward and cognitive control, and in combination with P2, on the development of substance use, to test the underlying mechanisms involved in the CARRS conceptual model. P1 will enroll 96 adolescents ages 13–15 (50% female) stratified by habitual sleep timing (early, intermediate, late, N=32 each). Participants will monitor sleep patterns at home with actigraphy and sleep diary, then complete fMRI measures of reward and cognitive control and a 60-hour lab session. The lab session includes two nights of polysomnographic (PSG) sleep studies, separated by 36 hours of sleep deprivation. After the first PSG, participants will follow a constant routine for the next 24 hours with wakeful bedrest; semi-recumbent posture; constant dim light; and hourly nutritional supplements. After 24 hours, participants will remain awake, but not confined to bed. Physiological circadian measures include salivary melatonin; core body temperature; and molecular rhythms from hair follicle cells (examined in P3). Physiological sleep homeostatic measures include waking EEG theta power. and delta sleep EEG response following 36 hours of wakefulness. Behavioral tests indexing cognitive control performance with and without reward modulation along with self-reports of mood and sleepiness will be collected every 2 hours. Finally, online surveys will index substance use every 6 months through study conclusion. P1 will draw directly on resources provided by the Center Cores. CARRS and P1 will innovatively advance understanding of distinct circadian and sleep homeostatic effects on reward-cognitive control function and the development of adolescent SU.