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

青春期的昼夜节律和稳态睡眠调节：对奖励、认知控制和物质使用风险的影响

• 批准号: 10655440
• 负责人: PETER L FRANZEN
• 金额: $ 54.32万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10655440
• 关键词: Adolescence; Adolescent; Adolescent Development; Affect; Age; Animals; Bed rest; Beds; Behavior Control; Behavioral; Binding; Body Temperature; Cells; Circadian Rhythms; Circadian desynchrony; Clinical; Cognitive; Complement component C1; Development; Developmental Process; Drowsiness; Electroencephalography; Enrollment; Environment; Environmental Risk Factor; Female; Financial cost; Functional Magnetic Resonance Imaging; Grant; Hair follicle structure; Health Care Costs; Home; Hour; Human; Incidence; Individual; Intervention; Laboratories; Laboratory Study; Life; Light; Link; Machine Learning; Masks; Measures; Melatonin; Modeling; Molecular; Moods; Participant; Patient Self-Report; Performance; Periodicity; Phase; Physical activity; Physiological; Physiology; Polysomnography; Posture; Predictive Factor; Prevention; Protocols documentation; Reporting; Resources; Rewards; Risk; Risk Factors; Risk Reduction; Saccades; Salivary; Sleep; Sleep Deprivation; Sleep disturbances; Slow-Wave Sleep; Social Interaction; Substance Use Disorder; Surveys; System; Teenagers; Testing; Wakefulness; Youth; actigraphy; awake; behavior test; circadian; cognitive control; diaries; dietary supplements; effective intervention; follow-up; indexing; innovation; mind control; modifiable risk; molecular marker; novel; nutrition; recruit; response; sleep pattern; sleep regulation; social factors; societal costs; statistics; stem; substance use; trait; trend; vigilance; young adult

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.

项目概要 项目 1 (P1) 物质使用障碍 (SUD) 广泛流行，并造成毁灭性的健康、财务和社会成本。 SU 的发病率在青春期增加，使这一发育敏感期成为两个时期之一 然而，要制定有效的呼吸风险和呼吸机会预防和干预措施。 干预措施中，我们需要确定昼夜节律的新的、可改变的危险因素和机制。 睡眠障碍与 SU 风险密切相关，并且它们对 SU 风险中间标志物的影响 青春期——奖励和抑制控制系统——提供了该中心的合理的机械基础。 概念模型认为青少年的发展与奖励功能的增强有关 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驱动力。 环境和社会因素与这些发育过程相互作用，通常导致晚睡 时间安排、睡眠时间短和昼夜节律失调——每一个都与物质增加有关 P1 在青少年和年轻人中的使用将利用恒定的常规范式来严格表征昼夜节律。 通过控制身体活动、姿势、饮食、 我们将研究它们对奖励和认知测量的单独和综合影响。 控制，并与 P2 结合，对物质使用的发展进行测试，以测试潜在的机制 参与 CARRS 概念模型的 P1 将招募 96 名 13-15 岁的青少年（50% 为女性），按性别分层。 习惯性睡眠时间（早、中、晚，各 N=32） 参与者将在家中监测睡眠模式。 体动记录仪和睡眠日记，然后完成奖励和认知控制的功能磁共振成像测量以及 60 小时的实验室 实验室会议包括两晚的多导睡眠图 (PSG) 睡眠研究，间隔 36 小时。 第一次 PSG 后，参与者将在接下来的 24 小时内遵循持续的惯例。 清醒的卧床休息；持续昏暗的光线；24小时后补充营养。 参与者将保持清醒，但不限于床上。生理昼夜节律测量包括唾液。 褪黑激素；核心体温；以及毛囊细胞的分子节律（在 P3 中检查）。 睡眠稳态测量包括 36 小时后的清醒 EEG θ 功率和 Delta 睡眠 EEG 反应。 行为测试对有或没有奖励调节的认知控制表现进行索引。 每 2 小时收集一次情绪和睡意自我报告，最后，在线调查将建立索引。 每 6 个月通过研究得出的物质使用结论 P1 将直接利用 P1 提供的资源。 Center Cores 和 P1 将创新性地促进对不同昼夜节律和睡眠的理解。 稳态对奖赏认知控制功能和青少年 SU 发展的影响。