Delayed sleep phase and risk for adolescent substance use

项目摘要 物质使用障碍（SUD）通常开始在青春期。越来越多的证据表明， 睡眠阶段（DSP）可能会增加青少年物质使用（SU）和SUD的风险。然而， 这种联系及其背后的机制仍不清楚。昼夜节律失调，晚期和晚期 睡眠时间和上学时间早，是青少年SU升高的一个引人注目的潜在因素 DSP与合理的神经行为机制。我们假设DSP相关的昼夜节律 错位降低冲动控制，增加奖赏敏感性，从而增加SUD风险。的 拟议的研究将首次（1）全面描述与以下因素相关的SUD风险状况： 青少年DSP，和（2）探测SUD风险是否通过改变睡眠/昼夜节律时间减少。研究 将评估SUD风险的既定标志物和假定的神经行为机制（冲动和 奖励敏感度）。具体来说，我们提出了一个全面的，多方法的方法来检查DSP的作用 在SUD风险，结合实验室，实验和纵向研究。我们将招募150名样本 12年级学生（17-19岁），分为100个DSP和50个正常阶段青少年。我们将重点关注大麻 和酒精的使用，因为它们在青少年中普遍使用，并且与DSP有明显的联系。实验室研究比较了 在行为和神经影像学（fMRI）上，将DSP青少年组与正常青少年组进行比较 利用冲动和奖励敏感性的任务，以及昼夜节律阶段评估。实验 研究中，我们将探讨是否稳定昼夜节律相位在DSP组通过使用睡眠调度， 时序方法（例如，明亮的光线）改善睡眠和与SUD相关的神经行为功能 风险最后，我们每月对睡眠和SU进行重复随访评估，以探索纵向 在高风险过渡到年轻的成年期。目的1（实验室研究）是比较 DSP组在睡眠/昼夜因素、神经行为标志物和SU方面与正常相组相比。目的2 （实验研究）探讨睡眠时相稳定手法对睡眠和昼夜节律的影响 节律，以及SUD风险的神经行为标志物。一个探索性的纵向目标是！检查 通过重复每月评估，DSP特征与SU变化之间的前瞻性关系 在高风险过渡到年轻的成年期。这项研究意义重大：它关注的是生物学- 在发育期间， DSP和学校规定的早期开始时间之间的不匹配是最糟糕的，整体SUD风险正在飙升。 本研究的创新之处在于：（1）探讨了几种有前途的青少年神经行为通路 SUD，（2）它结合了相关结构的全面和客观的措施，（3）它包括一个 实验操作，以探讨DSP的机制，SUD。最后，拟议的研究将有 实质性影响：它可能为预防和治疗SUD开辟新的基于睡眠/昼夜节律的途径。 !

PROJECT SUMMARY Substance use disorders (SUDs) often begin during adolescence. Mounting evidence indicates that delayed sleep phase (DSP) may confer risk for adolescent substance use (SU) and SUDs. However, the exact nature of this link and the mechanisms underlying it remain unclear. Circadian misalignment, a mismatch between late sleep hours and early school start times, is a compelling potential contributor to elevated SU in adolescent DSP with plausible neurobehavioral mechanisms. We hypothesize that DSP-associated circadian misalignment decreases impulse control and increases reward sensitivity, thereby increasing SUD risk. The proposed study will, for the first time, (1) comprehensively characterize the SUD risk profile associated with adolescent DSP, and (2) probe whether SUD risk is diminished by altering sleep/circadian timing. The study will assess both established markers of SUD risk and putative neurobehavioral mechanisms (impulsivity and reward sensitivity). Specifically, we propose a comprehensive, multi-method approach to examining DSP’s role in SUD risk, combining laboratory, experimental, and longitudinal studies. We will recruit a sample of 150 twelfth graders (17-19 y/o), divided between 100 DSP and 50 normal phase teens. We will focus on cannabis and alcohol use given their prevalent use in adolescents and evident links to DSP. The lab study compares a group of DSP adolescents to a group of normal phase adolescents on behavioral and neuroimaging (fMRI) tasks tapping impulsivity and reward sensitivity, as well as a circadian phase assessment. In the experimental study, we will probe whether stabilizing circadian phase in the DSP group by using sleep scheduling and chronotherapeutic approaches (e.g., bright light) improves sleep and neurobehavioral function relevant to SUD risk. Finally, we include repeated monthly follow-up assessments of sleep and SU to explore longitudinal associations during the high-risk transition to young adulthood. Aim 1 (Laboratory Study) is to compare a DSP group to a normal phase group on sleep/circadian factors, neurobehavioral markers, and SU. Aim 2 (Experimental Study) is to probe the impact of a sleep phase-stabilizing manipulation on sleep and circadian rhythms, as well as neurobehavioral markers of SUD risk. An Exploratory Longitudinal Aim is to!examine the prospective relationships between DSP characteristics and changes in SU via repeated monthly assessments during the high-risk transition to young adulthood. The proposed study is significant: it focuses a biologically- plausible and modifiable sleep phenotype of particular promise, during a developmental period when the mismatch between DSP and school-imposed early start times is at its worst and overall SUD risk is spiking. The proposed study is innovative: (1) it examines several promising neurobehavioral pathways to adolescent SUD, (2) it combines comprehensive and objective measures of relevant constructs, and (3) it includes an experimental manipulation to probe the mechanisms linking DSP to SUD. Finally, the proposed study will have substantial impact: it may open up novel sleep/circadian-based avenues for prevention and treatment of SUD. !