Mechanisms of Depression and Anhedonia in Adolescents: Linking Sleep Duration and Timing to Reward- and Stress-Related Brain Function

7.项目摘要/摘要 这项提案的长期目标是：1)评估抑郁症状的生物行为模型 以及2)利用睡眠和昼夜节律功能来促进心理健康。 这些目标与国家精神卫生研究所(NIMH)的两个关键优先事项一致：1) 确定精神病理学的机制，以及2)改进对精神病理学的预防和治疗。这个 提出的抑郁症模型认为，睡眠时间和/或时间安排会缓和压力事件的影响 通过扰乱奖赏和压力相关的大脑功能来治疗抑郁症状和快感缺失。这项研究 方法使用两个互补的研究设计来评估所提出的模型：1)观察性研究 (n=150)评估睡眠不足和晚睡在多大程度上预测奖赏和压力相关的大脑 功能、抑郁症状和快感缺乏；2)一项实验研究(n=100)，评估 睡眠时间和时间对奖赏和压力相关的大脑功能和抑郁的影响程度 症状和快感减退。样本包括高中生青少年(14-19岁)，他们患有 抑郁症状的风险，基于暴露于终生应激事件和目前的抑郁症状。 招募将分层，以包括睡眠短和晚的青少年(工作日睡眠持续时间≤6小时和 中点≥凌晨4点；与长时间和早睡(工作日睡眠持续时间≥8h和中点≤凌晨2：30； N=50)。这两项研究都包括两周的日常睡眠和压力事件的测量；实验室测量 与奖励和压力相关的大脑功能以及睡眠和昼夜节律特征；自我报告测量 生活中的压力事件；以及日常生活中抑郁症状和快感缺乏的自我报告测量 每周监测一次。实验研究包括随机分配短小和迟缓的青少年 从观察性研究到2周的睡眠：1)延长90分钟并提前睡眠机会 和定时(n=50)；或2)典型的睡眠机会和定时(n=50)。这一研究方法旨在 实现三个具体目标：1)评估睡眠时间和/或时间预测奖励的程度- 和应激相关的大脑功能，并缓和应激生活事件的影响；2)建立 哪些睡眠时间和/或时间会影响奖赏和压力相关的大脑功能，并缓和这些影响 以及3)决定奖赏或压力相关的大脑功能变化的程度 调节睡眠时间和/或时间与后来的抑郁症状和快感缺乏之间的关系。 调查小组在青少年抑郁症的病因和预防方面拥有专门知识，包括 睡眠和有压力的生活事件对压力和奖励系统的影响方面的具体专业知识 会导致抑郁和快感减退。所有四名调查人员也都是有执照的临床心理学家，他们 致力于将精神病理学机制的研究转化为预防性干预。

7. PROJECT SUMMARY/ABSTRACT The long-term objectives of this proposal are: 1) to evaluate a biobehavioral model of depressive symptoms and anhedonia in adolescents, and 2) to leverage sleep and circadian function to promote mental health. These objectives are consistent with two key priorities of the National Institute of Mental Health (NIMH): 1) identify mechanisms of psychopathology, and 2) improve prevention and treatment for psychopathology. The proposed model of depression posits that sleep duration and/or timing moderate the effects of stressful events on depressive symptoms and anhedonia by disrupting reward- and stress-related brain function. The research approach uses two complementary study designs to evaluate the proposed model: 1) an observational study (n=150) that assesses the degree to which short and late sleep predict reward- and stress-related brain function and depressive symptoms and anhedonia, and 2) an experimental study (n=100) that assesses the extent to which sleep duration and timing impact reward- and stress-related brain function and depressive symptoms and anhedonia. The sample includes high-school adolescents (14-19 years of age) with enhanced risk for depressive symptoms based on exposure to lifetime stressful events and current depressive symptoms. Recruitment will be stratified to include adolescents with short and late sleep (weekday sleep duration ≤ 6 h & midpoint ≥ 4 am; n=100) versus long and early sleep (weekday sleep duration ≥ 8 h & midpoint ≤ 2:30 am; n=50). Both studies include measurement of daily sleep and stressful events for 2 weeks; laboratory measures of reward- and stress-related brain function and sleep and circadian characteristics; self-report measures of lifetime stressful events; and self-report measures of depressive symptoms and anhedonia during daily and weekly monitoring. The experimental study includes random assignment of adolescents with short and late sleep from the observational study to 2 weeks of either: 1) 90 min extension and advance of sleep opportunity and timing (n=50); or 2) typical sleep opportunity and timing (n=50). This research approach is designed to accomplish three specific aims: 1) Evaluate the extent to which sleep duration and/or timing predict reward- and stress-related brain function, and moderate the effects of stressful life events; 2) Establish the extent to which sleep duration and/or timing impact reward- and stress-related brain function, and moderate the effects of stressful life events; and 3) Determine the extent to which changes in reward- or stress-related brain function mediate the associations between sleep duration and/or timing and later depressive symptoms and anhedonia. The investigative team has expertise in the etiology and prevention of depression in adolescents, including specific expertise in the impact of sleep and stressful life events on the stress and reward systems that contribute to depression and anhedonia. All four investigators are also licensed clinical psychologists who are committed to translating research on the mechanisms of psychopathology to preventative interventions.