Adolescent circadian misalignment: Mechanistic studies of sleep and light

青少年昼夜节律失调：睡眠和光的机制研究

• 批准号: 10368967
• 负责人: Stephanie Crowley McWilliam
• 金额: $ 53.19万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10368967
• 关键词: Adolescence; Adolescent; Adult; Age; Alcohol consumption; Alcohols; Attenuated; Beds; Behavior; Behavioral; Characteristics; Child; Chronic; Circadian Rhythms; Circadian desynchrony; Data; Depressed mood; Dose; Drowsiness; Drug usage; Effectiveness; Exposure to; Feeling suicidal; Goals; Health Personnel; Household; Impairment; Laboratories; Learning; Left; Light; Lighting; Measures; Melatonin; Moods; Nicotine; Obesity; Outcome; Outcome Measure; Parents; Participant; Performance; Phase; Phase response curves; Phototherapy; Problem Solving; Protocols documentation; Puberty; Randomized; Recommendation; Regimen; Risk; Risk-Taking; Satiation; Schedule; Schools; Side; Sleep; System; Teenagers; Testing; Time; Work; Wrist; Youth; actigraphy; aged; alertness; automobile accident; awake; base; circadian; circadian pacemaker; cognitive performance; conduct problem; cost effective; falls; improved; prevent; response; secondary outcome; sleep behavior; sleep onset; substance use; sunglasses; treatment guidelines; treatment strategy

PROJECT SUMMARY Circadian clocks shift later (delay) with the progression of puberty; this shift contributes to late sleep onsets in older adolescents. Early school start times, however, force teenagers awake earlier than their spontaneous wake time and the opportunity for sleep shortens. Indeed, a majority of adolescents in the U.S. are chronically sleep deprived, getting 1- 2 h less sleep than recommended. Also, many adolescents wake for school at the “wrong” circadian time. Chronic circadian misalignment and sleep restriction are at their peak during late adolescence, and are associated with morning daytime sleepiness, poor academic performance, conduct problems, depressed mood, suicidal ideation, substance use, and obesity. Morning bright light exposure from light boxes can shift rhythms earlier (phase advance) to facilitate earlier sleep onset, and reduce circadian misalignment and the associated risks. We constructed the first phase response curve (PRC) to light for adolescents and determined that the optimal time for bright light exposure to produce phase advances was ~1 h before habitual wake and light should be avoided around the time of habitual bedtime because it causes rhythms to shift later (delay). Studies of adults, however, indicate that restricted sleep and exposure to evening light due to late bedtimes – two classic features of older adolescent sleep – make morning bright light less effective in producing advances. Our pilot data in adolescents mimic this finding, but also suggest that staying awake late in normal household lighting and the subsequent sleep restriction before and during a 3-day morning bright light regimen, can shift the system in the wrong direction (phase delay). The overarching goal of this proposal is to examine the DOSE of sleep restriction and evening household light that prevents the desired phase advance to morning bright light in adolescents aged 14-17 years. Study 1 proposes to construct a sleep restriction with normal household evening light dose-response curve to determine the point at which morning bright light begins to lose its effectiveness. Following a baseline week with 10-h sleep opportunities, participants will keep the same wake time but be randomly assigned to one of 4 bedtimes which will be the same or later than baseline to produce 4 levels of sleep restriction with evening light (0, 1.5, 3, or 4.5 h). After 2 nights, we will gradually shift the sleep schedule earlier for 3 nights, and participants will receive bright light each morning. We hypothesize that the circadian system will advance with sufficient sleep, but with increasing sleep restriction/evening light, circadian rhythms will not shift or will delay despite the phase advancing morning bright light. Study 2 will test whether attenuating evening light exposure by wearing sunglasses before bedtime during sleep restriction can facilitate phase advances. Study 2 will test the same 4 “doses” of sleep restriction. The main outcome measures to build the dose-response curves will be phase shifts of the central circadian clock marked by the dim light melatonin onset (DLMO) and total sleep time measured from wrist actigraphy in the laboratory. Secondary outcomes include cognitive performance, sleepiness, and mood.

项目概要 随着青春期的进展，生物钟会变晚（延迟）；这种转变会导致睡眠开始较晚； 然而，年龄较大的青少年上学时间较早，迫使青少年比他们自然起床的时间更早。 事实上，美国大多数青少年都长期处于觉醒时间和睡眠机会缩短的状态。 睡眠不足，睡眠时间比建议的时间少 1 至 2 小时 此外，许多青少年早上起床去上学。 “错误的”昼夜节律时间在晚间达到高峰。 青春期，并与早晨白天嗜睡、学习成绩差、行为 问题、情绪低落、自杀意念、药物滥用和早晨强光照射引起的肥胖。 灯箱可以更早地改变节律（相位提前），以促进更早的睡眠开始，并减少昼夜节律 我们构建了第一阶段响应曲线（PRC）来分析。 青少年并确定亮光照射产生相位提前的最佳时间为〜1 习惯性起床前的几个小时和习惯性就寝时间前后应避免光照，因为这会导致 然而，对成年人的研究表明，睡眠和接触的时间受到限制。 晚睡造成的夜间光线——老年青少年睡眠的两个典型特征——使早晨光线明亮 我们在青少年中的试点数据模仿了这一发现，但也表明 在正常的家庭照明下保持清醒，并在三天前和期间进行随后的睡眠限制 早晨明亮的光线养生法，可以将系统转向错误的方向（相位延迟）。 该提案旨在检查睡眠限制和晚间家庭灯光的剂量，以防止所需的睡眠 研究 1 建议在 14-17 岁的青少年中建立一个睡眠阶段。 限制正常家庭夜间光剂量反应曲线，以确定早晨的点 在有 10 小时睡眠机会的基准周之后，明亮的光线开始失去效力。 参与者将保持相同的起床时间，但被随机分配到 4 个就寝时间之一，这将是 与基线相同或晚于基线，以产生 4 级夜间灯光睡眠限制（0、1.5、3 或 4.5 小时后）。 2晚，我们将逐渐将睡眠时间提前3晚，参与者将接受明亮的灯光 我们认为，昼夜节律系统会随着充足的睡眠而进步，但随着睡眠的增加。 睡眠限制/夜间光线，昼夜节律不会改变或延迟，尽管相位提前 研究 2 将测试佩戴太阳镜是否可以减弱傍晚的光线照射。 睡前 睡眠限制可以促进阶段推进 研究 2 将测试相同的 4 个“剂量”。 建立剂量反应曲线的主要结果指标是睡眠限制的相移。 中央生物钟以弱光褪黑激素开始 (DLMO) 和总睡眠时间为标志，测量时间为 实验室中的手腕活动记录包括认知表现、困倦和情绪。