Intrinsic Circadian Period: Development Delayed Phase and Genetic Associations

描述（由申请人提供）：本提案是一个项目的第二次修订，其主要目的是检查昼夜节律计时系统（特别是内在昼夜节律周期）从青春期到青年期的发育进程，评估患有延迟睡眠阶段综合征（DSPS）的青少年的内在周期，并检查与昼夜节律计时系统和睡眠调节过程的潜在基因关联。青少年人类发展的特点是睡眠时间明显延迟，这对生活在现代社会的青少年有严重的后果：许多青少年睡眠不足，有患情绪问题的风险。修订后的提案研究了成熟的青少年和年轻人的睡眠/觉醒过程，以寻找可能与睡眠阶段延迟有关的调节机制的发育变化。青少年延迟睡眠阶段综合征（DSPS）也进行了研究，并检查了遗传关联。研究1检验了内在昼夜节律周期在青春期发育期间延长，然后在成年早期缩短的假设。在青春期前青少年的新样本中，以及从以前的样本中返回的青少年和年轻人中，以28小时的强制不同步来评估周期。密集的调查要求参与者在家中保持固定的睡眠-觉醒时间表至少两周，然后在特定的测试条件下在实验室连续生活15个昼夜，以测量睡眠，褪黑激素分泌，情绪和表现。研究2使用同样的方法来观察被诊断患有睡眠迟缓症的青少年，这是一种主要的睡眠障碍，通常与情绪和行为问题有关。该研究验证了一个假设，即患有DSPS的青少年的内在周期更长，或者他们在夜间睡眠压力的衰减（慢波活动，SWA）方面有所不同。与研究1中年龄和青春期相匹配的对照组进行比较。研究3是对研究1和2中描述的内表型（例如，内在周期、睡眠压力）是否可归因于目标基因的特定变异的遗传关联的初步调查。将患者和健康参与者进行比较；发展变化也将被检查。公共卫生相关性：该研究项目将通过观察青春期和青年期身体的生物睡眠调节系统的变化，帮助解释青少年睡眠行为的主要变化，这种变化通常会导致睡眠剥夺和情绪问题。患有严重睡眠障碍的青少年，延迟睡眠阶段综合征（DSPS），可能与健康的青少年表现出极大的差异。对这些生物过程的遗传关联的基本知识的获得和发现，可以帮助找到改善青少年睡眠和清醒行为的方法，甚至可能有助于治疗青少年睡眠障碍和其他青少年睡眠障碍。

DESCRIPTION (provided by applicant): This proposal is a second revision of a project whose principal aims are to examine the developmental progression of the circadian timing system (specifically intrinsic circadian period) across adolescence into young adulthood, to evaluate intrinsic period in adolescents with Delayed Sleep Phase Syndrome (DSPS), and to examine potential gene associations with the circadian timing system and sleep regulatory process. Adolescent human development is characterized by a significant delay in the timing of sleep, which has serious consequences for teens living in modern society: many teens are sleep deprived and at risk for mood problems. The revised proposal examines sleep/wake processes in maturing adolescents and young adults for developmental changes in regulatory mechanisms that may relate to the phase delay of sleep. Teens with delayed sleep phase syndrome (DSPS) are also studied, and genetic associations are examined. Study 1 examines the hypothesis that intrinsic circadian period lengthens across adolescent development and then shortens in young adulthood. Period is assessed with 28-h forced desynchrony in a new sample of prepubertal youngsters followed at pubertal maturation, and in returning adolescents and young adults from previous samples. The intensive investigation requires participants to keep a fixed sleep-wake schedule at home for at least two weeks and then to live in the laboratory for 15 consecutive days and nights under specific testing conditions to measure sleep, melatonin secretion, mood, and performance. Study 2 uses the same measures to look at adolescents diagnosed with DSPS, a major sleep disorder often associated with mood and behavior problems. The study tests the hypothesis that intrinsic period is longer in adolescents with DSPS and/or that they differ in the nocturnal decay of sleep pressure (slow wave activitivity, SWA). Comparisons are made to the controls in Study 1 matched for age and pubertal stage. Study 3 is a pilot investigation of genetic associations for whether the endophenotypes described in Studies 1 and 2 (e.g., intrinsic period, sleep pressure) can be attributed to specific variations in target genes. Patients and healthy participants will be compared; developmental changes will be examined as well. PUBLIC HEALTH RELEVANCE: This research project will help explain a major change in teens' sleeping behavior which often leads to sleep deprivation and mood problems by looking at how the body's biological sleep regulation systems change during puberty and young adulthood. Teens with a major sleep disorder, Delayed Sleep Phase Syndrome (DSPS), may show extreme differences from the healthy youngsters. Basic knowledge gained and discovery of genetic associations with these biological processes can help target ways to improve teen sleep and waking behavior and may even help with treatment for DSPS and other adolescent sleep disorders.