Circadian & Genetic Evaluation of Extreme Sleep Timing

昼夜节律

• 批准号: 7822423
• 负责人: Jeanne F Duffy
• 金额: $ 1.53万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7822423
• 关键词: Abbreviations; Advanced Sleep Phase Syndrome; Analysis of Variance; Animals; Behavior; Chronic; Circadian Rhythm Sleep Disorders; Circadian Rhythms; Clinical Research; Crying; Data; Delayed Sleep Phase Syndrome; Disease; Electrocardiogram; Electroencephalogram; Electroencephalography; Electrooculogram; Evaluation; Exhibits; Gene Mutation; General Population; Generations; Genes; Genetic; Genetic Heterogeneity; Genetic Polymorphism; Genomics; Health Insurance Portability and Accountability Act; Heterogeneity; Hormonal; Hour; Human; Individual; Lead; Light; Link; MMPI; Melatonin; Methods; Molecular; Mutation; Output; Patients; Pattern; Periodicity; Personality; Phase; Phenotype; Physical environment; Physiology; Polymerase Chain Reaction; Polysomnography; Population; Principal Investigator; Protocols documentation; Publishing; Questionnaires; Regulation; Reporting; Research Personnel; Single Nucleotide Polymorphism; Sleep; Sleep Wake Cycle; Slow-Wave Sleep; Societies; Strigiformes; System; Temperature; Testing; Time; United States Dept. of Health and Human Services; Variant; Visual; Wakefulness; Work; analog; base; casein kinase I; circadian pacemaker; cryptochrome; cryptochrome 2; genetic analysis; genetic variant; preference; premenstrual dysphoric disorder; programs; rapid eye movement; sleep onset; social; suprachiasmatic nucleus; trait; vigilance

Although humans prefer to be active during the day and to sleep at night, diurnal preference("morning- ness-eveningness") is highly variable in the population and influenced by many factors. Recently, variations in circadian rhythmicity associated with moderate diurnal preference have been reported. Individuals with extreme diurnal preference (definite morning and evening types) often have an inability to sleep and/or wake at their desired times, and such misalignment between sleep timing and the 24-h social and physical environment can lead to the circadian rhythm sleep disorders Advanced or Delayed Sleep Phase Syndrome (ASPS, DSPS). In the past decade, the genetic basis of circadian rhythmicity has been well-established, including identification of "clock" genes that comprise the molecular mechanism for the generation of circadian rhythms. Because of the relationship between circadian rhythms and diurnal preference, and the established genetic regulation of the circadian system in animals, there is likely to be a genetic basis to extreme diurnal preference and the circadian rhythm sleep disorders. There are reports of associations between diurnal preference and polymorphisms in clock genes, and reports of clock gene alterations in patients with ASPS and DSPS, although not all studies agree. These discrepancies may be due to the phenotyping methods used in those studies. Much remains unknown about the chronobiologic and sleep mechanisms, as well as the genetic basis, of these phenotypes. Here we propose a thorough phenotypic and genetic evaluation of extreme diurnal types to determine the underlying chronobiologic and genetic basis of human diurnal preference, thereby linking specific genes with observable behavior. A careful evaluation of the endogenous circadian phase (Specific Aim 1), period (Specific Aim 2), and pattern of sleep propensity (Specific Aim 3), using well-established methods (constant routine and forced desynchrony protocols) is likely to yield distinct phenotypic groups exhibiting trait-like ¿ behaviors. Genetic analysis of extreme diurnal types (Specific Aim 4) may identify associated polymorphisms in clock genes. These data should provide better understanding of the chronobiologic and genetic basis of extreme diurnal preference, leading to better treatments for circadian rhythm sleep disorders.

虽然人类喜欢在白天活动，晚上睡觉，但昼夜偏好（“早晨- “夜间-夜间”）在人群中变化很大，并受许多因素影响。最近，变量 在与适度昼夜偏好相关的昼夜节律中，已经有报道。人士 极端的昼夜偏好（明确的早晨和晚上类型）通常无法入睡和/或醒来 在他们想要的时间，睡眠时间和24小时的社会和身体之间的这种不一致， 环境可导致昼夜节律睡眠障碍睡眠时相综合征晚期或延迟 (ASPS、DSPS）。 在过去的十年里，昼夜节律的遗传基础已经得到了很好的建立，包括 鉴定包括产生昼夜节律的分子机制的“时钟”基因 节奏由于昼夜节律和昼夜偏好之间的关系， 动物昼夜节律系统的遗传调节，极端昼夜节律可能存在遗传基础。 偏好和昼夜节律睡眠障碍。有报道称， 时钟基因的偏好和多态性，以及ASPS患者时钟基因改变的报告 和DSPS，虽然不是所有的研究都同意。这些差异可能是由于表型分析方法 在这些研究中使用。关于时间生物学和睡眠机制还有很多未知， 这些表型的遗传基础。 在这里，我们提出了一个彻底的表型和遗传评估极端昼夜类型，以确定 人类昼夜偏好的潜在时间生物学和遗传基础，从而将特定基因与 可观察的行为仔细评估内源性昼夜节律阶段（具体目标1）， （具体目标2）和睡眠倾向模式（具体目标3），使用完善的方法（常数 常规和强制性去甲协议）可能会产生不同的表型组，表现出性状类似的遗传特征。 行为。极端昼夜类型的遗传分析（具体目标4）可能会发现相关的多态性 生物钟基因这些数据应该提供更好的理解的时间生物学和遗传基础， 极端的昼夜偏好，导致更好的治疗昼夜节律睡眠障碍。