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.

尽管人类更喜欢白天活动、晚上睡觉，但昼夜偏好（“早晨- 夜间度”）在人群中变化很大，并受到许多因素的影响。最近，变化 据报道，昼夜节律与适度的昼夜偏好相关。个人有 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，以及睡眠时间与 24 小时社交和身体活动之间的不一致 环境可导致昼夜节律睡眠障碍提前或延迟睡眠阶段综合症 （ASPS、DSPS）。 在过去的十年中，昼夜节律的遗传基础已经被确立，包括 鉴定构成昼夜节律产生分子机制的“时钟”基因 节奏。由于昼夜节律和昼夜偏好之间的关系，以及既定的 动物昼夜节律系统的遗传调控，极端的昼夜节律可能有遗传基础 偏好和昼夜节律睡眠障碍。有报告称昼夜节律之间存在关联 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，尽管并非所有研究都同意。这些差异可能是由于表型分析方法造成的 在这些研究中使用。关于时间生物学和睡眠机制以及 这些表型的遗传基础。 在这里，我们建议对极端昼夜类型进行彻底的表型和遗传评估，以确定 人类昼夜偏好的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）、周期 （具体目标 2）和睡眠倾向模式（具体目标 3），使用行之有效的方法（恒定 常规和强制去同步协议）可能会产生表现出类似性状的不同表型组 ¿ 行为。极端昼夜类型的遗传分析（具体目标 4）可以识别相关的多态性 在时钟基因中。这些数据应该可以更好地理解时间生物学和遗传学基础 极端的昼夜偏好，可以更好地治疗昼夜节律睡眠障碍。