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.

尽管人类宁愿白天活跃，而晚上睡觉，但昼夜偏爱（“早上 - 在种群中，ness-eveningness''）是高度变化的，受许多因素的影响。最近，变化 在与中度昼夜偏好相关的昼夜节律上。有个人 极端的昼夜偏好（确定的早晨和晚上类型）通常无法入睡和/或唤醒 在他们所需的时间以及睡眠时间与24-H社交和身体的这种错位 环境可能导致昼夜节律睡眠障碍晚期或延迟睡眠期综合征 （ASP，DSP）。 在过去的十年中，昼夜节律的遗传基础已经建立了良好 鉴定构成生成昼夜节律的分子机制的“时钟”基因 节奏。由于昼夜节律与异常偏好之间的关系，以及已建立的 动物昼夜节律系统的遗传调节，可能存在遗传基础 偏好和昼夜节律睡眠障碍。有关于昼夜之间关联的报道 时钟基因的偏好和多态性，以及ASP患者的时钟基因改变的报告 和DSP，尽管并非所有研究都同意。这些差异可能是由于表型方法造成的 用于这些研究。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，我们提出了对极端昼夜类型的彻底表型和遗传评估，以确定 人类昼夜偏好的基本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相（特定目标1），时期 （特定的目标2）和睡眠模式承诺（特定目标3），使用良好的方法（恒定 常规和强迫性方案）可能会产生表现出类似性状的不同表型群体的不同 行为。极端昼夜类型的遗传分析（特定目标4）可能识别相关的多态性 在时钟基因中。这些数据应更好地理解对年级生物学和遗传基础的理解 极端的昼夜偏好，可以更好地治疗昼夜节律睡眠障碍。