Circadian rhythms and sleep in familial DSPS and ASPS

描述（由申请人提供）：在过去的几年里，巨大的进步导致了几个生物钟基因的鉴定。这使得确定人类生物钟基因的改变及其表达如何导致昼夜节律和睡眠/觉醒周期表型的差异成为可能。对理解人类昼夜节律系统的遗传学特别感兴趣的是患有睡眠阶段障碍的个体，如延迟睡眠阶段综合征（DSPS）和提前睡眠阶段综合征（ASPS），因为最近的研究表明这些疾病有遗传基础。虽然假设ASPS和DSPS都是昼夜节律紊乱，但对于昼夜节律系统或其与睡眠过程的相互作用如何在这些个体中受到影响，我们知之甚少。因此，拟议研究的总体目标之一是确定家族性ASPS或DSPS在受干扰和恒定常规条件下的昼夜节律特性（例如，相位、幅度和周期）。第二个目标是测试可以解释这些条件下相位扰动的机制（即，对光的响应，周期的变化）的假设。尽管人们通常认为，在昼夜睡眠阶段障碍中，睡眠本身是正常的，但有证据表明，睡眠稳态的调节可能在DSPS中发生改变。因此，拟制研究的第三个具体目的是通过脑电图/多导睡眠图来定义DSPS和ASPS受试者在基线睡眠和睡眠剥夺后的恢复睡眠期间的睡眠-觉醒特征，其中受试者被允许在正常或异常的昼夜节律时间开始恢复睡眠。研究家族性DSPS和ASPS的方法提供了一个独特的机会，可以清楚地定义个体的昼夜节律和睡眠表型，这些个体的睡眠/觉醒周期是由于内在的生物学变化，而不仅仅是环境影响和社会压力的结果。这些研究的结果不仅将为人类睡眠和昼夜节律的调节提供新的见解，而且还将为治疗睡眠/觉醒周期障碍提供新的治疗方法。

DESCRIPTION (provided by applicant): Tremendous progress in the past few years has led to the identification of several circadian clock genes. This now makes it possible to determine how alterations of human circadian clock genes, and their expression, could lead to differences in circadian and sleep/wake cycle phenotypes. Of particular interest for understanding genetics of the human circadian system are individuals with sleep phase disorders, such as delayed sleep phase syndrome (DSPS) and advanced sleep phase syndrome (ASPS), because recent studies indicate a genetic basis for these disorders. While it is assumed that both ASPS and DSPS are disorders of circadian timing, little is known about how the circadian clock system, or its interaction with sleep processes, are affected in these individuals. Therefore, one of the overall objectives of the proposed studies is to determine the properties (e.g., phase, amplitude, and period) of circadian rhythms under entrained and constant routine conditions in familial ASPS or DSPS. A second objective is to test hypotheses that could explain the mechanisms (i.e., response to light, alterations in period) that underlie the phase disturbance in these conditions. Although it is commonly assumed that sleep per se is normal in the circadian sleep phase disorders, there is some evidence to suggest that the regulation of sleep homeostasis may be altered in DSPS. Therefore, a third specific aim of the proposed studies is to define the sleep-wake characteristics via EEG/polysomnography in DSPS and ASPS subjects during baseline sleep and recovery sleep following sleep deprivation in which the subjects are allowed to begin recovery sleep at a normal or an abnormal circadian time. The approach of studying familial DSPS and ASPS provides a unique opportunity to clearly define circadian and sleep phenotypes in individuals whose sleep/wake cycle is due to intrinsic biological changes and not merely a result of environmental influences and societal pressures. The results of these studies are expected to not only lead to new insights into the regulation of sleep and circadian rhythms in humans, but also to new therapeutic approaches for the treatment of sleep/wake cycle disorders.