SLEEP-RELATED ENDOCRINE PROFILES IN SUBJECTS WITH CIRCADIAN PHASE DISORDERS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在过去的几年里，巨大的进展导致了几个生物钟基因的鉴定。 现在，这使得确定人类生物钟基因及其表达的改变如何导致昼夜节律和睡眠/觉醒周期表型的差异成为可能。 对于理解人类昼夜节律系统的遗传学特别感兴趣的是具有睡眠相位障碍的个体，例如睡眠相位延迟综合征（DSPS）和睡眠相位提前综合征（ASPS），因为最近的研究表明这些障碍的遗传基础。 虽然ASPS和DSPS都被认为是昼夜节律紊乱，但人们对这些个体的昼夜节律钟系统或其与睡眠过程的相互作用如何受到影响知之甚少。 因此，拟议研究的总体目标之一是确定性质（例如，相位、幅度和周期）的昼夜节律的诱导和恒定条件下，在家族性ASPS和DSPS。 第二个目标是测试可以解释这些条件下的干扰的假设。 虽然人们通常认为，睡眠本身是正常的昼夜睡眠时相障碍，有一些证据表明，睡眠稳态的调节可能会改变DSPS。 因此，所提出的研究的第三个具体目的是通过EEG/多导睡眠描记术定义DSPS和ASPS受试者在基线睡眠和睡眠剥夺后恢复睡眠期间的睡眠-觉醒特征，其中允许受试者在正常或异常昼夜节律时间开始恢复睡眠。 这些研究的结果预计不仅会导致对人类睡眠和昼夜节律调节的新见解，而且还会导致治疗睡眠/觉醒周期障碍的新治疗方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 conditions in familial ASPS and DSPS. A second objective is to test hypotheses that could explain the 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 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.