SLEEP-RELATED ENDOCRINE PROFILES IN SUBJECTS WITH CIRCADIAN PHASE DISORDERS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在过去的几年里，巨大的进步导致了几个生物钟基因的识别。这使得现在有可能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。对了解人类昼夜节律系统的遗传学特别感兴趣的是患有睡眠相障碍的个体，如睡眠相延迟综合征(DSSPS)和晚期睡眠相综合征(ASPS)，因为最近的研究表明这些疾病的遗传基础。虽然假设ASPS和DSPs都是昼夜节律紊乱，但对这些个体的生物钟系统或其与睡眠过程的相互作用是如何影响的知之甚少。因此，本研究的总体目标之一是确定家族性ASPS和DSPs在牵引性和恒定条件下的昼夜节律的特征(例如，相位、幅度和周期)。第二个目标是测试可以解释这些情况下的干扰的假设。尽管人们普遍认为在昼夜睡眠相紊乱中睡眠本身是正常的，但有一些证据表明，睡眠稳态的调节在DSPs中可能会发生改变。因此，拟议研究的第三个具体目标是通过脑电/多导睡眠图来确定在基线睡眠和睡眠剥夺后恢复睡眠期间的睡眠-觉醒特征，即允许受试者在正常或异常昼夜时间开始恢复睡眠。这些研究的结果不仅有望为人类睡眠和昼夜节律的调节带来新的见解，而且还将为治疗睡眠/觉醒周期紊乱提供新的治疗方法。

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.