Circadian Phase Assessments at Home

描述（由申请人提供）：估计有2300万美国人，包括青少年和老年人，患有昼夜节律睡眠障碍，如睡眠阶段延迟障碍、睡眠阶段提前障碍和冬季抑郁症。这些疾病的特点是持续失眠和/或白天过度嗜睡，表现受损，幸福感下降，生活质量下降。负面症状是由于睡眠时间和体内生物钟不一致造成的。临床研究表明，如果每个患者的昼夜节律阶段是已知的，那么昼夜节律睡眠障碍是最有效的诊断（与其他失眠原因区分开来）和治疗。主内部生物钟的时间是最可靠的，从内源性褪黑激素的昼夜节律开始测量，褪黑激素是一种神经内分泌激素，在昏暗的光线下测量（昏暗的褪黑激素开始，或“DLMO”）。然而，迄今为止，对DLMO的可靠和有效的评估仅限于研究实验室环境。此申请应PAR-08-212“行为和社会科学中的方法和测量”要求研究“通过数据收集技术和测量的创新来改进和发展行为科学中的方法和测量……特别鼓励将行为科学研究与生物科学研究相结合的方法……开发和验证研究工具，以填补研究需求的空白……改进现实环境中的测量方法。”我们的目标是开发一种简化的程序，在实验室之外准确评估昼夜节律阶段（DLMO），为临床医生和研究人员提供一种新的诊断和研究工具。通过这种方式，可以更容易地诊断和治疗患者失眠和/或昼夜节律紊乱的潜在神经生物学原因。具体目标1是在大量健康人群（n=120）中验证在家进行昼夜节律阶段评估的方法。验证将通过(1)客观地测量对家庭程序的依从性，(2)在受试者内部平衡设计中比较在家收集的DLMOs与实验室收集的DLMOs。我们有试点数据来支持我们在家里的程序的有效性。具体目标2是验证延迟睡眠阶段障碍患者的相同家庭程序（n=30）。具体目标3是进行严格的分析，以告知未来的用户，哪些受试者特征和光照水平可以预测(1)符合家庭程序和(2)有效的家庭dlmo。这项为期3年的研究结果将对基础和临床研究向社区的转化产生重大影响：(1)失眠和昼夜节律睡眠障碍的诊断和治疗将得到显著加强，从而改善公众健康和安全、情绪和生活质量；(2)社区对研究的参与将得到改善，特别是在弱势和代表性不足的人群中，从而增加科学知识；(3)研究和临床成本将大大降低。

DESCRIPTION (provided by applicant): An estimated 23 million Americans, including adolescents and the elderly, suffer from circadian rhythm sleep disorders, such as delayed sleep phase disorder, advanced sleep phase disorder and winter depression. These conditions are characterized by persistent insomnia and/or excessive daytime sleepiness, impaired performance, reduced well being and lower quality of life. The negative symptoms result from a misalignment between the timing of sleep and the internal circadian clock. Clinical research has demonstrated that circadian rhythm sleep disorders are most effectively diagnosed (differentiated from other causes of insomnia) and treated if each individual patient's circadian phase is known. The timing of the master internal circadian clock is most reliably measured from the onset of the endogenous circadian rhythm of melatonin, a neuroendocrine hormone, as measured in dim light (dim light melatonin onset, or "DLMO"). However to date the reliable and valid assessment of the DLMO is limited to the research laboratory setting. This application answers PAR-08-212 "Methodology and Measurement in the Behavioral and Social Sciences" which calls for research to "improve and develop methodology and measurement in the behavioral sciences through innovations in data collection techniques and measurement...approaches that integrate behavioral science research with biological science research are particularly encouraged...developing and validating research instruments that fill a gap in research needs...improve measurement in the real-world setting." Our goal is to develop a streamlined procedure for the accurate assessment of circadian phase (DLMO) outside of the laboratory that will provide clinicians and researchers with a novel diagnostic and research tool. In this way the underlying neurobiological cause of a patient's insomnia and/or circadian rhythm disorder can more readily be diagnosed and treated. Specific Aim 1 is to validate procedures for at-home circadian phase assessment in a large sample of healthy people (n=120). Validation will occur by (1) objectively measuring compliance to the at-home procedures and (2) comparing DLMOs collected at home to DLMOs collected in the laboratory, in a within-subjects counterbalanced design. We have pilot data to support the validity of our at home procedures. Specific Aim 2 is to validate the same at home procedures in patients with delayed sleep phase disorder (n=30). Specific Aim 3 is to conduct rigorous analyses to inform future users which subject characteristics and light levels predict (1) compliance to the at home procedures and (2) valid at-home DLMOs. The results of this 3 year study will have substantial implications for the translation of basic and clinical research to the community: (1) the diagnosis and treatment of insomnia and circadian rhythm sleep disorders will be significantly enhanced, thus improving public health and safety, mood and quality of life, (2) community participation in research will be improved, particularly in vulnerable and under represented populations, thus increasing scientific knowledge and (3) research and clinical costs will be substantially reduced.