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，如睡眠相位延迟障碍、睡眠相位提前障碍和冬季抑郁症。这些疾病的特征是持续失眠和/或白天过度嗜睡，表现受损，健康状况下降和生活质量下降。负面症状是由于睡眠时间和内部生物钟之间的不一致。临床研究表明，如果知道每个患者的昼夜节律，则昼夜节律睡眠障碍最有效地被诊断（与失眠的其他原因区分开）和治疗。主内部生物钟的定时最可靠地从褪黑激素（一种神经内分泌激素）的内源性昼夜节律的开始测量，如在昏暗光中测量的（昏暗光褪黑激素开始，或“DLMO”）。然而，迄今为止，DLMO的可靠和有效评估仅限于研究实验室环境。此应用程序回答PAR-08-212“行为和社会科学的方法和测量”，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，填补研究需求的空白.改善现实世界中的测量。“我们的目标是开发一种简化的程序，在实验室外准确评估昼夜节律相位（DLMO），为临床医生和研究人员提供一种新的诊断和研究工具。以这种方式，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是在大样本健康人群（n=120）中验证家庭昼夜节律相位评估程序。通过（1）客观测量对家庭程序的依从性和（2）在受试者内平衡设计中比较在家中收集的DLMO与在实验室收集的DLMO进行验证。我们有试验数据来支持我们在国内程序的有效性。具体目标2是在延迟睡眠期障碍患者（n=30）中验证相同的家庭程序。具体目标3是进行严格的分析，以告知未来用户哪些受试者特征和光照水平可预测（1）对家庭程序的依从性和（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，从而改善公共卫生和安全、情绪和生活质量，（2）社区参与研究的情况将得到改善，特别是在弱势和代表性不足的人群中，从而增加科学知识和（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.