Investigating Circadian Rhythms in Youth with Persistent Tic Disorders

摘要 持续性抽动障碍（PTD），包括图雷特氏症（TD），是一种神经精神疾病， 运动和/或发声存在超过一年，并与质量受损相关 生命许多人并没有从现有的行为和药物治疗中获益。 对PTD中涉及的病理生理机制的进一步了解可能有助于识别新的PTD。 治疗发展的目标。昼夜节律紊乱经常出现在精神病和 神经系统疾病，并可能涉及PTD。案例研究表明，早晨暴露于光疗法， 已知提前昼夜节律相位与适度至大的抽搐减少相关，表明存在 昼夜节律异常（即，相位延迟），这可能有助于抽动症状 发病、病程和治疗反应，并与潜在的PTD病理生理学相关。昼夜节律相位 通常通过昏暗的光褪黑激素的发作来评估，因为它是最可靠的标志物。最强阶段 转换剂是光疗法，其与昼夜节律睡眠中的昼夜相位转换相关 精神障碍、情绪障碍和其他精神和神经障碍。此外，光疗法是 与核心精神和神经症状的改善相关。光疗法在历史上 包括通过灯箱施用明亮的白色光。然而，由于不利因素， 强光带来的副作用，以及有限的移动性和时间限制带来的负担。一个可行的替代方案是 可穿戴短波长蓝光疗法-显示对相移昼夜节律更有效 其相对于白色光具有较低的强度和较短的持续时间。因此，本项目采用了 翻译的方法，以确定和测试新的机制，目标参与PTD。本研究将 评估35名13至17岁青年相对于35名性别和青春期的昼夜节律阶段和表型， 匹配的健康对照受试者，并评估可穿戴短波长光疗法 靶向这种假定的昼夜节律机制，并与改善抽搐症状有关。借鉴 项目共同导师的专业知识：Christopher科尔韦尔博士John Piacentini博士;和顾问： 梅雷迪思·科尔斯博士Dana McMakin博士，海伦·伯吉斯博士凯瑟琳·休格博士的 拟议的项目将提供全面的昼夜生理学培训;昼夜测量和 治疗;实验性治疗框架，因为它们涉及儿科精神病理学，包括抽搐 疾病和睡眠;和生物统计学。研究结果将增强我们对昼夜节律作用的理解 持续性抽动障碍，并可能为未来的治疗开发提供新的目标。

Abstract   Persistent Tic Disorders (PTD), including Tourette's Disorder (TD) are neuropsychiatric conditions marked by movements and/or vocalizations present for longer than one year, and associated with impairments in quality of life. Many individuals do not significantly benefit from existing behavioral and pharmacological treatments. Enhanced knowledge of the pathophysiological mechanisms implicated in PTDs may aid identification of new targets for treatment development. Circadian rhythm disruption frequently presents in psychiatric and neurological disorders and may be implicated in PTDs. Case studies show morning exposure to light therapy, known to advance circadian phase is associated with modest to large tic reductions suggesting the presence of circadian abnormalities (i.e., phase delay) in select individuals with PTDs, which may contribute to tic symptom onset, course, and treatment response, and be linked to underlying PTD pathophysiology. Circadian phase is commonly assessed through dim light melatonin onset, as it is the most reliable marker. The strongest phase shifting agent is light therapy, which is associated with circadian phase shifts in circadian rhythm sleep disorders, mood disorders, and other psychiatric and neurological disorders. Moreover, light therapy is associated with improvements in the core psychiatric and neurological symptoms. Light therapy historically has involved administration of bright white light via a light box. However, adherence may be reduced by adverse side effects from bright light, and burden due to limited mobility and time constraints. A viable alternative is wearable short wavelength blue light therapy – shown to be more effective at phase shifting circadian rhythms at lower intensities and shorter durations relative to white light. Therefore, the present project utilizes a translational approach to identify and test a new mechanism for target engagement in PTDs. This study will assess circadian phase and phenotype in 35 youth ages 13 to 17 relative to 35 sex- and pubertal stage- matched healthy control subjects, and assess the degree to which wearable short wavelength light therapy targets this putative circadian mechanism, and is associated with improvements in tic symptoms. Drawing on the expertise of project co-mentors: Christopher Colwell, Ph.D. and John Piacentini, Ph.D.; and consultants: Meredith Coles, Ph.D., Dana McMakin, Ph.D., Helen Burgess, Ph.D., and Catherine Sugar, Ph.D. the proposed project will provide comprehensive training in circadian physiology; circadian measurement and treatment; experimental therapeutic frameworks as they pertain to pediatric psychopathology, including tic disorders and sleep; and biostatistics. Findings will enhance our understanding of the role of circadian rhythms in Persistent Tic Disorders and may provide new targets for future treatment development.