Sleep Activity Patterns and Temperature in Childhood Onset Bipolar Disorder

描述(申请人提供)：睡眠和昼夜节律紊乱是双相情感障碍的常见特征。尤其是儿童期起病的双相情感障碍(COBD)，其特征是睡眠和觉醒调节改变的症状。一个相关的临床观察是，双相情感障碍的儿童表现出散热问题。尽管父母的抱怨无处不在，对这些问题的临床观察也很频繁，但关于COBD的睡眠和休息/活动模式的研究很少，而且与COBD的体温相关的数据几乎不存在。在患有精神障碍的儿童中获得这类数据的方法复杂性很可能是缺乏这类研究的主要原因。此外，早发性双相情感障碍的概念本身也存在争议，只是在最近十年才针对这一人群进行了实证调查。最近的发现支持将COBD归类为一种与成人起病的双相情感障碍和其他儿童精神障碍有许多相似之处，但在重要方面又不同的疾病。这项R21提案的目的是评估双相情感障碍儿童(表现出躁狂和精神病症状)和健康青少年对照组之间的夜间睡眠、昼夜和超常活动模式以及体温调节措施是否有所不同。这项研究将利用新的非侵入性技术，通过在家庭研究中使用运动记录仪和无线温度监测来增强评估儿童睡眠和节律参数的可行性。我们假设，与对照组相比，双相情感障碍儿童将表现出昼夜活动和褪黑素节律的相位延迟，这是一种一致的早间活动不足和晚上多动的超常模式，表现为日常活动节律的幅度增加，加上睡眠开始潜伏期延长和睡眠连续性降低。此外，双相情感障碍儿童夜间睡眠前后测得的皮肤温度梯度将与对照组不同，这提供了热量散失改变的证据。这一探索性项目被视为加强我们对COBD潜在的生物学和生理因素的理解的重要一步，并可能为COBD儿童睡眠和觉醒的体温调节和昼夜调节改变提供经验证据。通过这样做，它有可能为干预研究提供信息，或确定COBD的新治疗途径，如治疗性降温、外源性褪黑素注射或定时光疗。与公共卫生相关的双相情感障碍儿童会经历严重的社会、认知和发育后果。这项拟议的探索性研究将评估该人群的睡眠、昼夜活动模式和体温，目的是确认临床观察到的和父母报告的睡眠障碍的存在和严重程度。这项研究将阐明双相情感障碍的病因和生物学基础，最终目的是确定新的有效治疗方法，以管理导致双相情感障碍患者及其家人负担的睡眠问题。

DESCRIPTION (provided by applicant): Sleep and circadian rhythm disturbances are common features of bipolar disorder. Childhood onset bipolar disorder (COBD), in particular, is characterized by symptoms suggestive of altered regulation of sleep and wakefulness. An associated clinical observation is that children with bipolar disorder exhibit problems with heat dissipation. Despite the pervasiveness of parental complaints and frequent clinical observations of these issues, there are few studies of sleep and rest/activity patterns in COBD, and data relating to body temperature in COBD are virtually non-existent. It is likely that methodological complexities of obtaining such data in children with psychiatric disorders is a primary reason for the lack of studies of this nature. In addition, the very concept of early onset bipolar disorder has been controversial, and only in the last decade have empirical investigations targeting this population been conducted. Recent findings support the classification of COBD as a condition that shares many similarities with, yet is different in important ways, from adult onset bipolar disorder, and other childhood psychiatric disturbances. The aim of this R21 proposal is to evaluate whether nocturnal sleep, circadian and ultradian activity patterns, and thermoregulatory measures differ between children with bipolar disorder (who exhibit manic and psychotic symptoms) and healthy young controls. The study will take advantage of novel, non-invasive technology that enhances the feasibility of assessing sleep and rhythm parameters in children by using actigraphy and wireless temperature monitoring in a home-based study. We hypothesize that compared with controls, children with bipolar disorder will exhibit a phase delay of circadian activity and melatonin rhythms, a consistent ultradian pattern of morning hypoactivity and evening hyperactivity that manifests as enhanced amplitude of the daily activity rhythm, plus longer sleep onset latency and reduced sleep continuity. In addition, the skin temperature gradient measured before and following nocturnal sleep will differ in bipolar children relative to controls, providing evidence of altered heat dissipation. This exploratory project is viewed as an important step toward enhancing our understanding of the biological and physiological factors underlying COBD, and may provide empirical evidence of altered thermoregulatory and circadian regulation of sleep and wakefulness in children with the disorder. In doing so, it has the potential to inform intervention studies or identify novel treatment avenues for COBD, such as therapeutic cooling, exogenous melatonin administration, or timed light therapy. PUBLIC HEALTH RELEVANCE Children with bipolar disorder experience severe social, cognitive, and developmental consequences. The proposed exploratory study will assess sleep, circadian activity patterns, and temperature in this population with the aim of confirming the presence and severity of clinically observed and parent- reported sleep disturbance. The study will shed light on the etiology and biological underpinnings of the disorder, with the ultimate aim of identifying novel and effective treatment approaches for managing the sleep problems that contribute to the burden of bipolar disorder on both patients and their families.