Sleep and Circadian Dysregulation in Pediatric Bipolar Disorder

描述(申请人提供)：本次K01指导研究科学家发展奖申请的目的是促进我在睡眠和儿童双相情感障碍(PBD)领域的培训，并通过这样做，支持我的短期目标：(1)全面表征双相情感障碍(BD)青少年的睡眠和昼夜节律，以及(2)研究睡眠/昼夜节律失调与情绪失调之间的关系。拟议的培训和研究项目是为长期独立的、学术的、临床研究生涯奠定基础的关键的第一步，该职业生涯专注于儿童情绪障碍的发生、发展、病程和治疗中的睡眠和昼夜节律失调。多条证据表明，睡眠/昼夜节律紊乱是成人BD的核心特征，这些紊乱可能引发疾病发作。然而，几乎没有关于PBD睡眠/昼夜节律紊乱的性质和严重程度的信息，也没有关于睡眠/昼夜节律紊乱对情绪失调的潜在贡献的信息。鉴于BD的发病率在青春期达到高峰，并且BD在生命早期起病时与特别破坏性的后果有关，青春期为了解这种疾病的发展提供了一个关键窗口。之前评估PBD样本的睡眠和昼夜节律功能的研究在很大程度上依赖主观测量。这项拟议的研究将首次对患有BD的青少年相对于对照组的睡眠/昼夜节律进行全面、生态敏感和客观的表征。这项评估结合了两个晚上的动态多导睡眠监测(PSG)，以及两周的连续活动监测，以及对主观睡眠、社会节律和情绪的日常监测。还将收集关于社交、压力和沉思的日常测量数据。通过调查双相青年的睡眠，这项拟议的研究旨在解决关于睡眠和昼夜节律紊乱在PBD早期发展和进展中所起作用的知识空白。这些假说预测了两组在以下方面的差异：(H1a)睡眠结构，特别是睡眠效率、REM潜伏期、REM密度和持续时间；(H1b)睡眠和觉醒持续时间、睡眠碎片和白天活动水平；(H1c)睡眠障碍的总体比率； (H1d)主观睡眠测量和社会节奏的规律性。这项拟议的调查还将研究日常睡眠和日常情感之间的潜在联系，以测试睡眠-情感耦合程度的群体差异。拟议的研究、指导和教学培训的综合计划，加上斯坦福大学出色的研究环境，将培养我的长期职业目标，即成为儿科情绪障碍中睡眠和昼夜节律机制的独立调查员。

DESCRIPTION (provided by applicant): The purpose of this K01 Mentored Research Scientist Development Award application is to facilitate my training in the field of sleep and pediatric bipolar disorder (PBD) and in so doing, support my short-term objectives to: (1) comprehensively characterize sleep and circadian rhythms in adolescents with bipolar disorder (BD), and (2) investigate the relationship between sleep/circadian dysregulation and mood dysregulation in this population. The proposed training and research project represent the key first step in laying the groundwork for a long-term independent, academic, clinical research career focused on sleep and circadian dysregulation in the onset, development, course, and treatment of pediatric mood disorders. Multiple lines of evidence suggest that sleep/circadian disruptions are core features of adult BD, and that these disruptions may trigger episodes of illness. However, there is virtually no information on the nature and severity of sleep/circadian disruption in PBD, or on the potential contribution of sleep/circadian disruption to mood dysregulation. Given incidence rates of BD peak during adolescence and that BD is associated with particularly devastating outcomes when onset is early in life, adolescence offers a critical window for understanding the development of this disorder. Previous studies assessing sleep and circadian functioning in PBD samples have largely relied on subjective measures. The proposed research study will be the first to use a comprehensive, ecologically sensitive, and objective characterization of sleep/circadian rhythms in adolescents with BD relative to controls. This assessment combines two nights of ambulatory polysomnography (PSG), along with a two- week observation period of continuous actigraphy, and daily monitoring of subjective sleep, social rhythms, and affect. Daily measures of social interaction, stress, and rumination will also be collected. By investigating sleep in bipolar youth, the proposed study aims to address a gap in knowledge on the role of sleep and circadian disruption in the early development and progression of PBD. The hypotheses predict group differences in: (H1a) sleep architecture, specifically sleep efficiency, REM latency, and REM density and duration; (H1b) sleep and wake durations, sleep fragmentation, and daytime activity level; (H1c) overall rates of sleep disorders; (H1d) subjective sleep measures and regularity of social rhythms. The proposed investigation will also examine a potential link between daily sleep and daily affect in order to test for group differences in (H2) the degree of sleep-affect coupling. The proposed integrated program of research, mentorship and didactic training, combined with the outstanding research environment at Stanford University will foster my long-term career objective to be an independent investigator of sleep and circadian mechanisms in pediatric mood disorders.