Sleep and Circadian Dysregulation in Pediatric Bipolar Disorder

描述（由申请人提供）：本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科双相情感障碍（PBD）领域的培训，并在此过程中，支持我的短期目标：（1）全面描述双相情感障碍（BD）青少年的睡眠和昼夜节律，（2）探讨该人群睡眠/昼夜节律失调与情绪失调的关系。拟议的培训和研究项目代表了为长期独立的学术临床研究事业奠定基础的关键第一步，该研究事业专注于儿童情绪障碍的发病，发展，病程和治疗中的睡眠和昼夜节律失调。多种证据表明，睡眠/昼夜节律中断是成人BD的核心特征，这些中断可能引发疾病发作。然而，几乎没有关于PBD中睡眠/昼夜节律中断的性质和严重程度的信息，或者关于睡眠/昼夜节律中断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在生命早期发病时与特别具有破坏性的结局相关，青春期为了解这种疾病的发展提供了一个关键窗口。以前评估PBD样本中睡眠和昼夜节律功能的研究在很大程度上依赖于主观测量。拟议的研究将是第一个使用一个全面的，生态敏感的，客观的表征睡眠/昼夜节律的青少年与BD相对于控制。这种评估结合了两个晚上的动态多导睡眠图（PSG），沿着两周的连续活动记录仪观察期，以及对主观睡眠、社会节律和情感的每日监测。还将收集日常社会交往、压力和反刍的测量结果。通过调查双相青年的睡眠，这项拟议的研究旨在解决睡眠和昼夜节律中断在PBD早期发展和进展中的作用的知识空白。这些假设预测了以下方面的组间差异：（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）睡眠和清醒持续时间、睡眠碎片和白天活动水平;（H1c）睡眠障碍的总体发生率; (H1d)主观睡眠测量和社会节奏的规律性。拟议的调查还将检查日常睡眠和日常情绪之间的潜在联系，以测试（H2）睡眠-情绪耦合程度的组间差异。拟议的研究，导师和教学培训的综合计划，结合在斯坦福大学优秀的研究环境，将促进我的长期职业目标是成为一个独立的调查员的睡眠和昼夜节律机制在儿科情绪障碍。

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.