Social and Circadian Rhythms, Reward Sensitivity, and Risk for Bipolar Disorder

描述(由申请人提供)：尽管双相情感障碍的流行率和公共卫生意义重大，但关于双相情感障碍(BSD)易感性的机制仍存在重大悬而未决的问题。BSD的社会节律和昼夜(24小时)节律模型假设，情绪发作可能是由生活事件引起的昼夜节律异常的结果，这些生活事件扰乱了通常包含昼夜节律的社会节律(例如，就寝时间、用餐时间)。最近的研究也为BSD的行为接近系统(BAS)/奖励超敏反应理论提供了有力的支持。虽然对这些独特的理论模型的研究是平行进行的，但我们最近的工作证明了奖励敏感性对社交节奏扰乱和情绪症状的影响，导致我们在这个提议中将奖励敏感性和社交/昼夜节律扰乱进行了新的整合。我们的首要目标是使用一种创新的生物行为高风险设计来检验奖励敏感性以及社交和昼夜节律紊乱作为BSD情绪症状/发作的风险因素的双向影响。我们将前瞻性跟踪210名参与者(P)，部分来自BSD风险年龄的高和中等BAS/回报敏感P的现有样本。我们将比较高BAS P与BSD诊断，尚未表现但有BSD风险的高BAS P，以及没有BSD的中等BAS P，以确定奖励过敏是否会影响与奖励相关的事件发生后的社交和昼夜节律紊乱，以预测躁狂和抑郁症状/发作。这个三组设计将允许我们测试奖励过敏症及其与社交和昼夜节律紊乱的关系是BSD的先天弱点还是后果，或者两者兼而有之。社交节奏的规律性和奖励敏感度将在基线上进行评估。与奖励相关的生活事件、由这些事件引起的社交节奏中断以及情绪症状/事件将被前瞻性地评估长达4年。PS将完成一项为期4周的生态瞬时评估(EMA)研究，包括1周基线、2周高BAS/奖励激活和1周奖励结果期，以评估社交和昼夜节律中断与奖励敏感性之间的双向影响及其对BSD症状的协同效应。在EMA研究中，Ps将完成对生活事件、社交节律和睡眠日记的日常测量，对睡眠/清醒(动作图)和昼夜节律(皮肤温度)的连续测量，以及对情绪、症状和奖励动机的重复测量。昏暗的光线将褪黑素发作3次，以确定褪黑激素的昼夜节律变化。这项研究计划将为BSD脆弱性的潜在机制提供有价值的见解，并有助于制定有针对性的干预和预防战略。

DESCRIPTION (provided by applicant): Despite their prevalence and public health significance, major unanswered questions exist regarding the mechanisms involved in vulnerability to bipolar spectrum disorders (BSDs). Social and circadian (24-h) rhythm models of BSD risk hypothesize that mood episodes may be a result of circadian rhythm abnormalities caused by life events that disrupt social rhythms (e.g., bedtimes, mealtimes) that normally entrain circadian rhythms. Recent research also provides strong support for a Behavioral Approach System (BAS)/reward hypersensitivity theory of BSDs. Although research on these distinctive theoretical models has proceeded in parallel, our recent work demonstrates influences of reward sensitivity on social rhythm disruption and mood symptoms, leading us to a novel integration of reward sensitivity and social/circadian disruption in this proposal. Our overarching goal is to use an innovative biobehavioral high-risk design to examine bidirectional influences of reward sensitivity and social and circadian rhythm disruption as risk factors for BSD mood symptoms/ episodes. We will prospectively follow 210 participants (Ps) drawn in part from an existing sample of High and Moderate BAS/reward sensitive Ps at an age of risk for BSDs. We will compare High BAS Ps with a BSD diagnosis, High BAS Ps who have not yet exhibited but are at risk for BSD, and Moderate BAS Ps with no BSD to determine whether reward hypersensitivity influences social and circadian rhythm disruption following the occurrence of reward-relevant events to predict manic and depressive symptoms/episodes. This 3-group design will allow us to test whether reward hypersensitivity and its relationship with social and circadian rhythm disruption are pre-existing vulnerabilities or consequences of BSD, or both. Social rhythm regularity and reward sensitivity will be assessed at baseline. Reward-relevant life events, social rhythm disruption from these events, and mood symptoms/episodes will be assessed prospectively for up to 4 years. Ps will complete a 4-wk ecological momentary assessment (EMA) study including 1-wk baseline, 2-wk high BAS/reward activation, and 1-wk reward-outcome periods to assess bidirectional influences between social and circadian rhythm disruption and reward sensitivity and their synergistic effects on BSD symptoms. In the EMA study, Ps will complete daily measures of life events, social rhythms, and sleep diaries, continuous measures of sleep/wake (actigraphy) and circadian rhythms (skin temperature), and repeated within-day measures of mood, symptoms, and reward motivation. Dim light melatonin onset will be assessed 3 times to determine circadian melatonin phase changes. This research program will provide valuable insights into the mechanisms underlying vulnerability to BSDs and contribute to the development of targeted intervention and prevention strategies.