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

描述（由申请人提供）：尽管它们的流行和公共卫生意义，关于双相情感障碍（bsd）易感性的机制存在主要未解决的问题。BSD风险的社会和昼夜节律（24小时）节律模型假设，情绪发作可能是昼夜节律异常的结果，这种昼夜节律异常是由生活事件引起的，这些事件破坏了通常会影响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的行为方法系统(BAS)/奖励超敏感理论提供了强有力的支持。尽管对这些独特理论模型的研究是平行进行的，但我们最近的工作表明，奖励敏感性对社会节奏中断和情绪症状的影响，使我们在本提案中对奖励敏感性和社会/昼夜节律中断进行了新的整合。我们的总体目标是使用一种创新的生物行为高风险设计来检查奖励敏感性和社会和昼夜节律中断作为BSD情绪症状/发作的风险因素的双向影响。我们将前瞻性地跟踪210名参与者(p)，这些参与者部分来自现有的高和中度BAS/奖励敏感p样本，他们处于bsd风险年龄。我们将比较被诊断为BSD的高BAS p、尚未表现出BSD但有BSD风险的高BAS p和无BSD的中度BAS p，以确定奖励超敏感是否会影响与奖励相关事件发生后的社会和昼夜节律中断，从而预测躁狂和抑郁症状/发作。这种三组设计将允许我们测试奖励超敏症及其与社会和昼夜节律紊乱的关系是先前存在的脆弱性还是BSD的后果，或者两者兼而有之。社会节律规律和奖励敏感性将在基线进行评估。对与奖励相关的生活事件、这些事件造成的社会节律紊乱以及情绪症状/发作进行长达4年的前瞻性评估。Ps将完成一项为期4周的生态瞬时评估（EMA）研究，包括1周的基线期、2周的BAS/奖励高激活期和1周的奖励-结果期，以评估社会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将完成日常生活事件、社会节律和睡眠日记的测量，连续测量睡眠/清醒（活动记录仪）和昼夜节律（皮肤温度），并在一天内重复测量情绪、症状和奖励动机。昏暗光线下褪黑激素的发作将评估3次，以确定昼夜褪黑激素的相位变化。该研究项目将为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策略。

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.