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（BSD）的患病率和公共卫生意义，但关于双相情感障碍（BSD）易感性的机制存在重大未回答的问题。BSD风险的社会和昼夜（24小时）节律模型假设情绪发作可能是由扰乱社会节律的生活事件（例如，就寝时间、进餐时间），这些时间通常会影响昼夜节律。最近的研究也为行为接近系统（BAS）/BSD的奖励超敏性理论提供了强有力的支持。虽然对这些独特的理论模型的研究已经平行进行，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，导致我们在这个建议中奖励敏感性和社会/昼夜节律中断的新整合。我们的总体目标是使用创新的生物行为高风险设计来研究奖励敏感性和社会和昼夜节律中断的双向影响，作为BSD情绪症状/发作的风险因素。我们将前瞻性地跟踪210名参与者（Ps），这些参与者部分来自现有的处于BSD风险年龄的高和中等BAS/奖励敏感Ps样本。我们将比较患有BSD诊断的高BAS P、尚未表现出但有BSD风险的高BAS P和没有BSD的中度BAS P，以确定奖励超敏性是否会影响奖励相关事件发生后的社会和昼夜节律破坏，从而预测躁狂和抑郁症状/发作。这种3组设计将使我们能够测试奖励超敏性及其与社会和昼夜节律破坏的关系是否是预先存在的漏洞或BSD的后果，或两者兼而有之。将在基线时评估社会节律规律性和奖励敏感性。将前瞻性评估奖励相关生活事件、这些事件造成的社会节律破坏以及情绪症状/发作，持续时间长达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，以评估社会和昼夜节律破坏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、社交节奏和睡眠日记的测量，睡眠/觉醒（活动记录）和昼夜节律（皮肤温度）的连续测量，以及情绪、症状和奖励动机的重复日内测量。将对昏暗光褪黑激素起效进行3次评估，以确定褪黑激素昼夜节律相位变化。这项研究计划将提供有价值的见解的脆弱性，以BSD的机制，并有助于有针对性的干预和预防战略的发展。

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.