Integrated Reward-Circadian Rhythm Model of First Onset of Bipolar Spectrum Disorders in Adolescence

青春期双相谱系障碍首次发作的综合奖赏昼夜节律模型

• 批准号: 10645179
• 负责人: LAUREN Bersh ALLOY
• 金额: $ 71.26万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10645179
• 关键词: 16 year old; Adolescence; Adolescent; Affect; Age; Behavioral; Biological; Brain; Chronic; Circadian Dysregulation; Circadian Rhythms; Code; Development; Diagnostic; Dimensions; Disease; Ecological momentary assessment; Etiology; Event; Exclusion; Feedback; Goals; Hypersensitivity; Intervention; Joints; Life; Light; Literature; Longitudinal Studies; Manic; Measures; Mediating; Mediator; Melatonin; Modeling; Moods; Onset of illness; Participant; Pathway interactions; Patient Self-Report; Phase; Physiological; Prevalence; Procedures; Public Health; Recording of previous events; Recurrence; Research; Rewards; Risk; Risk Marker; Salivary; Sampling; Signal Transduction; Sleep; Stimulus; Symptoms; System; Tail; Testing; Time; Work; actigraphy; biobehavior; bipolar spectrum; circadian; depressive symptoms; design; functional MRI scan; high reward; high risk; hypomania; indexing; innovation; longitudinal design; mood symptom; negative affect; neural; neuroimaging; novel; prevent; prospective; reward processing; social; social engagement; synergism; tool; trait

7. Project Summary/Abstract Adolescence is an “age of risk” for the emergence of first onset of bipolar spectrum disorders (BSD). Despite their prevalence and public health significance, major unanswered questions exist regarding the mechanisms involved in vulnerability to BSDs. BSDs are associated with hypersensitivity to reward and elevated reward- related brain function. However, research has not yet tested whether chronically high reward responsivity (RR) or increases in RR development during adolescence, beyond baseline RR, predicts first onset of BSD. A separate literature documents circadian rhythm disruption in BSDs, and social rhythm disruption (SRD) can trigger BSD episodes. Yet, research has not tested whether baseline circadian dysregulation, chronic social and circadian rhythm disruptions, or increases in these rhythm disruptions during adolescence predict onset of BSD. Further, circadian and reward approaches to BSDs mostly have proceeded in parallel. However, we and others have proposed integrated reward-circadian models of BSDs based on evidence the two systems influence each other and interact to affect mood functioning. When dysregulated, reward and circadian system signaling may combine to form a positive feedback loop, whereby dysregulation in one system exacerbates dysregulation in the other. This proposal is the first systematic test of a novel, integrated reward-circadian model for first onset of BSD. We will use an innovative biobehavioral high-risk design to examine bidirectional relationships between multiple indices and domains (monetary, social) of RR and multiple indices of social and circadian rhythms and their joint prediction of first onset of BSD and increases in bipolar symptoms. Three hundred twenty 14-16 year old participants (Ps) will complete a prospective 3-year longitudinal study. Ps with no prior BSD will be selected along the entire dimension of self-reported RR, with oversampling at the high tail of the dimension in order to increase the likelihood of BSD onsets. At Times 1-6, every 6 months, Ps will complete assessments of reward-relevant and SRD life events and self-report and diagnostic assessments of bipolar symptoms and episodes. Yearly, at Times 1, 3, and 5, Ps also will complete self-report measures of circadian chronotype (morningness-eveningness) and social rhythm regularity, a salivary dim light melatonin onset (DLMO) procedure to assess circadian phase, self-report, behavioral, and neural (fMRI) assessments of monetary and social RR, and a 7-day EMA period. During each EMA period, Ps will complete continuous measures of sleep/wake and activity (actigraphy) and 3 within-day (morning, afternoon, evening) measures of life events coded for reward-relevance and SRD, monetary and social reward responsivity, positive and negative affect, and hypo/manic and depressive symptoms. The fMRI scan and DLMO procedure will occur on the day before the start of each EMA period, excluding weekends. This proposal is an innovative integration of research on reward and circadian signaling in understanding first onset of BSD in adolescence. It has the potential to facilitate reward and social/circadian rhythm interventions to treat, and ideally prevent, BSD.

7.项目摘要/摘要 青春期是首次出现双相情感障碍(BSD)的“风险年龄”。尽管 它们的流行率和公共卫生意义，在机制方面仍存在重大悬而未决的问题 涉及对BSD的脆弱性。BSD与奖赏过敏和奖赏升高有关- 相关的脑功能。然而，研究尚未测试长期较高的奖励响应度(RR) 或者青春期RR发育增加，超过基线RR，可以预测BSD的首次发病。一个 BSD中昼夜节律紊乱和社交节律紊乱(SRD)的单独文献文献可以 触发BSD事件。然而，研究还没有测试基线昼夜节律失调、慢性社交 而昼夜节律紊乱，或在青春期这些节律紊乱的增加预示着 BSD。此外，对BSD的昼夜节律和奖励方法大多是并行进行的。然而，我们和 其他人则根据两个系统的证据提出了BSD的综合奖励-昼夜节律模型 相互影响，相互作用，从而影响情绪功能。当失控时，奖励和昼夜节律系统 信号可能结合在一起形成正反馈环路，从而使一个系统中的失调加剧 另一种是监管失调。这一提议是对一种新颖的、综合的奖励-昼夜节律的首次系统测试 首次发病的BSD模型。我们将使用一种创新的生物行为高风险设计来检查双向 RR的多个指数和领域(货币、社会)与社会和社会的多个指数之间的关系 昼夜节律及其联合预测首次发病的BSD和双相情感障碍症状增加。三 120名14-16岁的参与者将完成一项为期3年的前瞻性纵向研究。PS与 不会沿着自报告RR的整个维度选择先前的BSD，并在高尾部进行过采样 以增加BSD首发的可能性。在时间1-6，每隔6个月，P将 完成与奖励相关和SRD生活事件的评估，以及自我报告和诊断评估 躁郁症和躁郁症。每年，在时报1、3和5，Ps还将完成自我报告的测量 一种唾液暗淡褪黑素的昼夜节律和社会节律 发病(DLMO)程序，以评估昼夜节律、自我报告、行为和神经(FMRI)评估 货币和社会RR，以及7天均线时期。在每个EMA期间，P将完成连续 睡眠/清醒和活动的测量(活动记录)和一天内(上午、下午、晚上)的3种测量 生活事件编码为奖励相关性和SRD、金钱和社会奖励响应性、积极和 消极情绪，以及低落/躁狂和抑郁症状。FMRI扫描和DLMO程序将在 每个EMA期间开始的前一天，不包括周末。这项提议是对 奖赏和昼夜节律信号在理解青春期BSD首发中的研究。它有一个 有可能促进奖励和社会/昼夜节律干预，以治疗和理想地预防BSD。