Risk for Bipolar Disorder: Reward-related Brain Function & Social Rhythms

描述（由申请人提供）：青春期是一个发展时期，涉及奖励敏感性和双相情感障碍（bsd）的风险。尽管这些疾病普遍存在并具有重要的公共卫生意义，但在易受bsd侵害的机制方面仍存在重大未解之谜。最近令人兴奋的研究为bsd的行为方法系统(BAS)/奖励超敏感理论提供了强有力和一致的支持，该理论在阐明和整合双相情感障碍潜在风险的神经生物学、行为和环境机制方面显示了巨大的希望。此外，对bsd的社会和昼夜节律模型的研究也很有前景，但这些研究是独立于奖励敏感性的研究进行的。然而，我们最近的工作证明了奖励敏感性对社会节奏中断和情绪症状的影响，这使我们在这一应用中发现了奖励敏感性和社会节奏失调的新整合。因此，本研究的总体目标是在青少年中使用一种创新的生物行为高风险设计来检验两个相互关联的过程，这两个过程可能有助于解释奖励超敏感和bsd之间的联系：1)涉及腹侧纹状体和眶额皮质的“奖励相关”神经网络的激活增强；2)奖赏敏感性/激活对社会节律紊乱的影响。我们将继续跟踪高和中度BAS/奖励敏感青少年，当他们进一步进入bsd风险期时，使用自我报告和行为测量奖励敏感性/处理，BAS相关认知风格，社会节奏，BAS相关和社会节奏中断生活事件，以及情绪症状/诊断。我们还将进行一项新的神经影像学研究。我们将在fMRI研究中比较患有BSD的高BAS青少年（HBAS+BSD）、尚未表现出BSD但有BSD风险的高BAS青少年（HBAS）和没有BSD的中度BAS青少年（MBAS）在预期和接受金钱奖励时的奖励相关脑活动和连通性。此外，我们将研究奖励敏感性/激活和社会节律失调对这三组青少年情绪症状的影响。这个研究项目是第一个基于假设的心理生物学脆弱性来研究有bsd风险的青少年的神经特征标记和社会节律失调。它将为早期识别青少年首次发病和更严重病程的风险提供工具，告知我们对疾病发病、复发和进展的特定病因途径和生物行为机制的理解，并有助于早期社会心理、药理学和神经保护策略的发展，以改善奖励处理异常。

DESCRIPTION (provided by applicant): Adolescence is a developmental period involving both heightened reward sensitivity and risk for bipolar spectrum disorders (BSDs). Despite their prevalence and public health significance, major unanswered questions exist regarding the mechanisms involved in vulnerability to BSDs. Recent exciting research provides strong and consistent support for a Behavioral Approach System (BAS)/reward hypersensitivity theory of BSDs that shows great promise for elucidating and integrating the neurobiological, behavioral, and environmental mechanisms underlying risk along the bipolar spectrum. In addition, research on social and circadian rhythm models of BSDs is also very promising, but has proceeded independently of research on reward sensitivity. Yet, 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 rhythm dysregulation in this application. Thus, the overarching goal of this proposal is to use an innovative biobehavioral high-risk design in adolescents to examine two interrelated processes that may help explain the association between reward hypersensitivity and BSDs: 1) heightened activation of a "reward-related" neural network involving the ventral striatum and orbitofrontal cortex; and 2) influences of reward sensitivity/activation on social rhythm disruption. We will continue to follow High and Moderate BAS/reward sensitive adolescents as they further age into the period of risk for BSDs with self-report and behavioral measures of reward sensitivity/processing, BAS-relevant cognitive styles, social rhythms, BAS-relevant and social rhythm disruption life events, and mood symptoms/ diagnoses. We also will conduct a new and novel neuroimaging study. We will compare High BAS adolescents who have developed BSD (HBAS+BSD), High BAS adolescents who have not yet exhibited, but are at risk for, BSD (HBAS), and Moderate BAS adolescents without BSD (MBAS) on reward-related brain activity and connectivity in response to the anticipation and receipt of monetary rewards in an fMRI study. In addition, we will examine the influence of reward sensitivity/activation and social rhythm dysregulation on mood symptoms in these same three groups of adolescents. This research program is the first to examine neural trait markers and social rhythm dysregulation in adolescents at risk for BSDs based on a hypothesized psychobiological vulnerability. It will provide tools for the early identification of adolescents at risk for first onset and a worse course of BSD, inform our understanding of specific etiological pathways and biobehavioral mechanisms involved in illness onset, recurrence, and progression, and contribute to the development of early psychosocial, pharmacological, and neuroprotective strategies targeted at ameliorating reward processing abnormalities.