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

描述（由申请人提供）：青春期是一个发育期，涉及更高的奖励敏感性和双相谱系障碍（BSD）的风险。尽管它们的流行和公共卫生的重要性，主要的悬而未决的问题存在的机制，涉及的脆弱性BSD。最近令人兴奋的研究提供了强有力的和一致的支持行为接近系统（BAS）/奖励超敏性理论的BSD显示出很大的希望，阐明和整合神经生物学，行为，和环境机制的风险沿着双极频谱。此外，社会和昼夜节律模型的BSD的研究也是非常有前途的，但独立于奖励敏感性的研究。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，这使我们在这个应用中实现了奖励敏感性和社会节奏失调的新整合。因此，本提案的总体目标是在青少年中使用创新的生物行为高风险设计来检查两个相互关联的过程，这可能有助于解释奖励超敏反应和BSD之间的关联：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;以及2）奖励敏感性/激活对社会节奏破坏的影响。我们将继续跟踪高度和中度BAS/奖励敏感的青少年，因为他们进一步进入BSD风险期，自我报告和奖励敏感性/处理的行为测量，BAS相关的认知方式，社会节奏，BAS相关和社会节奏破坏生活事件，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。我们将在一项fMRI研究中，比较患有BSD的高BAS青少年（HBAS+BSD）、尚未表现出BSD但有风险的高BAS青少年（HBAS）和没有BSD的中度BAS青少年（MBAS）对预期和接受金钱奖励的奖励相关大脑活动和连接的反应。此外，我们还将研究奖励敏感性/激活和社会节奏失调对这三组青少年情绪症状的影响。这项研究计划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质标志物和社会节律失调。它将为早期识别青少年首次发病和更严重的BSD风险提供工具，告知我们对疾病发作，复发和进展所涉及的特定病因学途径和生物行为机制的理解，并有助于早期心理社会，药理学和神经保护策略的发展，旨在改善奖励处理异常。

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.