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

描述(申请人提供)：青春期是一个发育期，包括高度的奖励敏感性和双相情感障碍(BSD)的风险。尽管BSD的流行率和公共卫生意义重大，但关于易受BSD影响的机制仍存在重大悬而未决的问题。最近激动人心的研究为BSD的行为方法系统(BAS)/奖赏超敏反应理论提供了强有力的和一致的支持，该理论为阐明和整合双极谱上潜在的风险的神经生物学、行为和环境机制带来了巨大的希望。此外，对BSD的社会和昼夜节律模型的研究也非常有前途，但一直独立于对奖励敏感性的研究。然而，我们最近的工作证明了奖赏敏感性对社会节奏扰乱和情绪症状的影响，导致我们在这一应用中发现了奖赏敏感性和社会节奏失调的新整合。因此，这项建议的首要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赏过敏和BSD之间的关联：1)涉及腹侧纹状体和眶前皮质的“奖赏相关”神经网络的高度激活；2)奖赏敏感性/激活对社交节律扰乱的影响。我们将继续跟踪高度和中度BAS/奖励敏感青少年进入BSD风险期的情况，包括自我报告和行为测量，包括奖励敏感性/处理、与BAS相关的认知方式、社交节律、与BAS相关和社交节律紊乱的生活事件，以及情绪症状/诊断。我们还将进行一项新的、新颖的神经成像研究。在一项功能磁共振研究中，我们将比较已经发展成BSD(HBA+BSD)的高BAS青少年、尚未表现出BSD但有患BSD风险的高BAS青少年(HBA)和没有BSD的中等BAS青少年(MBA)在预期和接受金钱奖励的反应中，与奖励相关的大脑活动和连接。此外，我们还将考察奖励敏感性/激活性和社交节律失调对这三组青少年情绪症状的影响。这项研究计划首次基于一种假设的心理生物学脆弱性，对患有BSD的青少年中的神经特征标记和社会节奏失调进行了检查。它将为早期识别首次发病和更糟糕病程的青少年提供工具，使我们了解疾病发生、复发和进展所涉及的特定病因途径和生物行为机制，并有助于制定针对改善奖赏加工异常的早期心理社会、药物和神经保护策略。

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.