Self/Brain/Behavior Systems in Depression

描述(由申请人提供)：接近和回避的生物行为模型在理解抑郁症的易感性方面很有价值，但不能为这种疾病提供充分的解释。这些模型中没有强调的一个关键部分是自我调节认知，它决定了个人是否认为自己在实现目标方面没有取得进展。在这份根据PAR-02-062(建立行为科学中的翻译研究)修订后的R24奖项的申请中，我们采用了基础科学的方法来扩展行为方法(BAS)和回避(BIS)系统，增加了这一关键的认知部分。扩展的BAS和BIS被称为自我/大脑/行为系统，因为个人显著目标和一个人朝着这些目标的进展的表现被假设为每个系统的功能的中心。我们的模型的基本预测是：(A)启动个人的重要目标将导致BAS或BIS的神经生理学的可预测变化，以及(B)启动个人目标的效果将因相关系统的功能状态而不同，这表明自我调节失败在抑郁易感性中的潜在贡献作用。将开发三项基本研究设计，每一项都将个人重要目标的启动作为一个独立变量：(1)通过功能磁共振确定提出成功和失败的促进反馈与预防目标对大脑激活模式的影响；(2)通过测量事件相关的大脑电位来检查成功/失败的促进反馈与预防目标之后的信息处理序列；以及(3)确定用多巴胺受体激动剂的急性药物挑战对启动促进或预防目标的反应的影响。反过来，每个设计都将在三个样本中进行测试，每个样本代表扩展的BAS的假设状态：愉快的样本(代表弹性状态)、处于风险的样本(代表脆弱状态)和抑郁的样本(代表功能失调的状态)。分析样本内部和样本之间的数据将为这两个主要预测提供测试。这项应用是致力于综合性转化研究的第一阶段，最终可能导致临床应用，如预测抑郁症的易感性，根据特定的脆弱性将患者与治疗相匹配，改进现有干预措施，以及开发新的干预/预防策略。

DESCRIPTION (provided by applicant): Biobehavioral models of approach and avoidance have been valuable in understanding vulnerability to depression but do not provide a sufficient explanation for the disorder. A critical component underemphasized in these models is the self-regulatory cognition that determines whether individuals see themselves as failing to make progress toward their goals. In this revised application for an R24 award under PAR-02-062 (Building Translational Research in Behavioral Science), we take a basic science approach to expanding the behavioral approach (BAS) and avoidance (BIS) systems by adding this critical cognitive component. The expanded BAS and BIS are referred to as self/brain/behavior systems, because the representation of personally salient goals and of one's progress toward those goals is hypothesized to be central to the function of each system. The basic predictions of our model are (a) that priming an individual's personally significant goals will lead to predictable changes in the neurophysiology of the BAS or BIS, and (b) that the effects of priming an individual's goals will differ according to the functional state of the relevant system, demonstrating a potential contributory role for self-regulatory failure in vulnerability to depression. Three basic study designs will be developed, each of which uses priming of personally significant goals as an independent variable: (1) determining the effects of presenting success and failure feedback for promotion vs. prevention goals on patterns of brain activation via fMRI; (2) examining sequences of information processing following success/failure feedback for promotion vs. prevention goals via measurement of event-related brain potentials; and (3) determining the impact of acute pharmacologic challenge with a dopamine receptor agonist on responses to priming of promotion or prevention goals. In turn, each design will be tested in three samples, each representing a hypothetical state of the expanded BAS: euthymic samples (representing a resilient state), at-risk samples (representing a vulnerable state), and depressed samples (representing a dysfunctional state). Analyzing data within and across samples will provide tests for both major predictions. This application is the first stage of a commitment to integrative translational research that may ultimately lead to clinical applications such as predicting vulnerability to depression, matching patients to treatments as a function of specific vulnerabilities, refining existing interventions, and developing new intervention/prevention strategies.