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因素是自我调节认知，它决定了个体是否认为自己无法朝着目标前进。在这项根据PAR-02-062（行为科学的构建转化研究）修订的R24奖申请中，我们采用基础科学方法通过添加这一关键的认知成分来扩展行为方法（BAS）和回避（BIS）系统。扩展的BAS和BIS被称为自我/大脑/行为系统，因为个人显著目标的表征和一个人朝着这些目标的进展被假设为每个系统功能的核心。我们的模型的基本预测是：(a)启动个人的个人重要目标将导致BAS或BIS的神经生理学可预测的变化，以及(b)启动个人目标的效果将根据相关系统的功能状态而有所不同，这表明了对抑郁症易感性的自我调节失败的潜在贡献作用。将开发三个基本研究设计，每个设计都将个人重要目标的启动作为一个独立变量：(1)通过fMRI确定为促进和预防目标提供成功和失败反馈对大脑激活模式的影响；(2)通过测量事件相关脑电位，考察促进与预防目标成功/失败反馈后的信息加工序列；(3)确定多巴胺受体激动剂急性药理刺激对促进或预防目标启动反应的影响。然后，每个设计将在三个样本中进行测试，每个样本代表扩展BAS的假设状态：健康样本（代表弹性状态），风险样本（代表脆弱状态）和抑郁样本（代表功能失调状态）。分析样本内部和样本之间的数据将为这两种主要预测提供检验。这一应用是致力于综合转化研究的第一阶段，最终可能会导致临床应用，如预测抑郁症的易感性，将患者与特定脆弱性的治疗相匹配，完善现有的干预措施，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.