Bottom-Up Mechanisms of Dysfunctional Self Evaluation in Depression

摘要 抑郁症是世界范围内残疾的主要原因，尽管有几种治疗方法， 在发展中国家，只有少数患者（<40%）响应并维持该响应一年，无论 他们得到的待遇。超过一年的持续答复率更低。因此，有一个重要的公众 健康需要更好地针对抑郁症状的持久性，并改善长期结果。 消极的自我评价是抑郁症的核心特征， 抑郁症消极的自我评价不仅与抑郁症状的持续存在直接相关， 但对许多人来说，即使在其他有效的治疗后，负面的自我评价仍然存在， 复发虽然我们对认知缺陷和负面信息处理偏见有很多了解， 在患有抑郁症的成年人中，记忆力和注意力的具体破坏知之甚少， 信息处理和大脑功能导致抑郁的成年人做出过度负面的自我评价 无论是在抑郁症发作期间还是之后。我们认为，我们可以大大改善长期 通过识别导致这些负面自我评价的潜在病理学， 可以开发出更有针对性和更持久的治疗方法。根据我们的初步数据， 其他人，这个短期项目的目标是提供一个新的假设的第一个测试，关于神经 机制，导致功能失调的自我评价在当前和缓解抑郁症的成年人，并开始开始， 检查这种病理对未来症状和功能的现实后果。来测试我们 假设，我们将评估行为和神经影像学标记的异常处理过程中的自我- 在30名目前抑郁症患者、30名缓解抑郁症患者和30名健康成人中进行评估。参与者将完成 基线临床和功能性磁共振成像（fMRI）评估，以及为期三周的 每日日记方案（超过四个月），将评估症状，日常生活中的自我评价， 真实世界的运作。该项目将审查导致非正常参与的进程， 自传体记忆（目标1）和社会认知（目标2）网络在抑郁症的成年人， 评估自我相关的材料，它将检查是否异常的大脑功能， 评估前瞻性预测精神症状和较差的人际和工作功能在日常生活中 （探索目标）。该项目的目标与国家心理研究所的战略目标非常吻合， 健康，而这项研究的结果有可能导致新的，基于大脑的治疗策略，以目标 已查明的负面自我评价背后的机制，以改善长期成果。

ABSTRACT Depression is the leading cause of disability worldwide, and despite the fact that several treatments have been developed, only a minority of patients (<40%) respond and sustain that response for a year, regardless of which treatment they receive. Sustained response rates beyond one year are lower still. Thus, there is a vital public health need to better target the enduring quality of depressive symptoms and to improve longer-term outcomes. Negative self-evaluations, a core characteristic of depressive illness, appear to contribute to the enduring nature of depression. Negative self-evaluations are not only linked directly to the persistence of depressive symptoms, but for many, negative self-evaluations persist even after otherwise effective treatments, increasing the risk of relapse. Although much is known about the cognitive deficits and negative information processing biases in memory and attention among adults with depression, very little is known about the specific disruptions in information processing and brain function that cause depressed adults to make overly negative self-evaluations either during or following episodes of depression. We argue that we can substantially improve longer-term outcomes by identifying the underlying pathology that leads to these negative self-evaluations so that better targeted and more enduring treatments can be developed. Building on our preliminary data, and the work of others, the goal of this short-term project is to provide the first test of a novel hypothesis about the neural mechanisms that lead to dysfunctional self-evaluations in current and remitted depressed adults and to begin to examine the real-world consequences of that pathology for future symptoms and functioning. To test our hypotheses, we will evaluate behavioral and neuroimaging markers of abnormal processing during self- evaluation in 30 currently depressed, 30 remitted depressed, and 30 healthy adults. Participants will complete baseline clinical and functional magnetic resonance imaging (fMRI) assessments, as well as three weeklong daily diary protocols (over the span of four months) that will assess symptoms, self-evaluations in daily life, and real-world functioning. The project will examine processes leading to the abnormal engagement of the autobiographical memory (Aim 1) and social-cognitive (Aim 2) networks among depressed adults when evaluating self-relevant material, and it will examine whether abnormalities in brain function during self- evaluation prospectively predict psychiatric symptoms and poorer interpersonal and work functioning in daily life (Exploratory Aim). The aims of the project match well with the strategic goals of the National Institute of Mental Health, and the results of this study have the potential to lead to new, brain-based treatment strategies to target the identified mechanisms underlying negative self-evaluations to improve longer-term outcomes.