Bottom-Up Mechanisms of Dysfunctional Self Evaluation in Depression

摘要 抑郁症是全世界导致残疾的主要原因，尽管有几种治疗方法已经 发展，只有少数患者(40%)有反应并保持这种反应一年，无论是哪一种 他们所接受的治疗。一年以上的持续应答率更低。因此，有一个至关重要的公众 卫生部门需要更好地针对抑郁症状的持久质量，并改善长期结果。 消极的自我评价是抑郁症的一个核心特征，它似乎有助于抑郁症的持久 抑郁的症状。消极的自我评价不仅与抑郁症状的持续存在直接相关， 但对于许多人来说，即使在进行了其他有效的治疗后，负面的自我评价仍然存在，增加了患上 旧病复发。尽管许多人都知道认知缺陷和消极的信息加工偏向 成年抑郁症患者的记忆和注意力，对抑郁症的具体干扰知之甚少 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 在抑郁症发作期间或之后。我们认为，从长远来看，我们可以大幅改善 通过确定导致这些负面自我评估的潜在病理来得出结果，以便更好地 可以开发更有针对性和更持久的治疗方法。以我们的初步数据为基础，以及 其他人，这个短期项目的目标是提供关于神经的新假说的第一个测试 导致当前和缓解期抑郁症成人功能障碍的机制，并开始 研究这种病理对未来症状和功能的现实后果。测试我们的 假设，我们将评估自我加工过程中异常加工的行为和神经成像标记物 对30名抑郁症患者、30名缓解性抑郁症患者和30名健康成人进行评估。参赛者将完成 基线临床和功能磁共振成像(FMRI)评估以及为期三周的 每日日记协议(在四个月内)，将评估症状，日常生活中的自我评估，以及 在现实世界中发挥作用。该项目将审查导致非正常参与的过程 抑郁症成年人的自传体记忆(目标1)和社会认知网络(目标2) 评估与自我相关的材料，它将检查自我过程中大脑功能的异常 评估前瞻性地预测精神症状以及日常生活中较差的人际关系和工作功能 (探索性目标)。该项目的目标与国家心理研究所的战略目标非常匹配 健康，这项研究的结果有可能导致新的、以脑为基础的治疗策略 确定了负面自我评价的潜在机制，以改善较长期的结果。

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.