Emotion regulation in depression: neural bases of reappraisal

描述（由申请人提供）：重度抑郁症（MDD）是一种使人衰弱的疾病，对个人和社会造成重大负担。对于个人来说，MDD与一系列症状有关，包括绝望和内疚的感觉，并扩展到快感缺乏，冷漠，食欲和睡眠障碍，以及注意力和记忆力问题。对于社会来说，MDD的负担表现为生产力的损失和与治疗相关的巨大成本。与抑郁症相关的症状的异质性对试图理解这种疾病的研究人员和试图治疗它的临床医生都提出了挑战。然而，两条独立的研究路线提出了一个简单的假设：抑郁症的多个方面可能从根本上是与情绪调节有关的神经系统功能障碍的结果。首先，研究基线神经活动和认知任务的表现表明，抑郁症与前额叶皮层（PFC），前扣带皮层（ACC）和杏仁核等神经区域的功能障碍有关。其次，对健康参与者的研究表明，这些神经区域直接参与情绪调节。该提案描述了两个旨在整合这些研究路线的实验。在这两个实验中，参与者将尝试使用重新评价来调节他们对情绪负面刺激的反应，这是一种由皮质-扣带回-杏仁核相互作用支持的自适应情绪调节策略。脑电图（EEG; Exp. 1)和功能性磁共振成像（fMRI; Exp. 2)将在MDD患者和健康对照进行重新评估尝试期间收集数据。EEG和功能磁共振成像数据将被用来生成一个详细的时空模型的大脑机制的基础上重新评价。这些数据也将被用来测试这一假设，即MDD的情绪调节失败与特定神经区域的功能障碍有关，包括外侧PFC，背侧ACC和杏仁核。公共卫生相关性：通过确定抑郁症的核心过程-情绪调节，并将情绪调节失败与特定神经回路的功能障碍联系起来，这些研究将有助于阐明抑郁症的病理生理学。最终，这种方法可能有助于改善诊断和治疗。

DESCRIPTION (provided by applicant): Major Depressive Disorder (MDD) is a debilitating condition that places a significant burden on individuals and society. For individuals, MDD is associated with a range of symptoms, including feelings of hopelessness and guilt and extending to anhedonia, apathy, disturbances in appetite and sleep, and problems with concentration and memory. For society, the/burden of MDD is manifested in lost productivity and in significant costs associated with treatment. The heterogeneity of symptoms associated with depression presents a challenge to both researchers trying to understand the disorder and clinicians trying to treat it. However, two separate lines of research suggest a straightforward hypothesis: multiple aspects of depressive illness may fundamentally be a consequence of dysfunction in neural systems implicated in emotion regulation. First, research examining baseline neural activity and performance on cognitive tasks demonstrates that depression is associated with dysfunction in neural regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and amygdala. Second, research with healthy participants shows that these same neural regions are directly implicated in emotion regulation. This proposal describes two experiments designed to integrate these lines of research. In both experiments, participants will attempt to regulate their responses to emotionally negative stimuli using reappraisal, an adaptive emotion regulation strategy supported by cortico-cingulate-amygdalar interactions. Electroencephalogram (EEG; Exp. 1) and functional magnetic resonance imaging (fMRI; Exp. 2) data will be collected during reappraisal attempts made by patients with MDD and healthy controls. In combination, the EEG and fMRI data will be used to generate a detailed spatiotemporal model of the brain mechanisms underlying reappraisal. These data will also be used to test the hypothesis that failures of emotion regulation in MDD are associated with dysfunction in specific neural regions, including lateral PFC, dorsal ACC, and the amygdala. PUBLIC HEALTH RELEVANCE: By identifying a core process-emotion regulation-implicated in depression and tying emotion regulation failures to dysfunction in specific neural circuits, the proposed studies will help clarify the pathophysiology of depression. Ultimately, this approach might contribute to improvements in diagnosis and treatment.