Emotion regulation in depression: neural bases of reappraisal

描述(由申请人提供)：严重抑郁障碍(MDD)是一种使人衰弱的疾病，给个人和社会带来重大负担。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，并延伸到快感缺失、冷漠、食欲和睡眠障碍，以及注意力和记忆力问题。对社会而言，MDD的负担表现为生产力的损失和与治疗相关的巨额费用。抑郁症相关症状的异质性给试图理解这种障碍的研究人员和试图治疗它的临床医生都带来了挑战。然而，两条不同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，对基线神经活动和认知任务表现的研究表明，抑郁症与前额叶皮质(PFC)、前扣带回皮质(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，这些相同的神经区域直接与情绪调节有关。该提案描述了两个旨在整合这些研究方向的实验。在这两个实验中，参与者将尝试使用重新评估来调节他们对情绪负面刺激的反应，重新评估是一种由皮质-扣带-杏仁核相互作用支持的适应性情绪调节策略。脑电(EEG；Exp.1)和功能磁共振成像(fMRI；Exp.2)数据将在MDD患者和健康对照的重新评估尝试过程中收集。结合使用，脑电和功能磁共振数据将被用来生成重新评估背后的大脑机制的详细时空模型。这些数据还将被用来检验这一假设，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。与公共健康相关：通过确定与抑郁症有关的核心过程-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，拟议的研究将有助于澄清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.