抑郁症患者及一级亲属奖励与惩罚处理神经机制研究

Anhedonia is associated with deficits in reward processing of the dopamine system, which may increase the risk of depression. Nevertheless, the neutral mechanism in relation to anhedonia is not well characterized. And surprisingly, reward-related disturbance in first-degree relatives of depression has received relatively little attention. In this study, we plan to use functional neuroimaging and computational modeling techniques measuring reward prediction processing in patients with major depression and their unaffected first-degree relatives, to explore the neural basis of trait anticipatory and consummatory anhedonia in these samples, and to assess the correlations between the specific neurocognitive abnormalities and their depressive symptoms developed during the next one year. We hypothesize that trait anhedonia is associated with abnormal Lateral habenula brain activity coding the negative motivational value, and baseline brain function change would predict the development of depression. This study will further our understanding of anhedonia and other reward-related constructs in depression, and facilitate the identification of the underlying pathophysiology associated with subtypes of major depressive disorder and the potential biomarkers for this disorder.

快感缺失被认为是引起抑郁症疾病发作的高风险特征，并与大脑奖励处理异常有关，然而目前研究对于抑郁症快感缺失脑神经损害机制了解并不多；同时，很少有研究探讨患者一级家属这一高风险人群中是否存在这种关联损害。研究拟采用功能性核磁共振(fMRI)和事件相关电位(ERP)研究相结合方式，测量抑郁症快感缺失亚型患者和患者未发病一级亲属在奖惩活动中脑功能、电生理和行为损害特点，并评估这些损害是否预测一年后的疾病症状发展。研究预测快感缺失与负责编码负性激励价值的外侧缰核脑区活动相关，相关联的脑区损害在抑郁发展中起重要作用。研究有助于鉴别抑郁症的生物标记，对疾病早期诊断和预后干预有重要作用。

研究探讨抑郁症患者以及未发病一级亲属的快感缺失症状的行为表现和神经作用机制。研究招募了约50例病人以及病人未发病家属，评估了在这些群体中有较高快感缺失症状的个体的奖励相关的脑活动，以及基线活动是否可以预测抑郁症状发展。.研究一的主要目标在探讨奖励处理关键脑区外侧缰核在抑郁症患者中活动情况以及与临床症状关联。研究使用了高分辨率的影像扫描设计以及计算模型范式，测量抑郁症患者和对照人群在一个概率性强化学习任务中表现。结果显示，正常人群显示出与预期一致的在受到惩罚反馈之后左侧缰核活动。抑郁症患者表现出对惩罚刺激减弱的左侧缰核减弱的活动倾向，同时更大的左侧缰核活动与快感缺失和抑郁症状相关联。.研究二的主要目标是测试病人一级亲属对奖励刺激的反应变化。研究使用一个概率性的视觉鉴别任务用于探查个体对奖励的敏感度。相比正常对照人群，抑郁症家属中有较高抑郁症的个体表现出减弱的奖励反应，然而家属中无抑郁症状个体表现与正常对照人群相近（完好的行为和量表表现）。在抑郁症家属中有较高抑郁症的个体中其量表评定的快感缺失与减弱的奖励敏感度存在相关。.综合上述研究，可见当临床患者接受惩罚刺激时外侧缰核脑区活动异常，同时异常的神经活动与抑郁症状（包括期待性、消费性以及整体的快感缺失症状）相关联；患者未发病家属也表现出快感缺失相关的行为损害，但主要集中在有较高抑郁症状的家属群体中。这项研究能促进对抑郁症快感缺失的神经机制理解，对寻找疾病治疗标记有帮助。