抗抑郁药治疗对抑郁症前额叶-皮层下情感管理环路的调控研究

Depression is a disease with high prevalence and disability, its etiology and pathology are still unclear. Recent understanding regarding the mechanism of antidepressant treatment is still confined to the receptor level, but how the antidepressant drugs improve depressive symptoms through the effects on neural circuit is not very clear. According to the core characteristics of depression - negative affective bias, and the results of related neuroimaging studies, researchers have raised a hypothesis of the prefrontal-subcortical emotional regulation circuit model of depression. However, how about the dynamic causal relationship of this circuit connectivity, how the antidepressant exerts a therapeutic effect through affecting the circuit, how the imaging indicators predict the patient's treatment efficacy, remain to be explored. In this study, 50 cases of first-episode, untreated patients with depression and 50 healthy controls would be recruited. The patients were treated with escitalopram. The "multi-band" rapid imaging sequence would be used to collect the high-resolution multi-modal magnetic resonance imaging data of subjects at baseline and after 8 weeks. We planned to use the effective connectivity and other imaging analysis methods to map the dynamic functional characteristics of the prefrontal-subcortical emotional regulation circuit, the fiber tracking and other white-matter analysis methods to identify the structural basis of circuit-related functional changes. Trough above work, we hope to provide new evidence for the understanding of the abnormalities of the prefrontal-subcortical emotional regulation circuit of depression. Taking the emotional regulation circuit as a sensitive feature, we aimed to investigate the network-level acting mechanism of antidepressants and find the imaging markers to predict the treatment efficacy of depressed patients.

抑郁症是高患病和高致残性疾病，其病因和病理机制仍不明确。目前对抗抑郁药治疗机制的认识局限于受体水平，药物如何通过影响神经环路来最终改善症状尚不清楚。根据抑郁症的核心特征-负性情感偏见及相关影像学研究结果，有学者提出了抑郁症前额叶-皮层下情感管理环路模型的假说。然而一些问题仍有待探讨，如抑郁症该环路连接的动态因果关系如何，抗抑郁药如何影响环路功能来产生疗效，环路特征能否预测治疗效果。本研究拟收集50例首发未用药的抑郁症患者和50例健康对照，给予患者艾司西酞普兰治疗，采用“multi-band”快速成像序列采集被试基线和8周随访期的高分辨率多模态磁共振数据，有效连接等方法分析前额叶-皮层下情感管理环路的连接性及其随治疗的变化，纤维追踪等方法分析环路功能改变的结构基础。预期结果将有助于深入理解抑郁症前额叶-皮层下情感管理环路的异常，揭示抗抑郁药的脑网络调控机制，发现能够预测药物治疗疗效的标记物。

抑郁症是高患病和高致残性疾病，其病因和病理机制仍不明确。目前对抗抑郁药治疗机制的认识局限于受体水平，尚不清楚药物如何通过影响神经环路来最终改善症状。本研究收集抑郁症患者和健康对照，给予患者为期8周的5-羟色胺及去甲肾上腺素再摄取抑制剂治疗，在基线和8周治疗结束时、健康对照8周间隔前后采集fMRI数据，分析23例患者和匹配健康对照的静息态fMRI数据，选取纹状体亚区(背侧尾状核、腹侧纹状体和壳核)为感兴趣区，分析感兴趣区至全脑的连接模式，发现患者较健康对照右侧纹状体多个亚区和额上回、右背侧尾状核和左侧楔前叶、右腹侧纹状体和左侧顶下小叶的连接增加，在抗抑郁药治疗后减低。相反，右腹侧纹状体和左侧小脑的连接减低，治疗后增加。治疗后更大程度的腹侧纹状体和额上回连接的减少可以预测更强的冥思反应的缓解。该研究为理解抗抑郁药治疗机制以及药物疗效预测提供了新证据。