BackgroundDepression is commonly associated with fronto-amygdala dysfunction during the processing of emotional face expressions. Interactions between these regions are hypothesized to contribute to negative emotional processing biases and as such have been highlighted as potential biomarkers of treatment response. This study aimed to investigate depression associated alterations to directional connectivity and assess the utility of these parameters as predictors of treatment response.MethodsNinety-two unmedicated adolescents and young adults (mean age 20.1; 56.5% female) with moderate-to-severe major depressive disorder and 88 healthy controls (mean age 19.8; 61.4% female) completed an implicit emotional face processing fMRI task. Patients were randomized to receive cognitive behavioral therapy for 12 weeks, plus either fluoxetine or placebo. Using dynamic causal modelling, we examined functional relationships between six brain regions implicated in emotional face processing, comparing both patients and controls and treatment responders and non-responders.ResultsDepressed patients demonstrated reduced inhibition from the dlPFC to vmPFC and reduced excitation from the dlPFC to amygdala during sad expression processing. During fearful expression processing patients showed reduced inhibition from the vmPFC to amygdala and reduced excitation from the amygdala to dlPFC. Response was associated with connectivity from the amygdala to dlPFC during sad expression processing and amygdala to vmPFC connectivity during fearful expression processing.ConclusionsOur study clarifies the nature of face processing network alterations in adolescents and young adults with depression, highlighting key interactions between the amygdala and prefrontal cortex. Moreover, these findings highlight the potential utility of these interactions in predicting treatment response.

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改变抑郁症患者扩展面部处理系统的有效连接性及其与治疗反应的关联：YoDA-C 随机对照试验的结果

背景抑郁症通常与情绪面部表情处理过程中的额杏仁核功能障碍有关。假设这些区域之间的相互作用会导致负面情绪处理偏差，因此已被强调为治疗反应的潜在生物标志物。本研究旨在调查抑郁症相关的方向连接性改变，并评估这些参数作为治疗反应预测因子的效用。方法 92 名患有中度至重度抑郁症的未接受药物治疗的青少年和年轻人（平均年龄 20.1 岁；56.5% 为女性） 88 名健康对照者（平均年龄 19.8 岁；61.4% 为女性）完成了隐式情绪面部处理功能磁共振成像任务。患者被随机接受为期 12 周的认知行为治疗，同时接受氟西汀或安慰剂治疗。使用动态因果模型，我们检查了与情绪面部处理有关的六个大脑区域之间的功能关系，比较了患者和对照组以及治疗反应者和无反应者。结果抑郁症患者表现出从 dlPFC 到 vmPFC 的抑制减少，从 dlPFC 到杏仁核的兴奋减少在处理悲伤的表情时。在恐惧表达处理过程中，患者表现出 vmPFC 对杏仁核的抑制减少，以及杏仁核对 dlPFC 的兴奋减少。反应与悲伤表达处理期间从杏仁核到 dlPFC 的连接以及恐惧表达处理期间杏仁核到 vmPFC 的连接有关。结论我们的研究阐明了患有抑郁症的青少年和年轻人面部处理网络改变的性质，强调了杏仁核和前额叶之间的关键相互作用皮质。此外，这些发现强调了这些相互作用在预测治疗反应方面的潜在效用。