Similar to patients with Major depressive disorder (MDD), healthy subjects at risk for depression show hyperactivation of the amygdala as a response to negative emotional expressions. The medial prefrontal cortex is responsible for amygdala control. Analyzing a large cohort of healthy subjects, we aimed to delineate malfunction in amygdala regulation by the medial prefrontal cortex in subjects at increased risk for depression, i.e., with a family history of affective disorders or a personal history of childhood maltreatment. We included a total of 342 healthy subjects from the FOR2107 cohort (www.for2107.de). An emotional face-matching task was used to identify the medial prefrontal cortex and right amygdala. Dynamic Causal Modeling (DCM) was conducted and neural coupling parameters were obtained for healthy controls with and without particular risk factors for depression. We assigned a genetic risk if subjects had a first-degree relative with an affective disorder and an environmental risk if subjects experienced childhood maltreatment. We then compared amygdala inhibition during emotion processing between groups. Amygdala inhibition by the medial prefrontal cortex was present in subjects without those two risk factors, as indicated by negative model parameter estimates. Having a genetic risk (i.e., a family history) did not result in changes in amygdala inhibition compared to no risk subjects. In contrast, childhood maltreatment as environmental risk has led to a significant reduction of amygdala inhibition by the medial prefrontal cortex. We propose a mechanistic explanation for the amygdala hyperactivity in subjects with particular risk for depression, in particular childhood maltreatment, caused by a malfunctioned amygdala downregulation via the medial prefrontal cortex. As childhood maltreatment is a major environmental risk factor for depression, we emphasize the importance of this potential early biomarker.

中文翻译：

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儿童虐待的长期神经解剖学后果：内侧前额叶皮层对杏仁核的抑制减少

与重度抑郁症 (MDD) 患者类似，处于抑郁风险中的健康受试者表现出杏仁核过度激活作为对负面情绪表达的反应。内侧前额叶皮层负责控制杏仁核。分析一大群健康受试者，我们旨在描述抑郁症风险增加的受试者（即有情感障碍家族史或童年虐待个人史）的内侧前额叶皮层调节杏仁核的功能障碍。我们包括来自 FOR2107 队列 (www.for2107.de) 的总共 342 名健康受试者。使用情感面部匹配任务来识别内侧前额叶皮层和右侧杏仁核。进行了动态因果建模 (DCM)，并获得了健康对照的神经耦合参数，其中有和没有特定的抑郁症风险因素。如果受试者的一级亲属患有情感障碍，我们分配了遗传风险，如果受试者经历了童年虐待，我们分配了环境风险。然后我们比较了组间情绪处理过程中的杏仁核抑制。如负模型参数估计所示，没有这两个风险因素的受试者存在内侧前额叶皮层对杏仁核的抑制作用。与没有风险的受试者相比，具有遗传风险（即家族史）不会导致杏仁核抑制发生变化。相比之下，作为环境风险的童年虐待导致内侧前额叶皮层对杏仁核的抑制显着减少。我们对具有抑郁症风险的受试者的杏仁核过度活跃提出了一种机制解释，尤其是儿童期虐待，这是由于杏仁核通过内侧前额叶皮层下调功能障碍引起的。由于儿童期虐待是抑郁症的主要环境风险因素，我们强调了这种潜在的早期生物标志物的重要性。