Understanding the neurobiological effects of stress is critical for addressing the etiology of major depressive disorder (MDD). Using a dimensional approach involving individuals with differing degree of MDD risk, we investigated 1) the effects of acute stress on cortico-cortical and subcortical-cortical functional connectivity (FC) and 2) how such effects are related to gene expression and receptor maps. Across 115 participants (37 control, 39 remitted MDD, 39 current MDD), we evaluated the effects of stress on FC during the Montreal Imaging Stress Task. Using partial least squares regression, we investigated genes whose expression in the Allen Human Brain Atlas was associated with anatomical patterns of stress-related FC change. Finally, we correlated stress-related FC change maps with opioid and GABA (gamma-aminobutyric acid A) receptor distribution maps derived from positron emission tomography. Results revealed robust effects of stress on global cortical connectivity, with increased global FC in frontoparietal and attentional networks and decreased global FC in the medial default mode network. Moreover, robust increases emerged in FC of the caudate, putamen, and amygdala with regions from the ventral attention/salience network, frontoparietal network, and motor networks. Such regions showed preferential expression of genes involved in cell-to-cell signaling (, , , , ), similar to previous genetic MDD studies. Acute stress altered global cortical connectivity and increased striatal connectivity with cortical regions that express genes that have previously been associated with imaging abnormalities in MDD and are rich in μ and κ opioid receptors. These findings point to overlapping circuitry underlying stress response, reward, and MDD.

中文翻译：

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急性压力会增加纹状体与富含 μ 和 κ 阿片受体的皮质区域的连通性

了解压力的神经生物学影响对于解决重度抑郁症 (MDD) 的病因至关重要。使用涉及不同程度 MDD 风险的个体的维度方法，我们研究了 1) 急性应激对皮质-皮质和皮质下-皮质功能连接 (FC) 的影响，以及 2) 这种影响如何与基因表达和受体图谱相关。我们在 115 名参与者（37 名对照组、39 名缓解 MDD、39 名当前 MDD）中评估了蒙特利尔成像压力任务期间压力对 FC 的影响。使用偏最小二乘回归，我们研究了艾伦人脑图谱中表达与压力相关 FC 变化的解剖模式相关的基因。最后，我们将与压力相关的 FC 变化图与源自正电子发射断层扫描的阿片类药物和 GABA（γ-氨基丁酸 A）受体分布图相关联。结果显示，压力对整体皮质连接产生强烈影响，额顶叶和注意力网络中的整体 FC 增加，而内侧默认模式网络中的整体 FC 减少。此外，尾状核、壳核和杏仁核的 FC 以及腹侧注意/显着网络、额顶网络和运动网络的区域出现了强劲的增加。这些区域显示出参与细胞间信号转导的基因的优先表达 (, , , , )，类似于之前的遗传 MDD 研究。急性应激改变了整体皮质连接，并增加了纹状体与皮质区域的连接，这些区域表达先前与 MDD 成像异常相关的基因，并且富含 μ 和 κ 阿片受体。这些发现表明压力反应、奖励和 MDD 之间存在重叠的回路。