The interplay between cortical and limbic regions in stress circuitry calls for a neural systems approach to investigations of acute stress responses in major depressive disorder (MDD). Advances in multimodal imaging allow inferences between regional neurotransmitter function and activation in circuits linked to MDD, which could inform treatment development. The current study investigated the role of the inhibitory neurotransmitter GABA in stress circuitry in females with current and remitted MDD. Multimodal imaging data were analyzed from 49 young female adults across three groups (current MDD, remitted MDD (rMDD), and healthy controls). GABA was assessed at baseline using magnetic resonance spectroscopy, and functional MRI data were collected before, during, and after an acute stressor and analyzed using a network modeling approach. The MDD group showed an overall lower cortisol response than the rMDD group and lower rostral anterior cingulate cortex (ACC) GABA than healthy controls. Across groups, stress decreased activation in the frontoparietal network (FPN) but increased activation in the default mode network (DMN) and a network encompassing the ventromedial prefrontal cortex–striatum–anterior cingulate cortex (vmPFC–Str–ACC). Relative to controls, the MDD and rMDD groups were characterized by decreased FPN and salience network (SN) activation overall. Rostral ACC GABA was positively associated with connectivity between an overlapping limbic network (Temporal–Insula–Amygdala) and two other circuits (FPN and DMN). Collectively, these findings indicate that reduced GABA in females with MDD was associated with connectivity differences within and across key networks implicated in depression. GABAergic treatments for MDD might alleviate stress circuitry abnormalities in females.

压力回路中皮质和边缘区域之间的相互作用需要一种神经系统方法来研究重度抑郁症 (MDD) 中的急性压力反应。多模态成像的进步允许推断区域神经递质功能和与 MDD 相关的电路中的激活，这可以为治疗开发提供信息。目前的研究调查了抑制性神经递质 GABA 在患有当前和缓解 MDD 的女性的压力回路中的作用。分析了三组（当前 MDD、缓解 MDD (rMDD) 和健康对照组）的 49 名年轻女性成人的多模态成像数据。使用磁共振波谱在基线评估 GABA，并在急性应激源之前、期间和之后收集功能性 MRI 数据，并使用网络建模方法进行分析。MDD 组的皮质醇反应总体低于 rMDD 组，而前扣带回皮层 (ACC) GABA 的水平低于健康对照组。在各组中，压力降低了额顶网络 (FPN) 的激活，但增加了默认模式网络 (DMN) 和包含腹内侧前额叶皮层-纹状体-前扣带皮层 (vmPFC-Str-ACC) 的网络的激活。相对于对照组，MDD 和 rMDD 组的特点是 FPN 和显着性网络 (SN) 整体激活减少。Rostral ACC GABA 与重叠边缘网络（颞叶-脑岛-杏仁核）和其他两个回路（FPN 和 DMN）之间的连接呈正相关。集体，这些发现表明，患有 MDD 的女性 GABA 减少与抑郁症相关的关键网络内部和之间的连通性差异有关。MDD 的 GABAergic 治疗可能会减轻女性的压力回路异常。