Objective:

Preclinical work suggests that excess glucocorticoids and reduced cortical γ-aminobutyric acid (GABA) may affect sex-dependent differences in brain regions implicated in stress regulation and depressive phenotypes. The authors sought to address a critical gap in knowledge, namely, how stress circuitry is functionally affected by glucocorticoids and GABA in current or remitted major depressive disorder (MDD).

Methods:

Multimodal imaging data were collected from 130 young adults (ages 18–25), of whom 44 had current MDD, 42 had remitted MDD, and 44 were healthy comparison subjects. GABA+ (γ-aminobutyric acid and macromolecules) was assessed using magnetic resonance spectroscopy, and task-related functional MRI data were collected under acute stress and analyzed using data-driven network modeling.

Results:

Across modalities, trait-related abnormalities emerged. Relative to healthy comparison subjects, both clinical groups were characterized by lower rostral anterior cingulate cortex (rACC) GABA+ and frontoparietal network amplitude but higher amplitude in salience and stress-related networks. For the remitted MDD group, differences from the healthy comparison group emerged in the context of elevated cortisol levels, whereas the MDD group had lower cortisol levels than the healthy comparison group. In the comparison group, frontoparietal and stress-related network connectivity was positively associated with cortisol level (highlighting putative top-down regulation of stress), but the opposite relationship emerged in the MDD and remitted MDD groups. Finally, rACC GABA+ was associated with stress-induced changes in connectivity between overlapping default mode and salience networks.

Conclusions:

Lifetime MDD was characterized by reduced rACC GABA+ as well as dysregulated cortisol-related interactions between top-down control (frontoparietal) and threat (task-related) networks. These findings warrant further investigation of the role of GABA in the vulnerability to and treatment of MDD.

中文翻译：

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下喙前扣带皮层 GABA+ 和皮质醇应激反应失调与终身抑郁症年轻人功能连接改变的关联：特质和状态影响的多模态成像研究

客观的：

临床前研究表明，过量的糖皮质激素和减少的皮质γ-氨基丁酸（GABA）可能会影响与压力调节和抑郁表型有关的大脑区域的性别依赖性差异。作者试图解决一个关键的知识空白，即在当前或缓解的重度抑郁症 (MDD) 中，压力回路如何受到糖皮质激素和 GABA 的功能影响。

方法：

多模态成像数据收集自 130 名年轻人（18-25 岁），其中 44 名患有当前 MDD，42 名已缓解 MDD，44 名是健康对照受试者。使用磁共振波谱评估 GABA+（γ-氨基丁酸和大分子），并在急性应激下收集与任务相关的功能 MRI 数据，并使用数据驱动的网络模型进行分析。

结果：

在各种模式中，出现了与特征相关的异常。相对于健康对照受试者，两个临床组的特点是头侧前扣带皮层 (rACC) GABA+ 和额顶叶网络振幅较低，但显着性和压力相关网络振幅较高。对于缓解的MDD组，与健康对照组的差异出现在皮质醇水平升高的背景下，而MDD组的皮质醇水平低于健康对照组。在对照组中，额顶叶和与压力相关的网络连接与皮质醇水平呈正相关（突出了假定的自上而下的压力调节），但在 MDD 和缓解 MDD 组中出现了相反的关系。最后，rACC GABA+ 与重叠默认模式和显着网络之间的连接性压力引起的变化相关。

结论：

终生 MDD 的特点是 rACC GABA+ 减少以及自上而下控制（额顶）和威胁（任务相关）网络之间与皮质醇相关的相互作用失调。这些发现值得进一步研究 GABA 在 MDD 易感性和治疗中的作用。