本研究旨在研究抑郁症的神经炎症假设以及电抽搐疗法(ECT)在体内潜在的抗炎作用，利用从血浆中分离出的星形胶质细胞衍生的细胞外囊泡（ADEVs）。总共招募了40名治疗抵抗性抑郁症（TRD）患者和35名匹配的健康对照组（HCs）在基线，其中34名TRD患者完成了ECT后的访视。在基线和ECT后收集了血液样本。分离并确认了血浆ADEVs，并测量了其中的两个星形胶质细胞标记物（胶质纤维酸性蛋白（GFAP）和S100β），一种EV标记物群集分化(CD) 81以及ADEV中的九种炎性标记物的浓度作为主要分析。此外，进行了临床特征和ADEV蛋白水平之间的相关性分析作为探索性分析。 在基线，TRD组的两个星形胶质细胞标记物GFAP和S100β以及CD81的水平明显高于HCs组。TRD组的干扰素(IFN)-γ，白细胞介素(IL)-1β，IL-4，IL-6，肿瘤坏死因子(TNF)-α，IL-10和IL-17A的炎性标记物水平也显著升高。经过ECT治疗后，GFAP，S100β和CD81的水平显著降低，IFN-γ和IL-4的水平也显著降低。此外，GFAP，S100β，CD81和炎性细胞因子的水平与抑郁症状更严重和认知功能更差有关。 本研究通过使用ADEVs提供了有关利用星形胶质细胞激活和神经炎症假设来支持抑郁症的直接见解。ECT可能通过抑制星形胶质细胞的激活来发挥抗炎作用。本文受版权保护。版权所有。

This study aimed to investigate the neuroinflammatory hypothesis of depression and the potential anti-inflammatory effect of electroconvulsive therapy (ECT) in vivo, utilizing astrocyte-derived extracellular vesicles (ADEVs) isolated from plasma.A total of 40 patients with treatment-resistant depression (TRD) and 35 matched healthy controls (HCs) were recruited at baseline, and 34 TRD patients completed the post-ECT visits. Blood samples were collected at baseline and post-ECT. Plasma ADEVs were isolated and confirmed, and the concentrations of two astrocyte markers (glial fibrillary acidic protein (GFAP) and S100β), an EV marker cluster of differentiation (CD) 81, and nine inflammatory markers in ADEVs were measured as main analyses. Additionally, correlation analysis was conducted between clinical features and ADEV protein levels as exploratory analysis.At baseline, the TRD group exhibited significantly higher levels of two astrocyte markers GFAP and S100β, as well as CD81 compared to the HCs. Inflammatory markers interferon (IFN)-γ, interleukin (IL)-1β, IL-4, IL-6, tumor necrosis factor (TNF)-α, IL-10, and IL-17A were also significantly higher in the TRD group. After ECTs, there was a significant reduction in the levels of GFAP, S100β, and CD81, along with a significant decrease in the levels of IFN-γ and IL-4. Furthermore, higher levels of GFAP, S100β, CD81 and inflammatory cytokines were associated with more severe depressive symptoms and poorer cognitive function.This study provides direct insight supporting the astrocyte activation and neuroinflammatory hypothesis of depression using ADEVs. ECT may exert anti-inflammatory effect through inhibition of such activation of astrocytes. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.