Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Clinical Laboratory, Affiliated Hospital of West Anhui Health Vocational College, Lu'an, Anhui, China.
Department of Psychiatry, Affied Hospital of West Anhui Health Vocational College, Lu'an, Anhui, China.
J Affect Disord. 2025 Jan 1;368:151-159. doi: 10.1016/j.jad.2024.09.073. Epub 2024 Sep 14.
Vascular endothelial growth factor (VEGF) is a candidate mediator of blood-brain barrier (BBB) disruption in depression. However, previous studies have mainly focused on peripheral blood VEGF levels, and the results are heterogeneous. Here we use astrocyte-derived extracellular vesicles (ADEVs) isolated from plasma to explore the in vivo changes of VEGF levels in patients with major depressive disorder (MDD).
Thirty-five unmedicated patients with MDD and 35 healthy controls (HCs) were enrolled, and plasma ADEVs were isolated from each participant. VEGF levels in ADEVs and glial fibrillary acidic protein (GFAP) in plasma were measured. Additionally, Alix and CD81, two established extracellular vesicle markers, were quantified in ADEVs.
At baseline, MDD patients exhibited significantly increased levels of VEGF in ADEVs and GFAP in plasma. Following four weeks of selective serotonin reuptake inhibitor treatment, these target protein levels did not significantly change. ROC curve analysis revealed an AUC of 0.711 for VEGF in ADEVs. In exploratory analysis, VEGF levels in ADEVs were positively correlated with Alix and CD81.
Multiple factors regulate BBB permeability. This study focused solely on VEGF and the sample size for longitudinal analysis was relatively small.
Our study is the first to confirm increased ADEV-derived VEGF levels in patients with MDD, thereby providing preliminary evidence supporting the hypothesis that the BBB is disrupted in depression.
血管内皮生长因子 (VEGF) 是抑郁症血脑屏障 (BBB) 破坏的候选介质。然而，以前的研究主要集中在外周血 VEGF 水平上，结果存在异质性。在这里，我们使用从血浆中分离的星形胶质细胞衍生的细胞外囊泡 (ADEV) 来探索重度抑郁症 (MDD) 患者体内 VEGF 水平的变化。
纳入 35 名未经治疗的 MDD 患者和 35 名健康对照者 (HCs)，从每位参与者中分离出血浆 ADEV。测量 ADEV 中的 VEGF 水平和血浆中的神经胶质纤维酸性蛋白 (GFAP)。此外，还定量了 ADEV 中的两种已建立的细胞外囊泡标志物 Alix 和 CD81。
基线时，MDD 患者的 ADEV 中 VEGF 和血浆中的 GFAP 水平显著升高。经过四周的选择性 5-羟色胺再摄取抑制剂治疗后，这些靶蛋白水平没有显著变化。ROC 曲线分析显示 ADEV 中 VEGF 的 AUC 为 0.711。在探索性分析中，ADEV 中的 VEGF 水平与 Alix 和 CD81 呈正相关。
多种因素调节 BBB 通透性。本研究仅关注 VEGF，纵向分析的样本量相对较小。
我们的研究首次证实 MDD 患者 ADEV 衍生的 VEGF 水平升高，从而为 BBB 在抑郁症中被破坏的假说提供了初步证据。
