累积证据表明，炎症和神经血管单元（NVU）功能障碍通过破坏血脑屏障（BBB）完整性对抑郁症起到贡献。 Claudin-5是一种在NVU中表达的内皮细胞紧密连接蛋白，对BBB完整性起到贡献，被认为与精神障碍相关，包括重度抑郁症（MDD）和精神分裂症。在一种抑郁样行为的动物模型中，发现促炎症细胞因子肿瘤坏死因子-α（TNF-α）会影响BBB通透性和 NVU内皮细胞claudin-5表达。据作者所知，本研究是首次评估了严重抑郁发作期（MDEs）期间血清claudin-5和TNF-α水平之间的关系。分析了40名被诊断为当前MDE [19名MDD患者和21名双相障碍（BD）患者]的患者和28名匹配的健康对照组（HC）的血清claudin-5和TNF-α水平。MDE组的claudin-5和TNF-α血清水平高于HC组。根据MDE类型进行离散分析表明，与HC相比，在BD患者中，但不在MDD患者中，claudin-5血清水平显著增加，即使在控制混杂因素后仍是如此。在MDE组中，claudin-5和TNF-α血清水平之间存在显著的正相关性。在补充分析中，发现MDE患者的促炎症细胞因子白细胞介素-6血清水平显著高于HC，然而，claudin-5水平未发现显著相关性。总之，根据临床前研究，我们的临床研究表明，在抑郁症的发病机制中，NVU / BBB标志物claudin-5和炎症标志物TNF-α之间可能存在特定的相互作用。版权所有©2023 Elsevier Inc.保留所有权利。

Accumulating evidence indicates that inflammation and neurovascular unit (NVU) dysfunction contribute to depression via disrupted blood-brain barrier (BBB) integrity. Claudin-5, an endothelial tight-junction protein expressed in the NVU and contributing to BBB integrity, has been implicated in psychiatric disorders, including major depressive disorder (MDD) and schizophrenia. In an animal model of depressive-like behavior, the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) was found to affect BBB permeability and claudin-5 expression of NVU endothelial cells. To the best of the authors' knowledge, this study is the first to assess the relationship between serum claudin-5 and TNF-α levels, during major depressive episodes (MDEs). Serum levels of claudin-5 and TNF-α of 40 patients diagnosed with current MDE [19 with MDD and 21 with bipolar disorder (BD)] and 28 matched healthy controls (HCs) were analyzed. Claudin-5 and TNF-α serum levels in the MDE group were significantly higher than in the HC one. Discrete analysis according to MDE type indicated significantly increased claudin-5 serum levels in BD but not in MDD patients, compared to HCs, even after controlling for confounders. In the MDE group, a significant positive correlation was found between claudin-5 and TNF-α serum levels. In complementary analysis, serum levels of the pro-inflammatory cytokine interleukin-6 were significantly higher among MDE patients compared to HCs, however, no significant correlation was found with claudin-5 levels. In conclusion, as indicated by preclinical studies, our clinical study suggests a possible specific interaction between the NVU/BBB marker claudin-5 and the inflammatory marker TNF-α in the pathogenesis of depression.Copyright © 2023 Elsevier Inc. All rights reserved.