The elevated plasma levels of Claudin-5 are associated with peripheral inflammatory activity in patients with major depressive disorder.

BACKGROUND

This study aimed to evaluate the functional status of the blood-brain barrier (BBB) in Major Depressive Disorder (MDD) patients and its association with systemic inflammation.

METHODS

We recruited 90 first-episode, drug-naïve MDD patients and 104 healthy controls (HC). Plasma concentrations of tight junction proteins (Claudin-5 and Occludin), adherens junction proteins [Platelet Endothelial Cell Adhesion Molecule 1 (PECAM1) and Vascular Endothelial-cadherin (VE-cadherin)], and CRP were measured using enzyme-linked immunosorbent assay. Inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) were quantified with Luminex multiplex assay. Statistical analyses were conducted using t-tests, chi-square tests, Mann-Whitney U tests, general linear models, analysis of covariance, and partial correlation analysis.

RESULTS

Plasma levels of Claudin-5 (F = 8.433, p = 0.004), IL-1β (F = 10.707, p = 0.001), and CRP (Z = -2.562, p = 0.010) were significantly elevated in MDD patients compared to HC. In MDD, Claudin-5 was positively correlated with IL-1β (r = 0.269, p = 0.012) and CRP (r = 0.408, p = 0.001). Importantly, plasma Claudin-5 levels in the high-CRP MDD group were significantly higher than those in the low-CRP MDD (p = 0.024, Bonferroni correction) and low-CRP HC (p < 0.001, Bonferroni correction), and were positively correlated with plasma CRP levels (r = 0.511, p = 0.018).

LIMITATIONS: Due to the cross-sectional design, causal relationships between Claudin-5 and the inflammatory cytokines cannot be established.

CONCLUSIONS

MDD patients may exhibit inflammation-related abnormalities in paracellular permeability of the BBB. Furthermore, Claudin-5-mediated BBB dysfunction may be a key feature in inflammatory MDD.