Serum claudin-5 levels among patients with unipolar and bipolar depression in relation to the pro-inflammatory cytokine tumor necrosis factor-alpha levels

Eldar Hochman, Michal Taler, Reut Flug, Shay Gur, Shira Dar, Gil Bormant, Dori Blattberg, Uri Nitzan, Amir Krivoy, Abraham Weizman

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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.

Original languageEnglish
Pages (from-to)162-167
Number of pages6
JournalBrain, Behavior, and Immunity
StatePublished - Mar 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Inc.


This research was supported by The Israel Science Foundation (Grant No. 2089/16 to Eldar Hochman) and by the Mordechai Ofer Foundation, Sackler Faculty of Medicine, Tel Aviv University (Grant No. 0601242342 to Eldar Hochman).

FundersFunder number
Mordechai Ofer Foundation
Israel Science Foundation2089/16
Sackler Faculty of Medicine, Tel-Aviv University0601242342


    • Blood–brain barrier
    • Claudin-5
    • Major depressive episode
    • Neurovascular unit
    • Tumor necrosis factor-alpha


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