What question did this study set out to answer?

This research aims to investigate the role of serum claudin-5 and peripheral inflammation in patients with major depressive disorder, particularly focusing on suicidality.

March 6, 2026ALPHA PSYCHIATRY1 citationsOpen Access

Serum Claudin-5 and Peripheral Inflammation in Major Depressive Disorder: A Case-Control Study with Focus on Suicidal Ideation

NKNurbanu KeskinMuğla University MSMahmut SelçukMuğla University ESErcan SaruhanMuğla University

Key Points

This research aims to investigate the role of serum claudin-5 and peripheral inflammation in patients with major depressive disorder, particularly focusing on suicidality.
Conducted a case-control study with 73 MDD patients and 74 healthy controls.
Measured serum claudin-5, C-reactive protein, and various inflammatory indices.
Evaluated depression severity and suicidality using standard rating scales (HAM-D, BSSI).
Performed between-group comparisons, correlation analyses, and ROC analyses.
MDD patients exhibited significantly lower claudin-5 levels and higher inflammatory indices (NLR, PLR, CRP, INFLA) compared to controls.
Claudin-5 levels did not correlate with symptom severity or suicidality.
ROC analysis demonstrated claudin-5 had fair accuracy in distinguishing MDD from controls but limited predictive value for suicidality.

Abstract

Background: Major depressive disorder (MDD) has been increasingly associated with neuroinflammatory and neurovascular dysfunction. Claudin-5, a key tight junction protein essential for blood–brain barrier integrity, has an unclear role as a peripheral biomarker in MDD. This study examined serum Claudin-5 alongside systemic inflammatory indices—including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), the inflammation score (INFLA), and suicidal ideation in antidepressant-naive or medication-free (for at least three months) adult MDD patients. Method: 73 antidepressant-naive or drug-free MDD patients and 74 age- and sex-matched healthy controls were enrolled. Depression severity and suicidality were assessed using the Hamilton Depression Rating Scale (HAM-D) and Beck Scale for Suicide Ideation (BSSI). Serum Claudin-5, C-reactive protein (CRP), and complete blood counts were measured, and inflammatory indices (NLR, PLR, MLR, INFLA) were calculated. Between-group comparisons, correlation analyses, and receiver operating characteristic (ROC) analyses were performed. Results: MDD patients showed significantly reduced Claudin-5 and elevated NLR, PLR, CRP, and INFLA scores compared with controls (all p < 0.05). Claudin-5 was not associated with symptom severity, suicidality, or inflammatory indices. ROC analysis for serum Claudin-5 indicated fair accuracy in distinguishing MDD from controls (AUC = 0.737) but limited value for predicting suicidal ideation (AUC = 0.628). Conclusion: Reduced serum Claudin-5 in untreated MDD may indicate relatively stable endothelial alterations rather than acute, state-dependent changes. Although Claudin-5 alone had limited prognostic value for suicidality, inflammatory indices—particularly NLR and INFLA—showed stronger associations. Integrating vascular and immune biomarkers may enhance biological stratification and suicide risk assessment in depression and guide future multimodal studies.

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