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

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.