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February 25, 2026Open Access

Association Between Clinical Symptoms and Inflammatory Markers in First-Episode Unmedicated Patients with Major Depressive Disorder

Key Points

This research aims to explore the relationship between clinical symptoms and inflammatory markers in first-episode unmedicated major depressive disorder (MDD) patients.
Measured inflammatory cytokine levels using enzyme-linked immunosorbent assay (ELISA) in serum samples.
Assessed clinical symptoms using HAMD-17, CTQ, and QIDS-SR16 scales.
Compared inflammatory markers in depressed patients versus healthy controls.
Depressed patients showed higher levels of IFN-γ and IL-17, and lower levels of IL-4, MCP-1, MIP-1β, and IL-8 compared to healthy controls (p<0.05).
IL-4 correlated positively with HAMD-17 (p=0.03) and QIDS-SR16 scores (p=0.009).
IL-17 showed a positive correlation with QIDS-SR16 score (p=0.04).
IL-4 had a high sensitivity for depression diagnosis with an AUC of 0.72 (p<0.01).

Abstract

Background: Depression represents a serious psychiatric disorder globally, imposing significant burdens on patients’daily lives. Numerous hypotheses including the inflammatory hypothesis. Changes in inflammatory factors within the bodies of individuals with depression may represent a key biological mechanism. Multiple clinical investigations have demonstrated that pro-inflammatory cytokine levels in the peripheral blood of depressed patients are markedly higher than in healthy controls, with the degree of elevation in these inflammatory markers positively correlating with the severity of depressive symptoms. We shall examine changes in specific pro-inflammatory and anti-inflammatory factors. Method: We employed the enzyme-linked immunosorbent assay (ELISA) to detect inflammatory cytokine levels in subject’s serum samples. Clinical symptoms were assessed using the Childhood Trauma Questionnaire (CTQ), the 17-item Hamilton Depression Rating Scale (HAMD-17), and the Quick Inventory of Depressive Symptomatology (Self-Rating) (QIDS-SR16). Results: Compared to the healthy group, the depression group exhibited a significantly higher IFN-γ and IL-17 (p< 0.05) and lower IL-4, MCP-1, MIP-1β, and IL-8 (p< 0.05). Serum IL-4 levels showed significant positive correlations with HAMD-17 score (p=0.03), QIDS-SR 16 scores (p=0.009). IL-17 level was positively correlated with the QIDS-SR16 score (p=0.04). Several markers showed significant discriminatory power. IL-4 demonstrated the highest AUC of 0.72 (P < 0.01), with a sensitivity of 87.10% and specificity of 51.61%, indicating a moderate predictive value for depression. Conclusion: The distinct inflammatory profile—characterized by elevated IFN-γ/IL-17 and reduced IL-4/MCP-1/IL-8/MIP-1β—in first-episode MDD patients underscores the role of immune imbalance in early depression pathophysiology. The strong association of IL-4 with symptom severity and its high sensitivity for disease identification highlight its potential as a valuable clinical biomarker. These findings support further investigation into immune-based stratification of MDD patients, which could pave the way for more personalized diagnostic and therapeutic strategies targeting specific inflammatory pathways”. Keywords: depression, inflammatory cytokine, IL-4, IL-17, MDD

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