Role of Inflammatory Cytokines (CRP and TNF Alpha) in Persistent Depressive Disorder

Background: A protracted depressive illness known as Persistent Depressive Disorder (PDD) is linked to poor outcomes, recurrence, and treatment resistance. Furthermore, there is growing evidence that the etiology of depression involves inflammation. Inflammatory biomarkers are linked to mood disorders in three main ways: both tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP).Aim of the work: To investigate the role of CRP and TNF-α in the pathogenesis and chronicity of PDD.Patients and methods: 80 participants were included in a cross-sectional comparative observational study: 40 patients with PDD and 40 healthy controls. The Hamilton Depression Rating Scale (HDRS) was employed to evaluate depression severity, and the SCID-5-TR-RV was employed to diagnose depression. The levels of TNF-α and CRP in the blood were measured using an enzyme-linked immunosorbent assay (ELISA).Results: CRP and TNF-α levels were significantly higher in PDD patients compared to controls (p < 0.001 and p = 0.006, respectively). CRP correlated strongly with HDRS scores (ρ = 0.800, p < 0.001), illness duration, and number of episodes. TNF-α showed significant associations with HDRS (ρ = 0.300, p = 0.007) and illness duration (ρ = 0.299, p = 0.007) but less than CRP. Regression analysis indicated HDRS as the only significant predictor of CRP.Conclusion: Inflammatory markers, particularly CRP, play a significant role in the chronicity and severity of PDD. CRP may serve as a robust biomarker for clinical monitoring, while TNF-α has a less consistent role. Targeting inflammation may provide future therapeutic approaches in treatment-resistant depression.