Association of Serum Cortisol, Interleukin-6, and Serotonin with Depression

Objective: To explore the relation between serum cortisol, interleukin-6 (IL-6), and serotonin (5-HT) levels in patients with melancholic depression, atypical depression, and healthy controls. Methodology: This cross-sectional comparative study was conducted from August 2023 to July 2024 at the Combined Military Hospital, Muzaffarabad. After ethical approval of the study, a total of 105 participants were enrolled using a non-probability convenience sampling method, including 35 healthy individuals, 35 with melancholic depression, and 35 with atypical depression. Serum levels of cortisol, IL-6, and serotonin were measured using enzyme-linked immunosorbent assay. The Statistical Package for the Social Sciences (SPSS) version 25 was used to analyze the data and determine associations between these biomarkers across different depression groups. Results: Elevated serum IL-6 levels were found in both depression groups compared to healthy controls (p <0.001). Serum cortisol levels were significantly higher in both depression groups as compared to controls, with a notable difference between the two depression types (p <0.001). Serum serotonin levels were lower in both depression groups as compared to controls with no significant variation between melancholic and atypical depression (p <0.001). Positive correlations were observed between serum IL-6 and cortisol (p =0.001; r=0.629) in melancholic depression, while IL-6 exhibited a negative correlation with serotonin (p =0.014; r= -0.411) in atypical depression. Serum cortisol also displayed a negative correlation with serotonin in melancholic depression but the results were statistically insignificant (r=-0.33, p= 0.05). Conclusion: This study revealed elevated cortisol & interleukin-6 levels and decreased serotonin levels in depression groups as compared to healthy controls. The melancholic & atypical depression subtypes did not significantly differ for interleukin-6 and serotonin levels. However, a significant elevation in serum cortisol levels was observed in patients with melancholic depression versus those with atypical depression.