Major depression is not an inflammatory disorder: depletion of the compensatory immunoregulatory system is a hallmark of a mild depression phenotype

This is the authors' abstract. We don't add key points for this paper.

Background Major depression comprises two discrete subtypes, major (MDMD) and simple (SDMD) dysmood disorder. MDMD, but not SDMD, patients were identified to have highly sensitized cytokine/growth factor networks using stimulated whole blood cultures. However, no information regarding serum cytokines/chemokines/growth factors in SDMD is available. Objectives This case-control study compares 48 serum cytokines/chemokines/growth factors in academic students with SDMD (n=64) and first episode (FE)-SDMD (n=47) to those of control students (n=44) using a multiplex assay. Findings Both FE-SDMD and SDMD exhibit a notable inhibition of immune profiles, such as the compensatory immunoregulatory response system (CIRS) and alternative M2 macrophage and T helper-2 (Th-2) profiles. We observed a substantial reduction in the serum concentrations of five proteins: interleukin (IL)-4, IL-10, soluble IL-2 receptor (sIL-2R), IL-12p40, and macrophage colony-stimulating factor. A significant proportion of the variability observed in suicidal behaviors (26.7%) can be accounted for by serum IL-4, IL-10, and sIL-2R (all decreased), and CCL11 (eotaxin) and granulocyte CSF (both increased). The same biomarkers (except for IL-10), accounted for 25.5% of the variance in SDMS severity. A significant correlation exists between decreased levels of IL-4 and elevated ratings of the brooding type of rumination. Conclusions The immune profile of SDMD and FE-SDMD exhibits a significant deviation from that observed in MDMD, providing additional evidence that SDMD and MDMD represent distinct phenotypes. SDMD is characterized by the suppression of the CIRS profile, which signifies a disruption of immune homeostasis and tolerance, rather than the presence of an inflammatory response.