Simple dysmood disorder, a mild subtype of major depression, is not an inflammatory condition: Depletion of the compensatory immunoregulatory system

Abstract

Background

A recent study conducted by the laboratory of the first author revealed that major depression is composed of two distinct subtypes: major dysmood disorder (MDMD) and simple dysmood disorder (SDMD). The latter is a less severe phenotype with fewer aberrant biological pathways. 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 exhibited 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 considerable 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), 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

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.