Premature T cell aging in major depression: A double hit by the state of disease and cytomegalovirus infection.

INTRODUCTION

Previous research indicates that premature T cell senescence is a characteristic of major depressive disorder (MDD). However, known senescence inducing factors like cytomegalovirus (CMV) infection or, probably, childhood adversity (CA) have not been taken into consideration so far.

OBJECTIVE

Differentiation and senescent characteristics of T cells of MDD patients were investigated in relation to healthy controls (HC), taking the CMV seropositivity and CA into account.

METHODS

127 MDD and 113 HC of the EU-MOODSTRATIFICATION cohort were analyzed. Fluorescence activated cell sorting (FACS) analysis was performed to determine B, NK, and T cell frequencies. In a second FACS analysis, naïve, effector memory (Tem), central memory (Tcm), effector memory cells re-expressing RA (TEMRA), as well as CD28 and CD27 memory populations, were determined of the CD4 and CD8 T cell populations in a subsample (N = 35 MDD and N = 36 HC). CMV-antibody state was measured by IgG ELISA and CA by the Childhood Trauma Questionnaire.

RESULTS

We detected a CMV-antibody positivity in 40% of MDD patients (35% HC, n. s.) with seropositive MDD cases showing a higher total childhood trauma score. Second, a higher inflation of memory CD4 T helper cells in CMV seronegative patients as compared to seronegative HC and reduced numbers of naïve CD4 T helper cells in CMV seropositive patients (not in CMV seropositive HC) were found. Third, a higher inflation of memory CD8 T cytotoxic cells in CMV seropositive cases as compared to CMV seropositive HC, particularly of the TEMRA cells, became apparent. Higher percentages of CD4 TEMRA and late stage CD27CD28 TEMRA cells were similar in both HC and MDD with CMV seropositivity. Overall, apportioning of T cell subpopulations did not differ between CA positive vs negative cases.

CONCLUSIONS

MDD patients show several signs of a CMV independent "MDD specific" premature T cell aging, such as a CMV independent increase in CD4 T memory cells and a latent naïve CD4 T-cell reduction and a latent CD8 T-cell increase. However, these two latent T cell senescence abnormalities only become evident with CMV infection (double hit).