Cytokine production by leukocytes of military personnel with depressive symptoms after deployment to a combat-zone: a prospective, longitudinal study

Abstract

Major depressive disorder (MDD) is frequently diagnosed in military personnel returning from deployment. Literature suggests that MDD is associated with a pro-inflammatory state. To the best of our knowledge, no prospective, longitudinal studies on the association between development of depressive symptomatology and cytokine production by peripheral blood leukocytes have been published. The aim of this study was to investigate whether the presence of depressive symptomatology six months after military deployment is associated with the capacity to produce cytokines, as assessed before and after deployment. 1023 military personnel were included before deployment. Depressive symptoms and LPS- and T-cell mitogen-induced production of 16 cytokines and chemokines in whole blood cultures were measured before (T0), 1 (T1), and 6 (T2) months after return from deployment. Exploratory structural equation modeling (ESEM) was used for data reduction into cytokine patterns. Multiple group latent growth modeling was used to investigate differences in the longitudinal course of cytokine production between individuals with (n = 68) and without (n = 665) depressive symptoms at T2. Individuals with depressive symptoms after deployment showed higher T-cell cytokine production before deployment. Moreover, pre-deployment T-cell cytokine production significantly predicted the presence of depressive symptomatology 6 months after return. There was an increase in T-cell cytokine production over time, but this increase was significantly smaller in individuals developing depressive symptoms. T-cell chemokine and LPS-induced innate cytokine production decreased over time and were not associated with depressive symptoms. These results indicate that increased T-cell mitogen-induced cytokine production before deployment may be a vulnerability factor for development of depressive symptomatology in response to deployment to a combat-zone. In addition, deployment to a combat-zone affects the capacity of T-cells and monocytes to produce cytokines and chemokines until at least 6 months after return.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Longitudinal course of T-cell cytokine production and T-cell counts.

Longitudinal course of CD2/CD28-induced Factor 1: T-cell cytokine production (A); CD2/CD28-induced Factor 2: T-cell chemokine/IL-6 production (B) and CD3+ T-cell counts (C); CD8+ cytotoxic/suppressor-effector T-cell counts (D) and CD4+ T helper-cell counts (E), as assessed before deployment (T0), 1 month (T1) and 6 months (T2) after return from deployment. The course of the group with depressive symptoms at T2 (n = 69) is depicted by the black circles (mean + SEM). The course of the group without depressive symptoms at T2 (n = 664) is depicted by the white rectangles (mean + SEM).

Figure 2. Longitudinal course of innate cytokine production and monocytes.

Longitudinal course LPS-induced Factor 3: innate cytokine production (A); and monocyte counts (B), as assessed before deployment (T0), 1 month (T1) and 6 months (T2) after return from deployment. The course of the group with depressive symptoms at T2 (n = 69) is depicted by the black circles (mean + SEM). The course of the group without depressive symptoms at T2 (n = 664) is depicted by the white rectangles (mean + SEM).