Plasma cytokine and growth factor response to acute psychosocial stress in major depressive disorder

Background Pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha are elevated in response to psychosocial stress; however, less is known about other inflammatory markers.Methods We explored response to the Trier Social Stress Test (TSST) of 16 cytokines and growth factors in patients with major depressive disorder (MDD, n = 12) vs. healthy volunteers (HV, n = 16). Outcomes were baseline and post-stress levels estimated by area under the curve (AUC(i)) and peak change over 3 timepoints. We also explored correlations between biomarkers and clinical characteristics.Results Baseline concentrations were higher in MDD for platelet-derived growth factor (PDGF)-AB/BB (p = 0.037, d = 0.70), granulocyte-macrophage colony-stimulating factor (GM-CSF, p = 0.033, d = 0.52), and IL-8 (p = 0.046, d = 0.74). After TSST, AUC(i) was higher in MDD for GM-CSF (p = 0.003, d = 1.21), IL-5 (p = 0.014, d = 1.62), and IL-27 (p = 0.041, d = 0.74). In MDD, depression severity correlated positively with soluble CD40L (sCD40L) for AUC(i) (Spearman's rho = 0.76, p = 0.004) and with baseline vascular endothelial growth factor A (VEGFA, r = 0.85, p < 0.001), but negatively with baseline monokine induced by gamma interferon (MIG, aka CXCL9; r = -0.77, p = 0.003).Conclusions Effect sizes were robust in this exploratory study, although interpretation of the results must be cautious, given small sample size and multiple comparisons. Differential study of stress-induced biomarkers may have important ramifications for MDD treatment.