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

J Psychiatr Res. 2024 Jan:169:224-230. doi: 10.1016/j.jpsychires.2023.11.029. Epub 2023 Nov 20.

Abstract

Background: Pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α 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 (AUCi) 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, AUCi 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 AUCi (Spearman's ρ = 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.

Keywords: Cytokines; Growth factors; Inflammation; Major depressive disorder; Psychosocial stress.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers
  • Cytokines*
  • Depressive Disorder, Major* / drug therapy
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • Humans
  • Stress, Psychological
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A / therapeutic use

Substances

  • Cytokines
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Vascular Endothelial Growth Factor A
  • Tumor Necrosis Factor-alpha
  • Biomarkers