Altered intracellular signaling cascades in peripheral blood mononuclear cells from BD patients

J Psychiatr Res. 2013 Dec;47(12):1949-54. doi: 10.1016/j.jpsychires.2013.08.019. Epub 2013 Sep 8.

Abstract

Bipolar disorder (BD) is a severe psychiatric disorder of complex physiopathology that has been associated with a pro-inflammatory state. The aim of the present study was to investigate intracellular pathways associated with inflammatory signaling, assessing the phosphorylation levels of transcription factor nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPKs) in peripheral blood mononuclear cells of euthymic BD patients and healthy controls. Fifteen BD euthymic type I patients, and 12 healthy controls matched by age and gender were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatry Interview and the patients also by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. Phosphorylation levels of p65 NF-κB subunit, and MAPK ERK1/2, and p38 were assessed by Western blot and flow cytometry. Plasma cytokines (IL-2, IL-4, IL6, IL-10, IFN-γ, TNF-α, and IL-17A) were measured using cytometric bead arrays. Western blot and flow cytometry analyses showed increased phosphorylation levels of p65 NF-κB subunit, and MAPKs ERK1/2, and p38 in BD patients in euthymia in comparison with controls. BD patients presented increased pro-inflammatory cytokines levels in comparison with controls, and TNF-α correlated with the levels of phosphorylated p65 NF-κB. The present study found increased activation of MAPK and NF-κB pathways in BD patients, which is in line with a pro-inflammatory status.

Keywords: Bipolar disorder; Immunology; Inflammation; MAPK; Mania; Nuclear factor kappa B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bipolar Disorder / blood*
  • Case-Control Studies
  • Cytokines / blood
  • Female
  • Flow Cytometry
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phosphorylation
  • Psychiatric Status Rating Scales
  • eIF-2 Kinase / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Cytokines
  • eIF-2 Kinase
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases