Affective symptoms are associated with markers of inflammation and immune activation in bipolar disorders but not in schizophrenia

J Psychiatr Res. 2011 Dec;45(12):1608-16. doi: 10.1016/j.jpsychires.2011.08.003. Epub 2011 Sep 1.


Objective: Elevated levels of inflammation are reported in bipolar disorders (BP), but how this relates to affective symptoms is unclear. We aimed to determine if immune markers that consistently have been reported elevated in BP were associated with depressive and manic symptoms, and if this was specific for BP.

Methods: From a catchment area, 112 BP patients were included together with 153 schizophrenia (SCZ) patients and 239 healthy controls. Depression and mania were assessed and the patients were grouped into depressed, neutral, and elevated mood. We measured the immune markers tumor necrosis factor receptor 1 (sTNF-R1), interleukin 1 receptor antagonist (IL-1Ra), interleukin 6 (IL-6), high sensitive C-reactive protein (hsCRP), osteoprotegerin (OPG) and von Willebrand factor (vWf) which have been found increased in severe mental disorders.

Results: In BP all inflammatory markers were lowest in depressed state, with significant group differences after control for confounders with respect to TNF-R1 (p = 0.04), IL-1Ra (p = 0.02), OPG (p = 0.004) and IL-6 (p = 0.005). STNF-R1 was positively correlated with the item elevated mood (p = 0.02) whereas sad mood was negatively correlated with OPG (p = 0.0003), IL-1Ra (p = 0.001) and IL-6 (p = 0.006). Compared to controls the neutral mood group had significantly higher levels of OPG (p = 0.0003) and IL-6 (p = 0.005), and the elevated mood group had higher levels of TNF-R1 (p = 0.000005) and vWf (p = 0.002). There were no significant associations between affective states orsymptoms in SCZ.

Conclusions: The current associations between inflammatory markers and affective symptomatology in BP and not SCZ suggest that immune related mechanisms are associated with core psychopathology of BP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Analysis of Variance
  • Biomarkers / blood*
  • Bipolar Disorder / blood*
  • Bipolar Disorder / complications
  • Body Mass Index
  • C-Reactive Protein
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Inflammation / blood*
  • Inflammation / complications
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-6
  • Male
  • Middle Aged
  • Osteoprotegerin
  • Psychiatric Status Rating Scales
  • Schizophrenia / blood*
  • Statistics as Topic
  • Tumor Necrosis Factor-alpha
  • von Willebrand Factor


  • Biomarkers
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-6
  • Osteoprotegerin
  • Tumor Necrosis Factor-alpha
  • von Willebrand Factor
  • C-Reactive Protein