Inflammatory evidence for the psychosis continuum model

Psychoneuroendocrinology. 2016 May:67:189-97. doi: 10.1016/j.psyneuen.2016.02.011. Epub 2016 Feb 17.

Abstract

Background: Inflammation and immune activation have been implicated in the pathophysiology of severe mental disorders. Previous studies of inflammatory markers, however, have been limited with somewhat inconsistent results.

Aims: We aimed to determine the effect sizes of inflammatory marker alterations across diagnostic groups of the psychosis continuum and investigate association to antipsychotic medications.

Methods: Plasma levels of soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin 1 receptor antagonist (IL-1Ra), osteoprotegerin (OPG), and von Willebrand factor (vWf) were measured in patients (n=992) with schizophrenia spectrum (SCZ, n=584), schizoaffective disorder (SA, n=93), affective spectrum disorders (AFF, n=315), and healthy controls (HC, n=638).

Results: Levels of sTNF-R1 (p=1.8×10(-8), d=0.23) and IL-1Ra (p=0.002, d=0.16) were increased in patients compared to HC. The SCZ group had higher levels of sTNF-R1 (p=8.5×10(-8), d=0.27) and IL-1Ra (p=5.9×10(-5), d=0.25) compared to HC, and for sTNF-R1 this was also seen in the SA group (p=0.01, d=0.3) and in the AFF group (p=0.002, d=0.12). Further, IL-1Ra (p=0.004, d=0.25) and vWf (p=0.02, d=0.21) were increased in the SCZ compared to the AFF group. There was no significant association between inflammatory markers and use of antipsychotic medication.

Conclusion: We demonstrate a small increase in sTNF-R1 and IL-1Ra in patients with severe mental disorders supporting a role of inflammatory mechanisms in disease pathophysiology. The increase was more pronounced in SCZ compared to AFF supporting a continuum psychosis model related to immune factors.

Keywords: Antipsychotics; Bipolar disorder; Inflammation; Psychosis continuum model; Schizophrenia.

MeSH terms

  • Adult
  • Antipsychotic Agents / blood
  • Antipsychotic Agents / therapeutic use
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Humans
  • Inflammation / blood*
  • Inflammation / complications
  • Interleukin 1 Receptor Antagonist Protein / blood*
  • Male
  • Models, Psychological
  • Mood Disorders / blood*
  • Mood Disorders / complications
  • Mood Disorders / drug therapy
  • Osteoprotegerin / blood*
  • Psychotic Disorders / blood*
  • Psychotic Disorders / complications
  • Psychotic Disorders / drug therapy
  • Psychotropic Drugs / therapeutic use
  • Receptors, Tumor Necrosis Factor, Type I / blood*
  • Schizophrenia / blood*
  • Schizophrenia / complications
  • Schizophrenia / drug therapy
  • Young Adult
  • von Willebrand Factor / metabolism*

Substances

  • Antipsychotic Agents
  • Biomarkers
  • Interleukin 1 Receptor Antagonist Protein
  • Osteoprotegerin
  • Psychotropic Drugs
  • Receptors, Tumor Necrosis Factor, Type I
  • von Willebrand Factor