Autoimmunity, inflammation, and psychosis: a search for peripheral markers

Biol Psychiatry. 2014 Feb 15;75(4):324-31. doi: 10.1016/j.biopsych.2013.09.037. Epub 2013 Oct 19.


Accumulating evidence supports the view that deregulation of the immune system represents an important vulnerability factor for psychosis. In a subgroup of psychotic patients, the high comorbidity with autoimmune and chronic inflammatory conditions suggests a common underlying immune abnormality leading to both conditions. The reviewed data of affective and nonaffective psychosis show that if immune biomarkers exist for such immune abnormality, they may be found in raised macrophage/monocyte inflammatory activation patterns (monocytosis, high-inflammatory gene expression, raised glucocorticoid receptor β/glucocorticoid receptor α ratio, and high levels of proinflammatory and anti-inflammatory monocyte/macrophage derived cytokines in serum/plasma), reduced T cell numbers/proliferation, and TH1 skewing. This activation of the inflammatory response system may be suggestive for microglia activation, as these cells are the macrophages of the brain. Indeed, there is some evidence of activation of the microglia as detected in positron emission tomography scans and in histopathology, and it is assumed that this activation disturbs the development and function of neuronal circuits in the brain. Further, animal models of psychotic conditions (maternal stress and inflammation paradigms) suggest that such monocyte/microglia activation could be seen as the result of a combination of genetic predisposition and an immune-mediated two-hit model. Infection but also environmental stressors during gestation/early life activate microglia, perturbing neuronal development, thereby setting the stage for vulnerability for later psychotic disorders. A second hit, such as endocrine changes, stress, or infection, could further activate microglia, leading to functional abnormalities of the neuronal circuitry in the brain and psychosis.

Keywords: Autoimmunity; biomarkers; bipolar; inflammation; microglia; postpartum psychosis; schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmunity*
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Cytokines / blood
  • Cytokines / metabolism
  • Humans
  • Inflammation / blood
  • Inflammation / metabolism*
  • Microglia / immunology
  • Microglia / metabolism
  • Monocytes / metabolism
  • Psychotic Disorders / immunology*
  • Psychotic Disorders / metabolism*
  • T-Lymphocytes / immunology


  • Biomarkers
  • Cytokines