Update on the inflammatory pathophysiology of mental illness

A chronic low-grade inflammation, both systemic and in the brain has been described in preclinical models of interest in psychosis and schizophrenia, most of which are based on the application of stress and immune challenges during periods of particular vulnerability in brain development. These data have been also described in humans, in plasma and in circulating peripheral blood cells as well as in brain tissue and cerebrospinal fluid. This inflammation consists not only of an increase in the activity of intracellular mechanisms and inflammatory and oxidative intercellular signals, but also in a failure in controlling mechanisms. The role of cytokines, innate immunity receptors, and inducible enzyme activation appear to be important. However, so far none of these factors have been identified as a specific and reliable trait or state biomarker of the disease. This review presents preclinical and clinical data on the inflammatory pathophysiology of schizophrenia on which the use of anti-inflammatory drugs, antioxidants, and regulators of the immune response added to standard antipsychotic treatment is based. The most recent meta-analyses indicate that the addition of aspirin, N-acetylcysteine, minocycline, and fatty acids to antipsychotic treatment improves the disease. The possibility of identifying patients with elevated levels of inflammatory markers is underlined as an interesting aspect to consider when introducing adjunctive drugs to antipsychotic treatment.