Neuroprogression in Schizophrenia and Psychotic Disorders: The Possible Role of Inflammation.

Schizophrenia is a disorder that shows a progressive course in 30-50% of the people concerned. The biology of chronification and progression is unclear. Genetic aspects may play a role, but details are unresolved. The fact that immune-mediated and autoimmune disorders such as rheumatoid arthritis or multiple sclerosis have a very similar course as schizophrenia has focused the interest on the immunopathogenesis of schizophrenia. A clear immune marker for neuroprogression in schizophrenia or psychosis could not be identified up to now, but a proinflammatory immune state (increased markers of cellular immunity) is regularly found in schizophrenia, e.g., increased levels of cytokines such as interleukin-6 (IL-6). Moreover, the tryptophan/kynurenine metabolism is regulated via pro- and anti-inflammatory cytokines and is closely related to the glutamatergic neurotransmission. Certain molecules of this metabolism, such as quinolinic acid or 3OH-kynurenine, have neurotoxic effects and seem to play a role in chronification. Studies with immune/anti-inflammatory-based therapeutic approaches show that acuity or chronicity of the inflammation influence the outcome of therapeutic interventions.