BIOLOGICAL BASES OF PSICHIATRY 

Minerva Psichiatrica 2011 December;52(4):205-18

Copyright © 2012 EDIZIONI MINERVA MEDICA

language: English

Inflammation and schizophrenia: pathophysiological and therapeutic aspects

Müller N.

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University Munich, Munich, Germany

For schizophrenia an inflammatory pathogenesis is postulated. Increased proinflammatory cytokines and other markers for inflammation have been observed. The proinflammatory immune state in schizophrenia seems to be associated with the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) of the tryptophan - kynurenine metabolism resulting in a disturbance of the glutamatergic and dopaminergic neurotransmissions and possible neurotoxic effects. The differential activation of microglia cells and astrocytes may be an additional mechanism contributing to this imbalance. Animal models support the view that an immune activation in early life might be crucial for the later increased vulnerability. Epidemiological and clinical studies show the involvement of various infectious agents in the pathogenesis of schizophrenia, an overlap with other psychiatric disorders is described. Genetic data reveal gene loci located in a region which includes several genes that are related to the immune function. The vulnerability-stress model of schizophrenia is highlighted because stress is associated with an increased release of proinflammatory cytokines and contributes to a proinflammatory immune state. Another characteristic of the immune system the kindling of the immune response is a further piece in the puzzle about what causes the symptoms of schizophrenia. Neuroimaging data showed a volume loss, positron emission tomography (PET) studies found microglial activation in schizophrenia, indicating an inflammatory process. A further line of evidence is the therapeutic benefit of anti-inflammatory medication. The immunological imbalance in schizophrenia results in an inflammatory state combined with increased prostaglandin E2 (PGE2) production and increased cyclo-oxygenase-2 (COX-2) expression. COX-2 inhibititors and possibly other anti-inflammatory agents seem to have favourable effects in schizophrenia, primarily during early stages of the disorder.