ReviewInflammatory Cytokines and Neurological and Neurocognitive Alterations in the Course of Schizophrenia
Section snippets
Overview of Link Between Schizophrenia and Infection
The first associations between schizophrenia and infection were found in ecologic studies (8). Although findings have been mixed, winter to spring births (a period of heightened infections) and pregnancy during influenza epidemics have been associated with risk for schizophrenia among offspring (3). However, ecologic studies are limited by their presumption of infection based on events that occur for an entire population without direct confirmation of exposure (3).
Nevertheless, the association
Cytokines
With the exception of parasitic infections, like toxoplasmosis gondii, most infections do not seem to cross the placenta; thus, damaging effects to the fetus are likely operating through maternal, fetal, and/or placental responses to infection 26, 27. Among these responses to infections, prime candidates have been cytokines associated with inflammation (termed proinflammatory cytokines), some of which seem to cross the placenta 28, 29. Cytokines are soluble polypeptide signaling proteins that
Immunological and Inflammatory Cytokine Alterations in Schizophrenia
Research on the influence of early life exposure to infection and inflammation on immune functioning across the lifespan is highly relevant, given repeated studies that have found immunological abnormalities in schizophrenia populations (66). Furthermore, schizophrenia has been associated with inflammation and increased levels of cytokines, IL-2 receptors, IL-1 receptor agonists (IL-1RA), and acute phase reactants such as IL-1β and IL-6 in plasma 67, 68. Potvin et al. (31) published a recent
Schizophrenia and Neuroinflammation
Neuroinflammation is characterized by activation of microglia cells, which are the resident macrophages of the brain and primary reservoirs of proinflammatory cytokines 93, 94. Findings on neuroinflammation in schizophrenia have been mixed, with some postmortem studies finding increases in activated microglia cells in the brains of schizophrenia patients 95, 96, 97, whereas others fail to find differences 98, 99, 100, 101. Active neuroinflammation can be assessed with a PET tracer, (R)-N-11
Remarks
Most studies on inflammation and schizophrenia have examined proinflammatory cytokines in the prenatal period and after schizophrenia onset, leaving the premorbid period unexamined. Understanding inflammation and immune abnormalities during the premorbid and prodromal periods of schizophrenia will play a crucial role in determining whether inflammation contributes to the neurodevelopmental course of schizophrenia. Currently, there are two primary theories with regard to how early immune insults
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