Inflammatory Cytokines and Neurological and Neurocognitive Alterations in the Course of Schizophrenia

Abstract

A growing body of evidence suggests that immune alterations, especially those related to inflammation, are associated with increased risk of schizophrenia and schizophrenia-related brain alterations. Much of this work has focused on the prenatal period, since infections during pregnancy have been repeatedly (albeit inconsistently) linked to risk of schizophrenia. Given that most infections do not cross the placenta, cytokines associated with inflammation (proinflammatory cytokines) have been targeted as potential mediators of the damaging effects of infection on the fetal brain in prenatal studies. Moreover, additional evidence from both human and animal studies suggests links between increased levels of proinflammatory cytokines, immune-related genes, and schizophrenia, as well as brain alterations associated with the disorder. Additional support for the role of altered immune factors in the etiology of schizophrenia comes from neuroimaging studies, which have linked proinflammatory cytokine gene polymorphisms with some of the structural and functional abnormalities repeatedly found in schizophrenia. These findings are reviewed and discussed using a life course perspective, examining the contribution of inflammation from the fetal period to disorder presentation. Unexplored areas and future directions, such as the interplay between inflammation, genes, and individual-level environmental factors (e.g., stress, sleep, and nutrition), are also discussed.

Efficacy of Anti-inflammatory Agents to Improve Symptoms in Patients With Schizophrenia: An Update

“…This proinflammatory status is thought to result from the interaction between genetic vulnerability and environmental factors such as infections, trauma, nutrition, and stress. 2 Associated with this increased proinflammatory status is a decrease in the neurotrophic function of microglia and other supportive central nervous system (CNS) cells and enhanced production of neurotoxic proinflammatory factors such as tumor necrosis factor-α (TNF-α), free radicals, complement factors, and kynurenic acid. 3,4 This shift leads to decreased proliferation of the neurons, resulting in reduced connectivity and eventually a loss of brain tissue.…”

Behavioral alterations in rat offspring following maternal immune activation and ELR-CXC chemokine receptor antagonism during pregnancy: Implications for neurodevelopmental psychiatric disorders

“…Given that a variety of pathogens are associated with increase d risk of psychiatric disorders, exposure of the developing fetus to maternal and/or fetal cytokines released during infection may alter normal development of the nervous system resulting in the behavioral and cognitive symptoms (Fineberg and Ellman, 2013;Gilmore et al, 2004;Watanabe et al, 2010). Chemokines, a sub-class of cytokines with chemotactic properties (Tran and Miller, 2003), and their associated G protein-coupled receptors are involved in brain development (Arrode-Bruses and Bruses, 2012;Brown et al, 2004;Cho and Miller, 2002;Deverman and Patterson, 2009;Garay et al, 2013;Ragozzino, 2002) and recent human epidemiological research has uncovered associations between numerous chemokines and neurodevelopmental disorders (Ashwood et al, 2011;Reale et al, 2011;Stuart and Baune, 2014).…”

Conventional and alternative preventive treatments in the first stages of schizophrenia

“…There is now a body of evidence to support a role for both inflammation and oxidative stress in the pathophysiology of psychotic disorders 20,21 . Environmental factors such as inflammation, obstetric complications, viral infections and stress have been associated with an increase in oxidative stress and are also considered risk factors for schizophrenia 22 .…”