title: Neuroinflammation and Oxidative Stress in Psychosis and Psychosis Risk.
abstract: Although our understanding of psychotic disorders has advanced substantially in the past few decades, very little has changed in the standard of care for these illnesses since the development of atypical anti-psychotics in the 1990s. Here, we integrate new insights into the pathophysiology with the increasing interest in early detection and prevention. First, we explore the role ofN-methyl-d-aspartate receptors in a subpopulation of cortical parvalbumin-containing interneurons (PVIs). Postmortem and preclinical data has implicated these neurons in the positive and negative symptoms, as well as the cognitive dysfunction present in schizophrenia. These neurons also appear to be sensitive to inflammation and oxidative stress during the perinatal and peripubertal periods, which may be mediated in large part by aberrant synaptic pruning. After exploring some of the molecular mechanisms through which neuroinflammation and oxidative stress are thought to exert their effects, we highlight the progress that has been made in identifying psychosis prior to onset through the identification of individuals at clinical high risk for psychosis (CHR). By combining our understanding of psychosis pathogenesis with the increasing characterization of endophenotypes that precede frank psychosis, it may be possible to identify patients before they present with psychosis and intervene to reduce the burden of the disease to both patients and families.
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada. henry.barron1@gmail.com.
authors.forename: Henry
authors.initials: H
authors.lastname: Barron
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada. sina.hafizi@camhpet.ca.
authors.forename: Sina
authors.initials: S
authors.lastname: Hafizi
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada. ana.andreazza@utoronto.ca.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada. ana.andreazza@utoronto.ca.|Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada. ana.andreazza@utoronto.ca.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Andreazza
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada. romina.mizrahi@camhpet.ca.|Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada. romina.mizrahi@camhpet.ca.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada. romina.mizrahi@camhpet.ca.|Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada. romina.mizrahi@camhpet.ca.
authors.forename: Romina
authors.initials: R
authors.lastname: Mizrahi
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D011618:Psychotic Disorders / Q000378:metabolism* / Q000473:pathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate
keywords: neuroinflammation; oxidative stress; psychosis; schizophrenia