title: The role of untreated psychosis in neurodegeneration: a review of hypothesized mechanisms of neurotoxicity in first-episode psychosis.
abstract: For over 20 years, studies have tried to measure the association between the duration of untreated psychosis (DUP) and changes in brain morphology. A hypothesis that untreated psychosis is neurotoxic has been postulated, but the mechanisms of that toxicity have not been described. We re-analyzed papers collected for a systematic review to extract data on the hypotheses that have been generated on the potential mechanisms by which DUP could impact brain morphology in first-episode psychosis. Dopaminergic hyperactivity, prolonged hypothalamic-pituitary-adrenal activation, and persistent activity of catecholamines have been hypothesized as mechanisms to explain these associations. However, the question remains as to whether the observed structural changes are permanent or may be reversed via antipsychotic treatment.
authors.affiliation: Post-Doctoral Fellow, Centre for Addiction and Mental Health, Toronto, Ontario.
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Anderson
authors.affiliation: Koerner New Scientist and Head of Kimel-Family Translational Imaging-Genetics Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario; Assistant Professor, Department of Psychiatry, University of Toronto, Toronto, Ontario.
authors.forename: Aristotle
authors.initials: A
authors.lastname: Voineskos
authors.affiliation: Physician-in-Chief, Centre for Addiction and Mental Health, Toronto, Ontario; Professor, Department of Psychiatry, University of Toronto, Toronto, Ontario.
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.affiliation: Clinical Director of the Schizophrenia Program and Medical Director of the Complex Illness Program, Centre for Addiction and Mental Health, Toronto, Ontario; Endowed Chair in Addiction Psychiatry and Professor, Department of Psychiatry, University of Toronto, Toronto, Ontario.
authors.forename: Tony P
authors.initials: TP
authors.lastname: George
authors.affiliation: Medical Director and Director of Health Equity, Centre for Addiction and Mental Health, Toronto, Ontario; Co-Director of Equity, Gender, and Population Psychiatry and Professor, Department of Psychiatry, University of Toronto, Toronto, Ontario.
authors.forename: Kwame J
authors.initials: KJ
authors.lastname: Mckenzie
mesh_terms: D001921:Brain / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000378:metabolism; D011618:Psychotic Disorders / Q000150:complications* / Q000378:metabolism; D012559:Schizophrenia / Q000150:complications* / Q000378:metabolism