The role of untreated psychosis in neurodegeneration: A review of hypothesized mechanisms of neurotoxicity in first-episode psychosis

Authors

Kelly K. Anderson, Centre for Addiction and Mental HealthFollow
Aristotle Voineskos, Centre for Addiction and Mental Health
Benoit H. Mulsant, Centre for Addiction and Mental Health
Tony P. George, University of Toronto
Kwame J. McKenzie, University of Toronto

Document Type

Article

Publication Date

10-1-2014

Journal

Canadian Journal of Psychiatry

Volume

59

Issue

10

First Page

513

Last Page

517

URL with Digital Object Identifier

10.1177/070674371405901003

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.