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Does active psychosis cause neurobiological pathology? A critical review of the neurotoxicity hypothesis

Published online by Cambridge University Press:  25 September 2013

B. R. Rund*
Department of Psychology, University of Oslo, and Vestre Viken Hospital Trust, Drammen, Norway
*Address for correspondence: Dr B. R. Rund, Department of Psychology, University of Oslo, PO Box 1094, Blindern, 0317 Oslo, Norway. (Email:



Since the neurotoxicity hypothesis was launched in 1991, it has generated a great deal of interest and given rise to several studies investigating the validity of the hypothesis that being psychotic has a toxic effect on the brain. The toxicity argument is used to justify early treatment. This review attempts to assess the studies that have addressed the question: Does an active psychosis, indexed by the duration of untreated psychosis (DUP), cause neurobiological pathology?


The validity of the hypothesis has been studied primarily by correlation analyses that assess whether there are significant correlations between DUP and changes in neurocognitive functioning or brain structure. In this review, relevant reports were identified by a literature survey.


Of the 35 studies (33 papers) evaluated, six neurocognitive studies supported the hypothesis and 16 did not. Eight morphology studies supported the hypothesis and five did not. In general, the studies that did not support the neurotoxicity hypothesis were larger in size and had more adequate designs (longitudinal) than those that supported the hypothesis.


Overall, there is limited empirical evidence for the neurotoxicity hypothesis in the studies reviewed. However, it is possible that there is a threshold value for a toxic effect of psychosis, rather than a linear relationship between DUP and a neurotoxic effect, and that several of the studies evaluated did not have a long enough DUP to detect a toxic effect of active psychosis.

Review Article
Copyright © Cambridge University Press 2013 

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