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Is Active Psychosis Neurotoxic?

Posted on 4 Oct 2006
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In our Forum discussion "journal club" series, the editors of Schizophrenia Bulletin or Schizophrenia Research provide access to the full text of a new article. A short introduction by a journal editor, below, gets us started, and then it's up to our readers to share their ideas and insights, questions and reactions to the selected paper. So read on"



Background Text
By Gunvant Thaker, Maryland Psychiatric Research Center, and Associate Editor, Schizophrenia Bulletin

In the latest issue of Schizophrenia Bulletin, Tom McGlashan raised an important question: Is active psychosis neurotoxic? (See McGlashan, 2006.) This has been a controversial issue for some time in our field and has tremendous implications for how we focus our treatment in our patients and our research activities to identify novel treatment strategies. The hypothesis originated based on an interesting paper by Wyatt on the effects of antipsychotic medications on the natural course of schizophrenia (Wyatt, 1991). Subsequent early intervention and first episode studies further supported the hypothesis. However, most of this supporting evidence is derived from correlational analyses where causal effects are impossible to infer, or from uncontrolled and/or observational studies where random assignment to different treatments didn"t occur. Tom McGlashan further points out that several predictions based on the neurotoxic hypothesis are not validated by the existing data. Controlled clinical trials of schizophrenia that used random assignment and placebo arm can be informative in this regard. John Bola recently reviewed these studies and concluded that there was no evidence of long-term harm to individuals whose psychosis remained untreated during the double-blind trial (Bola, 2005; SRF related news story).

The onset of schizophrenia is defined by the onset of psychotic symptoms ("first break"), whereas impairments in other domains such as cognitive and neurophysiological function, as well as social and occupational deterioration and negative symptoms, emerge at different times. Whether treatment of one domain of symptoms/impairments affects the emergence or the course of the other domains remains unknown. This question is as much relevant for identifying treatments for the neurophysiological and cognitive deficits of schizophrenia that frequently precede psychosis as it is for the early and aggressive treatment of psychosis.