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Updated 5 October 2006
Printable version

Forum Discussion: Is Active Psychosis Neurotoxic?

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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…

View Comments By:
Robert McClure — Posted 10 November 2006
Karl-Ludvig Reichelt — Posted 22 November 2006
Mariano Scolari — Posted 27 November 2006

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.

Comments on Online Discussion
Comment by:  Robert McClure (Disclosure)
Submitted 10 November 2006 Posted 10 November 2006

In 2001, in an Archives of General Psychiatry paper, Danny...  Read more

View all comments by Robert McClure

Comment by:  Karl-Ludvig Reichelt (Disclosure)
Submitted 17 November 2006 Posted 22 November 2006

Most of the evidence collected shows a considerable...  Read more

View all comments by Karl-Ludvig Reichelt

Comment by:  Mariano Scolari
Submitted 24 November 2006 Posted 27 November 2006

If active psychosis is neurotoxic, it is very important to...  Read more

View all comments by Mariano Scolari
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