title: Minimal evidence that untreated psychosis damages brain structures: a systematic review.
abstract: BACKGROUND
  A longer duration of untreated psychosis (DUP) is associated with poor outcomes in first-episode psychosis (FEP); however, it is unclear whether this is due to the effects of psychosis on brain structure. We systematically reviewed the literature on the association between the length of untreated psychosis and brain structure in first-episode psychosis.
  
  
  METHODS
  We searched three electronic databases and conducted forward and backward citation searching to identify relevant papers. Studies were included if they: (1) included patients with a psychotic disorder who were treatment naïve or minimally treated; and (2) had correlated measures of DUP or duration of untreated illness (DUI) with structural measures.
  
  
  RESULTS
  We identified 48 studies that met the inclusion criteria. Forty-three examined the correlation between DUP and brain structure, and 19 examined the correlation between DUI and brain structure. There was evidence of significant associations in brain regions considered important in psychosis; however, the proportion of significant associations was low and the findings were inconsistent across studies. The majority of included studies were not primarily designed to examine whether DUP/DUI is correlated with brain structure, and there were methodological limitations in many studies that prevent drawing a strong conclusion.
  
  
  CONCLUSIONS
  To date, there is minimal evidence of an association between untreated psychosis and brain structure in FEP. Although the body of literature is substantial, there are few hypothesis-driven studies with a primary objective to answer this question. Future studies should be specifically designed to examine whether untreated psychosis has a deleterious effect on brain structure.
authors: Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada. Electronic address: kelly.anderson@schulich.uwo.ca.
authors: Kelly K
authors: KK
authors: Anderson
authors: Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada. Electronic address: myancarodrigues@gmail.com.
authors: Myanca
authors: M
authors: Rodrigues
authors: Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada. Electronic address: kamalpreet.mann@mail.utoronto.ca.
authors: Kamalpreet
authors: K
authors: Mann
authors: Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario M5T 1R8, Canada. Electronic address: aristotle.voineskos@camh.ca.
authors: Aristotle
authors: A
authors: Voineskos
authors: Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario M5T 1R8, Canada. Electronic address: benoit.mulsant@camh.ca.
authors: Benoit H
authors: BH
authors: Mulsant
authors: Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario M5T 1R8, Canada. Electronic address: tony.george@camh.ca.
authors: Tony P
authors: TP
authors: George
authors: Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario M5T 1R8, Canada. Electronic address: kwame.mckenzie@camh.ca.
authors: Kwame J
authors: KJ
authors: McKenzie
mesh_terms: D001921:Brain / Q000473:pathology*; D006801:Humans; D011618:Psychotic Disorders / Q000473:pathology* / Q000628:therapy; D061665:Time-to-Treatment
keywords: Brain structure; Duration of untreated psychosis; First-episode psychosis; Neurotoxicity