title: Longitudinal volume reductions in people at high genetic risk of schizophrenia as they develop psychosis.
abstract: BACKGROUND
  Structural differences between the brains of people with schizophrenia and control subjects are highly replicated but the timing and clinical correlates are unclear. In the Edinburgh High Risk Study, we have followed up 162 individuals at high genetic risk of schizophrenia and 36 healthy control subjects over 10 years.
  
  
  METHODS
  Participants received detailed clinical and up to five structural magnetic resonance imaging (MRI) assessments at 2-year intervals. All 436 MRI scans acquired were parcellated and adjusted for between-scanner differences. The trajectory of any structural MRI changes was then investigated using mixed effects analysis of variance.
  
  
  RESULTS
  Seventeen of the 146 high-risk subjects who were scanned developed schizophrenia over the 8 years of the study. People at high genetic risk of schizophrenia had significantly greater reductions over time than the control group for whole brain volume and left and right prefrontal and temporal lobes. Greater prefrontal reductions were shown in high-risk subjects who subsequently became unwell compared with those who did not. These changes were significantly associated with increasing severity of psychotic symptoms.
  
  
  CONCLUSIONS
  Individuals at high genetic risk of schizophrenia exhibited reductions in cerebral volume that were not found in control subjects. Changes in brain structure were also associated with increasing psychotic symptom severity as people developed schizophrenia. The progressive reductions found in those who went on to develop schizophrenia suggest an additional brain insult near to the time of onset.
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, United Kingdom. andrew.mcintosh@ed.ac.uk
authors.forename: Andrew M
authors.initials: AM
authors.lastname: McIntosh
authors.forename: David C
authors.initials: DC
authors.lastname: Owens
authors.forename: William J
authors.initials: WJ
authors.lastname: Moorhead
authors.forename: Heather C
authors.initials: HC
authors.lastname: Whalley
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Stanfield
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hall
authors.forename: Eve C
authors.initials: EC
authors.lastname: Johnstone
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Lawrie
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000209:etiology*; D012307:Risk Factors; D012559:Schizophrenia / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D055815:Young Adult