title: Increased prefrontal gyrification in a large high-risk cohort characterizes those who develop schizophrenia and reflects abnormal prefrontal development.
abstract: BACKGROUND
  In our cohort considered at high risk (HR) of developing schizophrenia, we previously found a significant difference in extent of right prefrontal cortical folding between those who subsequently developed schizophrenia and a matched group who remained well. This study aimed to determine if this preexisting difference distinguished 17 individuals who developed schizophrenia from the 128 HR individuals in the cohort who remained well and to explore possible underlying differences in cortical composition.
  
  
  METHODS
  Prefrontal cortical folding was measured by an automated version of the Gyrification Index (A-GI), a ratio reflecting extent of folding. Multivariate logistic regression assessed the probability that prefrontal A-GI predicts diagnostic outcome and subsequently assessed the effect on A-GI of regional cerebrospinal fluid and gray and white matter.
  
  
  RESULTS
  High-risk individuals who subsequently developed schizophrenia were distinguished from the remaining cohort by increased right prefrontal cortex (PFC) A-GI. Mean right PFC gray matter volume also differed between groups, but white matter volume did not. Correlations of age with gray and white matter further distinguished groups and a linear regression analysis showed a significant interaction between age and diagnosis on mean volume of right PFC white matter.
  
  
  CONCLUSIONS
  Increased A-GI appears to indicate abnormal right prefrontal development in those who develop schizophrenia.
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom. jharris1@staffmail.ed.ac.uk
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Harris
authors.forename: T William J
authors.initials: TW
authors.lastname: Moorhead
authors.forename: Patrick
authors.initials: P
authors.lastname: Miller
authors.forename: Andrew M
authors.initials: AM
authors.lastname: McIntosh
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Bonnici
authors.forename: David G C
authors.initials: DG
authors.lastname: Owens
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; D015331:Cohort Studies; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016015:Logistic Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000002:abnormalities / Q000254:growth & development* / Q000473:pathology*; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012306:Risk; D012559:Schizophrenia / Q000134:cerebrospinal fluid / Q000473:pathology*