title: fMRI changes over time and reproducibility in unmedicated subjects at high genetic risk of schizophrenia.
abstract: BACKGROUND
  Functional brain abnormalities have been repeatedly demonstrated in schizophrenia but there is little data concerning their progression. For such studies to have credibility it is first important to establish the reproducibility of functional imaging techniques. The current study aimed to examine these factors in healthy controls and in unmedicated subjects at high genetic risk of the disorder: (i) to examine the reproducibility of task-related activation patterns, (ii) to determine if there were any progressive functional changes in high-risk subjects versus controls reflecting inheritance of the schizophrenic trait, and (iii) to examine changes over time in relation to fluctuating positive psychotic symptoms (i.e. state effects).
  
  
  METHODS
  Subjects were scanned performing the Hayling sentence completion test on two occasions 18 months apart. Changes in activation were examined in controls and high-risk subjects (n=16, n=63). Reproducibility was assessed for controls and high-risk subjects who remained asymptomatic at both time points (n=16, n=32).
  
  
  RESULTS
  Intra-class correlation values indicated good agreement between scanning sessions. No significant differences over time were seen between the high-risk and control group; however, comparison of high-risk subjects who developed symptoms versus those who remained asymptomatic revealed activation increases in the left middle temporal gyrus (p=0.026).
  
  
  CONCLUSIONS
  The current results suggest that functional changes over time occur in the lateral temporal cortex as high genetic risk subjects become symptomatic, further, they indicate the usefulness of functional imaging tools for investigating progressive changes associated with state and trait effects in schizophrenia.
authors.affiliation: Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, UK. hwhalley@staffmail.ed.ac.uk
authors.forename: H C
authors.initials: HC
authors.lastname: Whalley
authors.forename: V-E
authors.initials: VE
authors.lastname: Gountouna
authors.forename: J
authors.initials: J
authors.lastname: Hall
authors.forename: A M
authors.initials: AM
authors.lastname: McIntosh
authors.forename: E
authors.initials: E
authors.lastname: Simonotto
authors.forename: D E
authors.initials: DE
authors.lastname: Job
authors.forename: D G C
authors.initials: DG
authors.lastname: Owens
authors.forename: E C
authors.initials: EC
authors.lastname: Johnstone
authors.forename: S M
authors.initials: SM
authors.lastname: Lawrie
mesh_terms: D000328:Adult; D001288:Attention / Q000502:physiology; D001931:Brain Mapping; D002531:Cerebellum / Q000503:physiopathology; D018450:Disease Progression; D004292:Dominance, Cerebral / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D012660:Semantics; D013702:Temporal Lobe / Q000503:physiopathology*; D055815:Young Adult