title: The cortical thickness phenotype of individuals with DISC1 translocation resembles schizophrenia.
abstract: BACKGROUND
  The disrupted in schizophrenia 1 (DISC1) gene locus was originally identified in a Scottish pedigree with a high incidence of psychiatric disorders that is associated with a balanced t(1;11)(q42.1;q14.3) chromosomal translocation. Here, we investigated whether members of this family carrying the t(1;11)(q42.1;q14.3) translocation have a common brain-related phenotype and whether this phenotype is similar to that observed in schizophrenia (SCZ), using multivariate pattern recognition techniques.
  
  
  METHODS
  We measured cortical thickness, cortical surface area, subcortical volumes, and regional cerebral blood flow (rCBF) in healthy controls (HC) (n = 24), patients diagnosed with SCZ (n = 24), patients diagnosed with bipolar disorder (BP) (n = 19), and members of the original Scottish family (n = 30) who were either carriers (T+) or noncarriers (T-) of the DISC1 translocation. Binary classification models were developed to assess the differences and similarities across groups.
  
  
  RESULTS
  Based on cortical thickness, 72% of the T- group were assigned to the HC group, 83% of the T+ group were assigned to the SCZ group, and 45% of the BP group were classified as belonging to the SCZ group, suggesting high specificity of this measurement in predicting brain-related phenotypes. Shared brain-related phenotypes between SCZ and T+ individuals were found for cortical thickness only. Finally, a classification accuracy of 73% was achieved when directly comparing the pattern of cortical thickness of T+ and T- individuals.
  
  
  CONCLUSIONS
  Together, the results of this study suggest that the DISC1 translocation may increase the risk of psychiatric disorders in this pedigree by affecting neurostructural phenotypes such as cortical thickness.
  
  
  BACKGROUND
  This work was supported by the National Health Service Research Scotland, the Scottish Translational Medicine Research Collaboration, the Innovative Medicines Initiative (IMI), the Engineering and Physical Sciences Research Council (EPSRC), The Wellcome Trust, the National Institute of Health Research (NIHR), and Pfizer.
authors: Orla M
authors: OM
authors: Doyle
authors: Catherine
authors: C
authors: Bois
authors: Pippa
authors: P
authors: Thomson
authors: Liana
authors: L
authors: Romaniuk
authors: Brandon
authors: B
authors: Whitcher
authors: Steven C R
authors: SC
authors: Williams
authors: Federico E
authors: FE
authors: Turkheimer
authors: Hreinn
authors: H
authors: Stefansson
authors: Andrew M
authors: AM
authors: McIntosh
authors: Mitul A
authors: MA
authors: Mehta
authors: Stephen M
authors: SM
authors: Lawrie
mesh_terms: D001783:Blood Flow Velocity; D002540:Cerebral Cortex / Q000098:blood supply / Q000000981:diagnostic imaging; D002560:Cerebrovascular Circulation; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011859:Radiography; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D012606:Scotland; D014178:Translocation, Genetic
chemical_list: C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins