The cortical thickness phenotype of individuals with DISC1 translocation resembles schizophrenia

Orla M Doyle, Catherine Bois, Pippa Thomson, Liana Romaniuk, Brandon Whitcher, Steven C R Williams, Federico E Turkheimer, Hreinn Stefansson, Andrew M McIntosh, Mitul A Mehta, Stephen M Lawrie

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

CONCLUSION: 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.

FUNDING: 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.

Original languageEnglish
Pages (from-to)3714–3722
Number of pages9
JournalJournal of Clinical Investigation
Issue number9
Early online date24 Aug 2015
Publication statusPublished - 1 Sept 2015


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