The effects of DISC1 risk variants on brain activation in controls, patients with bipolar disorder and patients with schizophrenia

G. Chakirova, Heather Whalley, P. A. Thomson, W. Hennah, T. W. Moorhead, K. A. Welch, S. Giles, Jeremy Hall, E. C. Johnstone, S. M. Lawrie, D. J. Porteous, V. J. Brown, A. M. McIntosh

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Three risk variants (rs1538979, rs821577, and rs821633) in the Disrupted-in-Schizophrenia-1 (DISC1) gene have previously been associated with both schizophrenia and bipolar disorder in a recent collaborative analysis of European cohorts. In this study we examined the effects of these risk variants on brain activation during functional magnetic resonance imaging (fMRI) of the Hayling Sentence Completion Task (HSCT) in healthy volunteers (n=33), patients with schizophrenia (n=20) and patients with bipolar disorder (n=36). In the healthy controls the risk associated allele carriers of SNPs rs1538979 and rs821633 demonstrated decreased activation of the cuneus. Moreover, there was an effect of SNP rs1538979 in the pre/postcentral gyrus with decreased activation in healthy controls and increased activation in patients with schizophrenia. In the bipolar group there was decreased activation in the risk carriers of SNP rs821633 in the inferior parietal lobule and left cingulate cortex. Clusters in the precentral gyrus, left middle temporal gyrus and left cerebellum were found to be significant on examining the group x genotype interactions. These findings may provide a better understanding of the neural effects of DISC1 variants and on the pathophysiology of schizophrenia and bipolar disorder.
Original languageEnglish
Pages (from-to)20-28
Number of pages9
JournalPsychiatry Research
Issue number1
Publication statusPublished - 30 Apr 2011

Keywords / Materials (for Non-textual outputs)

  • Adult Analysis of Variance Bipolar Disorder/*genetics/*pathology Brain/blood supply/*pathology Brain Mapping Female Functional Laterality Gene Frequency Genetic Predisposition to Disease Genotype Humans Image Processing, Computer-Assisted Magnetic Resonance Imaging Male Middle Aged Nerve Tissue Proteins/*genetics Neuropsychological Tests Oxygen/blood Polymorphism, Single Nucleotide Psychiatric Status Rating Scales Risk Factors Schizophrenia/*genetics/*pathology


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