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Transcription and pathway analysis of the superior temporal cortex and anterior prefrontal cortex in schizophrenia

Authors

  • Michael R. Barnes,

    1. Computational Biology, Quantitative Sciences, Biopharmaceuticals, GlaxoSmithKline Medicines Research Centre, Stevenage, United Kingdom
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  • Julie Huxley-Jones,

    1. Computational Biology, Quantitative Sciences, Biopharmaceuticals, GlaxoSmithKline Medicines Research Centre, Stevenage, United Kingdom
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  • Peter R. Maycox,

    1. Neuroscience CEDD, Discovery Technologies Group, Genetic and Proteomic Sciences, GlaxoSmithKline, Harlow, Essex, United Kingdom
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  • Mark Lennon,

    1. Computational Biology, Quantitative Sciences, Biopharmaceuticals, GlaxoSmithKline Medicines Research Centre, Stevenage, United Kingdom
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  • Amy Thornber,

    1. Computational Biology, Quantitative Sciences, Biopharmaceuticals, GlaxoSmithKline Medicines Research Centre, Stevenage, United Kingdom
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  • Fiona Kelly,

    1. Computational Biology, Quantitative Sciences, Biopharmaceuticals, GlaxoSmithKline Medicines Research Centre, Stevenage, United Kingdom
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  • Stewart Bates,

    1. Computational Biology, Quantitative Sciences, Biopharmaceuticals, GlaxoSmithKline Medicines Research Centre, Stevenage, United Kingdom
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  • Adam Taylor,

    1. Computational Biology, Quantitative Sciences, Biopharmaceuticals, GlaxoSmithKline Medicines Research Centre, Stevenage, United Kingdom
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  • Juliet Reid,

    1. Computational Biology, Quantitative Sciences, Biopharmaceuticals, GlaxoSmithKline Medicines Research Centre, Stevenage, United Kingdom
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  • Neil Jones,

    1. Neuroscience CEDD, Discovery Technologies Group, Genetic and Proteomic Sciences, GlaxoSmithKline, Harlow, Essex, United Kingdom
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  • Jörn Schroeder,

    1. Neuroscience CEDD, Discovery Technologies Group, Genetic and Proteomic Sciences, GlaxoSmithKline, Harlow, Essex, United Kingdom
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  • Carol A. Scorer,

    1. Neuroscience CEDD, Discovery Technologies Group, Genetic and Proteomic Sciences, GlaxoSmithKline, Harlow, Essex, United Kingdom
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  • Ceri Davies,

    1. Neuroscience CEDD, Discovery Technologies Group, Genetic and Proteomic Sciences, GlaxoSmithKline, Harlow, Essex, United Kingdom
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  • Jim J. Hagan,

    1. Neuroscience CEDD, Discovery Technologies Group, Genetic and Proteomic Sciences, GlaxoSmithKline, Harlow, Essex, United Kingdom
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  • James N.C. Kew,

    1. Neuroscience CEDD, Discovery Technologies Group, Genetic and Proteomic Sciences, GlaxoSmithKline, Harlow, Essex, United Kingdom
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  • Claire Angelinetta,

    1. Centre for Neuroscience, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom
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  • Tariq Akbar,

    1. Centre for Neuroscience, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom
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  • Steven Hirsch,

    1. Centre for Neuroscience, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom
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  • Ann M. Mortimer,

    1. Centre for Neuroscience, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom
    2. Academic Unit of Psychiatry, University of Hull, Hull, United Kingdom
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  • Thomas R.E. Barnes,

    1. Centre for Neuroscience, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom
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  • Jackie de Belleroche

    Corresponding author
    1. Centre for Neuroscience, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom
    • Neurogenetics Group, Centre for Neuroscience, Division of Experimental Medicine, Department of Medicine, Imperial College London, Room E407, Burlington Danes Building, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom
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  • M.R.B., J.H.-J., P.R.M., M.L., A.Th., F.K., S.B., A.Ta., J.R., N.J., J.S., C.A.S., C.D., J.J.H., and J.N.C.K. are employees of and shareholders in GlaxoSmithKline. No other biomedical financial interests or potential conflicts of interest exist.

Abstract

The molecular basis of schizophrenia is poorly understood; however, different brain regions are believed to play distinct roles in disease symptomology. We have studied gene expression in the superior temporal cortex (Brodmann area 22; BA22), which may play a role in positive pathophysiology, and compared our results with data from the anterior prefrontal cortex (BA10), which shows evidence for a role in negative symptoms. Genome-wide mRNA expression was determined in the BA22 region in 23 schizophrenics and 19 controls and compared with a BA10 data set from the same subjects. After adjustments for confounding sources of variation, we carried out GeneGO pathway enrichment analysis in each region. Significant differences were seen in age-related transcriptional changes between the BA22 and the BA10 regions, 21.8% and 41.4% of disease-associated transcripts showing age association, respectively. After removing age associated changes from our data, we saw the highest enrichment in processes mediating cell adhesion, synaptic contact, cytoskeletal remodelling, and apoptosis in the BA22 region. For the BA10 region, we observed the strongest changes in reproductive signalling, tissue remodelling, and cell differentiation. Further exploratory analysis also identified potentially disease-relevant processes that were undetected in our more stringent primary analysis, including autophagy in the BA22 region and the amyloid process in the BA10 region. Collectively, our analysis suggests disruption of many common pathways and processes underpinning synaptic plasticity in both regions in schizophrenia, whereas individual regions emphasize changes in certain pathways that may help to highlight pathway-specific therapeutic opportunities to treat negative or positive symptoms of the disease. © 2011 Wiley-Liss, Inc.

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