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Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function

Molecular Psychiatry volume 14, pages 1083–1094 (2009)Cite this article

A Corrigendum to this article was published on 24 March 2010

A Corrigendum to this article was published on 18 November 2009

Abstract

Schizophrenia is a severe psychiatric disorder with a world-wide prevalence of 1%. The pathophysiology of the illness is not understood, but is thought to have a strong genetic component with some environmental influences on aetiology. To gain further insight into disease mechanism, we used microarray technology to determine the expression of over 30 000 mRNA transcripts in post-mortem tissue from a brain region associated with the pathophysiology of the disease (Brodmann area 10: anterior prefrontal cortex) in 28 schizophrenic and 23 control patients. We then compared our study (Charing Cross Hospital prospective collection) with that of an independent prefrontal cortex dataset from the Harvard Brain Bank. We report the first direct comparison between two independent studies. A total of 51 gene expression changes have been identified that are common between the schizophrenia cohorts, and 49 show the same direction of disease-associated regulation. In particular, changes were observed in gene sets associated with synaptic vesicle recycling, transmitter release and cytoskeletal dynamics. This strongly suggests multiple, small but synergistic changes in gene expression that affect nerve terminal function.

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Acknowledgements

We acknowledge the Harvard Brain Bank for depositing the raw data files for the McLean 66 cohort into the public domain. This study could not have undertaken without access to these data. TA and CA were supported by a research grant from GlaxoSmithKline.

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Authors and Affiliations

  1. Psychiatry CEDD, New Frontiers Science Park, GlaxoSmithKline, Harlow, Essex, UK

    P R Maycox, C Davies, J J Hagan & C A Scorer

  2. Genetic and Proteomic Sciences, New Frontiers Science Park, GlaxoSmithKline, Harlow, Essex, UK

    F Kelly, A Taylor, S Bates, J Reid & N Jones

  3. Computational Biology, New Frontiers Science Park, GlaxoSmithKline, Harlow, Essex, UK

    R Logendra, M R Barnes & C Larminie

  4. Statistical Sciences, New Frontiers Science Park, GlaxoSmithKline, Harlow, Essex, UK

    M Lennon

  5. Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK

    C Angelinetta, T Akbar, S Hirsch, A M Mortimer, T R E Barnes & J de Belleroche

  6. Academic Unit of Psychiatry, University of Hull, Hull, UK

    A M Mortimer

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  1. P R Maycox
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Correspondence to J de Belleroche.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Maycox, P., Kelly, F., Taylor, A. et al. Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function. Mol Psychiatry 14, 1083–1094 (2009). https://doi.org/10.1038/mp.2009.18

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