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Proteomic analysis of the anterior cingulate cortex in the major psychiatric disorders: Evidence for disease-associated changes

Authors

  • Clare L. Beasley,

    1. Department of Psychological Medicine, Institute of Psychiatry, London, UK
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    • These authors contributed equally to this work.

  • Kyla Pennington,

    1. Department of Psychological Medicine, Institute of Psychiatry, London, UK
    2. Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland
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    • These authors contributed equally to this work.

  • Aine Behan,

    1. Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland
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  • Robin Wait,

    1. Rheumatology Division, Imperial College, London, UK
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  • Michael J. Dunn,

    1. Proteome Research Centre, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
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  • David Cotter Professor

    Corresponding author
    1. Department of Psychological Medicine, Institute of Psychiatry, London, UK
    2. Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland
    • Department of Psychiatry, Royal College of Surgeons in Ireland, Beaumont, Dublin 9, Ireland Fax: +353-1-8093741
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Abstract

Abnormalities of the anterior cingulate cortex have previously been described in schizophrenia, major depressive disorder and bipolar disorder. In this study 2-DE was performed followed by mass spectrometric sequencing to identify disease-specific protein changes within the anterior cingulate cortex in these psychiatric disorders. The 2-DE system comprised IPGs 4–7 and 6–9 in the first, IEF dimension and SDS-PAGE in the second dimension. Resultant protein spots were compared between control and disease groups. Statistical analysis indicated that 35 spots were differentially expressed in one or more groups. Proteins comprising 26 of these spots were identified by mass spectroscopy. These represented 19 distinct proteins; aconitate hydratase, malate dehydrogenase, fructose bisphosphate aldolase A, ATP synthase, succinyl CoA ketoacid transferase, carbonic anhydrase, α- and β-tubulin, dihydropyrimidinase-related protein-1 and -2, neuronal protein 25, trypsin precursor, glutamate dehydrogenase, glutamine synthetase, sorcin, vacuolar ATPase, creatine kinase, albumin and guanine nucleotide binding protein β subunit. All but three of these proteins have previously been associated with the major psychiatric disorders. These findings provide support for the view that cytoskeletal and mitochondrial dysfunction are important components of the neuropathology of the major psychiatric disorders.

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