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Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder

Abstract

Severe psychiatric disorders such as schizophrenia, bipolar disorder and major depressive disorder are brain diseases of unknown origin. No biological marker has been documented at the pathological, cellular, or molecular level, suggesting that a number of complex but subtle changes underlie these illnesses. We have used proteomic technology to survey postmortem tissue to identify changes linked to the various diseases. Proteomics uses two-dimensional gel electrophoresis and mass spectrometric sequencing of proteins to allow the comparison of subsets of expressed proteins among a large number of samples. This form of analysis was combined with a multivariate statistical model to study changes in protein levels in 89 frontal cortices obtained postmortem from individuals with schizophrenia, bipolar disorder, major depressive disorder, and non-psychiatric controls. We identified eight protein species that display disease-specific alterations in level in the frontal cortex. Six show decreases compared with the non-psychiatric controls for one or more diseases. Four of these are forms of glial fibrillary acidic protein (GFAP), one is dihydropyrimidinase-related protein 2, and the sixth is ubiquinone cytochrome c reductase core protein 1. Two spots, carbonic anhydrase 1 and fructose biphosphate aldolase C, show increase in one or more diseases compared to controls. Proteomic analysis may identify novel pathogenic mechanisms of human neuropsychiatric diseases.

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Acknowledgements

We would like to thank the Stanley Foundation for funding this work. We would also like to thank Dr Maree Webster for her technical input, Dr Lydie Meheus of Innogenetics for sequencing and peptide IDs, and Ms Ann Cusic for the preparation of this manuscript.

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Correspondence to N L Johnston-Wilson.

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Johnston-Wilson, N., Sims, C., Hofmann, JP. et al. Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. Mol Psychiatry 5, 142–149 (2000). https://doi.org/10.1038/sj.mp.4000696

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  • DOI: https://doi.org/10.1038/sj.mp.4000696

Keywords

  • two-dimensional gel electrophoresis
  • postmortem human brain
  • glial acidic fibrillary acidic protein
  • dihydropyrimidinase-related protein 2
  • ubiquinol cytochrome c reductase complex core protein 1
  • fructose bisphosphate aldolase C
  • carbonic anhydrase I

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