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Comparative proteome analysis of the hippocampus implicates chromosome 6q in schizophrenia

Molecular Psychiatry volume 5, pages 85–90 (2000)Cite this article

Abstract

Comparative brain proteome analysis is a new strategy to discover proteins and therefore genes whose altered expression may underlie schizophrenia. This strategy does not require an a priori theory of the pathogenesis or the mode of inheritance of schizophrenia. Using proteome analysis we previously compared the hippocampal proteome, that is, those proteins expressed by the hippocampal genome, of seven schizophrenic individuals with the hippocampal proteome of seven control individuals, matched for age and post mortem delay.1 We found 18 proteins that were significantly altered in concentration in the schizophrenic hippocampus (P < 0.05), when compared to control tissue. One of these proteins was characterised, by N-terminal sequencing, as diazepam binding inhibitor whose gene maps to 6q12–q21. Here we characterise a further three of the 18 proteins as: manganese superoxide dismutase, 6q25.3, T-complex protein 1, 6q25.3–q26 and collapsin response mediator protein 2, 8p21. That three of these four characterised proteins should map to the long arm of the same chromosome is significant (P < 0.002) and suggests the importance of chromosome 6q in schizophrenia. These results indicate that antioxidant defence is altered in the schizophrenic hippocampus and suggest that segregation distortion, of schizophrenia susceptibility genes, may be a possible causative factor in the high incidence of schizophrenia.

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Acknowledgements

This work was supported by grants from the Health Research Council (NZ), The Foundation for Research Science and Technology (NZ), The Oakley Trust and The Schizophrenia Fellowship of NZ. Brain tissue was kindly provided by the NZ Neurological Foundation Human Brain Bank, Department of Anatomy with Radiology, University of Auckland, New Zealand.

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Authors and Affiliations

  1. School of Biological Sciences, University of Auckland, Auckland, New Zealand

    P F Edgar, J E Douglas & G J S Cooper

  2. Department of Psychiatry and Behavioural Sciences, University of Auckland, Auckland, New Zealand

    R Kydd

  3. Department of Anatomy with Radiology, University of Auckland, Auckland, New Zealand

    R L M Faull

  4. Mental Health Research Institute of Victoria, Australia

    B Dean

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  1. P F Edgar
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  3. G J S Cooper
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  6. R L M Faull
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Correspondence to P F Edgar.

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Edgar, P., Douglas, J., Cooper, G. et al. Comparative proteome analysis of the hippocampus implicates chromosome 6q in schizophrenia. Mol Psychiatry 5, 85–90 (2000). https://doi.org/10.1038/sj.mp.4000580

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