Mitochondrial dysfunction in schizophrenia: Evidence for compromised brain metabolism and oxidative stress

S. Prabakaran, J. E. Swatton, M. M. Ryan, S. J. Huffaker, J. T.J. Huang, J. L. Griffin, M. Wayland, T. Freeman, F. Dudbridge, K. S. Lilley, N. A. Karp, S. Hester, D. Tkachev, M. L. Mimmack, R. H. Yolken, M. J. Webster, E. F. Torrey, S. Bahn (Lead / Corresponding author)

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    361 Citations (Scopus)

    Abstract

    The etiology and pathophysiology of schizophrenia remain unknown. A parallel transcriptomics, proteomics and metabolomics approach was employed on human brain tissue to explore the molecular disease signatures. Almost half the altered proteins identified by proteomics were associated with mitochondrial function and oxidative stress responses. This was mirrored by transcriptional and metabolite perturbations. Cluster analysis of transcriptional alterations showed that genes related to energy metabolism and oxidative stress differentiated almost 90% of schizophrenia patients from controls, while confounding drug effects could be ruled out. We propose that oxidative stress and the ensuing cellular adaptations are linked to the schizophrenia disease process and hope that this new disease concept may advance the approach to treatment, diagnosis and disease prevention of schizophrenia and related syndromes.

    Original languageEnglish
    Pages (from-to)684-697
    Number of pages14
    JournalMolecular Psychiatry
    Volume9
    Issue number7
    Early online date20 Apr 2004
    DOIs
    Publication statusPublished - Jul 2004

    Keywords

    • Functional genomics
    • Gene ontology
    • Mitochondria
    • Oxidative stress
    • Schizophrenia
    • Systems-based approach

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  • Cite this

    Prabakaran, S., Swatton, J. E., Ryan, M. M., Huffaker, S. J., Huang, J. T. J., Griffin, J. L., Wayland, M., Freeman, T., Dudbridge, F., Lilley, K. S., Karp, N. A., Hester, S., Tkachev, D., Mimmack, M. L., Yolken, R. H., Webster, M. J., Torrey, E. F., & Bahn, S. (2004). Mitochondrial dysfunction in schizophrenia: Evidence for compromised brain metabolism and oxidative stress. Molecular Psychiatry, 9(7), 684-697. https://doi.org/10.1038/sj.mp.4001511