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Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia

Molecular Psychiatry volume 18, pages 206–214 (2013)Cite this article

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Abstract

Upregulation of the immune response may be involved in the pathogenesis of schizophrenia with changes occurring in both peripheral blood and brain tissue. To date, microarray technology has provided a limited view of specific inflammatory transcripts in brain perhaps due to sensitivity issues. Here we used SOLiD Next Generation Sequencing to quantify neuroimmune mRNA expression levels in the dorsolateral prefrontal cortex of 20 individuals with schizophrenia and their matched controls. We detected 798 differentially regulated transcripts present in people with schizophrenia compared with controls. Ingenuity pathway analysis identified the inflammatory response as a key change. Using quantitative real-time PCR we confirmed the changes in candidate cytokines and immune modulators, including interleukin (IL)-6, IL-8, IL-1β and SERPINA3. The density of major histocompatibility complex-II-positive cells morphologically resembling microglia was significantly increased in schizophrenia and correlated with IL-1β expression. A group of individuals, most of whom had schizophrenia, were found to have increased inflammatory mRNA expression. In summary, we have demonstrated changes in an inflammatory response pathway that are present in ∼40% of people diagnosed with schizophrenia. This suggests that therapies aimed at immune system attenuation in schizophrenia may be of direct benefit in the brain.

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Acknowledgements

We would like to thank Sarah Wagner at Queensland Pathology for performing the SOLiD library preparation and sequencing. We would also like to thank Shan Yuan-Tsai-Chin for her assistance in RNA isolation and Dr Claire Shepherd for her input into the microglia immunohistochemistry analysis. This work was supported by the Schizophrenia Research Institute (Australia), utilizing funding from the Macquarie Group Foundation, New South Wales Ministry of Health, Neuroscience Research Australia, and the University of New South Wales. Tissues were received from the New South Wales Tissue Resource Center at the University of Sydney, which is supported by the National Health and Medical Research Council of Australia, Schizophrenia Research Institute, National Institute of Alcohol Abuse and Alcoholism (NIH (NIAAA) R24AA012725). JW is supported by a National Health and Medical Research Council of Australia (NHMRC) Postdoctoral Training Fellowship (568884).

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Authors and Affiliations

  1. Schizophrenia Research Institute, Sydney, New South Wales, Australia

    S G Fillman, V S Catts, M Cairns & C S Weickert

  2. Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, New South Wales, Australia

    S G Fillman, V S Catts & C S Weickert

  3. School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia

    S G Fillman, V S Catts & C S Weickert

  4. Institute for Molecular Bioscience, University of Queensland, Brisbane

    N Cloonan

  5. Queensland, Australia

    N Cloonan

  6. Children's Medical Research Institute, Westmead, New South Wales, Australia

    L C Miller

  7. Illawarra Health and Medical Research Institute and the School of Biological Sciences, University of Wollongong, Wollongong, New South Wales, Australia

    J Wong

  8. Discipline of Pathology, The University of Sydney, Sydney, New South Wales, Australia

    T McCrossin

  9. School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia

    M Cairns

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Fillman, S., Cloonan, N., Catts, V. et al. Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia. Mol Psychiatry 18, 206–214 (2013). https://doi.org/10.1038/mp.2012.110

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