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Immune System Disturbances in Schizophrenia

  • Szatmár Horváth
    Affiliations
    Department of Psychiatry, Vanderbilt University, Nashville, Tennessee

    Department of Psychiatry, University of Szeged, 6725 Szeged, Hungary
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  • Károly Mirnics
    Correspondence
    Address correspondence to Károly Mirnics, M.D., Ph.D., Department of Psychiatry, Vanderbilt University, 8130A MRB III, 465 21st Avenue South, Nashville TN 37232
    Affiliations
    Department of Psychiatry, Vanderbilt University, Nashville, Tennessee

    Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, Tennessee

    Department of Psychiatry, University of Szeged, 6725 Szeged, Hungary
    Search for articles by this author
      Epidemiological, genetic, transcriptome, postmortem, peripheral biomarker, and therapeutic studies of schizophrenia all point to a dysregulation of both innate and adaptive immune systems in the disease, and it is likely that these immune changes actively contribute to disease symptoms. Gene expression disturbances in the brain of subjects with schizophrenia show complex, region-specific changes with consistently replicated and potentially interdependent induction of serpin peptidase inhibitor, clade A member 3 (SERPINA3) and interferon inducible transmembrane protein (IFITM) family transcripts in the prefrontal cortex. Recent data suggest that IFITM3 expression is a critical mediator of maternal immune activation. Because the IFITM gene family is primarily expressed in the endothelial cells and meninges, and because the meninges play a critical role in interneuron development, we suggest that these two non-neuronal cell populations might play an important role in the disease pathophysiology. Finally, we propose that IFITM3 in particular might be a novel, appealing, knowledge-based drug target for treatment of schizophrenia.

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      Linked Article

      • Is There a Flame in the Brain in Psychosis?
        Biological PsychiatryVol. 75Issue 4
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          For many decades, it was believed that the brain was immunologically privileged, hence it was surprising when Shatz and colleagues (1) reported in 2000 that a number of immune proteins (cytokines and major histocompatibility complex [MHC] proteins) were not just present in the brain but were localized at functional synapses. Subsequent work has shown that these molecules play a major role in brain development as well as in mature synaptic function and plasticity (2,3).
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