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The Cytokine Model of Schizophrenia: Emerging Therapeutic Strategies

  • Ragy R. Girgis
    Affiliations
    Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York

    New York State Psychiatric Institute, New York, New York
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  • Samhita S. Kumar
    Affiliations
    Department of Epidemiology, Columbia University College of Physicians and Surgeons, New York, New York

    New York State Psychiatric Institute, New York, New York
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  • Alan S. Brown
    Correspondence
    Address correspondence to Alan S. Brown, M.D., M.P.H., 1051 Riverside Drive, Unit 23, New York, NY 10032
    Affiliations
    Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York

    Department of Epidemiology, Columbia University College of Physicians and Surgeons, New York, New York

    New York State Psychiatric Institute, New York, New York
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Published:December 12, 2013DOI:https://doi.org/10.1016/j.biopsych.2013.12.002
      We discuss the rationale for a trial of a novel biological immunotherapy in schizophrenia (SCZ). Available antipsychotic treatments for SCZ are often limited by partial effectiveness and significant side effects. The search for novel medications is of high priority. All current antipsychotics function primarily by blocking D2-type dopamine receptors. An emerging theory of SCZ postulates disturbances of cytokines and inflammatory mediators (i.e., the cytokine model), possibly originating in part from infectious exposures. Cytokines are one of the most important components of the immune system that orchestrate the response to infectious and other exogenous insults. Preclinical models of SCZ support a convergence between a role for certain cytokines in the pathophysiology of SCZ and major neurochemical postulates of the disorder, including the dopamine and glutamate hypotheses. Several cytokines are elevated in plasma in SCZ, and positron emission tomography studies have shown active inflammation in the brains of patients with psychosis. Treatment studies of anti-inflammatory agents, such as celecoxib and aspirin, in patients with SCZ have provided further support for neuroinflammation in this disorder. The development of approved biological therapies for autoimmune diseases provides new opportunities to target cytokine signaling directly as a novel treatment strategy in SCZ. In addition, advances in imaging, immunology, and psychopharmacology have paved the way for using measures of target engagement of neuroimmune components that would facilitate the identification of patient subgroups who are most likely to benefit from cytokine modulation.

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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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