Gastroenterology Issues in Schizophrenia: Why the Gut Matters

Abstract

Genetic and environmental studies implicate immune pathologies in schizophrenia. The body’s largest immune organ is the gastrointestinal (GI) tract. Historical associations of GI conditions with mental illnesses predate the introduction of antipsychotics. Current studies of antipsychotic-naïve patients support that gut dysfunction may be inherent to the schizophrenia disease process. Risk factors for schizophrenia (inflammation, food intolerances, Toxoplasma gondii exposure, cellular barrier defects) are part of biological pathways that intersect those operant in the gut. Central to GI function is a homeostatic microbial community, and early reports show that it is disrupted in schizophrenia. Bioactive and toxic products derived from digestion and microbial dysbiosis activate adaptive and innate immunity. Complement C1q, a brain-active systemic immune component, interacts with gut-related schizophrenia risk factors in clinical and experimental animal models. With accumulating evidence supporting newly discovered gut–brain physiological pathways, treatments to ameliorate brain symptoms of schizophrenia should be supplemented with therapies to correct GI dysfunction.

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Conflict of Interest

James Castiglione declares that he has no conflict of interest.

Emily G. Severance reports that this work was supported by a NIMH P50 Silvio O. Conte Center at Johns Hopkins (grant no. MH-94268) and by the Stanley Medical Research Institute. Dr. Severance also has received a grant from the Brain & Behavior Research Foundation (NARSAD) and has received support for travel to meetings from the Stanley Medical Research Institute.

Emese Prandovszky has received a grant and support for travel to meetings from the Stanley Medical Research Institute.

Robert H. Yolken reports that this work was supported by a NIMH P50 Silvio O. Conte Center at Johns Hopkins (grant no. MH-94268) and by the Stanley Medical Research Institute. Dr. Yolken is a board member and has received travel support from the Stanley Medical Research Institute.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Correspondence to Emily G. Severance.

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This article is part of the Topical Collection on Schizophrenia and Other Psychotic Disorders

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Severance, E.G., Prandovszky, E., Castiglione, J. et al. Gastroenterology Issues in Schizophrenia: Why the Gut Matters. Curr Psychiatry Rep 17, 27 (2015). https://doi.org/10.1007/s11920-015-0574-0

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Keywords

  • Microbiome
  • Autoimmunity
  • Blood–brain barrier
  • Gluten
  • Autism
  • Synapses