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.
Publication types
- Historical Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Review
MeSH terms
- Animals
- Antipsychotic Agents / administration & dosage
- Antipsychotic Agents / adverse effects*
- Brain / immunology
- Brain / metabolism*
- Cell Membrane Permeability
- Comorbidity
- Complement C1q / immunology*
- Disease Models, Animal
- Food Hypersensitivity / immunology
- Gastrointestinal Diseases* / complications
- Gastrointestinal Diseases* / history
- Gastrointestinal Diseases* / physiopathology
- Gastrointestinal Motility / drug effects*
- Gastrointestinal Tract* / drug effects
- Gastrointestinal Tract* / immunology
- Gastrointestinal Tract* / metabolism
- Gastrointestinal Tract* / microbiology
- History, 19th Century
- History, 20th Century
- History, Ancient
- Humans
- Immunologic Factors / immunology
- Inflammation / immunology
- Irritable Bowel Syndrome / complications
- Microbiota* / immunology
- Neurotransmitter Agents / metabolism
- Probiotics / administration & dosage
- Risk Factors
- Schizophrenia / drug therapy
- Schizophrenia / etiology*
- Schizophrenia / immunology
- Schizophrenia / microbiology
- Toxoplasmosis / complications
Substances
- Antipsychotic Agents
- Immunologic Factors
- Neurotransmitter Agents
- Complement C1q