title: Gastrointestinal inflammation and associated immune activation in schizophrenia.
abstract: Immune factors are implicated in normal brain development and in brain disorder pathogenesis. Pathogen infection and food antigen penetration across gastrointestinal barriers are means by which environmental factors might affect immune-related neurodevelopment. Here, we test if gastrointestinal inflammation is associated with schizophrenia and therefore, might contribute to bloodstream entry of potentially neurotropic milk and gluten exorphins and/or immune activation by food antigens. IgG antibodies to Saccharomyces cerevisiae (ASCA, a marker of intestinal inflammation), bovine milk casein, wheat-derived gluten, and 6 infectious agents were assayed. Cohort 1 included 193 with non-recent onset schizophrenia, 67 with recent onset schizophrenia and 207 non-psychiatric controls. Cohort 2 included 103 with first episode schizophrenia, 40 of whom were antipsychotic-naïve. ASCA markers were significantly elevated and correlated with food antigen antibodies in recent onset and non-recent onset schizophrenia compared to controls (p≤0.00001-0.004) and in unmedicated individuals with first episode schizophrenia compared to those receiving antipsychotics (p≤0.05-0.01). Elevated ASCA levels were especially evident in non-recent onset females (p≤0.009), recent onset males (p≤0.01) and in antipsychotic-naïve males (p≤0.03). Anti-food antigen antibodies were correlated to antibodies against Toxoplasma gondii, an intestinally-infectious pathogen, particularly in males with recent onset schizophrenia (p≤0.002). In conclusion, gastrointestinal inflammation is a relevant pathology in schizophrenia, appears to occur in the absence of but may be modified by antipsychotics, and may link food antigen sensitivity and microbial infection as sources of immune activation in mental illness.
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 1105, Baltimore, MD 21287-4933, USA. eseverance@jhmi.edu
authors.forename: Emily G
authors.initials: EG
authors.lastname: Severance
authors.forename: Armin
authors.initials: A
authors.lastname: Alaedini
authors.forename: Shuojia
authors.initials: S
authors.lastname: Yang
authors.forename: Meredith
authors.initials: M
authors.lastname: Halling
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Gressitt
authors.forename: Cassie R
authors.initials: CR
authors.lastname: Stallings
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Origoni
authors.forename: Crystal
authors.initials: C
authors.lastname: Vaughan
authors.forename: Sunil
authors.initials: S
authors.lastname: Khushalani
authors.forename: F Markus
authors.initials: FM
authors.lastname: Leweke
authors.forename: Faith B
authors.initials: FB
authors.lastname: Dickerson
authors.forename: Robert H
authors.initials: RH
authors.lastname: Yolken
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000941:Antigens; D002364:Caseins / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D005512:Food Hypersensitivity / Q000150:complications* / Q000276:immunology; D005759:Gastroenteritis / Q000150:complications* / Q000276:immunology; D005983:Glutens / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007249:Inflammation; D008297:Male; D012559:Schizophrenia / Q000150:complications* / Q000276:immunology
chemical_list: D000906:Antibodies; D000941:Antigens; D002364:Caseins; D007074:Immunoglobulin G; D005983:Glutens