TY - JOUR
T1 - Gastrointestinal inflammation and associated immune activation in schizophrenia
AU - Severance, Emily G.
AU - Alaedini, Armin
AU - Yang, Shuojia
AU - Halling, Meredith
AU - Gressitt, Kristin L.
AU - Stallings, Cassie R.
AU - Origoni, Andrea E.
AU - Vaughan, Crystal
AU - Khushalani, Sunil
AU - Leweke, F. Markus
AU - Dickerson, Faith B.
AU - Yolken, Robert H.
N1 - Funding Information:
This work was supported by the Stanley Medical Research Institute and by the Brain and Behavior Research Foundation (formerly NARSAD) where Dr. Severance is a Scott-Gentle Foundation Investigator. These funding sources had no role in study design, data collection and analyses, report writing and in the decision to submit the paper for publication.
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - Environment
KW - Food hypersensitivity
KW - Immunology
KW - Intestine
KW - Mental disorder
KW - Microbiology
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U2 - 10.1016/j.schres.2012.02.025
DO - 10.1016/j.schres.2012.02.025
M3 - Article
C2 - 22446142
AN - SCOPUS:84862810848
SN - 0920-9964
VL - 138
SP - 48
EP - 53
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 1
ER -