Gastrointestinal inflammation and associated immune activation in schizophrenia.

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.