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.