Seroreactive marker for inflammatory bowel disease and associations with antibodies to dietary proteins in bipolar disorder

Abstract

Objectives: Immune sensitivity to wheat glutens and bovine milk caseins may affect a subset of individuals with bipolar disorder. Digested byproducts of these foods are exorphins that have the potential to impact brain physiology through action at opioid receptors. Inflammation in the gastrointestinal (GI) tract might accelerate exposure of food antigens to systemic circulation and help explain elevated gluten and casein antibody levels in individuals with bipolar disorder.

Methods: We measured a marker of GI inflammation, anti-Saccharomyces cerevisiae antibodies (ASCA), in non-psychiatric controls (n = 207), in patients with bipolar disorder without a recent onset of psychosis (n = 226), and in patients with bipolar disorder with a recent onset of psychosis (n = 38). We compared ASCA levels to antibodies against gluten, casein, Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), influenza A, influenza B, measles, and Toxoplasma gondii.

Results: Elevated ASCA conferred a 3.5-4.4-fold increased odds ratio of disease association (age-, race-, and gender-corrected multinomial logistic regressions, p ≤ 0.00001) that was independent of type of medication received. ASCA correlated with food antibodies in both bipolar disorder groups (R(2) = 0.29-0.59, p ≤ 0.0005), and with measles and T. gondii immunoglobulin G (IgG) in the recent onset psychosis bipolar disorder group (R(2) = 0.31-0.36, p ≤ 0.004-0.01).

Conclusions: Elevated seropositivity of a GI-related marker and its association with antibodies to food-derived proteins and self-reported GI symptoms suggest a GI comorbidity in at least a subgroup of individuals with bipolar disorder. Marker seroreactivity may also represent part of an overall heightened activated immune state inherent to this mood disorder.

Keywords: autoimmunity; environment; gastrointestinal; immunology; infection; mood disorder.

Figure 1

Quantitative ASCA IgG levels according to diagnosis and medication status. Panel A. ASCA IgG levels were significantly elevated in bipolar disorder (BP) without a recent onset of psychosis (ROP) and BP with ROP compared to controls (CO). Panel B. ASCA IgG levels between individuals who were medication-positive (+) and medication-negative (−) were not significantly different. LITH refers to lithium; VAL refers to valproate; AP refers to antipsychotic.

Figure 2

ASCA IgG correlates with food antigen IgG in bipolar disorder groups, but not controls. Gluten data points are shown with an “x” and a solid regression line; casein data points are shown with a closed “o” and a dashed regression line. Multiple linear regressions corrected for age, sex and race were used to generate the listed p-values. “NS” refers to not significant.

Figure 3

Correlations of ASCA and food antigen IgG levels according to self-reported symptoms of gastrointestinal discomfort. IgG against food antigens is correlated to ASCA in individuals with bipolar disorder without a recent onset of psychosis who reported GI symptoms (+GI symptoms), but not in those who did not report these symptoms. In bipolar disorder with a recent onset of psychosis, ASCA and food antigen IgG were correlated in both those who reported GI symptoms and those who did not. Gluten data points are shown with an “x” and a solid regression line; casein data points are shown with a closed “o” and dashed regression line. Multiple linear regressions corrected for age, sex and race were used to generate the listed p-values. “NS” refers to not significant.