Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

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Record number 404922
Title Immune activation by casein dietary antigens in bipolar disorder
Author(s) Severance, E.G.; Dupont, D.; Dickerson, F.B.; Stallings, C.R.; Origoni, A.E.; Krivogorsky, B.; Yang, S.; Haasnoot, W.; Yolken, R.H.
Source Bipolar Disorders 12 (2010). - ISSN 1398-5647 - p. 834 - 842.
DOI https://doi.org/10.1111/j.1399-5618.2010.00879.x
Department(s) RIKILT - Business Unit Safety & Health
Publication type Refereed Article in a scientific journal
Publication year 2010
Keyword(s) bovine beta-casein - common variants - cows milk - schizophrenia - hypothesis - antibodies - food - autoimmunity - polymorphism - resistance
Abstract Objectives: Inflammation and other immune processes are increasingly linked to psychiatric diseases. Antigenic triggers specific to bipolar disorder are not yet defined. We tested whether antibodies to bovine milk caseins were associated with bipolar disorder, and whether patients recognized different epitopes of the casein protein than control individuals. Methods: Anti-bovine casein immunoglobulin G (IgG) levels were measured with solid-phase immunoassays in 75 individuals with bipolar disorder and 65 controls. Epitope recognition was evaluated in immunoassays by cross neutralization with anti-bovine casein polyclonal antibodies of defined reactivity. Group-specific reactivity and associations with symptom severity scores were detected with age-, gender-, and race-controlled regression models. Results: Individuals with bipolar disorder had significantly elevated anti-casein IgG (t-test, p = 0.001) compared to controls. Casein IgG seropositivity conferred odds ratios of 3.97 for bipolar disorder [n = 75, 95% confidence interval (CI): 1.31–12.08, p = 0.015], 5.26 for the bipolar I subtype (n = 56, 95% CI: 1.66–16.64, p = 0.005), and 3.98 for bipolar disorder with psychosis (n = 54, 95% CI: 1.32–12.00, p = 0.014). Lithium and/or antipsychotic medication did not significantly affect anti-casein IgG levels. Casein IgG measures correlated with severity of manic (R2 = 0.15, 95% CI: 0.05–0.24, p = 0.02) but not depressive symptoms. Unlike controls, sera from individuals with bipolar disorder did not inhibit binding of casein-reactive animal sera (t-test/¿2, p = 0.0001). Conclusions: Anti-casein IgG associations with bipolar I diagnoses, psychotic symptom history, and mania severity scores suggest that casein-related immune activation may relate to the psychosis and mania components of this mood disorder. Case-control differences in epitope recognition implicate disease-related alterations in how the casein molecule is digested and/or how resulting casein-derived structures are rendered immunogenic.
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