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 (R(2) =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/χ(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.
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 (R(2) =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/χ(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.
Authors: Emily G Severance; Armin Alaedini; Shuojia Yang; Meredith Halling; Kristin L Gressitt; Cassie R Stallings; Andrea E Origoni; Crystal Vaughan; Sunil Khushalani; F Markus Leweke; Faith B Dickerson; Robert H Yolken Journal: Schizophr Res Date: 2012-03-24 Impact factor: 4.939
Authors: Emily G Severance; Kristin L Gressitt; Meredith Halling; Cassie R Stallings; Andrea E Origoni; Crystal Vaughan; Sunil Khushalani; Armin Alaedini; Didier Dupont; Faith B Dickerson; Robert H Yolken Journal: Neurobiol Dis Date: 2012-07-16 Impact factor: 5.996
Authors: Emily G Severance; Kristin L Gressitt; Shuojia Yang; Cassie R Stallings; Andrea E Origoni; Crystal Vaughan; Sunil Khushalani; Armin Alaedini; Faith B Dickerson; Robert H Yolken Journal: Bipolar Disord Date: 2013-12-06 Impact factor: 6.744
Authors: Emily G Severance; Kristin L Gressitt; Cassie R Stallings; Andrea E Origoni; Sunil Khushalani; F Markus Leweke; Faith B Dickerson; Robert H Yolken Journal: Schizophr Res Date: 2013-06-06 Impact factor: 4.939
Authors: Emily G Severance; Kristin L Gressitt; Armin Alaedini; Cathrin Rohleder; Frank Enning; J Malte Bumb; Juliane K Müller; Emanuel Schwarz; Robert H Yolken; F Markus Leweke Journal: Brain Behav Immun Date: 2014-09-20 Impact factor: 7.217
Authors: Emily G Severance; Geetha Kannan; Kristin L Gressitt; Jianchun Xiao; Armin Alaedini; Mikhail V Pletnikov; Robert H Yolken Journal: PLoS One Date: 2012-11-29 Impact factor: 3.240