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Infection-associated immune activation linked to bipolar disorder

Increased long-term antibody response to cytomegalovirus and decreased response to Toxoplasma gondii were linked to bipolar disorder, according to findings published in JAMA Psychiatry.

“Exposure to infectious agents and the associated immune activation underscore conceptualizing bipolar disorder as a multisystem inflammatory disease of the brain and the body,” Mark A. Frye, MD, from the department of psychiatry & psychology at Mayo Clinic, and colleagues wrote. “The disease risk or biologic mechanism of infectious environmental exposure, early immune activation, acute inflammation, dormant vs. viral reactivation, and the consequences of longer-term immunity have yet to be systematically studied to our knowledge.”

Researchers conducted a case-control study to determine whether antibodies to common infectious agents — including cytomegalovirus (CMV), T. gondii and measles — and the inflammatory marker C-reactive protein (CRP), differed between individuals with and without bipolar disorder.

Frye and colleagues measured antibody titers in serum samples from 1,207 patients with bipolar disorder and 745 controls, then stratified cases by bipolar disorder type I or type II, non-early (after age 19) and early onset, and history of psychosis during mania or no psychosis.

Analysis revealed that patients with bipolar disorder had significantly higher cytomegalovirus IgG and significantly lower toxoplasma IgG (OR = 1.33; 95% CI, 1.09-1.62) than individuals without bipolar disorder.

Frye and colleagues reported that the CMV-positive/T. gondii–negative IgG status was linked to bipolar cases type I (OR = 1.41; 95% CI, 1.14-1.75), non-early age at onset (OR = 1.41; 95% CI, 1.16-1.72) and history of manic psychosis (OR = 1.46; 95% CI, 1.13-1.88). In addition, mood stabilization drug treatment with antitoxoplasma activity was linked to significantly lower T. gondii IgM titers.

“During the past 20 years, drug development in bipolar disorder has been significantly less than that for schizophrenia and depression, and thus, we believe that further focused efforts in immune modulators and anti-inflammation interventions in patients with bipolar disorder should be encouraged. These and other immune targets should be considered for future drug development,” the researchers wrote. “Further work appears to be needed to better understand genetic vs. environmental disease risk and infection or immune activation contribution to overall disease pathogenesis with particular reference to disease onset.” – by Savannah Demko

Disclosure: The authors report numerous relevant financial disclosures; please see the full study.