Antibody Titers to Cytomegalovirus, Toxoplasma Linked to Bipolar Disorder

Investigators compared antibodies to common infectious agents, including cytomegalovirus, Toxoplasma gondii, and measles, as well as the inflammatory marker C-reactive protein, in serum samples in patients with bipolar disorder vs control participants without bipolar disorder.

According to study data published in JAMA Psychiatry, bipolar disorder was associated with increased long-term antibody response to cytomegalovirus (CMV) and decreased long-term antibody response to Toxoplasma gondii.

Investigators conducted a case-control study using whole blood samples from patients with bipolar disorder and control participants. Immunoassays captured immunoglobulin (Ig)M and IgG class antibodies to CMV and T gondii, IgG class antibodies to measles, and the serum levels of C-reactive protein. IgM titers were expressed as z scores; IgG titers were dichotomized as “seropositive” or “seronegative” outcomes.

Researchers also assessed joint CMV-positive/T gondii-negative IgG status in patient and control groups. They used linear and logistic regression analyses to identify trends in antibody titers across cases and control participants and adjusted analyses for age, sex, and educational level. Analyses also accounted for patient use of mood stabilization drugs with known antitoxoplasma activity.

Related Articles

The final study cohort included 1207 patients with bipolar disorder (61.5% women) and 745 control participants (59.6% women). Mean patient age was 43.2±15.1 years; mean control age was 44.5±15.5 years. Combined CMV-positive/T gondii-negative IgG status was significantly more common in patients with bipolar disorder compared with control participants (odds ratio [OR] 1.33; 95% CI, 1.09-1.62; P =.004). The CMV-positive/T gondii-negative titer was also associated with the subphenotypes of bipolar disorder type I (OR 1.41; 95% CI, 1.14-1.75; P =.001), nonearly onset (OR 1.41; 95% CI, 1.16-1.72; P =.001), and history of manic psychosis (OR 1.46; 95% CI, 1.13-1.88; P =.004). C-reactive protein level was not significantly different between patients and control participants. Patients who had received drug treatment with antitoxoplasma activity had significantly lower T gondii IgM titers compared with patients who had not received treatment (P =.02).

These findings indicate a possible link between immune activation and the pathogenesis of bipolar disorder. Further research is necessary to critically analyze the influence of immune activity on bipolar disorder phenotype and onset.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Frye MA, Coombes BJ, McElroy SL, et al. Association of cytomegalovirus and Toxoplasma gondii antibody titers with bipolar disorder [published online September 18, 2019]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2019.2499