Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders

Background: Common infectious pathogens have been associated with psychiatric disorders, self-violence and risk-taking behavior. Methods: This case-control study reviews register data on 81,912 individuals from the Danish Blood Donor Study to identify individuals who have a psychiatric diagnosis (N = 2591), have attempted or committed suicide (N = 655), or have had traffic accidents (N = 2724). For all cases, controls were frequency matched by age and sex, resulting in 11,546 participants. Plasma samples were analyzed for immunoglobulin G (IgG) antibodies against Toxoplasma gondii and cytomegalovirus (CMV). Results: T. gondii was detected in 25.9% of the population and was associated with schizophrenia (odds ratio [OR], 1.47; 95% confidence interval [CI], 1-03-2.09). Accounting for temporality, with pathogen exposure preceding outcome, the association was even stronger (IRR, 2.78; 95% CI, 1-27-6-09). A very weak association between traffic accident and toxoplasmosis (OR, 141; 95% CI, 1-00-1.23, p = 0.054) was found. CMV was detected in 60.8% of the studied population and was associated with any psychiatric disorder (OR, 147; 95% CI, 1.06-1-29), but also with a smaller group of neurotic, stress-related, and somatoform disorders (OR, 1.27; 95% CI, 1.12-1-44), and with attempting or committing suicide (OR, 1.31; 95% CI, 1.10-1-56). Accounting for temporality, any psychiatric disorder (IRR, 1.37; 95% CI, 1.08-174) and mood disorders (IRR, 1.43; 95% CI, 1.01-2-04) were associated with exposure to CMV. No association between traffic accident and CMV (OR, 1.06; 95% CI, 0.97-1-17) was found. Conclusions: This large-scale serological study is the first study to examine temporality of pathogen exposure and to provide evidence of a causal relationship between T. gondii and schizophrenia, and between CMV and any psychiatric disorder.