Kristoffer Sølvsten Burgdorf1, Betina B Trabjerg2, Marianne Giørtz Pedersen3, Janna Nissen4, Karina Banasik5, Ole Birger Pedersen6, Erik Sørensen4, Kaspar René Nielsen7, Margit Hørup Larsen4, Christian Erikstrup8, Peter Bruun-Rasmussen5, David Westergaard5, Lise Wegner Thørner4, Henrik Hjalgrim9, Helene Martina Paarup10, Søren Brunak5, Carsten B Pedersen3, E Fuller Torrey11, Thomas Werge12, Preben Bo Mortensen3, Robert H Yolken13, Henrik Ullum4. 1. Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Electronic address: kristoffer.soelvsten.burgdorf@regionh.dk. 2. National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark. 3. National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Centre for Integrated Register-based Research, CIRRAU, Aarhus University, Aarhus, Denmark. 4. Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 5. Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark. 6. Department of Clinical Immunology, Naestved Hospital, Naestved, Denmark. 7. Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark. 8. Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark. 9. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark,; Department of Hematology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 10. Department of Clinical Immunology, Odense University Hospital, Odense, Denmark. 11. Stanley Medical Research Institute, Kensington, MD, USA. 12. The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark. 13. Stanley Division of Developmental Neurovirology, Stanley Neurovirology Laboratory, Johns Hopkins University, USA.
Abstract
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, 1·11; 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, 1·17; 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, 1·08-1·74) 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.
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, 1·11; 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, 1·17; 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, 1·08-1·74) 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.
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