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

Kristoffer Sølvsten Burgdorf; Betina Trabjerg; Marianne Giørtz Pedersen; Janna Nissen; Karina Banasik; Ole Birger Pedersen; Erik Sørensen; Kaspar René Nielsen; Margit Hørup Larsen; Christian Erikstrup; Peter Bruun-Rasmussen; David Westergaard; Lise Wegner Thørner; Henrik Hjalgrim; Helene Martina Paarup; Søren Brunak; Carsten B. Pedersen; E Fuller Torrey; Thomas Werge; Preben Bo Mortensen; Robert Yolken; Henrik Ullum

doi:10.1016/j.bbi.2019.01.026

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

Kristoffer Sølvsten Burgdorf^*, Betina Trabjerg, Marianne Giørtz Pedersen, Janna Nissen, Karina Banasik, Ole Birger Pedersen, Erik Sørensen, Kaspar René Nielsen, Margit Hørup Larsen, Christian Erikstrup, Peter Bruun-Rasmussen, David Westergaard, Lise Wegner Thørner, Henrik Hjalgrim, Helene Martina Paarup, Søren Brunak, Carsten B. Pedersen, E Fuller Torrey, Thomas Werge, Preben Bo MortensenRobert Yolken, Henrik Ullum

^*Corresponding author for this work

44 Citations (Scopus)

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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=2,591), have attempted or committed suicide (N=655), or have had traffic accidents (N=2,724). 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.

Original language	English
Journal	Brain, Behavior, and Immunity
Volume	79
Pages (from-to)	152-158
ISSN	0889-1591
DOIs	https://doi.org/10.1016/j.bbi.2019.01.026
Publication status	Published - Jul 2019

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Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disordersFinal published version, 193 KBLicence: CC BY-NC-ND

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Burgdorf, K. S., Trabjerg, B., Giørtz Pedersen, M., Nissen, J., Banasik, K., Birger Pedersen, O., Sørensen, E., René Nielsen, K., Hørup Larsen, M., Erikstrup, C., Bruun-Rasmussen, P., Westergaard, D., Wegner Thørner, L., Hjalgrim, H., Martina Paarup, H., Brunak, S., Pedersen, C. B., Fuller Torrey, E., Werge, T., ... Ullum, H. (2019). Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders. Brain, Behavior, and Immunity, 79, 152-158. https://doi.org/10.1016/j.bbi.2019.01.026

Burgdorf, KS, Trabjerg, B, Giørtz Pedersen, M, Nissen, J, Banasik, K, Birger Pedersen, O, Sørensen, E, René Nielsen, K, Hørup Larsen, M, Erikstrup, C, Bruun-Rasmussen, P, Westergaard, D, Wegner Thørner, L, Hjalgrim, H, Martina Paarup, H, Brunak, S, Pedersen, CB, Fuller Torrey, E, Werge, T, Bo Mortensen, P, Yolken, R & Ullum, H 2019, 'Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders', Brain, Behavior, and Immunity, vol. 79, pp. 152-158. https://doi.org/10.1016/j.bbi.2019.01.026

@article{77f5beb5949943918d985ad7c707b1ea,

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

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=2,591), have attempted or committed suicide (N=655), or have had traffic accidents (N=2,724). 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.",

author = "Burgdorf, {Kristoffer S{\o}lvsten} and Betina Trabjerg and {Gi{\o}rtz Pedersen}, Marianne and Janna Nissen and Karina Banasik and {Birger Pedersen}, Ole and Erik S{\o}rensen and {Ren{\'e} Nielsen}, Kaspar and {H{\o}rup Larsen}, Margit and Christian Erikstrup and Peter Bruun-Rasmussen and David Westergaard and {Wegner Th{\o}rner}, Lise and Henrik Hjalgrim and {Martina Paarup}, Helene and S{\o}ren Brunak and Pedersen, {Carsten B.} and {Fuller Torrey}, E and Thomas Werge and {Bo Mortensen}, Preben and Robert Yolken and Henrik Ullum",

year = "2019",

month = jul,

doi = "10.1016/j.bbi.2019.01.026",

language = "English",

volume = "79",

pages = "152--158",

journal = "Brain, Behavior, and Immunity",

issn = "0889-1591",

publisher = "Academic Press",

}

TY - JOUR

T1 - Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders

AU - Burgdorf, Kristoffer Sølvsten

AU - Trabjerg, Betina

AU - Giørtz Pedersen, Marianne

AU - Nissen, Janna

AU - Banasik, Karina

AU - Birger Pedersen, Ole

AU - Sørensen, Erik

AU - René Nielsen, Kaspar

AU - Hørup Larsen, Margit

AU - Erikstrup, Christian

AU - Bruun-Rasmussen, Peter

AU - Westergaard, David

AU - Wegner Thørner, Lise

AU - Hjalgrim, Henrik

AU - Martina Paarup, Helene

AU - Brunak, Søren

AU - Pedersen, Carsten B.

AU - Fuller Torrey, E

AU - Werge, Thomas

AU - Bo Mortensen, Preben

AU - Yolken, Robert

AU - Ullum, Henrik

PY - 2019/7

Y1 - 2019/7

N2 - 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=2,591), have attempted or committed suicide (N=655), or have had traffic accidents (N=2,724). 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.

AB - 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=2,591), have attempted or committed suicide (N=655), or have had traffic accidents (N=2,724). 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.

U2 - 10.1016/j.bbi.2019.01.026

DO - 10.1016/j.bbi.2019.01.026

M3 - Journal article

C2 - 30685531

SN - 0889-1591

VL - 79

SP - 152

EP - 158

JO - Brain, Behavior, and Immunity

JF - Brain, Behavior, and Immunity

ER -

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

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