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Infection with Toxoplasma gondii increases the risk of psychiatric disorders in Taiwan: a nationwide population-based cohort study

Published online by Cambridge University Press:  30 July 2020

Hsin-An Lin ,
Wu-Chien Chien ,
Kuo-Yang Huang ,
Chi-Hsiang Chung ,
Lih-Chyang Chen ,
Hsin-Chung Lin  and
Jong-Long Guo Open the ORCID record for Jong-Long Guo [Opens in a new window]
Hsin-An Lin
Affiliation:
Division of Infection, Department of Medicine, Tri-Service General Hospital SongShan Branch, National Defense Medical Center, No. 131, Jiankang Rd., Songshan District, Taipei City10581, Taiwan Department of Health Promotion and Health Education, National Taiwan Normal University, No. 162, Section 1, Heping E. Rd., Taipei City106, Taiwan
Wu-Chien Chien
Affiliation:
School of Public Health, National Defense Medical Center, No. 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City11490, Taiwan Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, No. 131, Jiankang Rd., Songshan District, Taipei City10581, Taiwan Graduate Institute of Life Sciences, National Defense Medical Center, No. 161, Sec. 6, 1 Minquan E. Rd., Neihu Dist., Taipei City11490, Taiwan
Kuo-Yang Huang
Affiliation:
Graduate Institute of Pathology and Parasitology, National Defense Medical Center, No. 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City11490, Taiwan
Chi-Hsiang Chung
Affiliation:
School of Public Health, National Defense Medical Center, No. 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City11490, Taiwan Taiwanese Injury Prevention and Safety Promotion Association, Rm. 4112, No. 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City114, Taiwan
Lih-Chyang Chen
Affiliation:
Department of Medicine, Mackay Medical College, No. 46, Sec. 3, Zhongzheng Rd., Sanzhi Dist., New Taipei City252, Taiwan
Hsin-Chung Lin*
Affiliation:
Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu District, Taipei City11490, Taiwan
Jong-Long Guo*
Affiliation:
Department of Health Promotion and Health Education, National Taiwan Normal University, No. 162, Section 1, Heping E. Rd., Taipei City106, Taiwan
*
Authors for correspondence: Hsin-Chung Lin, E-mail: hsinchunglin@gmail.com and Jong-Long Guo, E-mail: jonglong@ntnu.edu.tw
Authors for correspondence: Hsin-Chung Lin, E-mail: hsinchunglin@gmail.com and Jong-Long Guo, E-mail: jonglong@ntnu.edu.tw
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Abstract

This study aimed to evaluate associations between toxoplasmosis and psychiatric disorders in Taiwan based on the National Health Insurance Research Database, Taiwan (1997–2013). Patients newly diagnosed with toxoplasmosis formed the case group (n = 259), and the control group included propensity-score matched patients without toxoplasmosis (n = 1036). The primary outcome was incidence of psychiatric disorders. Cox proportional hazards regression and stratified analyses were performed to examine risk of developing specific psychiatric disorders between patients with and without toxoplasmosis. Patients with toxoplasmosis had significantly higher incidence of psychiatric disorders than those without toxoplasmosis (P = 0.016). A significant difference was found in numbers of psychiatric disorders between the two groups during 14 years of follow-up (log-rank P < 0.001). Those with toxoplasmosis had significantly higher risk of bipolar disorder [adjusted hazard ratio (aHR = 3.60, 95% confidence interval (CI) = 2.07, 7.26), depression (aHR = 4.94, 95% CI = 2.15, 11.80) and anxiety (aHR = 5.36, 95% CI = 2.98, 25.88), but no significant between-group differences were found for schizophrenia and other psychiatric disorders. In conclusion, the present nationwide population-based analysis revealed that Toxoplasma gondii infection in Taiwan significantly increases the risk for developing bipolar disorder, depression and anxiety, but not for schizophrenia and other psychiatric disorders.

Keywords

Anxietybipolar disorderdepressionschizophreniaToxoplasma gondii
Type
Research Article
Information
Parasitology , Volume 147 , Issue 13 , November 2020 , pp. 1577 - 1586
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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References

Achaw, B, Tesfa, H, Zeleke, AJ, Worku, L, Addisu, A, Yigzaw, N and Tegegne, Y (2019) Sero-prevalence of Toxoplasma gondii and associated risk factors among psychiatric outpatients attending University of Gondar Hospital, Northwest Ethiopia. BMC Infectious Diseases 19, 581.CrossRefGoogle Scholar
Afifi, MA, Jiman-Fatani, AA, Al-Rabia, MW, Al-Hussainy, NH, El Saadany, S and Mayah, W (2018) More than an association: latent toxoplasmosis might provoke a local oxidative stress that triggers the development of bipolar disorder. Journal of Microscopy and Ultrastructure 6, 139–144.10.4103/JMAU.JMAU_22_18CrossRefGoogle ScholarPubMed
Alvarado-Esquivel, C, Martínez-Martínez, AL, Sánchez-Anguiano, LF, Hernández-Tinoco, J, Castillo-Orona, JM, Salas-Martínez, C, Sifuentes-Álvarez, A, Sandoval-Carrillo, AA, Salas-Pacheco, JM, Liesenfeld, O and Antuna-Salcido, EI (2017) Lack of association between Toxoplasma gondii exposure and depression in pregnant women: a case-control study. BMC Infectious Diseases 17, 190.CrossRefGoogle ScholarPubMed
Bay-Richter, C, Buttenschøn, HN, Mors, O, Eskelund, A, Budac, D, Kærlev, L and Wegener, G (2019a) Latent toxoplasmosis and psychiatric symptoms – a role of tryptophan metabolism? Journal of Psychiatric Research 110, 45–50.CrossRefGoogle Scholar
Bay-Richter, C, Petersen, E, Liebenberg, N, Elfving, B and Wegener, G (2019b) Latent toxoplasmosis aggravates anxiety- and depressive-like behaviour and suggest a role of gene–environment interactions in the behavioural response to the parasite. Behavioural Brain Research 364, 133–139.CrossRefGoogle Scholar
Berger-Schoch, AE, Herrmann, DC, Schares, G, Müller, N, Bernet, D, Gottstein, B and Frey, CF (2011) Prevalence and genotypes of Toxoplasma gondii in feline faeces (oocysts) and meat from sheep, cattle and pigs in Switzerland. Veterinary Parasitology 177, 290–297.CrossRefGoogle ScholarPubMed
Burgdorf, KS, Trabjerg, BB, Pedersen, MG, Nissen, J, Banasik, K, Pedersen, OB, Sorensen, E, Nielsen, KR, Larsen, MH, Erikstrup, C, Bruun-Rasmussen, P, Westergaard, D, Thorner, LW, Hjalgrim, H, Paarup, HM, Brunak, S, Pedersen, CB, Torrey, EF, Werge, T, Mortensen, PB, Yolken, RH and 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.CrossRefGoogle ScholarPubMed
Chalkowski, K, Wilson, AE, Lepczyk, CA and Zohdy, S (2019) Who let the cats out? A global meta-analysis on risk of parasitic infection in indoor versus outdoor domestic cats (Felis catus). Biology Letters 15, 20180840.CrossRefGoogle Scholar
Chen, X, Chen, B, Hou, X, Zheng, C, Yang, X, Ke, J, Hu, X and Tan, F (2019) Association between Toxoplasma gondii infection and psychiatric disorders in Zhejiang, Southeastern China. Acta Tropica 192, 82–86.10.1016/j.actatropica.2019.02.001CrossRefGoogle Scholar
Chiang, TY, Hsieh, HH, Kuo, MC, Chiu, KT, Lin, WC, Fan, CK, Fang, CT and Ji, DD (2012) Seroepidemiology of Toxoplasma gondii infection among healthy blood donors in Taiwan. PLoS One 7, e48139.CrossRefGoogle ScholarPubMed
Chiang, TY, Kuo, MC, Chen, CH, Yang, JY, Kao, CF, Ji, DD and Fang, CT (2014) Risk factors for acute Toxoplasma gondii diseases in Taiwan: a population-based case-control study. PLoS One 9, e90880.CrossRefGoogle ScholarPubMed
Dabritz, HA and Conrad, PA (2010) Cats and Toxoplasma: implications for public health. Zoonoses and Public Health 57, 34–52.10.1111/j.1863-2378.2009.01273.xCrossRefGoogle ScholarPubMed
Del Grande, C, Galli, L, Schiavi, E, Dell'Osso, L and Bruschi, F (2017) Is Toxoplasma gondii a trigger of bipolar disorder? Pathogens 6, 3.CrossRefGoogle ScholarPubMed
de Witte, LD, van Mierlo, HC, Litjens, M, Klein, HC, Bahn, S and Osterhaus, AD (2015) The association between antibodies to neurotropic pathogens and schizophrenia: a case-control study. NPJ Schizophrenia 1, 15041.CrossRefGoogle ScholarPubMed
Dubey, JP and Jones, JL (2008) Toxoplasma gondii infection in humans and animals in the United States. International Journal for Parasitology 38, 1257–1278.CrossRefGoogle ScholarPubMed
Elmore, SA, Jones, JL, Conrad, PA, Patton, S, Lindsay, DS and Dubey, JP (2010) Toxoplasma gondii: epidemiology, feline clinical aspects, and prevention. Trends in Parasitology 26, 190–196.Google ScholarPubMed
Flegr, J and Horáček, J (2020) Negative effects of latent toxoplasmosis on mental health. Frontiers in Psychiatry 10, 1012.10.3389/fpsyt.2019.01012CrossRefGoogle ScholarPubMed
Groër, MW, Yolken, RH, Xiao, JC, Beckstead, JW, Fuchs, D, Mohapatra, SS, Seyfang, A and Postolache, TT (2011) Prenatal depression and anxiety in Toxoplasma gondii-positive women. American Journal of Obstetrics and Gynecology 204, 433.e431–437.CrossRefGoogle ScholarPubMed
Hartmann, K, Addie, D, Belak, S, Boucraut-Baralon, C, Egberink, H, Frymus, T, Gruffydd-Jones, T, Hosie, MJ, Lloret, A, Lutz, H, Marsilio, F, Mostl, K, Pennisi, MG, Radford, AD, Thiry, E, Truyen, U and Horzinek, MC (2013) Toxoplasma gondii infection in cats: ABCD guidelines on prevention and management. Journal of Feline Medicine and Surgery 15, 631–637.CrossRefGoogle ScholarPubMed
Hill, DE, Chirukandoth, S and Dubey, JP (2005) Biology and epidemiology of Toxoplasma gondii in man and animals. Animal Health Research Reviews 6, 41–61.Google ScholarPubMed
Hu, IJ, Chen, PC, Su, FC, Hsieh, CJ, Jeng, SF, Liao, HF, Su, YN, Lin, SJ and Hsieh, WS (2006) Perinatal toxoplasmosis, northern Taiwan. Emerging Infectious Diseases 12, 1460–1461.CrossRefGoogle Scholar
Hung, CC, Chen, MY, Hsieh, SM, Hsiao, CF, Sheng, WH and Chang, SC (2005) Prevalence of Toxoplasma gondii infection and incidence of toxoplasma encephalitis in non-haemophiliac HIV-1-infected adults in Taiwan. International Journal of STD & AIDS 16, 302–306.CrossRefGoogle ScholarPubMed
Jones-Brando, L, Torrey, EF and Yolken, R (2003) Drugs used in the treatment of schizophrenia and bipolar disorder inhibit the replication of Toxoplasma gondii. Schizophrenia Research 62, 237–244.CrossRefGoogle ScholarPubMed
Kano, SI, Hodgkinson, CA, Jones-Brando, L, Eastwood, S, Ishizuka, K, Niwa, M, Choi, EY, Chang, DJ, Chen, Y, Velivela, SD, Leister, F, Wood, J, Chowdari, K, Ducci, F, Caycedo, DA, Heinz, E, Newman, ER, Cascella, N, Mortensen, PB, Zandi, PP, Dickerson, F, Nimgaonkar, V, Goldman, D, Harrison, PJ, Yolken, RH and Sawa, A (2018) Host–parasite interaction associated with major mental illness. Molecular Psychiatry 25, 194–205.CrossRefGoogle ScholarPubMed
Kern, EF, Maney, M, Miller, DR, Tseng, CL, Tiwari, A, Rajan, M, Aron, D and Pogach, L (2006) Failure of ICD-9-CM codes to identify patients with comorbid chronic kidney disease in diabetes. Health Services Research 41, 564–580.10.1111/j.1475-6773.2005.00482.xCrossRefGoogle ScholarPubMed
Khodaverdi, M and Razmi, G (2019) A serological and parasitological study of Toxoplasma gondii infection in stray cats of Mashhad, Khorasan Razavi province, Iran. Veterinary Research Forum 10, 119–123.Google ScholarPubMed
Li, Y, Severance, EG, Viscidi, RP, Yolken, RH and Xiao, J (2019) Persistent toxoplasma infection of the brain induced neurodegeneration associated with activation of complement and microglia. Infection and Immunity 87, 8.e00139-19.CrossRefGoogle ScholarPubMed
Lilly, EL and Wortham, CD (2013) High prevalence of Toxoplasma gondii oocyst shedding in stray and pet cats (Felis catus) in Virginia, United States. Parasites & Vectors 6, 266.CrossRefGoogle Scholar
Lin, HC, Huang, KY, Chung, CH, Lin, HA, Chen, RM, Tsao, CH, Chien, WC and Chiueh, TS (2019) Infection with Trichomonas vaginalis increases the risk of psychiatric disorders in women: a nationwide population-based cohort study. Parasites & Vectors 12, 88.CrossRefGoogle ScholarPubMed
Lindgren, M, Torniainen-Holm, M, Harkanen, T, Dickerson, F, Yolken, RH and Suvisaari, J (2018) The association between toxoplasma and the psychosis continuum in a general population setting. Schizophrenia Research 193, 329–335.10.1016/j.schres.2017.06.052CrossRefGoogle Scholar
Markovitz, AA, Simanek, AM, Yolken, RH, Galea, S, Koenen, KC, Chen, S and Aiello, AE (2015) Toxoplasma gondii and anxiety disorders in a community-based sample. Brain, Behavior, and Immunity 43, 192–197.CrossRefGoogle Scholar
Montoya, JG and Liesenfeld, O (2004) Toxoplasmosis. Lancet 363, 1965–1976.CrossRefGoogle ScholarPubMed
Nayeri Chegeni, T, Sharif, M, Sarvi, S, Moosazadeh, M, Montazeri, M, Aghayan, SA, Balalami, NJ, Gholami, S, Hosseininejad, Z, Saberi, R, Anvari, D, Gohardehi, S and Daryani, A (2019) Is there any association between Toxoplasma gondii infection and depression? A systematic review and meta-analysis. PLoS One 14, e0218524.CrossRefGoogle ScholarPubMed
Ngô, HM, Zhou, Y, Lorenzi, H, Wang, K, Kim, TK, Zhou, Y, El Bissati, K, Mui, E, Fraczek, L, Rajagopala, SV, Roberts, CW, Henriquez, FL, Montpetit, A, Blackwell, JM, Jamieson, SE, Wheeler, K, Begeman, IJ, Naranjo-Galvis, C, Alliey-Rodriguez, N, Davis, RG, Soroceanu, L, Cobbs, C, Steindler, DA, Boyer, K, Noble, AG, Swisher, CN, Heydemann, PT, Rabiah, P, Withers, S, Soteropoulos, P, Hood, L and McLeod, R (2017) Toxoplasma modulates signature pathways of human epilepsy, neurodegeneration & cancer. Scientific Reports 7, 11496.CrossRefGoogle ScholarPubMed
Palerme, JS, Lamperelli, E, Gagne, J, Cazlan, C, Zhang, M and Olds, JE (2019) Seroprevalence of Leptospira spp., Toxoplasma gondii, and Dirofilaria immitis in free-roaming cats in Iowa. Vector-Borne and Zoonotic Diseases 19, 193–198.CrossRefGoogle ScholarPubMed
Pappas, G, Roussos, N and Falagas, ME (2009) Toxoplasmosis snapshots: global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis. International Journal for Parasitology 39, 1385–1394.10.1016/j.ijpara.2009.04.003CrossRefGoogle ScholarPubMed
Parlog, A, Schluter, D and Dunay, IR (2015) Toxoplasma gondii-induced neuronal alterations. Parasite Immunology 37, 159–170.CrossRefGoogle ScholarPubMed
Robert-Gangneux, F and Darde, ML (2012) Epidemiology of and diagnostic strategies for toxoplasmosis. Clinical Microbiology Reviews 25, 264–296.CrossRefGoogle ScholarPubMed
Rougier, S, Montoya, JG and Peyron, F (2017) Lifelong persistence of toxoplasma cysts: a questionable dogma? (Trends in Parasitology 33, 93–101; 2017). Trends in Parasitology 33, 414.CrossRefGoogle ScholarPubMed
Stepanova, EV, Kondrashin, AV, Sergiev, VP, Morozova, LF, Turbabina, NA, Maksimova, MS, Romanov, DV, Kinkulkina, MA, Lazareva, AV and Morozov, EN (2019) Toxoplasmosis and mental disorders in the Russian Federation (with special reference to schizophrenia). PLoS One 14, e0219454.CrossRefGoogle Scholar
Sugden, K, Moffitt, TE, Pinto, L, Poulton, R, Williams, BS and Caspi, A (2016) Is Toxoplasma gondii infection related to brain and behavior impairments in humans? Evidence from a population-representative birth cohort. PLoS One 11, e0148435.Google ScholarPubMed
Sutterland, AL, Fond, G, Kuin, A, Koeter, MW, Lutter, R, van Gool, T, Yolken, R, Szoke, A, Leboyer, M and de Haan, L (2015) Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis. Acta Psychiatrica Scandinavica 132, 161–179.CrossRefGoogle ScholarPubMed
Torrey, EF and Yolken, RH (2019) Schizophrenia as a pseudogenetic disease: a call for more gene-environmental studies. Psychiatry Research 278, 146–150.CrossRefGoogle Scholar
Torrey, EF, Bartko, JJ and Yolken, RH (2012) Toxoplasma gondii and other risk factors for schizophrenia: an update. Schizophrenia Bulletin 38, 642–647.CrossRefGoogle ScholarPubMed
Wang, X, Zhang, L, Lei, Y, Liu, X, Zhou, X, Liu, Y, Wang, M, Yang, L, Zhang, L, Fan, S and Xie, P (2014) Meta-analysis of infectious agents and depression. Scientific Reports 4, 4530.CrossRefGoogle ScholarPubMed
Wang, AW, Avramopoulos, D, Lori, A, Mulle, J, Conneely, K, Powers, A, Duncan, E, Almli, L, Massa, N, McGrath, J, Schwartz, AC, Goes, FS, Weng, L, Wang, R, Yolken, R, Ruczinski, I, Gillespie, CF, Jovanovic, T, Ressler, K, Pulver, AE and Pearce, BD (2019) Genome-wide association study in two populations to determine genetic variants associated with Toxoplasma gondii infection and relationship to schizophrenia risk. Progress in Neuro-Psychopharmacology & Biological Psychiatry 92, 133–147.CrossRefGoogle ScholarPubMed
Weiss, LM and Dubey, JP (2009) Toxoplasmosis: a history of clinical observations. International Journal for Parasitology 39, 895–901.Google ScholarPubMed
Wu, TY, Majeed, A and Kuo, KN (2010) An overview of the healthcare system in Taiwan. London Journal of Primary Care (Abingdon) 3, 115–119.CrossRefGoogle ScholarPubMed
Ybanez, RHD, Busmeon, CGR, Viernes, ARG, Langbid, JZ, Nuevarez, JP, Ybanez, AP and Nishikawa, Y (2019) Endemicity of Toxoplasma infection and its associated risk factors in Cebu, Philippines. PLoS One 14, e0217989.10.1371/journal.pone.0217989CrossRefGoogle ScholarPubMed
Yolken, R, Torrey, EF and Dickerson, F (2017) Evidence of increased exposure to Toxoplasma gondii in individuals with recent onset psychosis but not with established schizophrenia. PLoS Neglected Tropical Diseases 11, e0006040.CrossRefGoogle Scholar
Zulpo, DL, Sammi, AS, Dos Santos, JR, Sasse, JP, Martins, TA, Minutti, AF, Cardim, ST, de Barros, LD, Navarro, IT and Garcia, JL (2018) Toxoplasma gondii: a study of oocyst re-shedding in domestic cats. Veterinary Parasitology 249, 17–20.CrossRefGoogle ScholarPubMed