La asociación entre Toxoplasma gondii y la esquizofrenia: revisión narrativa de la evidencia seroepidemiológica
DOI:
https://doi.org/10.18004/mem.iics/1812-9528/2025.e23162501Palabras clave:
Toxoplasma gondii, esquizofrenia, seroprevalencia, infección crónicaResumen
La esquizofrenia es un trastorno neuropsiquiátrico complejo, cuya etiología involucra la interacción entre factores genéticos y ambientales. Dentro de estos últimos, la infección por Toxoplasma gondii ha sido propuesta como un posible factor de riesgo, debido a su capacidad para establecer infecciones latentes en el sistema nervioso central y modular funciones neuroinmunológicas. Esta revisión analiza la evidencia disponible sobre la relación entre T. gondii y la esquizofrenia en el contexto seroepidemiológico. Numerosos trabajos reportan una mayor seroprevalencia de anticuerpos IgG anti-T. gondii en pacientes con esquizofrenia en comparación con controles sanos, con variaciones regionales significativas. Asimismo, algunos estudios encuentran niveles de anticuerpos más elevados en pacientes, lo que sugiere una respuesta inmune más activa o persistente. Sin embargo, los resultados son inconsistentes, y varios estudios no logran demostrar asociaciones significativas. Esta heterogeneidad podría explicarse por diferencias metodológicas, factores sociodemográficos, variabilidad genética y comorbilidades infecciosas. Los datos respaldan parcialmente la hipótesis de que T. gondii actúa como un cofactor dentro de un modelo etiológico multifactorial. Se destaca la necesidad de investigaciones longitudinales y controladas que permitan clarificar la relación temporal y los mecanismos subyacentes.
Descargas
Referencias
1. American Psychiatric Association. Manual diagnóstico y estadístico de los trastornos mentales. 5ª ed. Madrid: Editorial Médica Panamericana; 2014.
2. Wahbeh MH, Avramopoulos D. Gene-Environment Interactions in Schizophrenia: A Literature Review. Genes (Basel). 2021; 12(12): 1850.
3. El Mouhawess A, Hammoud A, Zoghbi M, Hallit S, Haddad C, El Haddad K, et al. Relationship between Toxoplasma gondii seropositivity and schizophrenia in the Lebanese population: potential implication of genetic polymorphism of MMP-9. BMC Psychiatry. 2020; 20(1): 264.
4. Yuksel P, Alpay N, Babur C, Bayar R, Saribas S, Karakose AR, et al. The role of latent toxoplasmosis in the aetiopathogenesis of schizophrenia--the risk factor or an indication of a contact with cat? Folia Parasitol (Praha). 2010; 57(2): 121-8.
5. Hussein EAM, Khalifa H, Ramadan GK, Hassaan SH, Shaaban I, Farrag HMM. Seroprevalence of Toxoplasma gondii among patients with schizophrenia and bipolar disorder in Upper Egypt: a comparative study with a control group. Ann Parasitol. 2020; 66(2): 183-92.
6. Sullivan WJ, Jeffers V. Mechanisms of Toxoplasma gondii persistence and latency. FEMS Microbiol Rev. 2012; 36(3): 717-33.
7. Dubey JP. Toxoplasmosis - a waterborne zoonosis. Vet Parasitol. 2004; 126(1-2): 57-72.
8. Tenter AM, Heckeroth AR, Weiss LM. Toxoplasma gondii: from animals to humans. Int J Parasitol. 2000; 30(12-13): 1217-58.
9. Molan A, Nosaka K, Hunter M, Wang W. Global status of Toxoplasma gondii infection: systematic review and prevalence snapshots. Trop Biomed. 2019; 36(4): 898-925. [
10. Mendez OA, Koshy AA. Toxoplasma gondii: Entry, association, and physiological influence on the central nervous system. PLoS Pathog. 2017; 13(7): e1006351.
11. Torrey EF, Yolken RH. Toxoplasma gondii and Schizophrenia. Emerg Infect Dis. 2003; 9(11): 1375-80.
12. Parlog A, Schlüter D, Dunay IR. Toxoplasma gondii‐induced neuronal alterations. Parasite Immunol. 2015; 37(3): 159-70.
13. Morais FB, Arantes TEFE, Muccioli C. Seroprevalence and Manifestations of Ocular Toxoplasmosis in Patients with Schizophrenia. Ocul Immunol Inflamm. 2019; 27(1): 134-7.
14. Guimarães AL, Richer Araujo Coelho D, Scoriels L, Mambrini J, Ribeiro do Valle Antonelli L, Henriques P, et al. Effects of Toxoplasma gondii infection on cognition, symptoms, and response to digital cognitive training in schizophrenia. Schizophr. 2022; 8(1): 104.
15. Rosado D, Intriago B, Loor E, Alcívar F, Avila J, Sotomayor M, et al. Associations between Toxoplasma gondii seropositivity and psychopathological manifestations in schizophrenic patients: A single-center study from Ecuador. PLOS ONE. 2024; 19(2): e0297523.
16. Alvarado-Esquivel C, Alanis-Quiñones OP, Arreola-Valenzuela MA, Rodríguez-Briones A, Piedra-Nevarez LJ, Duran-Morales E, et al. Seroepidemiology of Toxoplasma gondii infection in psychiatric inpatients in a northern Mexican city. BMC Infect Dis. 2006; 6: 178.
17. Alvarado-Esquivel C, Urbina-Álvarez JD, Estrada-Martínez S, Torres-Castorena A, Molotla-de-León G, Liesenfeld O, et al. Toxoplasma gondii infection and schizophrenia: a case control study in a low Toxoplasma seroprevalence Mexican population. Parasitol Int. 2011; 60(2): 151-5.
18. Niebuhr DW, Millikan AM, Cowan DN, Yolken R, Li Y, Weber NS. Selected infectious agents and risk of schizophrenia among U.S. military personnel. Am J Psychiatry. 2008; 165(1): 99-106.
19. Bamne M, Wood J, Chowdari K, Watson AM, Celik C, Mansour H, et al. Evaluation of HLA polymorphisms in relation to schizophrenia risk and infectious exposure. Schizophr Bull. 2012; 38(6): 1149-54.
20. Yolken R, Torrey EF, Dickerson F. Evidence of increased exposure to Toxoplasma gondii in individuals with recent onset psychosis but not with established schizophrenia. PLoS Negl Trop Dis. 2017; 11(11): e0006040.
21. Kezai AM, Lecoeur C, Hot D, Bounechada M, Alouani ML, Marion S. Association between schizophrenia and Toxoplasma gondii infection in Algeria. Psychiatry Res. 2020; 291: 113293.
22. Esshili A, Thabet S, Jemli A, Trifa F, Mechri A, Zaafrane F, et al. Toxoplasma gondii infection in schizophrenia and associated clinical features. Psychiatry Res. 2016; 245: 327-32.
23. Tedla Y, Shibre T, Ali O, Tadele G, Woldeamanuel Y, Asrat D, et al. Serum antibodies to Toxoplasma gondii and Herpesvidae family viruses in individuals with schizophrenia and bipolar disorder: a case-control study. Ethiop Med J. 2011; 49(3): 211-20.
24. Ansari-Lari M, Farashbandi H, Mohammadi F. Association of Toxoplasma gondii infection with schizophrenia and its relationship with suicide attempts in these patients. Trop Med Int Health. 2017; 22(10): 1322-7.
25. Hamidinejat H, Ghorbanpoor M, Hosseini H, Alavi SM, Nabavi L, Jalali MH, et al. Toxoplasma gondii infection in first-episode and inpatient individuals with schizophrenia. Int J Infect Dis. 2010; 14(11): e978-81. [
26. Banihashem SS, Yousefi Saber F, Motazedian S, Mardani M, Shamsi A, Nazari M, et al. Serologic evaluation of cytomegalovirus (CMV), Toxoplasma gondii and Brucella in schizophrenia patients. Caspian J Intern Med. 2023; 14(3): 560-6.
27. Al-Hussainy NH, Al-saedi AM, Al-lehaibi JH, Al-lehaibi YA, Al-Sehli YM, Afifi MA. Serological evidences link toxoplasmosis with schizophrenia and major depression disorder. J Microsc Ultrastruct. 2015; 3(3): 148-53.
28. Omar A, Bakar OC, Adam NF, Osman H, Osman A, Suleiman AH, et al. Seropositivity and serointensity of Toxoplasma gondii antibodies and DNA among patients with schizophrenia. Korean J Parasitol. 2015; 53(1): 29-34.
29. Emelia O, Amal RN, Ruzanna ZZ, Shahida H, Azzubair Z, Tan KS, et al. Seroprevalence of anti-Toxoplasma gondii IgG antibody in patients with schizophrenia. Trop Biomed. 2012; 29(1): 151-9.
30. Park MH, Kwon YJ, Jeong HY, Lee HY, Hwangbo Y, Yoon HJ, et al. Association between Intracellular Infectious Agents and Schizophrenia. Clin Psychopharmacol Neurosci. 2012; 10(2): 117-23.
31. Wang HL, Wang GH, Li QY, Shu C, Jiang MS, Guo Y. Prevalence of Toxoplasma infection in first-episode schizophrenia and comparison between Toxoplasma-seropositive and Toxoplasma-seronegative schizophrenia. Acta Psychiatr Scand. 2006; 114(1): 40-8.
32. Xu F, Ma X, Zhu Y, Sutterland A, Cheng R, Miao S, et al. Effects of Toxoplasma gondii infection and schizophrenia comorbidity on serum lipid profile: A population retrospective study from Eastern China. Microb Pathog. 2020; 149: 104587.
33. Abramova O, Zorkina Y, Goncharov D, Abbazova E, Baranets M, Berdalin A, et al. Association of neurobiological and immune serum biomarkers with Toxoplasma gondii infection in patients with schizophrenia. Parasitol Res. 2025; 124(5): 53.
34. Karabulut N, Bilgiç S, Gürok MG, Karaboğa F. Is there any role of latent toxoplasmosis in schizophrenia disease? J Chin Med Assoc. 2015; 78(9): 533-7.
35. Cetinkaya Z, Yazar S, Gecici O, Namli MN. Anti-Toxoplasma gondii antibodies in patients with schizophrenia--preliminary findings in a Turkish sample. Schizophr Bull. 2007; 33(3): 789-91.
36. Tamer GS, Dundar D, Yalug I, Caliskan S, Yazar S, Aker A. The schizophrenia and Toxoplasma gondii connection: infectious, immune or both? Adv Ther. 2008; 25(7): 703-9.
37. Fond G, Boyer L, Schürhoff F, Berna F, Godin O, Bulzacka E, et al. Latent toxoplasma infection in real-world schizophrenia: Results from the national FACE-SZ cohort. Schizophrenia Research. 2018; 201: 373-80.
38. Hamdani N, Daban-Huard C, Lajnef M, Richard JR, Delavest M, Godin O, et al. Relationship between Toxoplasma gondii infection and bipolar disorder in a French sample. J Affect Disord. 2013; 148(2-3): 444-8.
39. Hinze-Selch D, Däubener W, Eggert L, Erdag S, Stoltenberg R, Wilms S. A controlled prospective study of toxoplasma gondii infection in individuals with schizophrenia: beyond seroprevalence. Schizophr Bull. 2007; 33(3): 782-8.
40. Yolken RH, Bachmann S, Ruslanova I, Lillehoj E, Ford G, Torrey EF, et al. Antibodies to Toxoplasma gondii in individuals with first-episode schizophrenia. Clin Infect Dis. 2001; 32(5): 842-4.
41. Grada S, Mihu AG, Petrescu C, Suciu O, Marincu I, Lupu MA, et al. Toxoplasma gondii Infection in Patients with Psychiatric Disorders from Western Romania. Medicina (Kaunas). 2022; 58(2): 208.
42. Stepanova EV, Kondrashin AV, Sergiev VP, Morozova LF, Turbabina NA, Maksimova MS, et al. Toxoplasmosis and mental disorders in the Russian Federation (with special reference to schizophrenia). PLoS One. 2019; 14(7): e0219454.
43. Holub D, Flegr J, Dragomirecká E, Rodriguez M, Preiss M, Novák T, et al. Differences in onset of disease and severity of psychopathology between toxoplasmosis-related and toxoplasmosis-unrelated schizophrenia. Acta Psychiatr Scand. 2013; 127(3): 227-38.
44. Sugden K, Moffitt TE, Pinto L, Poulton R, Williams BS, Caspi A. Is Toxoplasma Gondii Infection Related to Brain and Behavior Impairments in Humans? Evidence from a Population-Representative Birth Cohort. PLoS One. 2016; 11(2): e0148435.
45. Liu T, Gao P, Bu D, Liu D. Association between Toxoplasma gondii infection and psychiatric disorders: a cross-sectional study in China. Sci Rep. 2022; 12(1): 15092.
46. Chen X, Chen B, Hou X, Zheng C, Yang X, Ke J, et al. Association between Toxoplasma gondii infection and psychiatric disorders in Zhejiang, Southeastern China. Acta Trop. 2019; 192: 82-6.
47. Grada S, Mihu AG, Oatis DA, Marc CC, Chicea LM, Petrescu C, et al. Seroprevalence and Associated Risk Factors of Toxoplasma gondii in Patients Diagnosed with Schizophrenia: A Case–Control Cross Sectional Study. Biomedicines. 2024; 12(5): 998.
48. Ibrahim Ali M, Abdel Gawad Mousa Ismail M, Abd-Elftah Abd-Allah G, Abdel-Latif M, Mohamed Shaapan R, Salah H, et al. Toxoplasmosis in Schizophrenic Patients: Immune-diagnosis and Serum Dopamine Level. Pak J Biol Sci. 2020; 23(9): 1131-7.
49. Rovira P, Gutiérrez B, Sorlózano-Puerto A, Gutiérrez-Fernández J, Molina E, Rivera M, et al. Toxoplasma gondii Seropositivity Interacts with Catechol-O-methyltransferase Val105/158Met Variation Increasing the Risk of Schizophrenia. Genes (Basel). 2022; 13(6): 1088.
50. Burgdorf KS, Trabjerg BB, Pedersen MG, Nissen J, Banasik K, Pedersen OB, et al. Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders. Brain Behav Immun. 2019; 79: 152-8.
51. Akgül Ö, Demirel ÖF, Aksoy Poyraz C, Tanriöver Aydin E, Uysal N, Bulu E, et al. Toxoplasma gondii infection by serological and molecular methods in schizophrenia patients with and without suicide attempts: An age-sex-matched case-control study. Int J Clin Pract. 2021; 75(8): e14449.
52. Alvim PHP, Cavalari VC, Bianchini AJ, Frizon GF, Ferreira GM, Savian HFH, et al. Toxoplasmosis infection and schizophrenia: Elevated IgM reactivity index as a predictor of symptom worsening in chronic schizophrenia. Schizophr Res. 2025; 278: 20-5.
53. Lori A, Avramopoulos D, Wang AW, Mulle J, Massa N, Duncan EJ, et al. Polygenic risk scores differentiate schizophrenia patients with toxoplasma gondii compared to toxoplasma seronegative patients. Compr Psychiatry. 2021; 107: 152236.
54. Krause D, Matz J, Weidinger E, Wagner J, Wildenauer A, Obermeier M, et al. The association of infectious agents and schizophrenia. World J Biol Psychiatry. 2010; 11(5): 739-43.
55. Avramopoulos D, Pearce BD, McGrath J, Wolyniec P, Wang R, Eckart N, et al. Infection and Inflammation in Schizophrenia and Bipolar Disorder: A Genome Wide Study for Interactions with Genetic Variation. PLOS ONE. 2015; 10(3): e0116696.
56. Lin HA, Chien WC, Huang KY, Chung CH, Chen LC, Lin HC, et al. Infection with Toxoplasma gondii increases the risk of psychiatric disorders in Taiwan: a nationwide population-based cohort study. Parasitology. 2020; 147(13): 1577-86.
57. Pedersen MG, Stevens H, Pedersen CB, Nørgaard-Pedersen B, Mortensen PB. Toxoplasma infection and later development of schizophrenia in mothers. Am J Psychiatry. 2011; 168(8): 814-21.
58. Li Y, Weber NS, Fisher JA, Yolken RH, Cowan DN, Larsen RA, et al. Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel. Schizophr Res. 2013; 51(1): 36-42.
59. Brown AS, Schaefer CA, Quesenberry CP, Liu L, Babulas VP, Susser ES. Maternal Exposure to Toxoplasmosis and Risk of Schizophrenia in Adult Offspring. AJP. 2005; 162(4): 767-73.
60. Blomström A, Karlsson H, Wicks S, Yang S, Yolken RH, Dalman C. Maternal antibodies to infectious agents and risk for non-affective psychoses in the offspring--a matched case-control study. Schizophr Res. 2012; 140(1): 25-30.
61. Blomström Å, Gardner RM, Dalman C, Yolken RH, Karlsson H. Influence of maternal infections on neonatal acute phase proteins and their interaction in the development of non-affective psychosis. Transl Psychiatry. 2015; 5(2): e502.
62. Bachmann S, Schröder J, Bottmer C, Torrey EF, Yolken RH. Psychopathology in first-episode schizophrenia and antibodies to Toxoplasma gondii. Psychopathology. 2005; 38(2): 87-90.
63. Andreou D, Steen NE, Jørgensen KN, Ueland T, Wortinger LA, Mørch-Johnsen L, et al. Increased Herpes simplex virus 1, Toxoplasma gondii and Cytomegalovirus antibody concentrations in severe mental illness. Transl Psychiatry. 2024; 14: 498
64. Severance EG, Alaedini A, Yang S, Halling M, Gressitt KL, Stallings CR, et al. Gastrointestinal inflammation and associated immune activation in schizophrenia. Schizophr Res. 2012; 138(1): 48-53.
