Abstract
We sought to determine the association between Toxoplasma gondii (T. gondii) infection of the central nervous system and suicide in a sample of decedents in Mexico City. One hundred and forty-seven decedents (87 who committed suicide and 60 who did not commit suicide) were studied. Brain tissues (amygdala and prefrontal cortex) of decedents were examined for the detection of T. gondii using immunohistochemistry. Detection of T. gondii was positive in 7 (8.0%) of the 87 cases (6 found in prefrontal cortex and one in amygdala), and in one (1.7%) of the 60 controls (found in prefrontal cortex) (OR: 5.16; 95% CI: 0.61–43.10; P = 0.14). Results suggest that T. gondii infection in brain is not associated with suicide. Further studies to confirm this finding are needed.
Introduction
Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan [1]. This successful parasite cycles between definitive felid hosts and a broad range of intermediate hosts including humans [2]. Toxoplasmosis, the disease caused by T. gondii, is one of the most common parasitic infections of man and other warm-blooded animals [3]. It is estimated that 30% of the global human population is chronically infected by T. gondii [4]. In addition, T. gondii is a major problem for health economics in many countries [5]. Transmission of T. gondii usually occurs by ingestion of food or water that is contaminated with oocysts shed by cats or by eating undercooked or raw meat containing tissue cysts [6]. Primary infection with T. gondii during pregnancy may lead to congenital toxoplasmosis [7]. Transmission of T. gondii may also occurs by organ transplantation [8], or blood transfusion [9]. Toxoplasmosis has a wide spectrum of clinical outcomes [10]. Infection with T. gondii is generally asymptomatic but some patients experience lymphadenitis [11], ocular disease or, in immunocompromised patients, a life-threatening encephalitis [6]. T. gondii is able to persist in the central nervous system in a variety of hosts including humans [12]. After infection, T. gondii persists as intraneuronal cysts that are controlled, but not eliminated by the immune system [13]. This parasite can modify the structure and function of neurons leading to specific behavioral changes in the host [14]. Neuroinflammation associated with T. gondii infection may contribute to depression and suicidal behavior [15]. In murine models, researchers have shown that type 1 innate lymphoid cells regulate the onset of T. gondii-induced neuroinflammation [16], and the immunoproteasome subunits LMP2, LMP7 and MECL-1 are crucial along the induction of cerebral toxoplasmosis [17]. Infection with T. gondii has been associated with schizophrenia [18, 19], mixed anxiety and depressive disorder [20], generalized anxiety disorder, obsessive-compulsive disorder [21], and aggression and impulsivity [22]. Furthermore, seropositivity to T. gondii has been associated with suicidal behavior. Several studies have demonstrated a higher frequency of T. gondii exposure in suicide attempters than in controls [23–25]. However, other studies have reported no association between T. gondii exposure and suicide attempts [26–27]. These studies have searched for the link between T. gondii exposure and suicidal behavior in live persons, but the link between T. gondii infection and completed suicide has been scarcely studied. Therefore, in the present study we sought to determine the association between T. gondii infection of the central nervous system and suicide.
Materials and methods
Study design
An age- and gender-matched case-control study was performed.
Study population
One hundred and forty-seven decedents of whom 87 had committed suicide (cases) and 60 had not died by suicide (controls) were included in the study. Cases were enrolled at the “Instituto de Ciencias Forenses” in Mexico City, Mexico from November 2015 to December 2016, whereas controls were enrolled at the same forensic Institute from January to December 2016. Decedent cases were included in the study if they had a forensic diagnosis of completed suicide. Age and gender were not restrictive criteria for enrollment. Decedent controls were included in the study if they had a forensic diagnosis of death by causes other than suicide. Of the 87 decedent cases studied, 67 were male and 20 were females. They were 10–90 years old (mean age: 34.8 ± 17.4 years). Of the 60 decedent controls studied, 49 were males and 11 were females. They were 8–75 years old (mean age: 31.7 ± 14.8 years). No statistically significant difference in gender (P = 0.49) or age (P = 0.25) between cases and controls was found. Autopsies were performed >12 h after death.
Detection of T. gondii in brain by immunohistochemistry
Brain tissues (amygdala and prefrontal cortex) of decedents were examined for detection of T. gondii using immunohistochemistry. Brain tissues were formalin-fixed, and paraffin-embedded sections were examined using the Tinto Detector Immuno DNA System equipment (Bio SB, Santa Barbara, CA, USA) and Digital Pressure Cooker, Model PC-2000 (Bio SB). The Mouse/Rabbit Immunodetector HRP/DAB (Bio SB) was used for immunohistochemistry. Paraffin-embedded 2 µm tissue sections were used for immunostaining. We used the primary antibody “T. gondii, rabbit polyclonal” (Bio SB) and the positive control “T. gondii positive control slides” (Bio SB). All assays were performed according to the manufacturer's instructions. No information about the specificity of the polyclonal antibodies was included in the package insert. Slides were read by an anatomopathologist (author LFSA). A brown coloration of cysts or tachyzoites structural forms were considered positive results.
Statistical analysis
The software Epi Info version 7 and Microsoft Excel were used for the statistical analysis. Age of cases and controls were compared with the Student's t-test. The Fisher’s exact test was used to compare the frequencies of T. gondii in brain tissues between the groups. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Statistical significance was set at a P value <0.05.
Ethical aspects
This project was approved by the Ethical Committee of the “Instituto de Ciencias Forenses” in Mexico City (Reference Number: CEI-014-2016).
Results
Detection of T. gondii by immunohistochemistry was positive in 7 (8.0%) of the 87 decedent cases (6 found in prefrontal cortex and one in amygdala). Figure 1 shows T. gondii in brain (found in prefrontal cortex, case No. 25). Detection of T. gondii by immunohistochemistry was positive in 1 (1.7%) of the 60 decedent controls (found in prefrontal cortex, Fig. 2). No difference in the prevalence of T. gondii infection in brain by immunohistochemistry in cases and controls was found (OR: 5.16; 95% CI: 0.61–43.10; P = 0.14). Table 1 shows a stratification by age and gender and prevalence of T. gondii infection in brain by immunohistochemistry in cases and controls. No difference in prevalence rates of T. gondii infection in brain with respect to gender and age between cases and controls was found.
T. gondii cysts in brain tissue (prefrontal cortex, case No. 25)
Citation: European Journal of Microbiology and Immunology 13, 3; 10.1556/1886.2023.00033
Free T. gondii tachyzoites in brain tissue (prefrontal cortex, control No. 8)
Citation: European Journal of Microbiology and Immunology 13, 3; 10.1556/1886.2023.00033
Association between prevalence of T. gondii infection in the brain by immunohistochemistry and suicide: a stratification by gender and age groups
| Characteristic | Cases | Controls | 95% Confidence interval | P value | |||||
| No. tested | Positivity to T. gondii | No. tested | Positivity to T. gondii | ||||||
| No. | % | No. | % | OR | |||||
| Gender | |||||||||
| Male | 67 | 5 | 7.5 | 49 | 1 | 2.0 | 3.87 | 0.43–34.24 | 0.39 |
| Female | 20 | 2 | 10.0 | 11 | 0 | 0.0 | – | – | 0.52 |
| Age (years) | |||||||||
| ≤30 | 42 | 1 | 2.4 | 36 | 1 | 2.8 | 0.85 | 0.05–14.15 | 1.00 |
| 31–50 | 30 | 5 | 16.7 | 16 | 0 | 0.0 | – | – | 0.14 |
| >50 | 15 | 1 | 6.7 | 8 | 0 | 0.0 | – | – | 1.00 |
| All | 87 | 7 | 8.0 | 60 | 1 | 1.7 | 5.16 | 0.61–43.10 | 0.14 |
Discussion
The link between exposure to T. gondii and suicidal behavior has been examined in a number of epidemiological studies [23–28]. Those studies have been based on serological analysis of anti-T. gondii antibodies in live persons. However, to the best of our knowledge, studies of the link between T. gondii infection of the brain and suicide using an age- and gender-matched case-control study design of decedents have not been reported. Therefore, in the present study, we assessed the association between T. gondii infection of the brain and completed suicide in decedents received for postmortem examinations in a forensic institute in Mexico City. Controls were similar to cases with respect to age, gender, and forensic center. Our approach was examining the infection with T. gondii in two sites (prefrontal cortex and amygdala) of the brain of decedents using immunohistochemistry. We found that persons who died by suicide had a somewhat higher, but not statistically significant, prevalence of T. gondii infection of the brain detected by immunohistochemistry than persons who died by causes other than suicide. Our findings thus suggest that infection with T. gondii in the central nervous system is not associated with completed suicide. We are not aware of another study about the association of suicide and T. gondii infection in brain detected by immunohistochemistry and therefore, we cannot compare our results with others of similar studies. There are few studies that have linked completed suicide to T. gondii seroprevalence rates. In a study about the seroprevalence of T. gondii infection in people who died due to sudden dead in Poland, a significantly higher T. gondii seroprevalence in suicide cases aged 38–58 years than in controls was found [29]. Suicide rates were positively associated with T. gondii seroprevalence rates in postmenopausal women of 20 European countries [30]. Comparison of results of such studies with the ones found in our study should be interpreted with care since different biological samples among the studies were analyzed. We examined prefrontal cortex and amygdala because these brain sites have been found consistently infected with T. gondii in experimentally infected mice [31, 32]. In addition, these brain sites are involved in clinical outcomes of T. gondii infection. For instance, infection of cortex and amygdala resulted in memory impairment in mice [33], and infection in amygdala was linked to reduced predator aversion in rats [34]. Furthermore, the amygdala and prefrontal cortex form a circuit implicated in emotion regulation, the pathogenesis of major depressive disorder, and might be related to the pathogenesis of suicidal behavior since structural and functional abnormalities in these brain sites were demonstrated in patients with major depressive disorder and suicide attempts [35]. Little is known about the distribution of T. gondii in brain in humans using immunohistochemistry. We selected a sample of prefrontal cortex because the frontal lobe of brain has been successfully used to detect T. gondii in humans by immunohistochemistry [36]. T. gondii can also be found in choroid plexus by immunohistochemistry [36]. In a study of postmortem examinations of 17 AIDS patients with cerebral toxoplasmosis, choroid plexus infection was found in 53% of all cases by immunohistochemistry [37]. The precise location of T. gondii in brain in humans is limited, and a study of 102 autopsy cases on the presence of parasite DNA in four regions of the brain showed no specific distribution [38]. The choroid plexus might be an important location for detection of T. gondii. Experiments in mice have shown a close interaction between T. gondii infection at the choroid plexus and the impairment of the blood-cerebrospinal fluid barrier function indicating that infection-related neuroinflammation is initiated in the choroid plexus [39]. In a recent study of decedents, we found no association between completed suicide and the presence of anti-T. gondii antibodies in serum [40]. In the present study, we assessed this association beyond seropositivity by analyzing the presence of T. gondii directly in the central nervous system using immunohistochemistry in brain samples. To the best of our knowledge, this strategy has not been used in case-control studies of suicide decedents. In a cross-sectional study of decedents who committed suicide, we found an association between a history of depression and T. gondii infection in brain using immunohistochemistry [41]. Therefore, it is possible that the association between T. gondii infection in brain and completed suicide, albeit no currently observed in general in the present study, might be found in subsets of decedents with a history of clinical conditions including depression. The frequency of T. gondii infection in brain of decedents by immunohistochemistry found in the present study is lower than the 31% T. gondii seroprevalence reported in the population in Mexico City by indirect immunofluorescence [42].
We cannot rule out a link between suicide and T. gondii infection because our study have some limitations: 1) the sample size was small; 2) we examined only two brain sites by immunohistochemistry; and 3) we did not use other laboratory tests for increasing the sensitivity of detection of T. gondii infection in brain including molecular assays. Therefore, the lack of association between completed suicide and infection with T. gondii in brain found in our study should be confirmed in other studies with large sample sizes, examination of several brain sites, and using a diversity of tests for detection of T. gondii in brain. In addition, studies using not only qualitative tests but also quantitative tests for detection of T. gondii in brain to determine the association between suicide and T. gondii infection should be conducted.
Conclusions
Results suggest that T. gondii infection in brain is not associated with suicide. Further studies to confirm this finding are needed.
Funding
This research study was funded by Juárez University of Durango State, Mexico.
Authors contributions
LAML and FGD obtained samples and data of the study population. LFSA read the immunohistochemistry slices. EIAS performed the immunohistochemistry tests. JHT and LFSA obtained funding. JHT, ARS, MAS, ASA and CAE performed the data analysis. CAE performed study concept and design, laboratory tests, analysis and interpretation of data, statistical analysis, and wrote the manuscript.
Conflicts of interest
The authors declare that no conflict of interest exists.
References
- 1.↑
Liu Q, Wang ZD, Huang SY, Zhu XQ. Diagnosis of toxoplasmosis and typing of Toxoplasma gondii. Parasit Vectors. 2015;8:292. https://doi.org/10.1186/s13071-015-0902-6.
- 2.↑
Melchor SJ, Ewald SE. Disease tolerance in toxoplasma infection. Front Cell Infect Microbiol. 2019;9:185. https://doi.org/10.3389/fcimb.2019.00185.
- 3.↑
Hill D, Dubey JP. Toxoplasma gondii: transmission, diagnosis and prevention. Clin Microbiol Infect. 2002;8(10):634–40. https://doi.org/10.1046/j.1469-0691.2002.00485.x.
- 4.↑
Zhao XY, Ewald SE. The molecular biology and immune control of chronic Toxoplasma gondii infection. J Clin Invest. 2020;130(7):3370–3380. https://doi.org/10.1172/JCI136226.
- 5.↑
Pleyer U, Gross U, Schlüter D, Wilking H, Seeber F. Toxoplasmosis in Germany. Dtsch Arztebl Int. 2019;116(25):435–444. https://doi.org/10.3238/arztebl.2019.0435.
- 6.↑
Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet. 2004;363(9425):1965–76. https://doi.org/10.1016/S0140-6736(04)16412-X.
- 7.↑
Piao LX, Cheng JH, Aosai F, Zhao XD, Norose K, Jin XJ. Cellular immunopathogenesis in primary Toxoplasma gondii infection during pregnancy. Parasite Immunol. 2018;40(9):e12570. https://doi.org/10.1111/pim.12570.
- 8.↑
Galván-Ramírez ML, Sánchez-Orozco LV, Gutiérrez-Maldonado AF, Rodriguez Pérez LR. Does Toxoplasma gondii infection impact liver transplantation outcomes? A systematic review. J Med Microbiol. 2018;67(4):499–506. https://doi.org/10.1099/jmm.0.000694.
- 9.↑
Alvarado-Esquivel C, Sánchez-Anguiano LF, Hernández-Tinoco J, Ramos-Nevarez A, Estrada-Martínez S, Cerrillo-Soto SM, et al. Association between Toxoplasma gondii infection and history of blood transfusion: a case-control seroprevalence study. J Int Med Res. 2018;46(4):1626–1633. https://doi.org/10.1177/0300060518757928.
- 10.↑
Dard C, Fricker-Hidalgo H, Brenier-Pinchart MP, Pelloux H. Relevance of and new developments in serology for toxoplasmosis. Trends Parasitol. 2016;32(6):492–506. https://doi.org/10.1016/j.pt.2016.04.001.
- 11.↑
Pomares C, Holmes TH, Estran R, Press CJ, Ramirez R, Talucod J, et al. Cytokine profiles in patients with toxoplasmic lymphadenitis in the setting of pregnancy. Cytokine. 2017;90:14–20. https://doi.org/10.1016/j.cyto.2016.09.021.
- 12.↑
Mendez OA, Koshy AA. Toxoplasma gondii: entry, association, and physiological influence on the central nervous system. Plos Pathog. 2017;13(7):e1006351. https://doi.org/10.1371/journal.ppat.1006351.
- 13.↑
Blanchard N, Dunay IR, Schlüter D. Persistence of Toxoplasma gondii in the central nervous system: a fine-tuned balance between the parasite, the brain and the immune system. Parasite Immunol. 2015;37(3):150–8. https://doi.org/10.1111/pim.12173.
- 14.↑
Parlog A, Schlüter D, Dunay IR. Toxoplasma gondii-induced neuronal alterations. Parasite Immunol. 2015;37(3):159–70. https://doi.org/10.1111/pim.12157. PMID: 25376390.
- 15.↑
Kamal AM, Kamal AM, Abd El-Fatah AS, Rizk MM, Hassan EE. Latent toxoplasmosis is associated with depression and suicidal behavior. Arch Suicide Res. 2022 Apr-Jun;26(2):819–830. https://doi.org/10.1080/13811118.2020.1838368.
- 16.↑
Steffen J, Ehrentraut S, Bank U, Biswas A, Figueiredo CA, Hölsken O, et al. Type 1 innate lymphoid cells regulate the onset of Toxoplasma gondii-induced neuroinflammation. Cell Rep. 2022 Mar 29;38(13):110564. https://doi.org/10.1016/j.celrep.2022.110564.
- 17.↑
French T, Israel N, Düsedau HP, Tersteegen A, Steffen J, Cammann C, et al. The immunoproteasome subunits LMP2, LMP7 and MECL-1 are crucial along the induction of cerebral toxoplasmosis. Front Immunol. 2021 Apr 21;12:619465. https://doi.org/10.3389/fimmu.2021.619465.
- 18.↑
Yolken RH, Dickerson FB, Fuller Torrey E. Toxoplasma and schizophrenia. Parasite Immunol. 2009 Nov;31(11):706–15. https://doi.org/10.1111/j.1365-3024.2009.01131.x.
- 19.↑
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. https://doi.org/10.1016/j.parint.2010.12.003.
- 20.↑
Alvarado-Esquivel C, Sanchez-Anguiano LF, Hernandez-Tinoco J, Berumen-Segovia LO, Torres-Prieto YE, Estrada-Martinez S, et al. Toxoplasma gondii infection and mixed anxiety and depressive disorder: a Case-Control Seroprevalence Study in Durango, Mexico. J Clin Med Res. 2016;8(7):519–23. https://doi.org/10.14740/jocmr2576w.
- 21.↑
Akaltun İ, Kara SS, Kara T. The relationship between Toxoplasma gondii IgG antibodies and generalized anxiety disorder and obsessive-compulsive disorder in children and adolescents: a new approach. Nord J Psychiatry. 2018;72(1):57–62. https://doi.org/10.1080/08039488.2017.1385850.
- 22.↑
Cook TB, Brenner LA, Cloninger CR, Langenberg P, Igbide A, Giegling I, et al. "Latent" infection with Toxoplasma gondii: association with trait aggression and impulsivity in healthy adults. J Psychiatr Res. 2015;60:87–94. https://doi.org/10.1016/j.jpsychires.2014.09.019.
- 23.↑
Bak J, Shim SH, Kwon YJ, Lee HY, Kim JS, Yoon H, et al. The Association between suicide attempts and Toxoplasma gondii infection. Clin Psychopharmacol Neurosci. 2018;16(1):95–102. https://doi.org/10.9758/cpn.2018.16.1.95.
- 24.
Coryell W, Wilcox H, Evans SJ, Pandey GN, Jones-Brando L, Dickerson F, et al. Latent infection, inflammatory markers and suicide attempt history in depressive disorders. J Affect Disord. 2020;270:97–101. https://doi.org/10.1016/j.jad.2020.03.057.
- 25.
Sutterland AL, Kuin A, Kuiper B, van Gool T, Leboyer M, Fond G, et al. Driving us mad: the association of Toxoplasma gondii with suicide attempts and traffic accidents - a systematic review and meta-analysis. Psychol Med. 2019;49(10):1608–1623. https://doi.org/10.1017/S0033291719000813.
- 26.↑
Sari SA, Kara A. Association of suicide attempt with seroprevalence of Toxoplasma gondii in adolescents. J Nerv Ment Dis. 2019;207(12):1025–1030. https://doi.org/10.1097/NMD.0000000000001046.
- 27.
Alvarado-Esquivel C, Sánchez-Anguiano LF, Arnaud-Gil CA, López-Longoria JC, Molina-Espinoza LF, Estrada-Martínez S, et al. Toxoplasma gondii infection and suicide attempts: a case-control study in psychiatric outpatients. J Nerv Ment Dis. 2013;201(11):948–52. https://doi.org/10.1097/NMD.0000000000000037.
- 28.
Yucel H, Acikel SB, Senel S. An investigation into the association between latent toxoplasmosis and suicide attempts among adolescents. J Infect Dev Ctries. 2020;14(12):1437–1442. https://doi.org/10.3855/jidc.13632.
- 29.↑
Samojłowicz D, Borowska-Solonynko A, Gołab E. Prevalence of Toxoplasma gondii parasite infection among people who died due to sudden death in the capital city of Warsaw and its vicinity. Przegl Epidemiol. 2013;67(1):29–33, 115–8.
- 30.↑
Ling VJ, Lester D, Mortensen PB, Langenberg PW, Postolache TT. Toxoplasma gondii seropositivity and suicide rates in women. J Nerv Ment Dis. 2011;199(7):440–4. https://doi.org/10.1097/NMD.0b013e318221416e.
- 31.↑
Berenreiterová M, Flegr J, Kuběna AA, Němec P. The distribution of Toxoplasma gondii cysts in the brain of a mouse with latent toxoplasmosis: implications for the behavioral manipulation hypothesis. PLoS One. 2011;6(12):e28925. https://doi.org/10.1371/journal.pone.0028925.
- 32.↑
McConkey GA, Martin HL, Bristow GC, Webster JP. Toxoplasma gondii infection and behaviour - location, location, location? J Exp Biol. 2013;216(Pt 1):113–9. https://doi.org/10.1242/jeb.074153.
- 33.↑
Ihara F, Nishimura M, Muroi Y, Mahmoud ME, Yokoyama N, Nagamune K, et al. Toxoplasma gondii infection in mice impairs long-term fear memory consolidation through dysfunction of the cortex and amygdala. Infect Immun. 2016;84(10):2861–70. https://doi.org/10.1128/IAI.00217-16.
- 34.↑
Hari Dass SA, Vyas A. Toxoplasma gondii infection reduces predator aversion in rats through epigenetic modulation in the host medial amygdala. Mol Ecol. 2014;23(24):6114–22. https://doi.org/10.1111/mec.12888.
- 35.↑
Wang L, Zhao Y, Edmiston EK, Womer FY, Zhang R, Zhao P, et al. Structural and functional Abnormities of amygdala and prefrontal cortex in major depressive disorder with suicide attempts. Front Psychiatry. 2020;10:923. https://doi.org/10.3389/fpsyt.2019.00923.
- 36.↑
Alvarado-Esquivel C, Sánchez-Anguiano LF, Mendoza-Larios A, Hernández-Tinoco J, Pérez-Ochoa JF, Antuna-Salcido EI, et al. Prevalence of Toxoplasma gondii infection in brain and heart by immunohistochemistry in a hospital-based autopsy series in Durango, Mexico. Eur J Microbiol Immunol (Bp). 2015 Jun 18;5(2):143–9. https://doi.org/10.1556/1886.2015.00014.
- 37.↑
Falangola MF, Petito CK. Choroid plexus infection in cerebral toxoplasmosis in AIDS patients. Neurology. 1993 Oct;43(10):2035–40. https://doi.org/10.1212/wnl.43.10.2035.
- 38.↑
Samojłowicz D, Twarowska-Małczyńska J, Borowska-Solonynko A, Poniatowski ŁA, Sharma N, Olczak M. Presence of Toxoplasma gondii infection in brain as a potential cause of risky behavior: a report of 102 autopsy cases. Eur J Clin Microbiol Infect Dis. 2019 Feb;38(2):305–317. https://doi.org/10.1007/s10096-018-3427-z.
- 39.↑
Figueiredo CA, Steffen J, Morton L, Arumugam S, Liesenfeld O, Deli MA, et al. Immune response and pathogen invasion at the choroid plexus in the onset of cerebral toxoplasmosis. J Neuroinflammation. 2022 Jan 13;19(1):17. https://doi.org/10.1186/s12974-021-02370-1.
- 40.↑
Mendoza-Larios LA, García-Dolores F, Sánchez-Anguiano LF, Hernández-Tinoco J, Alvarado-Esquivel C. Association between suicide and Toxoplasma gondii seropositivity. Pathogens. 2021 Aug 27;10(9):1094. https://doi.org/10.3390/pathogens10091094.
- 41.↑
Alvarado-Esquivel C, Mendoza-Larios LA, García-Dolores F, Sánchez-Anguiano LF, Antuna-Salcido EI, Hernández-Tinoco J, et al. Association between Toxoplasma gondii infection in brain and a history of depression in suicide decedents: a cross-sectional study. Pathogens. 2021 Oct 13;10(10):1313. https://doi.org/10.3390/pathogens10101313.
- 42.↑
Velasco-Castrejón O, Salvatierra-Izaba B, Valdespino JL, Sedano-Lara AM, Galindo-Virgen S, Magos C, et al. Seroepidemiología de la toxoplasmosis en México [Seroepidemiology of toxoplasmosis in Mexico]. Salud Publica Mex. 1992 Mar-Apr;34(2):222–9.
