Schizophrenia and toxoplasmosis: association with catatonic symptoms

Abstract

Introduction. The association between schizophrenia and toxoplasmosis has been demonstrated in a number of studies: the prevalence of schizophrenia is significantly higher in toxoplasmosis positive subjects than in those with T.gondii negative status. However, the clinical significance of this association remains poorly understood.

Objectives. To identify clinical phenomena that are typical for toxoplasmosis-associated (T.gondii seropositive) schizophrenia compared to Toxoplasma-seronegative schizophrenia.

Methods. A retrospective database analysis of serum samples from 105 inpatients with schizophrenia (ICD-10 code: F20; including 55 male patients; mean age of 27.4 ± 6.4 years) was carried out. The clinical examination involved a structured interview including ICD-10 and E. Bleuler’s criteria for schizophrenia and psychometric tests (Positive and Negative Scales of PANSS). Serum antibodies (IgG) to T.gondii were identified using ELISA. The statistical significance of any differences were evaluated using the non-parametric Mann-Whitney (U) and χ2 tests.

Results. The proportion of seropositive patients in the sample was 16.2%. Comparing schizophrenia patients, who were seropositive or seronegative for toxoplasmosis, there were no statistically significant differences for the mean total PANSS score, mean PANSS-P, PANSS-N or PANSS-G scores. For the majority of PANSS items, differences were also statistically insignificant, except for G5 and G6—mannerism and posturing. Seropositive patients had a higher score for this item than seronegative patients: 3.5 versus 2.1 points (U=389.5; р=0.001). Depression, on the contrary, was less pronounced in seropositive than seronegative patients: 1.4 versus 2.4 points (U=509.5; р=0.023). In addition, in seropositive patients, the frequency of symptoms such as mutism according to ICD-10 criteria for schizophrenia  was significantly higher (23.5% versus 3.4%, χ2=9.27, р=0.013), and the whole group of catatonic symptoms according to the E. Bleuler’s criteria for schizophrenia was higher (52.9% versus 28.4%, χ2=3.916, p = 0.048).

Conclusion. The association between a positive toxoplasmosis status in patients with schizophrenia and catatonic symptoms has been revealed for the first time and should be verified in larger studies.

Keywords

schizophrenia / toxoplasmosis / T.gondii / catatonia / Positive and Negative Syndrome Scale / PANSS

References

[1] Gutiérrez-Fernández J, Luna Del Castillo Jde D, Mañanes-González S, Carrillo-Ávila JA, Gutiérrez B, Cervilla JA, Sorlózano-Puerto A. Different presence of Chlamydia pneumoniae, herpes simplex virus type 1, human herpes virus 6, and Toxoplasma gondii in schizophrenia: meta-analysis and analytical study. Neuropsychiatr Dis Treat. 2015 Mar 27;11:843-52. doi: 10.2147/NDT.S79285. PMID: 25848282; PMCID: PMC4384747.

[2] Burgdorf KS, Trabjerg BB, Pedersen MG, Nissen J, Banasik K, Pedersen OB, Sørensen E, Nielsen KR, Larsen MH, Erikstrup C, Bruun-Rasmussen P, Westergaard D, Thørner LW, Hjalgrim H, Paarup HM, Brunak S, Pedersen CB, Torrey EF, Werge T, Mortensen PB, Yolken RH, Ullum H. Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders. Brain Behav Immun. 2019 Jul;79:152-158. doi: 10.1016/j.bbi.2019.01.026. Epub 2019 Jan 29. PMID: 30685531.

[3] Torrey EF, Bartko JJ, Lun ZR, Yolken RH. Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis. Schizophr Bull. 2007 May;33(3):729-36. doi: 10.1093/schbul/sbl050. Epub 2006 Nov 3. PMID: 17085743; PMCID: PMC2526143.

[4] Torrey EF, Bartko JJ, Yolken RH. Toxoplasma gondii and other risk factors for schizophrenia: an update. Schizophr Bull. 2012 May;38(3):642-7. doi: 10.1093/schbul/sbs043. Epub 2012 Mar 23. PMID: 22446566; PMCID: PMC3329973.

[5] Dickerson F, Boronow J, Stallings C, Origoni A, Yolken R. Toxoplasma gondii in individuals with schizophrenia: association with clinical and demographic factors and with mortality. Schizophr Bull. 2007 May;33(3):737-40. doi: 10.1093/schbul/sbm005. Epub 2007 Feb 20. PMID: 17314085; PMCID: PMC2526149.

[6] Celik T, Kartalci S, Aytas O, Akarsu GA, Gozukara H, Unal S. Association between latent toxoplasmosis and clinical course of schizophrenia - continuous course of the disease is characteristic for Toxoplasma gondii-infected patients. Folia Parasitol (Praha). 2015 Jan 1;62:2015.015. doi: 10.14411/fp.2015.015. PMID: 25960559.

[7] Stepanova EV, Kondrashin AV, Sergiev VP, Morozova LF, Turbabina NA, Maksimova MS, Romanov DV, Kinkulkina MA, Lazareva AV, Morozov EN. Toxoplasmosis and mental disorders in the Russian Federation (with special reference to schizophrenia). PLoS One. 2019 Jul 10;14(7):e0219454. doi: 10.1371/journal.pone.0219454. PMID: 31291336; PMCID: PMC6636601.

[8] Amminger GP, McGorry PD, Berger GE, Wade D, Yung AR, Phillips LJ, Harrigan SM, Francey SM, Yolken RH. Antibodies to infectious agents in individuals at ultra-high risk for psychosis. Biol Psychiatry. 2007 May 15;61(10):1215-7. doi: 10.1016/j.biopsych.2006.09.034. Epub 2007 Jan 3. PMID: 17207471.

[9] Holub D, Flegr J, Dragomirecká E, Rodriguez M, Preiss M, Novák T, Čermák J, Horáček J, Kodym P, Libiger J, Höschl C, Motlová LB. Differences in onset of disease and severity of psychopathology between toxoplasmosis-related and toxoplasmosis-unrelated schizophrenia. Acta Psychiatr Scand. 2013 Mar;127(3):227-38. doi:10.1111/acps.12031. Epub 2012 Nov 5. PMID: 23126494.

[10] Wang HL, Wang GH, Li QY, et al. Prevalence of Toxoplasma infection in first-episode schizophrenia and comparison between Toxoplasma-seropositive and Toxoplasma-seronegative schizophrenia. Acta Psychiatrica Scandinavica. 2006 Jul;114(1):40-48. DOI: 10.1111/j.1600-0447.2006.00780.x.

[11] Bleuler E. Dementia praecox oder Gruppe der Schizophrenien. Handbuch der Psychiatrie (Herausgeb. von G. Aschaffenburg). Spezieller Teil. 4. Abteilung, 1. Haelfte. Leipzig und Wien: Franz Deuticke; 1911.

[12] Kay SR, Opler LA, Lindenmayer JP. The Positive and Negative Syndrome Scale (PANSS): rationale and standardisation. Br J Psychiatry Suppl. 1989 Nov;(7):59-67. PMID: 2619982.

[13] Mosolov SN. Shkaly psihometricheskoj ocenki simptomatiki shizofrenii i koncepcija pozitivnyh i negativnyh rasstrojstv [Scales for psychometric evaluation of symptoms in schizophrenia and the concept of positive and negative disorders]. Moscow: Moscow; 2001. 238 p. Russian.

[14] KliuevaTD, SamobumskaiaEN, TikhovskaiaTM. Psikhozypri toksoplazmoze[Psychosesintoxoplasmosis]. ZhNevropatolPsikhiatrImS SKorsakova. 1966;66(3):454-8. Russian. PMID: 6000444.

[15] Mikhalev PV, Genaĭlo SP, Mikhaleva LV. Ob oneĭroidnykh i oniricheskikh sostoianiiakh pri tserebral'nom toksoplazmoze [Oneiroid and oneiric states in cerebral toxoplasmosis]. Zh Nevropatol Psikhiatr Im S S Korsakova. 1978;78(2):251-5. Russian. PMID: 636721.

[16] Holub D, Flegr J, Dragomirecká E, Rodriguez M, Preiss M, Novák T, Čermák J, Horáček J, Kodym P, Libiger J, Höschl C, Motlová LB. Differences in onset of disease and severity of psychopathology between toxoplasmosis-related and toxoplasmosis-unrelated schizophrenia. Acta Psychiatr Scand. 2013 Mar;127(3):227-38. doi:10.1111/acps.12031. Epub 2012 Nov 5. PMID: 23126494.

[17] Esshili A, Thabet S, Jemli A, Trifa F, Mechri A, Zaafrane F, Gaha L, Juckel G, Babba H, Bel Hadj Jrad B. Toxoplasma gondii infection in schizophrenia and associated clinical features. Psychiatry Res. 2016 Nov 30;245:327-332. doi: 10.1016/j.psychres.2016.08.056. Epub 2016 Aug 22. PMID: 27573055.

[18] HoracekJ, FlegrJ, TinteraJ, VerebovaK, SpanielF, NovakT, Brunovsky M, Bubenikova-ValesovaV, HolubD, PalenicekT, HöschlC. Latent toxoplasmosisreducesgraymatterdensityinschizophreniabutnotincontrols: voxel-based-morphometry(VBM) study. WorldJBiolPsychiatry.2012Oct;13(7):501-9. doi: 10.3109/15622975.2011.573809. Epub2011May 23. PMID: 21599563.

[19] Flegr J, Preiss M, Klose J, Havlícek J, Vitáková M, Kodym P. Decreased level of psychobiological factor novelty seeking and lower intelligence in men latently infected with the protozoan parasite Toxoplasma gondii Dopamine, a missing link between schizophrenia and toxoplasmosis? Biol Psychol. 2003 Jul;63(3):253-68. doi: 10.1016/s0301-0511(03)00075-9. PMID: 12853170.

[20] Gaskell EA, Smith JE, Pinney JW, Westhead DR, McConkey GA. A unique dual activity amino acid hydroxylase in Toxoplasma gondii. PLoS One. 2009;4(3):e4801. doi: 10.1371/journal.pone.0004801. Epub 2009 Mar 11. PMID: 19277211; PMCID: PMC2653193.

[21] Schwarcz R, Hunter CA. Toxoplasma gondii and schizophrenia: linkage through astrocyte-derived kynurenic acid? Schizophr Bull. 2007 May;33(3):652-3. doi: 10.1093/schbul/sbm030. Epub 2007 Apr 13. PMID: 17434932; PMCID: PMC2526138.

[22] Smulevich AB, Briko NI, Andryushchenko AV, Romanov DV, Shuliak YA, Brazhnikov АY, Gerasimov AN, Melik-Pashaian AE, Mironova EV, Pushkarev DF. Komorbidnost' depressii i rasstroistv neaffektivnogo shizofrenicheskogo spektra: kliniko-epidemiologicheskoe issledovanie EDIP [Comorbidity of depression and nonaffective – schizophrenia spectrum disorders: the clinical-epidemiological study EDIP]. Zh Nevrol Psikhiatr Im S S Korsakova. 2015;115(11 Pt 2):6-19. Russian. doi: 10.17116/jnevro20151151126-19. PMID: 26978259.

RIGHTS & PERMISSIONS

Romanov D.V., Brazhnikov A.I., Andreyuk D.S., Zakharova N.V., Bravve L.V., Kovaleva V.A., Abbazova E.V., Goncharov D.B., Titova I.V., Domonova E.A., Kostyuk G.P.