Comparative analysis of anti-toxoplasmic activity of antipsychotic drugs and valproate

  • Guillaume Fond
  • Alexandra Macgregor
  • Ryad Tamouza
  • Nora Hamdani
  • Alexandre Meary
  • Marion Leboyer
  • Jean-Francois Dubremetz
Short Communication


Recent studies have shown a strong link between Toxoplasma gondii infection and psychiatric disorders, especially schizophrenia and bipolar disorders (odd ratio ≈2.7 for each disorder). Antipsychotic drugs and mood stabilizers may have anti-toxoplasmic activity that potentially may be associated with better effectiveness in these disorders, but previous results have been few in number and conflicting. We therefore sought to determine which daily prescribed antipsychotics and mood stabilizer have the best anti-toxoplasmic activity during the development phase of the parasite. In the present study, we examined the effects of commonly used antipsychotic drugs (amisulpride, cyamemazine, fluphenazine, haloperidol, levomepromazine, loxapine, olanzapine, risperidone and tiapride) and one mood-stabilizing agent (valproate) on toxoplasmic activity. We replicated that fluphenazine has a high anti-toxoplasmic activity, but it does not seem to be a phenothiazine-specific class effect: indeed, we found that another first-generation antipsychotic, zuclopenthixol, has a high anti-toxoplasmic activity. Valproate, tiapride and amisulpride have no anti-toxoplasmic activity on parasite growth, and the other antipsychotic drugs showed low or intermediate anti-toxoplasmic activity. As it is not possible to know the intracellular concentrations of antipsychotics in the brain, further clinical studies are warranted to determine whether these in vitro findings have potential implications in treatment of toxo-positive patients with schizophrenia. These findings may be potentially relevant for the choice of the first-line antipsychotic drug or mood stabilizer in previously infected patients.


Toxoplasma gondii Antipsychotic Mood stabilizer Schizophrenia Calmodulin Phenothiazine 



This work was supported by CHRU Montpellier, INSERM, Assistance Publique—Hôpitaux de Paris, and RTRS Santé Mentale (Fondation Fondamental). We thank Hélène Boudon and Arti Jetshan, fellows in pharmacy, Université Montpellier 1, Montpellier, F-34000, France, for their contribution in experiments.

Conflict of interest

Dr. G. Fond, Dr. A. Macgregor, Pr. M. Leboyer, Pr. R. Tamouza, Dr. N. Hamdani, Dr. A. Meary, and Dr. J. F. Dubremetz declare no conflict of interests in connection with the present study.


  1. 1.
    Alipour A, Shojaee S, Mohebali M, Tehranidoost M, Abdi Masoleh F, Keshavarz H (2011) Toxoplasma infection in schizophrenia patients: a comparative study with control group. Iran J Parasitol 6:31–37PubMedCentralPubMedGoogle Scholar
  2. 2.
    Arias I, Sorlozano A, Villegas E, de Dios Luna J, McKenney K, Cervilla J, Gutierrez B, Gutierrez J (2012) Infectious agents associated with schizophrenia: a meta-analysis. Schizophr Res 136:128–136PubMedCrossRefGoogle Scholar
  3. 3.
    Brown AS, Patterson PH (2011) Maternal infection and schizophrenia: implications for prevention. Schizophr Bull 37:284–290PubMedCrossRefGoogle Scholar
  4. 4.
    da Silva RC, Langoni H (2009) Toxoplasma gondii: host-parasite interaction and behavior manipulation. Parasitol Res 105:893–898PubMedCrossRefGoogle Scholar
  5. 5.
    Emelia O, Amal RN, Ruzanna ZZ, Shahida H, Azzubair Z, Tan KS, Noor Aadila S, Siti NA, Aisah MY (2012) Seroprevalence of anti-Toxoplasma gondii IgG antibody in patients with schizophrenia. Trop Biomed 29:151–159PubMedGoogle Scholar
  6. 6.
    Flegr J (2007) Effects of Toxoplasma on human behavior. Schizophr Bull 33:757–760PubMedCrossRefGoogle Scholar
  7. 7.
    Fond G, Capdevielle D, Macgregor A, Attal J, Larue A, Brittner M, Ducasse D, Boulenger JP (2013) Toxoplasma gondii: a potential role in the genesis of psychiatric disorders. Encephale 39:38–43PubMedCrossRefGoogle Scholar
  8. 8.
    Goodwin DG, Strobl JS, Lindsay DS (2011) Evaluation of five antischizophrenic agents against Toxoplasma gondii in human cell cultures. J Parasitol 97:148–151PubMedCrossRefGoogle Scholar
  9. 9.
    Hamdani N, Daban-Huard C, Lajnef M, Richard JR, Delavest M, Godin O, Guen EL, Vederine FE, Lepine JP, Jamain S, Houenou J, Corvoisier PL, Aoki M, Moins-Teisserenc H, Charron D, Krishnamoorthy R, Yolken R, Dickerson F, Tamouza R, Leboyer M (2012) Relationship between Toxoplasma gondii infection and bipolar disorder in a French sample. J Affect Disord 148(2–3):444–448Google Scholar
  10. 10.
    Hamdani N, Tamouza R, Leboyer M (2012) Immuno-inflammatory markers of bipolar disorder: a review of evidence. Front Biosci (Elite Ed) 4:2170–2182CrossRefGoogle Scholar
  11. 11.
    Hinze-Selch D, Daubener W, Eggert L, Erdag S, Stoltenberg R, Wilms S (2007) A controlled prospective study of Toxoplasma gondii infection in individuals with schizophrenia: beyond seroprevalence. Schizophr Bull 33:782–788PubMedCrossRefGoogle Scholar
  12. 12.
    Holfels E, McAuley J, Mack D, Milhous WK, McLeod R (1994) In vitro effects of artemisinin ether, cycloguanil hydrochloride (alone and in combination with sulfadiazine), quinine sulfate, mefloquine, primaquine phosphate, trifluoperazine hydrochloride, and verapamil on Toxoplasma gondii. Antimicrob Agents Chemother 38:1392–1396PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Jones-Brando L, Torrey EF, Yolken R (2003) Drugs used in the treatment of schizophrenia and bipolar disorder inhibit the replication of Toxoplasma gondii. Schizophr Res 62:237–244PubMedCrossRefGoogle Scholar
  14. 14.
    Kim K, Weiss LM (2008) Toxoplasma: the next 100 years. Microbes Infect 10:978–984PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Kirchherr H, Kuhn-Velten WN (2006) Quantitative determination of forty-eight antidepressants and antipsychotics in human serum by hplc tandem mass spectrometry: a multi-level, single-sample approach. J Chromatogr B Analyt Technol Biomed Life Sci 843:100–113PubMedCrossRefGoogle Scholar
  16. 16.
    Leboyer M, Tamouza R, Charron D, Faucard R, Perron H (2011) Human endogenous retrovirus type w (herv-w) in schizophrenia: a new avenue of research at the gene-environment interface. World J Biol PsychiatryGoogle Scholar
  17. 17.
    Nascimento FS, de Rosalmeida Dantas C, Netto MP, Mella LF, Suzuki LA, Banzato CE, Rossi CL (2012) Prevalence of antibodies to Toxoplasma gondii in patients with schizophrenia and mood disorders. Schizophr ResGoogle Scholar
  18. 18.
    Okusaga O, Langenberg P, Sleemi A, Vaswani D, Giegling I, Hartmann AM, Konte B, Friedl M, Groer MW, Yolken RH, Rujescu D, Postolache TT (2011) Toxoplasma gondii antibody titers and history of suicide attempts in patients with schizophrenia. Schizophr Res 133:150–155PubMedCrossRefGoogle Scholar
  19. 19.
    Prandovszky E, Gaskell E, Martin H, Dubey JP, Webster JP, McConkey GA (2011) The neurotropic parasite Toxoplasma gondii increases dopamine metabolism. PLoS One 6:e23866PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Skallova A, Kodym P, Frynta D, Flegr J (2006) The role of dopamine in Toxoplasma-induced behavioural alterations in mice: an ethological and ethopharmacological study. Parasitology 133:525–535PubMedCrossRefGoogle Scholar
  21. 21.
    Stibbs HH (1985) Changes in brain concentrations of catecholamines and indoleamines in Toxoplasma gondii infected mice. Ann Trop Med Parasitol 79:153–157PubMedGoogle Scholar
  22. 22.
    Torrey EF, Bartko JJ, Lun ZR, Yolken RH (2007) Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis. Schizophr Bull 33:729–736PubMedCrossRefGoogle Scholar
  23. 23.
    Torrey EF, Bartko JJ, Yolken RH (2012) Toxoplasma gondii and other risk factors for schizophrenia: an update. Schizophr Bull 38:642–647PubMedCrossRefGoogle Scholar
  24. 24.
    Torrey EF, Yolken RH (2003) Toxoplasma gondii and schizophrenia. Emerg Infect Dis 9:1375–1380PubMedCrossRefGoogle Scholar
  25. 25.
    Van Putten T, Marder SR, Wirshing WC, Aravagiri M, Chabert N (1991) Neuroleptic plasma levels. Schizophr Bull 17:197–216PubMedCrossRefGoogle Scholar
  26. 26.
    Wang HL, Wang GH, Li QY, Shu C, Jiang MS, Guo Y (2006) Prevalence of Toxoplasma infection in first-episode schizophrenia and comparison between Toxoplasma-seropositive and Toxoplasma-seronegative schizophrenia. Acta Psychiatr Scand 114:40–48PubMedCrossRefGoogle Scholar
  27. 27.
    Webster JP (2001) Rats, cats, people and parasites: the impact of latent toxoplasmosis on behaviour. Microbes Infect 3:1037–1045PubMedCrossRefGoogle Scholar
  28. 28.
    Yolken RH, Bachmann S, Ruslanova I, Lillehoj E, Ford G, Torrey EF, Schroeder J (2001) Antibodies to Toxoplasma gondii in individuals with first-episode schizophrenia. Clin Infect Dis 32:842–844PubMedCrossRefGoogle Scholar
  29. 29.
    Yolken RH, Dickerson FB, Fuller Torrey E (2009) Toxoplasma and schizophrenia. Parasite Immunol 31:706–715PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Guillaume Fond
    • 1
  • Alexandra Macgregor
    • 2
  • Ryad Tamouza
    • 3
  • Nora Hamdani
    • 1
  • Alexandre Meary
    • 1
  • Marion Leboyer
    • 1
  • Jean-Francois Dubremetz
    • 4
  1. 1.Fondation FondaMental Fondation de Coopération Scientifique en Santé Mentale, Eq Psychiatrie Génétique, INSERM U955, DHU Pepsy, Pôle de Psychiatrie du Groupe des Hôpitaux Universitaires de MondorUniversité Paris Est-CréteilCréteilFrance
  2. 2.INSERM U1061, Service Universitaire de Psychiatrie Adulte, Hôpital La ColombièreCHRU de MontpellierMontpellierFrance
  3. 3.Jean Dausset Department and INSERM UMRS 940Hôpital Saint LouisParisFrance
  4. 4.UMR 5235 CNRSUniversité de Montpellier 2MontpellierFrance

Personalised recommendations