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(Toxoplasma gondii: A potential role in the genesis of psychiatric disorders.)
Fond G., Capdevielle D., Macgregor A., Attal J., Larue A., Brittner M., Ducasse D., Boulenger J.-P.
Encéphale (2012) epub ahead of print - http://www.hal.inserm.fr/inserm-00750381
[Toxoplasma gondii: A potential role in the genesis of psychiatric disorders.]
Guillaume Fond () 1, 2, Delphine Capdevielle1, 2, Alexandra Macgregor1, 2, Jérôme Attal1, 2, A. Larue1, 2, Marie Brittner1, 2, Deborah Ducasse1, 2, Jean-Philippe Boulenger1, 2, 3
1 :  Neuropsychiatrie : recherche épidémiologique et clinique
INSERM : U1061 – Université Montpellier I
Hôpital La Colombière 39 AV Charles Flahault BP 34493 -Pav 42 Calixte Cavalier 34093 CEDEX 5 Montpellier
2 :  Service Universitaire de Psychiatrie Adulte
CHRU Montpellier – Hôpital La Colombière
34000, Montpellier
3 :  Département de psychiatrie adulte
CHRU Montpellier – Hôpital La Colombière
39, avenue Charles Flahault, 34295 Montpellier Cedex
INTRODUCTION: Toxoplasma gondii is the most common protozoan parasite in developed nations. Up to 43% of the French population may be infected, depending on eating habits and exposure to cats, and almost one third of the world human's population may be infected. Two types of infection have been described: a congenital form and an acquired form. Although the medical profession treats these latent cases as asymptomatic and clinically unimportant, results of animal studies and recent studies of personality profiles, behavior, and psychomotor performance have led to reconsider this assumption. PRECLINICAL DATA: Among rats: parasite cysts are more abundant in amygdalar structures than those found in other regions of the brain. Infection does not influence locomotion, anxiety, hippocampal-dependent learning, fear conditioning (or its extinction) and neophobia in rats. Rats' natural predator is the cat, which is also T. gondii's reservoir. Naturally, rats have an aversion to cat urine, but the parasite suppresses this aversion in rats, thus influencing the infection cycle. Tachyzoites may invade different types of nervous cells, such as neurons, astrocytes and microglial cells in the brain, and Purkinje cells in cerebellum. Intracellular tachyzoites manipulate several signs for transduction mechanisms involved in apoptosis, antimicrobial effectors functions, and immune cell maturation. Dopamine levels are 14% higher in mice with chronic infections. These neurochemical changes may be factors contributing to mental and motor abnormalities that accompany or follow toxoplasmosis in rodents and possibly in humans. Moreover, the antipsychotic haloperidol and the mood stabilizer valproic acid most effectively inhibit Toxoplasma growth in vitro with synergistic activity. CLINICAL DATA: The effects of the parasite are not due to the manipulation in an evolutionary sense but merely due to neuropathological or neuroimmunological effects of the parasite's presence. Toxoplasmosis and schizophrenia: epidemiological studies point to a role for toxoplasmosis in schizophrenia's etiology, probably during pregnancy and early life, this association being congruent with studies in animal models indicating that animal exposures of the developing brain to infectious agents or immune modulating agents can be associated with behavioral changes that do not appear until the animal reaches full maturity. Psychiatric patients have increased rates of toxoplasmic antibodies, the differences between cases and controls being greatest in individuals who are assayed near the time of the onset of their symptoms. The increase of dopamine in the brain of infected subjects can represent the missing link between toxoplasmosis and schizophrenia. Toxoplasmosis and Obsessive Compulsive Disorder (OCD): the seropositivity rate for anti-T. gondii IgG antibodies among OCD patients is found to be significantly higher than the rate in healthy volunteers. Infection of basal ganglia may be implicated in the pathogenesis of OCD among Toxoplasma seropositive subjects. Toxoplasmosis and personality: infected men appear to be more dogmatic, less confident, more jealous, more cautious, less impulsive and more orderly than others. Conversely, infected women seem warmest, more conscientious, more insecure, more sanctimonious and more persistent than others. It is possible that differences in the level of testosterone may be responsible for the observed behavioral differences between Toxoplasma-infected and Toxoplasma-free subjects. CONCLUSION: In the future two major avenues for research seem essential. On one hand, prospective studies and research efforts must still be carried out to understand the mechanisms by which the parasite induces these psychiatric disorders. On the other hand, it has not yet been demonstrated that patients with positive toxoplasmic serology may better respond to haloperidol's or valproic acid's antiparasitic activity. These results may appear as a major issue in the drug's prescribing choices and explain variability in response to the treatment of patients with schizophrenia that is not explained by the genetic polymorphism.
Sciences du Vivant/Médecine humaine et pathologie/Psychiatrie et santé mentale

Articles dans des revues avec comité de lecture
Encéphale (Encephale)
Publisher Elsevier Masson
ISSN 0013-7006 
epub ahead of print

Toxoplasma gondii – schizophrenia – obsessive compulsive disorder – etiopathogenesis – personality – rhesus
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