Treatment with anti-toxoplasmic activity (TATA) for Toxoplasma positive patients with bipolar disorders or schizophrenia: A cross-sectional study
Fond, G., Boyer, L., Gaman, A., Laouamri, H., Attiba, D., Richard, J. R., Delavest, M., Houenou, J., Le Corvoisier, P., Charron, D., Krishnamoorthy, R., Oliveira, J., Tamouza, R., Yolken, R., Dickerson, F., Leboyer, M., Hamdani, N.
Journal of Psychiatric Research 2015; 63: 58-64.
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Objective: The association between Toxoplasma gondii seropositivity and respectively Bipolar Disorder (BD) and Schizophrenia/Schizoaffective disorder (SZ) is one of the most studied link between one pathogen and psychiatric disorders. The aim of the present study was thus to retrospectively determine if the administration of an antipsychotic and/or a mood stabilizer having known in vitro Anti-Toxoplasmic Activity (TATA+) was associated with a better clinical outcome in a population of 152 BD or 114 SZ patients and seropositive for T gondii infection compared to patients receiving a treatment without anti-toxoplasmic activity (TATA-). Methods: This multicenter study was conducted in an academic public hospital during a 3-years period between 2009 and 2011. All consecutive inpatients and outpatients with SZ or BD diagnosis with a stable treatment for more than 4 weeks were recruited. socio-demographic and clinical characteristics measured with validated scales as well as a serological status for toxoplasmic infection were included. Treatments were classified according to their in vitro antitoxoplasmic activity. A multivariate model was used to determine the clinical characteristics that were significantly different between patients receiving a treatment with no antitoxoplasmic activity compared to others. Results: BD patients with positive serum antibodies against T gondii presented more lifetime depressive episodes (p = 0.048) after adjustment forage, sex and sociodemographic characteristics when treated by drug having no anti-toxo activity, compared to patients having received drugs with anti-toxo activity. A significant difference was not found in BD toxonegative patients and in SZ toxopositive or toxonegative patients. Conclusions: It seems to be of importance to consider prescribing a drug with a clear anti-toxoplasmic activity (TATA+) for BD patients seropositive to T. gondii, in particular valproate that was found as the mood stabilizer with the highest antitoxoplasmic activity. Prospective randomized controlled trials are warranted to confirm this preliminary data.
Prenatal factors associated with autism spectrum disorder (ASD)
Ornoy, A., Weinstein-Fudim, L., Ergaz, Z.
Reproductive Toxicology 2015; 56: 155-169
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Autism spectrum disorder (ASD) affecting about 1% of all children is associated, in addition to complex genetic factors, with a variety of prenatal, perinatal and postnatal etiologies. We discuss the known associated prenatal factors affecting the fetus throughout pregnancy; whenever relevant, also summarize some animal data. Among the maternal diseases in pregnancy associated with ASD are pregestational and/or gestational diabetes mellitus (PGDM, GDM), maternal infections (i.e. rubella, cytomegalovirus (CMV)), prolonged fever and maternal inflammation, which cause changes in a variety of inflammatory cytokines. Among the drugs are valproic acid, thalidomide, and possibly misoprostol and serotonin reuptake inhibitors (SSRIs). Associations were described with ethanol, and possibly cocaine, heavy metals heavy smoking and Folic acid deficiency. Heavy exposure to pesticides and air pollution during pregnancy was recently associated with ASD. We need more epidemiologic data to establish many of these associations; if proven, they might be promising avenues for prevention. (C) 2015 Elsevier Inc. All rights reserved
Autism spectrum disorders may be due to cerebral toxoplasmosis associated with chronic neuroinflammation causing persistent hypercytokinemia that resulted in an increased lipid peroxidation, oxidative stress, and depressed metabolism of endogenous and exogenous substances
Research in Autism Spectrum Disorders 2010; 4: 119-155
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Worldwide, approximately 2 billion people are chronically infected with Toxoplasma gondii with largely yet unknown consequences. Patients with autism spectrum disorders (ASD) similarly as mice with chronic toxoplasmosis have persistent neuroinflammation, hypercytokinemia with hypermetabolism associated with enhanced lipid peroxidation, and extreme changes in the weight resulting in obesity or wasting. Data presented in this review suggest that environmental triggering factors such as pregnancy, viral/bacterial infections, vaccinations, medications, and other substances caused reactivation of latent cerebral toxoplasmosis because of changes in intensity of latent central nervous system T. gondii infection/inflammation and finally resulted in development of ASD. Examples of such environmental factors together with their respective biomarker abnormalities are: pregnancy (increased NO, IL-1 beta, TNF-alpha, IL-6, IL-10, prolactin: decreased IFN-gamma, IL-12), neuroborreliosis (increased IL-1 beta, sIL-1R2, TNF-alpha, IFN-gamma, IL-6, IL-10, IL-12, IL-18, transforming growth factor-beta 1 (TGF-beta 1)), vital infections (increased IL-1 beta, IL-6, IL-8, TNF-alpha, IFN-gamma/alpha/beta,TGF-beta 1), thimerosal (increased IL-5, IL-13; decreased IFN-gamma,TNF-alpha,IL-6, IL-12p70, NOS), and valproic acid (increased NO, reactive oxygen species; decreased TNF-alpha, IL-6, IFN-gamma). The imbalances in pro- and antiinflammatory processes could markedly hinder [lost defense mechanisms important for immune control of the parasite, such as the production of NO, cytokines, and reactive oxygen/nitrogen species, tryptophan degradation by indoleamine 2,3-dioxygenase and/or tryptophan 2,3-dioxygenase, limitation of the availability of intracellular iron to T gondii, and the mechanisms mediated by an IFN-gamma responsive gene family. These fluctuations could result in a recurrent profuse multiplication of T. gondii in the brain associated with persistent neuroinflammation, chronic overproduction of pro- and antiinflammatory cytokines, and NO causing increased oxidative stress, and significantly depressed activity of several enzymes including cytochrome P450 monooxygenase family responsible for metabolism of physiological substrates and xenobiotics, such as steroids, fatty acids, prostaglandins, drugs, pollutants, and carcinogens, finally leading to development of ASD. This reasoning may be supported by such abnormal metabolic events as: (1) patients with ASD have significantly decreased melatonin levels caused by marked deficit in acetylserotonin methyltransferase activity, possibly resulting from maternal and/or fetal/postnatal overproduction of NO, characteristic for this clinical entity; (2) thimerosal inhibited both insulin-like growth factor-1- and dopamine-stimulated methylation reactions, and depressed methionine synthase activity, the metabolic events important for promoting normal neurodevelopment; (3) valproic acid, a strong histone deacetylase inhibitor, have potent anti-T. gondii activity. Thus, patients with ASD should be tested for T. gondii infection. (C) 2009 Elsevier Ltd. All rights reserved
Parasitosis, dopaminergic modulation and metabolic disturbances in schizophrenia: evolution of a hypothesis
Treuer T, Martenyi F, Karagianis J.
Neuroendocrinology Letters 2007; 28: 535-540.
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Recent meta-analyses have provided a comprehensive overview of studies investigating Toxoplasma gondii antibodies in schizophrenic patients, thus attempting to clarify the potential role these infections might play in causing schizophrenia. Issues for further research have been suggested. Associations and theories that may enrich the current level of knowledge with regard to this significant subject deserve attention. Anti-parasitic agents as well as antipsychotics are effective in treating parasitosis. Both classes of drugs have been shown to exert dopaminergic activity. Parasites and human organisms have a long history of mutual contact. The effect of parasitosis on the host and the host's response to infection are undoubtedly the product of a long evolutionary process. The neurochemical background of delusions of parasitosis is potentially similar to ancient evolutionary traces of altered neurotransmission and neuropeptide gene expression caused by parasites; these include fungal and viral infections. This is very unique in medicine if a class of drugs is effective in the treatment of an illness but also cures the delusion of the same disorder as well. Furthermore, metabolic disturbances such as hyperglycemia and insulin resistance were reported several decades before the antipsychotic era. Toxoplasmosis may also be linked to insulin resistance. Schizophrenia research can benefit from understanding this evolutionary link. New chemical entities that are liable to alter neurochemical changes related to the brain's perception of the risk of predation secondary to parasites may result in new approaches for the treatment of psychosis. These findings suggest that further research is needed to clarify this evolutionary link between parasite infection and delusions of parasitosis. We believe this model may well open up new avenues of research in the discovery of drugs to counteract schizophrenia.