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Toxoplasma gondii & Human Phenotype

Compendium of Known Effects and Ongoing Research

il-6

Cognitive deterioration among bipolar disorder patients infected by Toxoplasma gondii is correlated to interleukin 6 levels

October 6, 2015
Hamdani, N., Daban-Huard, C., Lajnef, M., Gadel, R., Le Corvoisier, P., Delavest, M., Carde, S., Lepine, J. P., Jamain, S., Houenou, J., Galeh, B., Richard, J. R., Aoki, M., Charron, D., Krishnamoorthy, R., Yolken, R., Dickerson, F., Tamouza, R., Leboyer, M.
Journal of Affective Disorders 2015; 179: 161-166
Click for abstract
Background: Cognitive deficits are present in a large majority of Bipolar Disorder (BD) patients and known to be a marker of bad prognosis. Because, these deficits encompass several domains and no specific medical treatment seems to be effective, it is important to better understand the mechanisms underlying cognitive deterioration. As Toxoplasma gondii is known to induce the synthesis of pro-inflammatory cytokines such as IL-6, we will explore here the possible role of T. gondii in the cognitive decline observed in BD. Methods: 42 euthymic BD patients and 36 controls were assessed for episodic verbal memory using the CVLT and for working memory and verbal ability using the WAIS Ill. Patients and controls were also screened for seropositivity to I gondii and evaluated for the levels of IL-fl transcripts. Results: The seropositivity for I gondii was significantly higher in BD patients as compared to controls (p-0.005). The cognitive deterioration index (Dl) was higher in BD patients (p=5.10 ') and correlated to high IL-6 mRNA expression only among those infected by T gondii (rho-0.43, p-0.01). Among deteriorated patients (defined by scores above 0.10 according to Weschler's definition), the IL-6 mRNA expression was twice greater (p=0.01). Limitations: Our results are to be interpreted with caution because of our small sample size and the cross-sectional design. Conclusions: A long-term exposure to inflammation, measured here with IL-6 mRNA expression in T. gonciii infected BD may alter cognitive functioning. IL-6 could thus be a useful predictive marker of cognitive deterioration in BD and may help to design personalized treatment.

Tagged: antibodies, association, bipolar disorder, cognitive deterioration, exposure, il-6, impairment, individuals, Major depression, risk, Schizophrenia, simplex-virus type-1, t. gondii, traffic accidents

Cognitive functionsMental health

Relationship between Toxoplasma gondii infection and bipolar disorder in a French sample

October 11, 2013
Hamdani, N., Daban-Huard, C., Lajnef, M., Richard, J. R., Delavest, M., Godin, O., Le Guen, E., Vederine, F. E., Lepine, J. P., Jamain, S., Houenou, J., Le Corvoisier, P., Aoki, M., Moins-Teisserenc, H., Charron, D., Krishnamoorthy, R., Yolken, R., Dickerson, F., Tamouza, R., Leboyer, M.
Journal of Affective Disorders 2013; 148: 444-448
Click for abstract
Background: Prenatal exposure to viruses or parasites with tropism for the central nervous system is one of the risk factors for psychotic disorders. However, the relationship between past exposure to Toxoplasma gondii (T. gondii) and incidence of bipolar disorders (BD) is poorly documented across populations. Methods: We explored the potential association between T. gondii exposure and BD in France, a country of high prevalence of Toxoplasmosis, comparing the prevalence of serological markers (IgG/IgM class antibodies) for T. gondii infection in 110 BD patients and 106 healthy controls all living in France. In a subgroup of 42 patients and 42 controls we also evaluated the levels of interleukin 6 (IL-6) transcripts, an adjunct marker of inflammation. Results: We found that the sero-positive group for IgG antibodies to T. gondii had a 2.7 fold odds of having BD as compared to the sero-negative group (OR = 2.17 CI 95% = 1.09-4.36, p = 0.028). Despite the fact that BD patients had significantly higher levels of IL-6 than the non-patient controls, no notable association between T. gondii status and IL-6 transcript levels was found. We did not find any clinical or demographic correlates of Toxoplasma exposure in the study population. Limitations: Our results are to be interpreted with caution because of our small sample size. Results: We confirm the association between seropositive status to T. gondii and bipolar disorders reported in other populations and extend it to French patients. Our data strengthen the importance of early detection of T. gondii infected patients in order to propose specific and adequate treatments.

Tagged: antibodies, bipolar disorder, Epidemiology, health, il-6, neuro-immunology, pathophysiology, pregnant women, prevalence, Schizophrenia, seropositivity, Toxoplasma gondii

Mental health

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

October 19, 2010
Prandota J.
Research in Autism Spectrum Disorders 2010; 4: 119-155
Click for abstract
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

Tagged: abnormalities, abnormality, acid, acids, aktivity, autism, autistic spectrum disorders, availability, beta, biomarker, brain, cell-mediated-immunity, central-nervous-system, cerebral, Cerebral toxoplasmosis, change, changes, chronic, chronic neuroinflammation, chronic toxoplasmosis, clinical, congenital cytomegalovirus-infection, consequence, consequences, control, could, cytochrome, cytochrome p450, cytokine, cytokines, data, defense, defense-mechanisms, deficit, degradation, depressed enzyme activities, development, disorder, disorders, drug, drugs, environmental, environmental factors, enzyme, enzymes, event, events, example, families, family, fluctuation, fluctuations, gene, gene families, gene family, gondii, gondii infection, growth, growth-factor-beta, hepatic drug-metabolism, herpes-simplex-virus, histone, histone deacetylase, hypercytokinemia, hypermetabolic state, il-1, il-10, il-12, il-13, il-6, immune, immune irregularities, important, infection, infections, inhibitor, insulin-like, intensity, interferon-inducing agents, intracellular, iron, latent, level, limitation, lipid, lipid-peroxidation, maternal, mechanism, mechanisms, medication, melatonin, metabolism, methionine, methylation, methyltransferase, methyltransferase aktivity, mice, multiplication, nervous, nervous system, neurodevelopment, nf-kappa-b, nitric oxide, nitric-oxide synthase, obesity, or, overproduction, oxidative stress, oxygen, p-450-dependent monooxygenase systems, Parasite, patient, patients, people, persistent, pregnancies, pregnancy, proces, prolactin, prostaglandins, reaction, reactivation, review, species, spectrum, spectrum disorders, spektra, steroids, stress, substrate, systém, t, tgf-beta, tnf-alpha, Toxoplasma, Toxoplasma gondii, toxoplasmosis, tryptophan, tumor-necrosis-factor, vaccination, vital, weight, xenobiotics

Mental health

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  • Cognitive functions 64
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  • Morphology 6
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Recent articles

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  • The role of latent toxoplasmosis in the aetiopathogenesis of schizophrenia–the risk factor or an indication of a contact with cat? February 6, 2020
  • The Association between Toxoplasma gondii Infection and Risk of Parkinson’s Disease: A Systematic Review and Meta-Analysis February 6, 2020

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