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Toxoplasma gondii & Human Phenotype

Compendium of Known Effects and Ongoing Research

cytokines

Latent toxoplasmosis aggravates anxiety- and depressive-like behaviour and suggest a role of gene-environment interactions in the behavioural response to the parasite

February 4, 2020
Bay-Richter, C., Petersen, E., Liebenberg, N., Elfving, B., Wegener, G.
Behavioural Brain Research 2019, 364: 133 - 139
Click for abstract
Toxoplasma gondii (TOX) is an intracellular parasite which infects warm-blooded animals including humans. An increasing number of clinical studies now hypothesize that latent toxoplasmosis may be a risk factor for the development of psychiatric disease. For depression, the results have been varied and we speculate that genetic background is important for the response to latent toxoplasmosis. The main objective of this study was to elucidate gene - environment interactions in the behavioural response to TOX infection by use of genetically vulnerable animals (Flinders sensitive line, FSL) compared to control animals (Flinders resistant line, FRL). Our results show that all infected animals displayed increased anxiety-like behaviour whereas only genetically vulnerable animals (FSL rats) showed depressive-like behaviour as a consequence of the TOX infection. Furthermore, peripheral cytokine expression was increased following the infection, primarily independent of strain. In the given study 14 cytokines, chemokines, metabolic hormones, and growth factors were quantified with the bead-based Luminex200 system, however, only IL-1 alpha expression was affected differently in FSL animals compared to FRL rats. These results suggest that latent TOX infection can induce anxiety-like behaviour independent of genetic background. Intriguingly, we also report that for depressive-like behaviour only the vulnerable rat strain is affected. This could explain the discrepancy in the literature as to whether TOX infection is a risk factor for depressive symptomatology. We propose that the low grade inflammation caused by the chronic infection is related to the development of behavioural symptoms.

Tagged: altered behavior, antidepressant, anxety, cytokines, disorders, dpression, gene-environment interaction, gondii infection, induction, level, miceexpression, tests, Toxoplasma gondii

Mental health

Maternal infection during pregnancy and risk of autism spectrum disorders: A systematic review and meta-analysis

January 4, 2016
Jiang, H. Y., Xu, L. L., Shao, L., Xia, R. M., Yu, Z. H., Ling, Z. X., Yang, F., Deng, M., Ruan, B.
Brain Behavior and Immunity 2016; 58: 165-172
Click for abstract
Conflicting evidence exists with regard to the relationship between maternal infection during pregnancy and the risk of autism spectrum disorder (ASD) in offspring. The aim of this meta-analysis was to systematically assess this relationship. To identify relevant studies, we conducted systematic searches in PubMed and Embase of scientific articles published through March 2016. Random-effects models were adopted to estimate overall relative risk. A total of 15 studies (2 cohort and 13 case-control studies) involving more than 40,000 ASD cases were included in our meta-analysis. Our results showed that maternal infection during pregnancy was associated with an increased risk of ASD in offspring (OR = 1.13, 95% confidence interval (CI): 1.03-1.23), particularly among those requiring hospitalization (OR = 1.30, 95% CI: 1.14-1.50). Subgroup analyses suggested that risk may be modulated by the type of infectious agent, time of infectious exposure, and site of infection. These findings indicate that maternal infection during pregnancy increases the risk of ASD in offspring. Possible mechanisms may include direct effects of pathogens and, more indirectly, the effects of inflammatory responses on the developing brain. (C) 2016 Elsevier Inc. All rights reserved.

Tagged: autism, brain-development, childhood, children, cytokines, Epidemiology, exposure, hospitalization, immune activation, infectious, prenatal, prenatal infection, prevalence, viral-infection

Mental health

Prenatal maternal infection, neurodevelopment and adult schizophrenia: a systematic review of population-based studies

October 11, 2013
Khandaker, G. M., Zimbron, J., Lewis, G., Jones, P. B.
Psychological Medicine 2013; 43: 239-257
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Background. Disruption of foetal development by prenatal maternal infection is consistent with a neurodevelopmental model of schizophrenia. Whether specific prenatal infections are involved, their timing and the mechanisms of any effect are all unknown. We addressed these questions through a systematic review of population-based studies. Method. Electronic and manual searches and rigorous quality assessment yielded 21 studies that included an objective assessment of individual-level prenatal maternal infection and standardized psychotic diagnoses in adult offspring. Methodological differences between studies necessitated a descriptive review. Results. Results for prenatal maternal non-specific bacterial, respiratory or genital and reproductive infection differed between studies, which reported up to a two-to fivefold increased risk of schizophrenia. Evidence for herpes simplex virus type 2 (HSV-2) and Toxoplasma gondii was mixed; some studies reported up to a doubling of schizophrenia risk. Prenatal HSV-1 or cytomegalovirus (CMV) infections were not associated with increased risk. Exposure to influenza or other infections during early pregnancy may be more harmful than later exposure. Increased proinflammatory cytokines during pregnancy were also associated with risk. Prenatal infection was associated with structural and functional brain abnormalities relevant to schizophrenia. Conclusions. Prenatal exposure to a range of infections and inflammatory responses may be associated with risk of adult schizophrenia. Larger samples, mediation and animal models should be used to investigate whether there is a 'sensitive period' during development, and the effects of prenatal infections on neurodevelopment. Inclusion of genetic and immunological information should help to elucidate to what extent genetic vulnerability to schizophrenia may be explained by vulnerability to infection.

Tagged: brain-development, cardiovascular-disease, common variants, cytokines, fetal exposure, herpes-simplex-virus, infection, influenza infection, national birth cohort, neurodevelopment, pregnancy, psychosis, reproductive infections, risk factors, Schizophrenia

Mental healthReviews

Immunity, inflammation, and bipolar disorder: Diagnostic and therapeutic implications

October 11, 2013
Hamdani, N., Doukhan, R., Kurtlucan, O., Tamouza, R., Leboyer, M.
Current Psychiatry Reports 2013; 15
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Bipolar disorder is now known to be associated not only with highly prevalent co-occurring psychiatric and substance use disorders but also with medical comorbidities, such as cardiovascular diseases, diabetes mellitus, obesity and thyroid dysfunction. Inflammatory disturbances repeatedly observed in bipolar disorder, can explain some of the comorbidity between bipolar disorder and medical disorder. This revised perspective of bipolar disorders should promote the development of therapeutic tools. Immuno-inflammatory dysfunction may well represent a significant component of the underlying pathophysiology of the disorder. We therefore propose to review the immuno-inflammatory hypothesis in bipolar disorder considering the co-occurence with autoimmune diseases, immunological and inflammatory markers, as well as immuno-genetic markers which could lead to personalized treatments.

Tagged: auto-antibody, autoimmune diseases, bipolar disorder, borna-disease virus, c-reactive protein, cardiovascular risk-factors, cell-mediated-immunity, crp, cytokines, depressive patients, endogenous retroviruses comorbid substance use disorder, immuno-genetic, lithium treatment, medical comorbidity, metabolic syndrome, mood disorders, psychiatry, 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
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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

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

Anti-Toxoplasma gondii antibodies in patients with chronic heart failure

October 30, 2006
Yazar, S., Gur, M., Ozdogru, I., Yaman, O., Oguzhan, A., Sahin, I.
Journal of Medical Microbiology 2006; 55: 89-92
Click for abstract
Chronic heart failure (CHF) involves interactions between the cardiovascular, neuroendocrine and immune systems. This study investigated the seropositivity rate for anti-Toxoplasma IgG and IgM antibodies by ELISA in patients with CHF. Ninety-seven patients with CHF and 50 healthy volunteers were selected for this investigation. The seropositivity rate for anti-Toxoplasma IgG antibodies among CHF patients (68%) was significantly higher than in healthy volunteers (36%). Thus, parasitological screening of this group of patients should be periodically performed to prevent the possible dissemination of toxoplasmosis.

Tagged: cytokines, immunity, infections, mechanisms, natural-killer-cells, receptors, resistance

Physical health

Topics

  • Behavior 105
  • Cognitive functions 64
  • Mental health 439
  • Morphology 6
  • Motor functions 10
  • Personality 36
  • Physical health 134
  • Reproduction 36
  • Reviews 40
  • Sensory functions 3
  • Uncategorized 2

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Recent articles

  • Mortality Patterns of Toxoplasmosis and Its Comorbidities in Tanzania: A 10-Year Retrospective Hospital-Based Survey February 6, 2020
  • 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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