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Toxoplasma gondii & Human Phenotype

Compendium of Known Effects and Ongoing Research

maternal exposure

Epidemiologic studies of exposure to prenatal infection and risk of schizophrenia and autism

February 1, 2020
Brown, A. S.
Developmental Neurobiology 2012, 72: 1272 - 1276
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In this review, we provide a synopsis of work on the epidemiologic evidence for prenatal infection in the etiology of schizophrenia and autism. In birth cohort studies conducted by our group and others, in utero exposure to infectious agents, prospectively obtained after biomarker assays of archived maternal sera and by obstetric records was related to an increased risk of schizophrenia. Thus far, it has been demonstrated that prenatal exposure to influenza, increased toxoplasma antibody, genitalreproductive infections, rubella, and other pathogens are associated with schizophrenia. Anomalies of the immune system, including enhanced maternal cytokine levels, are also related to schizophrenia. Some evidence also suggests that maternal infection and immune dysfunction may be associated with autism. Although replication is required, these findings suggest that public health interventions targeting infectious exposures have the potential for preventing cases of schizophrenia and autism. Moreover, this work has stimulated translational research on the neurobiological and genetic determinants of these conditions.

Tagged: adult schizophrenia, association, birth cohort, Epidemiology, herpes-simplex-virus, immune activation, infection, influenza, maternal exposure, pregnancy, reproductive infections, Schizophrenia, spectrum disorders, toxoplasmosis

Mental health

Mental Health Disorders Associated with Foodborne Pathogens

January 4, 2016
Bolton, D. J., Robertson, L. J.
Journal of Food Protection 2016, 79: 2005-2017
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Human infections with foodborne pathogenic organisms are relatively well described in terms of their overt physical symptoms, such as diarrhea, abdominal cramps, vomiting, fever, and associated sequelae. Indeed, some of these are key for diagnosis and treatment, although it should be noted that, for some foodborne pathogens, the physical symptoms might be more diffuse, particularly those associated with some of the foodborne parasites. In contrast, the impact of these pathogens on mental health is less well described, and symptoms such as depression, anxiety, and general malaise are usually ignored when foodborne infections are recorded. Despite this, it is generally accepted that there are several psychiatric disorders of unknown etiology that may be associated with microbial pathogens. Depression, autism, hypochondriasis and anxiety, schizophrenia, and Tourette syndrome probably have multiple contributing causes, among which foodborne pathogens may play a decisive or contributory role, possibly sharing pathophysiological pathways with other environmental triggers. This review focuses on foodborne parasites and bacterial pathogens. Some foodborne parasites, such as metacestodes of Taenia soliunz and tissue cysts (bradyzoites) of Toxoplasma gondii, may affect mental health by directly infecting the brain. In contrast, bacterial infections and other parasitic infections may contribute to mental illness via the immune system and/or by influencing neurotransmission pathways. Thus, cytokines, for example, have been associated with depression and schizophrenia. However, infectious disease models for psychiatry require a more complete understanding of the relationship between psychiatric disorders and microbial triggers. This article reviews the current state of knowledge on the role of foodborne parasitic and bacterial pathogens in mental illness and identifies some of the gaps that should be addressed to improve diagnosis and treatment of mental health issues that are not solely related to psychiatric factors.

Tagged: autistic spectrum disorders, bacteria, bipolar disorder, chronic-fatigue-syndrome, foodborne pathogens, gastrointestinal symptoms, induced sickness behavior, intestinal microbiota, irritable-bowel-syndrome, maternal exposure, mental health, mood disorders, parasites, toxoplasma gondii infection

Mental health

The potential of immune biomarkers to advance personalized medicine approaches for schizophrenia

May 28, 2015
Cox, D., Chan, M. K., Bahn, S.
Journal of Nervous and Mental Disease 2015; 203: 393-399
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Molecular profiling studies have helped increase the understanding of the immune processes thought to be involved in the etiology and pathophysiology of psychiatric disorders such as schizophrenia. Current therapeutic interventions with first-and second-generation antipsychotics are suboptimal. Poor response rates and debilitating side effects often lead to poor treatment compliance. This highlights the pressing need to identify more effective treatments as well as objective biomarker based tests, which can help predict treatment response and identify diagnostic subpopulations. Such tests could enable early detection of patients who will benefit from particular therapeutic interventions. In this review, we discuss studies relating to dysfunctions of the immune system in patients with schizophrenia and the effects of antipsychotic medication on the molecular components of these systems. Immune system dysfunction may in part be related to genetic risk factors for schizophrenia, but there is substantial evidence that a wide range of environmental factors ranging from exposure to infectious agents such as influenza and Toxoplasma gondii to HPA axis dysfunction play an important role in the etiopathogenesis of schizophrenia. Ongoing research efforts, testing therapeutic efficacy of anti-inflammatory agents used as add-on medications are also discussed. From a therapeutic perspective, these represent the initial steps toward novel treatment approaches and more effective patient care in the field of mental health.

Tagged: antipsychotic drugs, antipsychotic medication, biomarkers, c-reactive protein, cytokine alterations, herpes-simplex-virus, infectious agents, maternal exposure, n-acetylcysteine, oxidative stress, personalized medicine, placebo-controlled trial, prenatal exposure, Schizophrenia

Mental health

Maternal antibodies to infectious agents and risk for non-affective psychoses in the offspring–a matched case-control study

October 16, 2012
Blomstrom, A., Karlsson, H., Wicks, S., Yang, S. J., Yolken, R. H., Dalman, C.
Schizophrenia Research 2012; 140: 25-30
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BACKGROUND: An increasing number of studies suggest that certain maternal infections are associated with non-affective psychoses in the offspring. Here we investigated if maternal exposure to Toxoplasma gondii, cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) prior to delivery was associated with future diagnosis of schizophrenia or other non-affective psychoses in the offspring. METHODS: This case-control study included 198 individuals born in Sweden 1975-85, diagnosed with schizophrenia (ICD-10, F20) and other non-affective psychoses (ICD-10, F21-29) as in- or outpatients, and 524 matched controls. Specific immunoglobulin G (IgG) levels in archived neonatal dried blood samples from these individuals were determined by immunoassays. Reference levels were determined by prevalences among pregnant women in Sweden 1975-85. Odds ratios (OR) for schizophrenia and other non-affective psychoses were calculated, considering maternal and gestational factors as covariates. RESULTS: Levels of IgG directed at T. gondii corresponding to maternal exposure was associated with subsequent schizophrenia (OR=2.1, 95% CI 1.0-4.5) as were levels of IgG directed at CMV (OR=2.2, 95% CI 1.0-5.1) but not at HSV-1 or -2. There were even stronger associations with higher levels of T. gondii or CMV antibodies. There were no associations between any of the infectious agents and other non-affective psychoses. CONCLUSIONS: This study supports findings of maternal exposure to T. gondii and schizophrenia risk in offspring, and extends the risk to also include maternal exposure to CMV. Future studies should confirm the association with CMV exposure and identify mechanisms underlying these associations.

Tagged: adult, case-control studies, cytomegalovirus/immunology, female, humans, immunoglobulin G/blood, male, maternal exposure, odds ratio, pregnancy, psychotic disorders/blood/*immunology, risk factors, schizophrenia/*immunology/parasitology/virology, simplexvirus/immunology, Sweden, Toxoplasma/*immunology

Mental health

The association of infectious agents and schizophrenia

October 19, 2010
Krause, D., Matz, J., Weidinger, E., Wagner, J., Wildenauer, A., Obermeier, M., Riedel, M., Muller, N.
World Journal of Biological Psychiatry 2010; 11: 739-743
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Objectives. The influence of infectious agents on the pathogenesis of psychiatric disorders has been discussed for decades. Pre- and postnatal infections are risk factors for schizophrenia. This may be explained by chronic infections or an altered immune status. However most of the studies have only focused on one single pathogen and not on the impact of different infectious agents. We investigated the association between schizophrenia and various neurotophic infectious agents. Methods. A total of 31 schizophrenic patients and 30 healthy matched individuals were included. Antibody titres of cytomegalovirus, herpes simplex virus, Epstein-Barr virus, mycoplasma, chlamydia and toxoplasma were evaluated. For statistical analysis we used Fisher's exact and Wilcoxon test. Results. Significantly elevated positive antibody titres within schizophrenic patients were found only for Chlamydia trachomatis (P=0.005) and a trend to significance for herpes simplex virus (P=0.055). Combining the different agents, schizophrenics had a significantly higher rate of positive titres to infectious agents as compared to controls (P=0.04). Conclusions. The higher prevalence of antibodies within schizophrenic patients emphasizes a possible role of infectious agents in the pathogenesis of schizophrenia. Our data indicates that not one specific agent might be responsible for schizophrenic symptoms but the resulting immune response in the central nervous system.

Tagged: antibodies, childhood, chlamydia, etiology, herpes-simplex, immune system, individuals, infection, influenza, maternal exposure, psychosis, risk, Schizophrenia, virus

Mental health

Serological pattern consistent with infection with type I Toxoplasma gondii in mothers and risk of psychosis among adult offspring

October 26, 2009
Xiao, J.C., Buka, S. L., Cannon, T.D., Suzuki, Y., Viscidi, R.P., Torrey, E. F., Yolken, R. H.
Microbes and Infection 2009; 11: 1011-1018.
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Previous studies have shown that maternal antibodies to Toxoplasma measured during pregnancy are associated with an increased risk of schizophrenia and other psychoses in adult offspring Recently. it has been recognized that different genotypes of Toxoplasma have distinct neuropathogenic potential. The objective of this study was to investigate whether parasite genotype is a contributing factor to disease risk. We have developed an enzyme-linked immunosorbent assay (ELISA) that use., polymorphic polypeptides specific to the three clonal parasite lineages and derived from three dense granule antigens. GRA5, GRA6 and GRA7. We used this assay to measure type-specific antibodies in the sera from 219 pregnant women whose children developed schizophrenia and affective psychotic illnesses in adult life, and 618 matched unaffected control mothers from three cohorts of the Collaborative Perinatal Project. We found that the offspring of mothers with a serological pattern consistent with Toxoplasma type I infection were at significantly increased risk for the development of psychoses as compared with the matched unaffected control mothers (odds ratio = 1.94, 95% confidence interval = 1.08-3.46; p = 0.03). The risk was particularly elevated for affective psychoses (OR = 5.24, 95% CI = 1.67-16 5; p = 0 005). In contrast, we did not find an association between maternal antibodies to other genotypes and risk of psychoses in the offspring These findings suggest in influence of the parasite genotype on increased risk of psychosis and provide further support for a substantive role of Toxoplasma in the etiology of psychosis. (C) 2009 Elsevier Masson SAS All rights reserved

Tagged: congenital toxoplasmosis, disease, genotype, gra7, immunocompromised patients, maternal exposure, maternal infection, peptide, peptides, psychosis, samples, Schizophrenia, serotyping, strains, toxoplasma gondii type i

Mental health

Toxoplasma gondii as a risk factor for early-onset schizophrenia: Analysis of filter paper blood samples obtained at birth

October 27, 2007
Bo Mortensen P, Norgaard-Pedersen, B Waltoft, B.L., Sorensen, T.L., Hougaard, D., Torrey, E. E., Yolken, R.H.
Biological Psychiatry 2007; 61: 688-693.
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Background: Infections during fetal life or neonatal period, including infections with Toxoplasma gondii, may be associated with a risk for schizophrenia and other mental disorders. The objectives of this study were to study the association between serological markers for maternal and neonatal infection and the risk for schizophrenia, related psychoses, and affective disorders in a national cohort of newborns. Methods: This study was a cohort-based, case-control study combining data from national population registers and patient registers and a national neonatal screening biobank in Denmark. Patients included persons born in Denmark in 1981 or later followed up through 1999 with respect to inpatient or outpatient treatment for schizophrenia or related disorders (ICD-10 F2) or affective disorders (ICD-10 F3). Results: Toxoplasma gondii immunoglobulin G (IgG) levels corresponding to the upper quartile among control subjects were significantly associated with schizophrenia risk (odds ratio [OR] = 1.79, p =.045) after adjustment for urbanicity of place of birth, year of birth, gender, and psychiatric diagnoses among first-degree relatives. There was no significant association between any marker of infection and other schizophrenia-like disorders or affective disorders. Conclusions: Our study supports an association between Toxoplasma gondii and early-onset schizophrenia. Further studies are needed to establish if the association is causal and if it generalizes to cases with onset after age 18.

Tagged: adult schizophrenia, affective disorder, antibodies, family-history, individuals, infections, maternal exposure, neonatal, prenatal influenza, psychosis, register, Schizophrenia, Toxoplasma gondii, viral encephalitis

Mental health

Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring

October 30, 2005
Brown, A. S., Schaefer, C. A., Quesenberry, C. P., Liu, L. Y., Babulas, V. P., Susser, E. S.
American Journal of Psychiatry 2005; 162: 767-773
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Objective: The authors examined the relationship between maternal antibody to toxoplasmosis and the risk of schizophrenia and other schizophrenia spectrum disorders in offspring. Toxoplasmosis is known to adversely affect fetal brain development. Method: In a nested case-control design of a large birth cohort born between 1959 and 1967, the authors conducted serological assays for Toxoplasma antibody on maternal serum specimens from pregnancies giving rise to 63 cases of schizophrenia and other schizophrenia spectrum disorders and 123 matched comparison subjects. Toxoplasma immunoglobulin (Ig) G antibody was quantified by using the Sabin-Feldman dye test. The Ig titers were classified into three groups: negative (< 1: 16) reference), moderate ( 1: 16 - 1: 64), and high (>= 1: 128). Results: The adjusted odds ratio of schizophrenia/schizophrenia spectrum disorders for subjects with high maternal Toxoplasma IgG antibody titers was 2.61 ( 95% confidence interval = 1.00 - 6.82). There was no association between moderate Toxoplasma Ig antibody titers and the risk of schizophrenia/spectrum disorders. Conclusions: These findings suggest that maternal exposure to toxoplasmosis may be a risk factor for schizophrenia. The findings may be explained by reactivated infection or an effect of the antibody on the developing fetus. Given that toxoplasmosis is a preventable infection, the findings, if replicated, may have implications for reducing the incidence of schizophrenia.

Tagged: antibodies, diagnosis, etiology, gondii infection, maternal exposure, shizophrenia

Mental 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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