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Toxoplasma gondii & Human Phenotype

Compendium of Known Effects and Ongoing Research

agents

Infection and inflammation in schizophrenia and bipolar disorder

January 3, 2017
Tanaka, T., Matsuda, T., Hayes, L. N., Yang, S. J., Rodriguez, K., Severance, E. G., Yolken, R. H., Sawa, A., Eaton, W. W.
Neuroscience Research 2017; 115: 59-63
Click for abstract
The present study investigated the relationship between exposure to infectious agents and inflammation markers in individuals with schizophrenia (SZ), bipolar disorder (BP), and controls without a psychiatric disorder. We measured plasma levels of antibodies and innate immune markers and correlated them with clinical symptoms and cognitive function. In both SZ and BP, we found an increase in soluble CD14, and in BP an increase in C-reactive protein, IgM class antibodies against cytomegalovirus (CMV), and IgG class antibodies against herpes simplex virus 2. Furthermore in BP, we observed a negative relationship between IgG antibodies against CMV and scores for cognitive function. (C) 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Tagged: agents, antibodies, antibody level, bipolar disorder, cognitive deficits, glial tnf-alpha, individuals, inflammation, markers, metaanalysis, neurocognition, recent-onset schizophrenia, Schizophrenia, synapses, Toxoplasma gondii

Mental health

Toxoplasma gondii-A gastrointestinal pathogen associated with human brain diseases

October 3, 2016
Severance, E. G., Xiao, J., Jones-Brando, L., Sabunciyan, S., Li, Y., Pletnikov, M., Prandovszky, E., Yolken, R.
In: Cryan JF, Clarke G, eds. Gut Microbiome and Behavior 2016: pp. 143-163. (International Review of Neurobiology).
Click for abstract
Serious psychiatric disorders such as schizophrenia, bipolar disorder, and major depression are important causes of mortality and morbidity worldwide. While these are primarily diseases involving altered brain functioning, numerous studies have documented increased rates of gastrointestinal inflammation and dysfunction in many individuals with these disorders. Toxoplasma gondii is an apicomplexan protozoan intracellular parasite with a widespread distribution in both developed and developing countries. Toxoplasma organisms enter the ecosystem through the shedding of oocysts by Toxoplasma-infected felines. In almost all cases of postnatal human infection, Toxoplasma enters its hosts through the intestinal tract either by the ingestion of oocysts or by the consumption of meat from food animals which themselves were infected by Toxoplasma oocysts. It had previously been thought that most cases of Toxoplasma infection in immune competent children and adults were inapparent and asymptomatic. However, recent studies cast doubt on this concept as exposure to Toxoplasma has been associated with a range of acute and chronic symptoms. Of particular note has been the finding of an increased rate of a range of neurological and psychiatric disorders associated with serological evidence of Toxoplasma exposure. A role of Toxoplasma infection in brain diseases is also supported by the consistent finding of altered cognition and behavior in animal models of infections. Much of the attention relating to the role of Toxoplasma infection in neuropsychiatric disorders has focused on the brain, where Toxoplasma tissue cysts can persist for extended periods of time. However, recent discoveries relating to the role of the gastrointestinal tract in cognition and behavior suggest that Toxoplasma may also increase susceptibility to human brain diseases through immune activation, particularly involving the gastrointestinal mucosa. The study of the pathways relating to the pathobiology and immunology of Toxoplasma infection may provide insights into the pathogenesis of a range of human neuropsychiatric disorders as well as into cognitive functioning in otherwise healthy individuals.

Tagged: agents, antibodies, bipolar disorder, individuals, infection, inflammatory-bowel-disease, risk factors, Schizophrenia, self-directed violence, united-states

Cognitive functionsMental health

Association between latent toxoplasmosis and clinical course of schizophrenia – continuous course of the disease is characteristic for Toxoplasma gondii-infected patients

October 9, 2015
Celik, T., Kartalci, S., Aytas, O., Akarsu, G. A., Gozukara, H., Unal, S.
Folia Parasitologica 2015; 62
Click for abstract
The aim of the present study was to investigate the association between various clinical aspects of schizophrenia and seropositivity against Toxoplasma gondii (Nicolle et Manceaux, 1908). We selected 94 patients with schizophrenia and investigated the seropositivity rate for anti-T. gondii IgG antibodies by ELISA. Clinical parameters of schizophrenic patients such as illness type and status, clinical course, awareness of the illness and need for electroconvulsive therapy (ECT) were compared with their serological status. Anti-T. gondii IgG antibodies were detected in 43 (46%) of schizophrenic patients. Chronic patients had a rate of 34 (72%) seropositivity, whereas 9 (22%) of the patients with partial remission showed evidence of latent toxoplasmosis. Of continuous patients, 35 (81%) were found to be seropositive and this rate was significantly more than in the other groups. The rate of latent toxoplasmosis was detected significantly higher in patients who lack awareness of schizophrenia (36, i.e. 72%) than the patients who were aware of their illnesses (7, i.e. 16%). Anti-T. gondii IgG antibodies were detected in 38 (70%) of ECT performed patients while this percentage was 13% in the ones who had never been treated with ECT. This difference was also statistically significant. We showed that Toxoplasma-infected subjects had 15x higher probability of having continuous course of disease than Toxoplasma-free subjects. Our results put forth the possibility of latent toxoplasmosis to have a negative impact on the course of schizophrenia and treatment response of schizophrenic patients.

Tagged: agents, antibodies, cell-cultures, CMV, Dopamine, individuals, mechanism, mice, prognosis, risk factors, schizophrenia patients, serology, toxoplasmosis

Mental health

Treatment with anti-toxoplasmic activity (TATA) for Toxoplasma positive patients with bipolar disorders or schizophrenia: A cross-sectional study

October 9, 2015
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.
Click for abstract
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.

Tagged: agents, antipsychotic drugs, bipolar disorder, depression, drugs, gondii infection, individuals, metaanalysis, mood stabilizer, onset, rating-scale, Schizophrenia, suicide attempts, Toxoplasma gondii, validity, valproate

Mental health

An observational study of inflammation in the central nervous system in patients with bipolar disorder

January 5, 2015
Stich, O., Andres, T. A., Gross, C. M., Gerber, S. I., Rauer, S., Langosch, J. M.
Bipolar Disorders 2015; 17: 291-302
Click for abstract
ObjectivesThe potential influence of infections and immunological changes on the aetiology and pathogenesis of bipolar disorder (BD) has been discussed. Our aim was to detect intrathecal specific antibody synthesis against the neurotropic infectious agents that have previously been linked to BD. MethodsPaired cerebrospinal fluid (CSF) and serum samples from 40 patients with BD were analysed using the enzyme-linked immunosorbent assay to detect the concentration of antibodies against the following neurotropic infectious pathogens: Toxoplasma gondii (T.gondii), herpes simplex virus (HSV) types 1 and 2, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). The specific antibody index (AI) was calculated, and an AI>1.4 was considered to be evidence of intrathecal specific antibody synthesis. Twenty-six patients with pseudotumour cerebri served as controls. ResultsEight out of 40 patients with BD displayed specific intrathecal antibody synthesis against at least one of the tested neurotropic agents compared to only one patient in the control group (p=0.061, not significant). Of these eight patients with BD, no significant prevalence of any particular neurotropic pathogen was evident. Five out of 40 patients with BD showed oligoclonal bands in the CSF, suggestive of a chronic immune reaction in the central nervous system (CNS). ConclusionsWe found evidence for increased production of antibody in the CSF of individuals with BD. However, the trend for polyspecific intrathecal antibody synthesis, as well as the presence of oligoclonal bands, might indicate activation of the intrathecal humoral immune system in a subgroup of patients with BD, as it is known to be associated with autoimmune disorders of the CNS.

Tagged: agents, antibodies, antibody index, autoimmunity, bipolar disorder, cerebrospinal fluid, cognitive deficits, cytomegalovirus, disease, epstein-barr-virus, herpes-simplex, herpesviridae, infection, intrathecal synthesis, networks, neurotropic agents, psychosis, Schizophrenia, simplex-virus type-1, Toxoplasma gondii, toxoplasma gondii infection

Mental health

Antibodies to Toxoplasma gondii and cognitive functioning in schizophrenia, bipolar disorder, and nonpsychiatric controls

October 9, 2014
Dickerson, F., Stallings, C., Origoni, A., Katsafanas, E., Schweinfurth, L., Savage, C., Khushalani, S,. Yolken, R.
Journal of Nervous and Mental Disease 2014; 202: 589-593
Click for abstract
Increased rates of exposure to Toxoplasma gondii have been found in individuals with schizophrenia and bipolar disorder, but the association between Toxoplasma and cognitive functioning has not previously been examined. We measured IgG and IgM class antibodies to Toxoplasma in 408 nonelderly individuals with schizophrenia, 347 with bipolar disorder, and 352 nonpsychiatric controls. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status. Multivariate linear and regression analyses showed significant associations between Toxoplasma IgM antibody level and cognitive scores within the control group and the bipolar disorder group but not the schizophrenia group. Within the control group, having an elevated Toxoplasma IgM antibody level, greater than or equal to the 50th and 75th levels of the control group, was associated with significantly elevated odds of a low total cognitive score. Exposure to Toxoplasma may confer risk for lower cognitive functioning in persons without a psychiatric disorder and those with bipolar disorder.

Tagged: agents, bipolar disorder, cognition, deficits, impairment, infection, Parasite, Schizophrenia, simplex-virus type-1, Toxoplasma gondii

Cognitive functionsMental health

Prevalence of Toxoplasma gondii infection among individuals with severe mental illness in Nigeria: a case control study

October 11, 2013
James, B. O., Agbonile, I. O., Okolo, M., Lawani, A. O., Omoaregba, J. O.
Pathogens and Global Health 2013; 107: 189-193
Click for abstract
Background: While the aetiology for most psychotic disorders is unknown, a strong association has been observed between Toxoplasma gondii infection and psychosis. The proportion of individuals with psychotic disorders who have current or past infection with toxoplasma has been varied. Reports from the African continent have however been scanty. Methods: A case control study of patients with a psychotic disorder presenting for the first time to a regional psychiatric facility was undertaken and compared to age and sex-matched healthy controls. In addition to socio-demographic and clinical characteristics, seroprevalence (IgG and IgM) of T. gondii was undertaken using an immunoassay test kit. Results: IgG seropositivity was significantly higher among cases (30.7% vs 17.85%, OR=2.04, 95% CI=1.12-3.74, P<0.02). In contrast, IgM seropositivity was significantly lower among the cases (7.14% vs 8.57%, OR=0.82, 95% CI=0.31-2.16, P=0.82). Cases who were IgG seropositive to T. gondii were more likely to be older (P<0.001) and female (P<0.001). There was no statistically significant difference in terms of T. gondii infection and, eaten poorly cooked meat (0.88), and diagnostic group (P=0.53). Though there was a trend towards exposure to cats, this failed to reach significance (P=0.08). Conclusion: T. gondii (IgG) infection is common among individuals with severe mental illness sampled and significantly higher compared to controls.

Tagged: agents, antibodies, behavior, nigeria, posttraumatic-stress-disorder, risk factors, Schizophrenia, severe mental illness, Toxoplasma gondii

Mental health

Toxoplasma infection and later development of schizophrenia in mothers

January 5, 2011
Pedersen, M. G., Stevens, H., Pedersen, C. B., Norgaard-Pedersen, B., Mortensen, P. B
American Journal of Psychiatry 2011;168: 814-821
Click for abstract
Objective: Several studies based on clinical samples have found an association between Toxoplasma gondii infection and schizophrenia, and a case-control study among U. S. military personnel with specimens available from both before and after diagnosis found a positive association between T. gondii immunoglobulin G (IgG) antibody level and schizophrenia. These findings have never been replicated in a prospective cohort study. The purpose of this study was to determine whether mothers infected with T. gondii have an elevated risk of schizophrenia or related disorders and whether the risk depends on IgG antibody level. Method: In a register-based prospective cohort study of 45,609 women born in Denmark, the level of T. gondii-specific IgG antibodies was measured in connection with childbirth between 1992 and 1995. Women were followed up from the date of delivery until 2008. Results: A significant positive association between T. gondii IgG antibody level and schizophrenia spectrum disorders was found. Mothers with the highest IgG level had a relative risk of 1.73 (95% confidence interval [CI]=1.12-2.62) compared with mothers with the lowest IgG level. For schizophrenia, the relative risk was 1.68 (95% CI=0.77-3.46). When the mothers were classified according to IgG level, only those with the highest IgG levels had a significantly higher risk of schizophrenia spectrum disorders. Conclusions: Women with high levels of T. gondii-specific IgG antibodies have a significantly elevated risk of developing schizophrenia spectrum disorders.

Tagged: acid, agents, antibodies, brain, disease, gondii infection, molecular mimicry, systém

Mental health

Toxoplasmosis as a cause for behaviour disorders – overview of evidence and mechanisms

October 19, 2010
Fekadu A, Shibre T, Cleare AJ.
Folia Parasitologica 2010; 57: 105-113
Click for abstract
Background - There is growing interest in the role of microbial agents in the causation of psychiatric disorders. The neurotropic protozoan parasite Toxoplasma gondii is one of the main candidates and has been associated with various psychiatric conditions, including schizophrenia. Methods - A narrative review of the literature from the main medical databases (Medline, PubMed, PsycINFO), Google Scholar and Google using combinations of applicable terms. Results - T. gondii affects the brain in both the acute and the latent stages of infection causing apparent brain pathologies in infected rodents and both immuno-compromised and immuno-competent humans. In immuno-competent individuals, behavioural disorders are primarily related to the latent stages of the illness. Behavioural/mental disorders that include schizophrenia, mood disorders, personality changes and cognitive impairments may be related to infection with T gondii. Evidence for a behavioural effect of T gondii comes from observational reports in animal models and controlled behavioural analysis in humans. Indirect clues of infection also come from raised seroprevalence or serotitres of antitoxoplasma antibodies among those with mental disorders. The pathophysiologic mechanism through which T gondii may exert its effect is not clear, but direct impact on the brain and changes in neuroimmunomodulation, neurotransmission and some gene-environment interactions are postulated. Conclusion - There is evidence supporting a potential role of T gondii infection in the onset of some behavioural disorders. Confirmation of such a role would prove a significant breakthrough in the search for the aetiology, treatment and prevention of behavioural disorders, such as schizophrenia. However, the associations remain preliminary.

Tagged: 1st-episode schizophrenia, agents, antibodies, behavioural disorder, decreased level, gondii infection, individuals, mental-health surveys, mood, mood disorders, novelty seeking, personality changes, review, risk, Schizophrenia, Toxoplasma gondii, toxoplasmosis

Mental healthReviews

Toxoplasma gondii infection in first-episode and inpatient individuals with schizophrenia

January 9, 2010
Hamidinejat, H., Ghorbanpoor, M., Hosseini, H., Alavi, S. M., Nabavi, L., Jalali, M. H., Borojeni, M. P., Jafari, H., Mohammadaligol, S.
International Journal of Infectious Diseases 2010; 14: E978-E981
Click for abstract
Background: A high seroprevalence of Toxoplasma gondii infection has been detected in psychiatric patients, particularly in schizophrenia cases. Methods: In the present study 98 patients suffering from schizophrenia (58 inpatients and 40 first-episode patients) and 96 control patients (50 healthy volunteers and 46 with a depressive disorder) were examined for the presence of both IgG and IgM antibodies against T. gondii by enzyme-linked immunosorbent assay (ELISA). We applied the Bradford Hill criteria to identify the weight of causal inference. Results: The positivity rate of anti-T. gondii IgG antibodies among individuals with schizophrenia (57.1%) was significantly higher than in healthy controls (29.2%). There were no associations between immune status ratio (ISR) values and the risk of schizophrenia. The weight of evidence approach using the Bradford Hill criteria revealed a 92% probability of a causal association. Conclusion: Our results show that exposure to T. gondii may lead to schizophrenia. (C) 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Tagged: agents, antibodies, behavior, depressive disorder, disorders, mice, rats, Schizophrenia, Toxoplasma gondii

Mental health

Psychosis may be associated with toxoplasmosis

October 26, 2009
Zhu S.
Medical Hypotheses 2009; 73: 799-801.
Click for abstract
Many parasites induce characteristic changes in their host. The effect of Toxoplasma gondii infection on the cerebrum and neuropsychiatric patients has been increasingly emphasized in recent years. T gondii has a high affinity for brain tissue where tachyzoites may form tissue cysts and persist for a life long time. Some psychiatric symptoms such as schizophrenia and mental retardation may be induced by the infection of T gondii. Furthermore, experiments demonstrated that some antipsychotics and mood stabilizers used to treat psychosis displayed the function of inhibiting T. gondii replication. Investigations from various regions in China in psychotic patients support the hypotheses that psychosis may be linked to T gondii infection. (C) 2009 Elsevier Ltd. All rights reserved.

Tagged: agents, behavior, Dopamine, gondii, host, infection, parasitosis, rats, risk, Schizophrenia

Mental health

The schizophrenia and Toxoplasma gondii connection: Infectious, immune or both?

October 26, 2008
Tamer, G. S., Dundar, D., Yalug, I., Caliskan, S., Yazar, S., Aker, A.
Advances in Therapy 2008; 25: 703-709
Click for abstract
Introduction: Recent research has suggested a possible link between toxoplasmic agents and schizophrenia. We aimed to assess this by measuring Toxoplasma gondii-associated antibodies in schizophrenia patients and controls. Methods: We used a commercially available enzyme-linked immunosorbent assay (ELISA) kit to measure the level of immunoglobulin G (IgG) and IgM antibodies in serum samples from schizophrenia patients (n= 40) and from a group of non-schizophrenic control subjects (n= 37). Results: Among schizophrenic patients, 16 (40%) showed IgG seropositivity and two (5%) showed IgM seropositivity. Among the control group, five (13.5%) were found have IgG seropositivity and one (2.7%) showed IgM seropositivity. In our study we found that IgG T gondii antibodies were significantly higher in schizophrenia patients compared with controls. Conclusion: This study supports the theory that toxoplasmic agents may have a role in the aetiology of schizophrenia.

Tagged: agents, antibodies, enzyme immunoassay, exposure, individuals, personality, psychosis, risk, Schizophrenia, Toxoplasma gondii

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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