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Toxoplasma gondii & Human Phenotype

Compendium of Known Effects and Ongoing Research

brain

Seroprevalence of Toxoplasma gondii infection in cancer patients: A systematic review and meta-analysis

February 4, 2020
Anvari, D., Sharif, M., Sarvi, S., Aghayan, S. A., Gholami, S., Pagheh, A. S., Hosseini, S. A., Saberi, R., Chegeni, T. N., Hosseininejad, Z., Daryani, A.
Microbial Pathogenesis 2019, 129: 30 - 42
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Toxoplasmosis, caused by Toxoplasma gondii, is a great public health concern in cancer patients, which can induce serious pathological effects. This systematic review and meta-analysis was performed to evaluate the worldwide seroprevalence rate of T. gondii infection among cancer patients. A search was conducted on five electronic databases that reported data on T. gondii seroprevalence in cancer patients. The searching process resulted in the inclusion of 57 studies. The results showed that T. gondii had the pooled prevalence of 30.8% in cancer patients using a random-effect model (95% CI: 26.3-35.6). Cancer patients had a higher overall prevalence of T. gondii infection, compared to those without cancer. Furthermore, the odds ratio of toxoplasmosis in cancer patients was 3.1 times, compared to that of controls (95% CI: 2.5-3.8, P < 0.0001). Toxoplasmosis had a higher prevalence in females (40%) than in males (33%). Furthermore, the age group of upper 40 years had the highest prevalence infection rate (30%). In addition, a significant association was also observed between toxoplasmosis infection and year (P < 0.001), type of cancer (P < 0.001), country (P < 0.001), gender (P < 0.001), age (P = 0.006) and diagnostic method (P < 0.001) in cancer patients. Considering the high prevalence of T. gondii infection in cancer patients and its serious outcomes, the researchers are suggested to carry out further studies to prevent and control toxoplasmosis among this population.

Tagged: antibodies, b1 gene, brain, childern, cncer patients, epidemiologymalignancies, healthy, individuals, liver-disease, meta-analysis, systematic review, Toxoplasma gondii, toxoplasmosis

Reviews

Presence of Toxoplasma gondii infection in brain as a potential cause of risky behavior: a report of 102 autopsy cases

February 1, 2020
Samojlowicz, D. Twarowska-Malczynska, J. Borowska-Solonynko, A. Poniatowski, L. A. Sharma, N. Olczak, M.
European Journal of Clinical Microbiology and Infectious Diseases 2019, 38: 305 - 317 Toxoplasma gondii Toxoplasmosis Brain Risky behavior Alcohol Mental health Drivers cerebral toxoplasmosis decreased level novelty seeking dopamine parasite host schizophrenia personality depression strategies
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Toxoplasmosis was linked to impairment in brain function, encompassing a wide range of behavioral and neuropsychiatric changes. Currently, the precise localization of Toxoplasma gondii in the human brain is limited and the parasite DNA was not found in population-based screening of autopsy cases. The aim of proposed study was to identify the presence of parasite DNA within the brain and its association with risky behavior and alcohol consumption in postmortem examination. Preliminarily, 102 cases with certain circumstances of death at time of forensic autopsy was included. Due to high risk of bias, the females were excluded from the analysis and final study group consists 97 cases divided into three groups: risky behavior, inconclusively risky behavior, and control group. The obtained tissue samples for Nested PCR covered four regions of the brain: symmetric left/right and anterior/posterior horns of lateral ventricles comprising lining ependyma and hippocampus. The second type of material comprised blood evaluated for antibodies prevalence using ELISA and alcohol concentration using HS-GC-FID. Analysis demonstrated 16.5% prevalence concerning the parasite DNA presence in examined brain tissue samples without specific distribution and association with age at death or days after death until an autopsy was performed. Results have shown correlation between occurrence of risky behavior leading to death and higher proportions of positive parasite DNA presence within the brain. Correlation was not observed between parasite DNA presence and excessive alcohol consumption. Conducted screening demonstrated correlation between parasite DNA presence in the brain with risky behavior and provided new information on possible effects of latent toxoplasmosis.

Tagged: alcohol, brain, Cerebral toxoplasmosis, decreased level, depression, health, host, mental, novelty seeking, Parasite, personality, risky behavior, Schizophrenia, Toxoplasma gondii, toxoplasmosis

BehaviorMental healthPersonality

Host-parasite interaction associated with major mental illness

January 29, 2020
Kano, S., Hodgkinson, C. A., Jones-Brando, L., Eastwood, S., Ishizuka, K., Niwa, M., Choi, E. Y., Chang, D. J., Chen, Y., Velivela, S. D., Leister, F., Wood, J., Chowdari,K., Ducci, F., Caycedo, D. A., Heinz, E., Newman, E. R., Cascella, N., Mortensen, P. B., Zandi, P. P., Dickerson, F., Nimgaonkar, V., Goldman, D., Harrison, P. J., Yolken, R. H., Sawa, A.
Molecular Psychiatry 2020, 25: 194 - 205
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Clinical studies frequently report that patients with major mental illness such as schizophrenia and bipolar disorder have comorbid physical conditions, suggesting that systemic alterations affecting both brain and peripheral tissues might underlie the disorders. Numerous studies have reported elevated levels of anti-Toxoplasma gondii (T. gondii) antibodies in patients with major mental illnesses, but the underlying mechanism was unclear. Using multidisciplinary epidemiological, cell biological, and gene expression profiling approaches, we report here multiple lines of evidence suggesting that a major mental illness-related susceptibility factor, Disrupted in schizophrenia (DISC1), is involved in host immune responses against T. gondii infection. Specifically, our cell biology and gene expression studies have revealed that DISC1 Leu607Phe variation, which changes DISC1 interaction with activating transcription factor 4 (ATF4), modifies gene expression patterns upon T. gondii infection. Our epidemiological data have also shown that DISC1 607 Phe/Phe genotype was associated with higher T. gondii antibody levels in sera. Although further studies are required, our study provides mechanistic insight into one of the few well-replicated serological observations in major mental illness.

Tagged: bipolar disorder, brain, catechol-o-methyltransferase, genetic, olfactory cells, risk faktor, Schizophrenia, toxoplasma gondii infection

Mental health

Impact of ApoE genotypes variations on Toxoplasma patients with dementia

December 8, 2017
Yahya, R. S., Awad, S. I., El-Baz, H. A., Saudy,N., Abdelsalam, O. A., Al-Din, M. S. S.
Journal of Clinical Neuroscience 2017;39:184-188
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Background: Toxoplasma deprives host neuron cells from cholesterol and leads to its ability to potentiate dementia. ApoE intermediates neuronal transmission of cholesterol, which is a key constituent for axonal development, redesigning occasions that are important for education and synaptic arrangement, development of memory and repair of neuron. The aim of this work is to investigate the effect of ApoE genotypes on dementia associated with neurodegeneration in latent Toxoplasma gondii in elderly population. Methods: This study comprised: 133 patients with dementia (78 were positive for toxoplasma IgG and 55 were negative) and 95 subjects as control group without dementia (30 were positive for toxoplasma IgG and 65 were negative). All of them were subjected to a cognitive assessment, T. gondii seropositivity (ELISA) and determination of ApoE allelic forms (PCR). Results: The ApoE genotype distribution shows that the most predominant genotype is ApoE3/3 and the most widely recognized allele is E3. Both patients and control were further divided into Toxoplasma IgG positive group (n = 108) and Toxoplasma IgG negative group (n = 120). ApoE4 non carrier, ApoE 2/3 and ApoE 3/3 alleles have highly significant differences (P < 0.001) between dementia and non-dementia patients in Toxoplasma infected patients in comparison to non-infected ones. Conclusion: Toxoplasma positive patients have more risk to develop dementia regardless ApoE4 carriage. (C) 2017 Elsevier Ltd. All rights reserved.

Tagged: alzheimers-disease, apoE, apolipoprotein-e, association, brain, cells, dementia, gondii, neurocognitive dysfunctions, Toxoplasma

Mental health

Association between anti-Toxoplasma gondii antibodies and schizophrenia and psychotic bipolar in patients hospitalized in the psychiatric ward

October 6, 2016 12 Comments
Dalimiasl, A., Mosayebi, M., Ghorbanzadeh, B., Ghasemi, M., Hajihossein, R.
Australasian Medical Journal 2016; 9: 313-318
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Background Toxoplasmosis is caused by an intracellular parasite and is a worldwide disease. In laboratory, the parasites that cause the disease increases levels of dopamine in the brain tissue of treated mice. The evidence showed that dopamine releasing in the nucleus accumbens by activating the retro hippocampal region can disrupt the fornix section of brain as evolve to develop a psychosis in human. Methods This retrospective case-control study was conducted in patients with schizophrenia and psychotic bipolar referred to psychiatric clinic in Amir Kabir hospital, Arak. After psychiatric diagnosis of patients with schizophrenia and bipolar disorder, 2ml of blood samples were acquired from 76 patients and 75 controls without any psychotic illness or bipolar disorder and other mental illnesses with safety issues. The serum of samples was separated in laboratory and was kept until the time of testing at -20 degrees C. After collecting all the samples; Anti-Toxoplasma IgG on the case and control samples were analysed by ELISA. Results were analysed by SPSS software version 16 and were calculated by chi 2 tests. Results 55.26 per cent of patients (42 persons) were infected with Toxoplasma gondii and in the control group 36 per cent (27 patients) were infected, that the different between them was significant (p<0/05). Toxoplasmosis in psychotic men was more than psychotic women significantly (p<0/05). Toxoplasma gondii infection in patients with schizophrenia with psychotic bipolar patients showed no significant difference. Conclusion Patients with schizophrenia and bipolar disorder showed significantly higher rate than healthy people against Toxoplasma gondii infection. Whether prevention of infection with these parasites is effective in reducing the risk of psychosis requires further investigation.

Tagged: bipolar, brain, Dopamine, infection, latent toxoplasmosis, psychotic, risk, Schizophrenia, Toxoplasma gondii, traffic accidents

Mental health

Toxoplasma gondii infection and schizophrenia: an inter-kingdom communication perspective

October 6, 2016 59 Comments
Elsheikha, H.M., Zhu, X.Q.
Current Opinion in Infectious Diseases 2016; 29: 311-318.
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Purpose of review The apicomplexan protozoan Toxoplasma gondii has a striking predilection for infecting the central nervous system and has been suggested as a risk factor for schizophrenia. Here, we address some of the mechanisms by which T. gondii achieves this by manipulating signaling pathways of the host brain cells. Recent findings Recent years have brought notable progress in the understanding of how the opportunistic parasite T. gondii establishes a successful infection in mammalian brain by secreting effector molecules that manipulate multiple cell functions. Many pathways involved in this inter-kingdom signaling, such as dopaminergic, GABAergic and kynurenine pathways, also have key roles in the development of schizophrenia. More understanding of T. gondii-brain cell interaction holds the key to unlocking the mystery of T. gondii-mediated schizophrenia pathogenesis. Summary T. gondii usurps a variety of host signaling pathways to ensure physiological adaptation, evasion of host immune defense systems, and efficient replication. A detailed knowledge of T. gondii signaling molecules involved in this cross-kingdom communication with host brain cells will probably provide novel means of pharmacologically manipulating host cellular pathways to promote efficient elimination of the parasite and may permit the development of new schizophrenia-modifying therapeutics.

Tagged: acid, behavior, brain, cell-cultures, cognitive impairment, host-pathogen interaction, inter-kingdom signaling, mice, nadph oxidase, Parasite, reproducing increased dopamine, Schizophrenia, Toxoplasma gondii, tyrosine-hydroxylase activity

Mental health

Reduced ERPs and theta oscillations underlie working memory deficits in Toxoplasma gondii infected seniors

October 6, 2016 Leave a Comment
Gajewski, P. D., Falkenstein, M., Hengstler, J. G., Golka, K.
Psychology 2016; 120: 35-45.
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Toxoplasma gondii is one of the most widespread infections in humans. Recent studies give evidence for memory deficits in infected older adults. To investigate working memory dysfunction in infected elderly, a double-blinded electrophysiological study was conducted. 84 persons derived from a sample of 131 healthy participants with the mean age of 70 years were assigned to two groups of 42 non-infected and 42 infected individuals. The outcome measures were behavioral performance, target and response-related ERPs, and time-frequency wavelets during performance in a n-back working-memory task. The infected individuals showed a reduced rate of detected targets and diminished P3b amplitude both in target-locked as well as response-locked data compared to the non-infected group. Time-frequency decomposition of the EEG-signals revealed lower evoked power in the theta frequency range in the target-locked as well as in the response-locked data in infected individuals. The reported effects were comparable with differences between healthy young and old adults described previously. Taking together, the reduced working-memory performance accompanied by an attenuated P3b and frontal theta activity may suggest neurotransmitter imbalance like dopamine and norepinephrine in T. gondii infected individuals. In face of a high prevalence of T. gondii infection and the increasing ratio of older population their accelerated memory decline may have substantial socioeconomic consequences.

Tagged: (erps) aging, behavior, brain, Dopamine, eeg-dynamics, event-related potentials, latent toxoplasmosis, norepinephrine, p300, performance, response-locked erps, Schizophrenia, stimulus-locked erps, task, theta, time-window, Toxoplasma gondii, working memory

Cognitive functions

Infection and characterization of Toxoplasma gondii in human induced neurons from patients with brain disorders and healthy controls

October 3, 2016 15 Comments
Passeri E, Jones-Brando, L Bordon, C Sengupta, S Wilson, AM Primerano, A Rapoport, JL Ishizuka, K Kano, S Yolken, RH Sawa, A
Microbes and Infection 2016; 18: 153-158
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Toxoplasma gondii is a protozoan parasite capable of establishing persistent infection within the brain. Serological studies in humans have linked exposure to Toxoplasma to neuropsychiatric disorders. However, serological studies have not elucidated the related molecular mechanisms within neuronal cells. To address this question, we used human induced neuronal cells derived from peripheral fibroblasts of healthy individuals and patients with genetically-defined brain disorders (i.e. childhood-onset schizophrenia with disease-associated copy number variations). Parasite infection was characterized by differential detection of tachyzoites and tissue cysts in induced neuronal cells. This approach may aid study of molecular mechanisms underlying individual predisposition to Toxoplasma infection linked to neuropathology of brain disorders

Tagged: antibodies, bipolar disorder, brain, cells, conversion, cysts, diseases, disorders, fibroblasts, functional-neurons, induced neuronal cells, risk, Schizophrenia, tachyzoites, Toxoplasma gondii

Physical health

Relationship of Toxoplasma Gondii Exposure with Multiple Sclerosis

January 4, 2016
Oruc, S.
European Journal of General Medicine, 2016, 13: 58-63
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Objective: Toxoplasma gondii infection is a very common parasitic disease in human. In Turkey, the rate of seropositivity was reported as 23.1% to 36%. Because of the high affinity of parasite into Central Nervous System (CNS), chronic toxoplasma infection has been found correlated with many neuropsychiatric disorders, including altered mental status, obsessive-compulsive disorder, cognitive impairment, epilepsy, headache and schizophrenia. In this study, we aimed to investigate whether T. gondii has any role in Multiple Sclerosis (MS) by measuring anti-T. gondii IgG antibodies. Methods: Fifty-two MS patients followed up and 45 controls with similar age and socioeconomic status were included in the study. Anti-T. gondii IgL antibodies of the patients and controls were studied in blood with micro-enzyme-linked immunosorbent assay (ELISA) technique. Results: Of 52 MS patients included in the study, 37 had RRMS, 10 PPMS and 5 SPMS. Mean age of onset of the disease was 31.7 +/- 10.4 (min; 14 and max; 53). Twenty three of 52 (44.2%) cases with MS and 11 of 45 (24.4%) healthy controls were positive for anti-T. gondii IgG antibodies. There was a statistically significant difference between the rates of positivity between the MS patient group and control group (p=0.042). Conclusion: This study shows a relation of chronic T. Gondii infection with MS. According to this study, experienced T. gondii infection may be one of the several environmental risk factors for MS.

Tagged: activated microglia, autoimmunity, brain, chronic infection, disease, environmental risk-factors, hygiene hypothesis, infection, inflammation, interferon-gamma, metaanalysis, multiple sclerosis, pathogenesis, Toxoplasma gondii

Physical health

Seropositivity and serointensity of Toxoplasma gondii antibodies and DNA among patients with schizophrenia

October 29, 2015
Omar, A., Bakar, O. C., Adam, N. F., Osman, H., Osman, A., Suleiman, A. H., Manaf, M. R. A., Selamat, M. I.
Korean Journal of Parasitology 2015; 53: 29-34
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The aim of this cross sectional case control study was to examine the serofrequency and serointensity of Toxoplasma gondii (Tg) IgG, IgM, and DNA among patients with schizophrenia. A total of 101 patients with schizophrenia and 55 healthy controls from Sungai Buloh Hospital, Selangor, Malaysia and University Malaya Medical Center (UMMC) were included in this study. The diagnosis of schizophrenia was made based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The presence of Tg infection was examined using both indirect (ELISA) and direct (quantitative real-time PCR) detection methods by measuring Tg IgG and IgM and DNA, respectively. The serofrequency of Tg IgG antibodies (51.5%, 52/101) and DNA (32.67%, 33/101) among patients with schizophrenia was significantly higher than IgG (18.2%, 10/55) and DNA (3.64%, 2/55) of the controls (IgG, P=0.000, OD=4.8, CI=2.2-10.5; DNA, P=0.000, OD=12.9, CI=2.17-10.51). However, the Tg IgM antibody between patients with schizophrenia and controls was not significant (P>0.005). There was no significant difference (P>0.005) in both serointensity of Tg IgG and DNA between patients with schizophrenia and controls. These findings have further demonstrated the strong association between the active Tg infection and schizophrenia.

Tagged: 1st-episode, behavior, brain, disorders, Dopamine, individuals, infectious agents, meta-analysis, mice, receptor-binding, Schizophrenia, serofrequency, serointensity, Toxoplasma gondii

Mental health

Neurobiological studies on the relationship between toxoplasmosis and neuropsychiatric diseases

October 9, 2015 Leave a Comment
Fabiani, S., Pinto, B., Bonuccelli, U., Bruschi, F.
Journal of the Neurological Sciences 2015; 35:3-8
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Toxoplasma gondii is a widespread protozoan parasite infecting approximately one third of the world population. After proliferation of tachyzoites during the acute stage, the parasite forms tissue cysts in various anatomical sites including the Central Nervous tissue, and establishes a chronic infection. Clinical spectrum normally ranges from a completely asymptomatic infection to severe multi-organ involvement. Many studies have suggested T. gondii infection as a risk factor for the development of some neuropsychiatric disorders, particularly schizophrenia. During the last years, a potential link with other neurobiological diseases such as Parkinson disease and Alzheimer disease has also been suggested. This review will focus on neurobiological and epidemiological data relating infection with T. gondii to neuropsychiatric diseases. (C) 2015 Elsevier B.V. All rights reserved.

Tagged: 1st-episode schizophrenia, brain, encephalitis, expression, gondii infection, immune-response, kynurenic acid, mechanisms, neurobiology, neurological diseases, neurotransmitter pathway, risk behavior, schizophrenia spectrum disorders, seroprevalence, t. gondii

Mental health

Association between latent toxoplasmosis and cognition in adults: a cross-sectional study

October 9, 2015 13 Comments
Gale, S. D., Brown, B. L., Erickson, L. D., Berrett, A., Hedges, D. W.
Parasitology 2015; 142: 557-565
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Latent infection from Toxoplasma gondii (T. gondii) is widespread worldwide and has been associated with cognitive deficits in some but not all animal models and in humans. We tested the hypothesis that latent toxoplasmosis is associated with decreased cognitive function in a large cross-sectional dataset, the National Health and Nutrition Examination Survey (NHANES). There were 4178 participants aged 20-59 years, of whom 191% had IgG antibodies against T. gondii. Two ordinary least squares (OLS) regression models adjusted for the NHANES complex sampling design and weighted to represent the US population were estimated for simple reaction time, processing speed and short-term memory or attention. The first model included only main effects of latent toxoplasmosis and demographic control variables, and the second added interaction terms between latent toxoplasmosis and the poverty-to-income ratio (PIR), educational attainment and race-ethnicity. We also used multivariate models to assess all three cognitive outcomes in the same model. Although the models evaluating main effects only demonstrated no association between latent toxoplasmosis and the cognitive outcomes, significant interactions between latent toxoplasmosis and the PIR, between latent toxoplasmosis and educational attainment, and between latent toxoplasmosis and race-ethnicity indicated that latent toxoplasmosis may adversely affect cognitive function in certain groups.

Tagged: attention, behavior, brain, cognition, deficits, disease, gondii infection, memory, Mexico, performance, processing speed, Schizophrenia, seroprevalence, socioeconomic position, Toxoplasma gondii, toxoplasmosis

Cognitive functions

Seropositivity and serointensity of Toxoplasma gondii antibodies and DNA among patients with schizophrenia

October 6, 2015 Leave a Comment
Omar, A., Bakar, O. C., Adam, N. F., Osman, H., Osman, A., Suleiman, A. H., Manaf, M. R. A., Selamat, M. I.
Korean Journal of Parasitology 2015; 53: 29-34.
Click for abstract
The aim of this cross sectional case control study was to examine the serofrequency and serointensity of Toxoplasma gondii (Tg) IgG, IgM, and DNA among patients with schizophrenia. A total of 101 patients with schizophrenia and 55 healthy controls from Sungai Buloh Hospital, Selangor, Malaysia and University Malaya Medical Center (UMMC) were included in this study. The diagnosis of schizophrenia was made based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The presence of Tg infection was examined using both indirect (ELISA) and direct (quantitative real-time PCR) detection methods by measuring Tg IgG and IgM and DNA, respectively. The serofrequency of Tg IgG antibodies (51.5%, 52/101) and DNA (32.67%, 33/101) among patients with schizophrenia was significantly higher than IgG (18.2%, 10/55) and DNA (3.64%, 2/55) of the controls (IgG, P=0.000, OD=4.8, CI=2.2-10.5; DNA, P=0.000, OD=12.9, CI=2.17-10.51). However, the Tg IgM antibody between patients with schizophrenia and controls was not significant (P>0.005). There was no significant difference (P>0.005) in both serointensity of Tg IgG and DNA between patients with schizophrenia and controls. These findings have further demonstrated the strong association between the active Tg infection and schizophrenia.

Tagged: 1st-episode disorders, behavior, brain, Dopamine, individuals, infectious agents, metaanalysis, mice, receptor-binding, Schizophrenia, serofrequency, serointensity, Toxoplasma gondii

Mental health

Association between latent toxoplasmosis and major depression, generalised anxiety disorder and panic disorder in human adults

October 9, 2014 Leave a Comment
Gale, S. D., Brown, B. L., Berrett, A., Erickson, L. D., Hedges, D. W.
Folia Parasitologica 2014; 61: 285-292.
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Latent infection with the apicomplexan Toxoplasma gondii (Nicolle et Manceaux, 1908) has been associated with schizophrenia, bipolar disorder and self-harm behaviour. However, the potential relationship between T. gondii immunoglobulin G antibody (IgG) seropositivity and generalised-anxiety disorder (GAD) and panic disorder (PD) has not been investigated. The associations between serum reactivity to T. gondii and major depressive disorder (MDD), GAD and PD were evaluated in a total sample of 1846 adult participants between the ages of 20 and 39 years from the United States Center for Disease Control's National Health and Nutrition Examination Survey (NHANES). Approximately 16% of the overall sample was seropositive for T. gondii and 7% of the sample met criteria for MDD, 2% for GAD and 2% for PD. There were no significant associations between T gondii IgG seroprevalence and MDD (OR = 0.484, 95% CI = 0.186-1.258), GAD (OR = 0.737, 95% CI = 0.218-2.490) or PD (OR = 0.683, 95% CI = 0.206-2.270) controlling for sex, ethnicity, poverty-to-income ratio and educational attainment. However, limited evidence suggested a possible association between absolute antibody titres for T. gondii and GAD and PD but not MDD. Toxoplasma gondii seroprevalence was not associated with MDD, GAD or PD within the context of the limitations of this study, although there may be an association of T. gondii serointensity with and GAD and PD, which requires further study.

Tagged: antibodies, behavior, behaviour, bipolar disorder, brain, gondii infection, mood, mood disorders, national health and nutrition examination survey (nhanes), psychiatric, risk factors, Schizophrenia, seroprevalence, Toxoplasma gondii, united-states

Mental health

Toxoplasmosis and neuropsychiatric diseases: can serological studies establish a clear relationship?

October 11, 2013 13 Comments
Fabiani, S., Pinto, B., Bruschi, F.
Neurological Sciences 2013; 34: 417-425
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Toxoplasmosis is a widespread infection, with clinical spectrum ranging from a completely asymptomatic infection to multi-organ involvement. After entering the body, the parasite forms tissue cysts and establishes a chronic infection, involving also the central nervous system (CNS). During the last years, a lot of research has focused on the possible link between exposure to T. gondii and development of neuropsychiatric disorders such as schizophrenia and Parkinson's disease (PD). If a firm association between Toxoplasma infection and neuropsychiatric disorders will be established, this would lead to novel strategies for their prevention and treatment. We will review data from serological and neurodevelopment studies relating infection with T. gondii to such neuropsychiatric diseases.

Tagged: acquired-immunodeficiency-syndrome, brain, Cerebral toxoplasmosis, frontal-cortex, gondii infection, movement-disorders, parkinson's disease, parkinsonian symptoms, prenatal infection, Risk factor, Schizophrenia, schizophrenia spectrum disorders, serological studies, Toxoplasma gondii

Mental health

Is latent infection with Toxoplasma gondii a risk factor for suicidal behavior?

October 11, 2013 Leave a Comment
Postolache, T.T., Cook, T.B.
Expert Review of Anti-Infective Therapy 2013; 11: 339-342
Tagged: antibody-titers, brain, cohort, history, individuals, mental-disorders, mood disorders, Schizophrenia, seropositivity, women

BehaviorMental health

Possible role of Toxoplasma gondii in brain cancer through modulation of host microRNAs

October 10, 2013 31 Comments
Thirugnanam S, Rout N, Gnanasekar M.
Infectious agents and cancer 2013; 8
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Background: The obligate intracellular protozoan parasite Toxoplasma gondii infects humans and other warm-blooded animals and establishes a chronic infection in the central nervous system after invasion. Studies showing a positive correlation between anti-Toxoplasma antibodies and incidences of brain cancer have led to the notion that Toxoplasma infections increase the risk of brain cancer. However, molecular events involved in Toxoplasma induced brain cancers are not well understood. Presentation of the hypothesis: Toxoplasma gains control of host cell functions including proliferation and apoptosis by channelizing parasite proteins into the cell cytoplasm and some of the proteins are targeted to the host nucleus. Recent studies have shown that Toxoplasma is capable of manipulating host micro RNAs (miRNAs), which play a central role in post-transcriptional regulation of gene expression. Therefore, we hypothesize that Toxoplasma promotes brain carcinogenesis by altering the host miRNAome using parasitic proteins and/or miRNAs. Testing the hypothesis: The miRNA expression profiles of brain cancer specimens obtained from patients infected with Toxoplasma could be analyzed and compared with that of normal tissues as well as brain cancer tissues from Toxoplasma uninfected individuals to identify dysregulated miRNAs in Toxoplasma-driven brain cancer cells. Identified miRNAs will be further confirmed by studying cancer related miRNA profiles of the different types of brain cells before and after Toxoplasma infection using cell lines and experimental animals. Expected outcome: The miRNAs specifically associated with brain cancers that are caused by Toxoplasma infection will be identified. Implications of the hypothesis: Toxoplasma infection may promote initiation and progression of cancer by modifying the miRNAome in brain cells. If this hypothesis is true, the outcome of this research would lead to the development of novel biomarkers and therapeutic tools against Toxoplasma driven brain cancers.

Tagged: activation, biology, brain, cancer, cell apoptosis, differentiation, expression, glioblastoma, infected-cells, microarray analysis, mirna, nf-kappa-b, t. gondii, tumors

Physical health

Toxoplasma gondii infection and behaviour – location, location, location?

March 26, 2013
McConkey, G. A., Martin, H. L., Bristow, G. C., Webster, J. P.
Journal of Experimental Biology 2013; 216: 113-119
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Parasite location has been proposed as an important factor in the behavioural changes observed in rodents infected with the protozoan Toxoplasma gondii. During the chronic stages of infection, encysted parasites are found in the brain but it remains unclear whether the parasite has tropism for specific brain regions. Parasite tissue cysts are found in all brain areas with some, but not all, prior studies reporting higher numbers located in the amygdala and frontal cortex. A stochastic process of parasite location does not, however, seem to explain the distinct and often subtle changes observed in rodent behaviour. One factor that could contribute to the specific changes is increased dopamine production by T. gondii. Recently, it was found that cells encysted with parasites in the brains of experimentally infected rodents have high levels of dopamine and that the parasite encodes a tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of this neurotransmitter. A mechanism is proposed that could explain the behaviour changes due to parasite regulation of dopamine. This could have important implications for T. gondii infections in humans

Tagged: brain, Dopamine, dopamine hypothesis, host behavior, manipulation., mice, mood disorders, neurotransmitter, obsessive-compulsive disorder, Parasite, parkinsonian symptoms, psychiatric patients, rattus-norvegicus, Schizophrenia, wild brown-rats

BehaviorMental health

The relationship between Toxoplasma gondii infection and mood disorders in the third national health and nutrition survey

October 12, 2012
Pearce, B.D., Kruszon-Moran, D., Jones, J.L.
Biological Psychiatry 2012; 72: 290-295
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Background: Toxoplasma gondii (T. gondii) is a neurotropic protozoan parasite that causes persistent infection in humans. A substantial literature suggests that schizophrenia is associated with increased seroprevalence of T. gondii, but a possible link of the parasite with mood disorders has not been as thoroughly investigated. Methods: We examined the association of Toxoplasma-specific immunoglobulin G results with mood disorder outcomes in 7440 respondents from the third National Health and Nutrition Survey, which is a nationally representative sample of the United States noninstitutionalized civilian population. Regression models were adjusted for numerous potential confounders, including tobacco smoking and C-reactive protein levels. Results: No statistically significant associations were found between T. gondii seroprevalence and a history of major depression (n = 574; adjusted odds ratio [OR]:.8; 95% confidence interval [CI]:.5-1.2), severe major depression (n = 515; adjusted OR:.8; 95% CI:.6-1.2), dysthymia (n = 548; adjusted OR: 1.1; 95% CI:.7-1.8), or dysthymia with comorbid major depression (n = 242, adjusted OR: 1.2; 95% CI:.6-2.4), all p values were > .05, including analysis stratified by gender. However, there was a significant relationship between T. gondii seroprevalence and bipolar disorder type I for respondents in which both manic and major depression symptoms were reported (n = 41; adjusted OR: 2.4; 95% CI: 1.2-4.8; p < .05). Conclusions: In a population-based sample, T. gondii seroprevalence is not elevated in unipolar mood disorders but is higher in a subset of respondents with a history of bipolar disorder type 1.

Tagged: 1st-episode, bipolar disorder, brain, c-reactive protein, depression, dysthymia, host behavior, individuals, Major depression, neuroimmunology, Schizophrenia, seroprevalence, skeletal-muscle, Toxoplasma

Mental health

Toxoplasma infection in schizophrenia patients: A comparative study with control group

October 19, 2011
Alipour, A., Shojaee, S., Mohebali, M., Tehranidoost, M., Masoleh, F. A., Keshavarz, H.
Iranian Journal of Parasitology 2011; 6: 31-37
Click for abstract
Background: Schizophrenia is a serious, chronic, and often debilitating neuropsychiatric disorder. Its causes are still poorly understood. Besides genetic and non-genetic (environmental) factors are thought to be important as the cause of the structural and functional deficits that characterize schizophrenia. This study aimed to compare Toxoplasma gondii infection between schizophrenia patients and non-schizophrenia individuals as control group. Methods: A case-control study was designed in Tehran, Iran during 2009-2010. Sixty-two patients with schizophrenia and 62 non-schizophrenia volunteers were selected. To ascertain a possible relationship between T. gondii infection and schizophrenia, anti-Toxoplasma IgG antibodies were detected by indirect-ELISA. Data were statistically analyzed by chi- square at a confidence level of 99%. Results: The sero-positivity rate among patients with schizophrenia (67.7%) was significantly higher than control group (37.1) (P <0.01). Conclusion: A significant correlation between Toxoplasma infection and schizophrenia might be expected.

Tagged: antibodies, behavior, bipolar disorder, brain, elisa, episode schizophrenia, gondii infection, individuals, Iran, metaanalysis, personality, recent-onset schizophrenia, Schizophrenia, Toxoplasma gondii

Mental health

Could Toxoplasma gondii have any role in Alzheimer disease?

October 19, 2011
Kusbeci, O. Y., Miman, O., Yaman, M., Aktepe, O. C., Yazar, S.
Alzheimer Disease and Associated Disorders 2011; 25: 1-3
Tagged: activated microglia, alzheimer disease, antibodies, brain, infection, inflammation, interferon-gamma, mechanism, neurodegeneration, neuroinflammation, parkinson's disease, pathogenesis, Schizophrenia, Toxoplasma gondii, toxoplasmosis

Mental health

Toxoplasma gondii seropositivity and suicide rates in women

October 19, 2011
Ling, V. J., Lester, D., Mortensen, P. B., Langenberg, P. W., Postolache, T. T.
Journal of Nervous and Mental Disease 2011; 199: 440-444
Click for abstract
Toxoplasma gondii (T. gondii) is an intracellular protozoan parasite that infects roughly a third of the world population. In an immunocompetent host, infection is generally chronic and asymptomatic, as the immune system keeps T. gondii confined to cysts and the intracellular space within the muscle and brain. Seropositivity has been linked to schizophrenia, car accidents, changes in personality, and more recently, suicidal attempts. Very recently, seroprevalence for 20 European countries was found to be associated with increased suicide rates. Although suicide rates were age-standardized, given that T. gondii seroprevalence increases with age and that the blood samples were drawn in women, we now retested in women only the association between suicide and T. gondii seropositivity, stratified by age. Simple correlations between ranked T. gondii seropositivity and suicide rate identified statistically significant relationships in women 60 years or older (p < 0.05); adjusting for GDP, the statistical significance expanded to include women 45 years and older. The strongest association was in the 60- to 74-year-old group where, after adjustment for GDP, the relationship (p = 0.007) resisted Bonferroni adjustment for multiple comparisons. In conclusion, the results suggest that a positive relationship between rates of infection with T. gondii and suicide is apparent in women of postmenopausal age. Prospective studies are necessary to further confirm this association predictively and to explore mechanisms mediating this relationship.

Tagged: behavior, brain, cat, depletion, depression, europe, infection, latent toxoplasmosis, risk, suicide, Toxoplasma gondii, toxoplasmosis, traffic accidents, tryptophan

BehaviorMental 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

The probable relation between Toxoplasma gondii and Parkinson’s disease

October 19, 2010
Miman, O., Kusbeci, O. Y., Aktepe, O. C., Cetinkaya, Z.
Neuroscience Letters 2010; 475: 129-131
Click for abstract
Parkinson's disease (PD), a chronic progressive neurodegenerative disorder, has a mainly unknown multifactorial etiology. Neuroinflammatory mechanisms might contribute to the cascade of events leading to neuronal degeneration. Toxoplasmosis can be associated with various neuropsychiatric disorders. The most commonly affected central nervous system (CNS) region in toxoplasmosis is the cerebral hemisphere, followed by the basal ganglia, cerebellum and brain stem. Therefore, in this study, we aimed to investigate the possible association between Toxoplasma infection and PD by evaluating the serum anti-Toxoplasma gondii IgG antibodies. There were no difference between the socioeconomic status of the patients and control subjects and magnetic resonance images of the patients were normal. Serum anti-T. gondii IgG levels were measured using ELISA. There was no statistically significant differences among the patients and control subjects with respect to age (66.01 +/- 12.14 years, 62.42 +/- 5.93 years, p = 0.089; respectively) and gender. The sero-positivity rate for anti-T. gondii IgG antibodies in PD patients and control groups were 42.3 and 22.5%, respectively, and they were statistically significant (p = 0.006). These results suggest that Toxoplasma infection may be involved in the pathogenetic mechanisms of PD. If confirmed, this hypothesis would represent a valuable advancement in care of patients with Parkinson's disease. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Tagged: antibodies, brain, cryptogenic epilepsy, encephalitis, host, infection, metaanalysis, mice, neurodegeneration, neuroinflammation, neurons, parkinson's disease, Schizophrenia, Toxoplasma gondii, toxoplasmosis

Mental health

Is there any role of Toxoplasma gondii in the etiology of obsessive-compulsive disorder?

October 19, 2010
Miman, O., Mutlu, E. A., Ozcan, O., Atambay, M., Karlidag, R., Unal, S.
Psychiatry Research 2010; 177: 263-265
Click for abstract
Obsessive-compulsive disorder (OCD) is a common psychiatric illness. Although the aetiology of OCD is still unknown, the family-genetic data show that familial forms of OCD may be associated with a specific genetic susceptibility. Recent investigations have associated development of OCD with infectious illness. Toxoplasmic encephalitis (TE) is a common presentation of Toxoplasma gondii infection of the central nervous system (CNS). The most commonly affected CNS region in TE is the cerebral hemisphere, followed by the basal ganglia, cerebellum and brain stem. The basal ganglia has been implicated in the development of OCD. Therefore, in this study, it was aimed to investigate a possible association between Toxoplasma infection and OCD. We selected 42 patients with OCD and 100 healthy volunteers, and investigated the sero-positivity rate for anti-Toxoplasma IgG antibodies by Enzyme Linked Immunosorbent Assay (ELISA). The sero-positivity rate for anti-T. gondii IgG antibodies among OCD patients (47.62%) was found to be significantly higher than the rate in healthy volunteers (19%). This is the first report to examine a potential association between Toxoplasma infection and OCD. The main finding of the present study is an increased level of IgG antibodies to T. gondii in OCD patients when compared with the level in healthy controls. There might be a causal relationship between chronic toxoplasmosis and the aetiology of OCD. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Tagged: basal ganglia, brain, children, disease, elisa, infection, obsessive-compulsive disorder (ocd), plasticity, 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

The role of latent toxoplasmosis in the aetiopathogenesis of schizophrenia – the risk factor or an indication of a contact with cat?

October 19, 2010
Yuksel, P., Alpay, N., Babur, C., Bayar, R., Saribas, S., Karakose, A. R., Aksoy, C., Aslan, M., Mehmetali, S., Kilic, S., Balcioglu, I., Hamanca, O., Dirican, A., Kucukbasmaci, O., Oner, A., Torun, M. M., Kocazeybek, B.
Folia Parasitologica 2010; 57: 121-128
Click for abstract
We assessed IgG antibody to Toxoplasma gondii in 300 inpatients with schizophrenia (SG), 150 outpatients with anxiety and depressive disorders (PCG), and 150 healthy blood donors (HCG). Seropositivity rates were 60.7% for SG, 36.7% for PCG, and 45.3% for HCG (p<0.001). The seropositivity rate for anti-Toxoplasma IgG antibodies in SG was significantly higher that in PCG (X(2) = 23.11, OR = 2.66, p = 0.001) and HCG (X(2) = 9.52, OR = 1.86, p = 0.002). Among SG, 85% of those who reported close cat contact had IgG antibodies to T gondii. Close cat contacts were reported by 59% of SG, 6% of PCG, and 9% of HCG (p<0.001). There was a nonsignificant positive association between toxoplasmosis and schizophrenia for people with a contact with a cat (OR = 2.221, p = 0.127, CI(95) = 0.796-6.192), and significant negative association between toxoplasmosis and schizophrenia for people without contact with a cat (OR = 0.532, p = 0.009, CI(95) = 0.332-0.854). Close cat contact (OR = 2.679, p<0.001), 51-65-year age group (OR = 1.703, p<0.001) and education [illiterate+primary (OR = 6.146, p<0.001) and high school (OR = 1.974, p = 0.023)] were detected as independent risk factors in multivariate logistic regression. The effect of toxoplasmosis on risk of schizophrenia disappeared in the complex model analyzed with multivariate logistic regression. In conclusion, our data suggest that the toxoplasmosis has no direct effect on the risk of schizophrenia in Turkey but is just an indication of previous contacts with a cat

Tagged: antibodies, behavioral-changes, brain, Dopamine, gondii infection, individuals, latent toxoplasmosis, mice, pregnant women, Schizophrenia, seroprevalence, Toxoplasma gondii, turkey, viral encephalitis

Mental health

Toxoplasma gondii: host-parasite interaction and behavior manipulation

October 26, 2009
da Silva, R.C., Langoni, H.
Parasitology Research 2009; 105: 893-898
Click for abstract
Toxoplasma gondii is an obligate intracellular parasite that causes different lesions in men and other warm-blooded animals. Humoral and cellular immune response of the host against the parasite keeps the protozoan in a latent stage, and clinical disease ensues when immunological response is compromised. Brain parasitism benefits the parasite causing behavioral changes in the host, not only in animals but also in humans. Schizophrenia and epilepsy are two neurological disorders that have recently been reported to affect humans coinfected with T. gondii. Further studies based on host-parasite interaction in several wild or domestic warm-blooded species are still necessary in order to better understand parasitism and behavioral changes caused by T. gondii.

Tagged: brain, Cerebral toxoplasmosis, cryptogenic epilepsy, infection, mortality, odors, personality, rats, Schizophrenia, women

Mental health

A possible relationship between Toxoplasma gondii and schizophrenia: A seroprevalence study

October 26, 2009
Dogruman-Al, F., Aslan, S., Yalcin, S., Kustimur, S., Turk, S.
International Journal of Psychiatry in Clinical Practice 2009; 13: 82-87.
Click for abstract
Objective. Schizophrenia is a pervasive neuropsychiatric disease of uncertain etiology. We aimed to investigate a possible association between Toxoplasma gondii infection and schizophrenia in this study. Method. We selected individuals with schizophrenia (n=88) and tested them with commercially available enzyme-linked immunosorbent assay (ELISA) for anti-Toxoplasma IgG and IgM antibodies and compared these seropositivity rate to those of controls without psychiatric disease (n=88). Results. The rate of IgG antibody in the schizophrenia patients (47.7%) was higher than the control groups (20.4%) (P0.001). We did not find any anti-Toxoplasma IgM seropositivity in both schizophrenia patients and control group. In schizophrenic patients with and without anti-Toxoplasma IgG groups statistical analysis did not reveal any correlation between demographic variables and Toxoplasma infection. Conclusion. Our findings supported previous studies indicate that T.gondii may play a role in etiopathogenesis in some cases of schizophrenia.

Tagged: 1st-episode schizophrenia, anti-toxoplasma igg, anti-toxoplasma igm, antibodies, association, behavior, bipolar disorder, brain, exposure, individuals, infection, necrosis-factor-alpha, Schizophrenia, Toxoplasma gondii

Mental health

Selected infectious agents and risk of schizophrenia among US military personnel

October 26, 2008
Nielbuhr, D.W., Millikan, A. M., Cowan, D. N., Yolken, R., Li, Y. Z., Weber, N. S.
American Journal of Psychiatry 2008; 165: 99-106
Click for abstract
Objective: A number of studies have reported associations between Toxoplasma gondii (T gondii) infection and the risk of schizophrenia. Most existing studies have used small populations and postdiagnosis specimens. As part of a larger research program, the authors conducted a hypothesis-generating case control study of T. gondii antibodies among individuals discharged from the U.S. military with a diagnosis of schizophrenia and serum specimens available from both before and after diagnosis. Method: The patients (N=180) were military members who had been hospitalized and discharged from military service with a diagnosis of schizophrenia. Healthy comparison subjects (3:1 matched on several factors) were members of the military who were not discharged. The U.S. military routinely collects and stores serum specimens of military service members. The authors used microplate-enzyme immunoassay to measure immunoglobulin G (IgG) antibody levels to T gondii, six herpes viruses, and influenza A and B viruses and immunoglobulin M (IgM) antibody levels to T. gondii in pre- and postdiagnosis serum specimens. Results: A significant positive association between the T gondii IgG antibody and schizophrenia was found; the overall hazard ratio was 1.24. The association between IgG and schizophrenia varied by the time between the serum specimen collection and onset of illness. Conclusion: The authors found significant associations between increased levels of scaled T gondii IgG antibodies and schizophrenia for antibodies measured both prior to and after diagnosis.

Tagged: antibodies, association, bipolar disorder, brain, exposure, host, individuals, mice, rats, toxoplasma gondii infection

Mental health

Antibodies to Toxoplasma gondii in patients with schizophrenia: A meta-analysis

March 26, 2007
Torrey, E. F., Bartko, J. J., Lun, Z. R., Yolken, R. H.
Schizophrenia Bulletin 2007; 33: 729-736
Click for abstract
Recent studies have linked infectious agents to schizophrenia. The largest number of studies has involved the analysis of Toxoplasma gondii; these studies were subjected to a meta-analysis. Published articles and abstracts were identified by searches of MEDLINE, Ovid, and Google Scholar; by a search of Chinese publications; through letters to researchers; and by visiting China. Published and unpublished controlled studies that used serological methods for measuring T. gondii antibodies to assess inpatients and/or outpatients diagnosed with schizophrenia were selected for analysis, and source documents were translated as needed. Forty-two studies carried out in 17 countries over 5 decades were identified; 23 of these (6 unpublished) met selection criteria. The combined odds ratio (OR) was 2.73 (95% confidence interval, 2.10 to 3.60; chi-square with I df 263; P <.000001). Seven studies that included only patients with first-episode schizophrenia (OR 2.54) did not differ significantly from 16 studies that included patients in all clinical phases (OR 2.79). The results suggest that individuals with schizophrenia have an increased prevalence of antibodies to T. gondii. This association is consistent with other epidemiological studies as well as with animal studies. Although the OR of 2.73 is modest, it exceeds that for genetic or other environmental factors identified to date and suggests that Toxoplasma is in some way associated with a large number of cases of schizophrenia. If an etiological association can be proven, it would have implications for the design of measures for the prevention and treatment of this disease.

Tagged: adult schizophrenia, apicomplexa, bipolar disorder, brain, individuals, infection, neurons, prenatal exposure, protozoa, psychosis, risk, transmission

Mental health

Parasites as causative agents of human affective disorders? The impact of anti-psychotic, mood-stabilizer and anti-parasite medication on Toxoplasma gondii ‘s ability to alter host behaviour

October 30, 2006
Webster, J.P., Lamberton, P.H.L., Donnelly, C.A., Torrey, E.F.
Proceedings of the Royal Society B-Biological Sciences 2006; 273: 1023-1030
Click for abstract
With increasing pressure to understand transmissible agents, renewed recognition of infectious causation of both acute and chronic diseases is occurring. Epidemiological and neuropathological studies indicate that some cases of schizophrenia may be associated with environmental factors, such as exposure to the ubiquitous protozoan Toxoplasma gondii. Reasons for this include T gondii's ability to establish persistent infection within the central nervous system, its ability to manipulate intermediate host behaviour, the occurrence of neurological and psychiatric symptoms in some infected individuals, and an association between infection with increased incidence of schizophrenia. Moreover, several of the medications used to treat schizophrenia and other psychiatric disease have recently been demonstrated in vitro to possess antiparasitic, and in particular anti-T gondii, properties. Our aim here was thus to test the hypothesis that the anti-psychotic and mood stabilizing activity of some medications may be achieved, or at least augmented, through their in vivo inhibition of T gondii replication and invasion in infected individuals. In particular we predicted, using the epidemiologically and clinically applicable rat-T gondii model system, and following a previously described and neurologically characterized 'feline attraction' protocol that haloperidol (an antipsychotic used in the treatment of mental illnesses including schizophrenia) and/or valproic acid (a mood stabilizer used in the treatment of mental illnesses including schizophrenia), would be, at least, as effective in preventing the development of T gondii-associated behavioural and cognitive alterations as the standard anti-T gondii chemotherapeutics pyrimethamine with Dapsone. We demonstrate that, while T gondii appears to alter the rats' perception of predation risk turning their innate aversion into a 'suicidal' feline attraction, anti-psychotic drugs prove as efficient as anti-T gondii drugs in preventing such behavioural alterations. Our results have important implications regarding the aetiology and treatment of such disorders.

Tagged: acquired toxoplasmosis, antibodies, brain, cat odor, dapsone, Dopamine, infection, medication, parasite-altered behaviour, pyrimethamine, rattus-norvegicus, Schizophrenia, Toxoplasma gondii

BehaviorMental health

Infection and mental illness: Do bugs make us batty?

January 8, 2005
Lorber, B.
Anaerobe 2005;11: 303-307
Tagged: adult schizophrenia, bipolar disorder, borna-disease virus, brain, influenza, mice, neuropsychiatric disorders, onset schizophrenia, pandas, Toxoplasma gondii

Mental health

Paranoid Schizophrenia May Be Caused by Dopamine Hyperactivity of Ca1 Hippocampus

November 8, 1991
Krieckhaus EE, Donahoe JW, Morgan MA
Biological Psychiatry 1992; 31: 560-570
Click for abstract
Explicit consolidation of memory, or fixation of declarative belief, appears to be physically represented in changes of synaptic conductances of neurons in the parietal-temporal-occipital association cortex (PTO) of the mammalian forebrain. This fixation of belief in PTO is postulated to be critically dependent on a diffuse reinforcement signal via the inferior temporal cortex (ITC) ultimately caused by an increased output of the CA1 pyramidal cells of hippocampus. Analogous to the reinforcing mechanisms of other forebrain systems, this updating of the connection weights of the neural nets in PTO by the output of the critical neurons in CA1 is directly related to concentrations of dopamine (DA). We propose that the delusions (i.e., unreasonable beliefs) of paranoid schizophrenia are caused by a hyperactivity of the same DA-sensitive CA1 neurons that are responsible for the fixation of normal beliefs. The dramatic reduction in delusions with administration of neuroleptics, as DA D2 blockers, in schizophrenics may thus be explained by their acting to ameliorate the hyperactivity of these CA1 DA D2 receptors.

Tagged: amnesia, autoradiographic localization, brain, cortex, d2 receptors, disorder, long-term potentiation, memory impairment, modulation, psychosis

Mental health

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