association
Lower performance of Toxoplasma-infected, Rh-negative subjects in the weight holding and hand-grip tests
Flegr, J., Sebankova, B., Priplatova, L., Chvatalova, V., Kankova, S.
PLoS ONE 2018; 13
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Background Toxoplasma, a protozoan parasite of cats, infects many species of intermediate and paratenic hosts, including about one-third of humans worldwide. After a short phase of acute infection, the tissue cysts containing slowly dividing bradyzoites are formed in various organs and toxoplasmosis proceeds spontaneously in its latent form. In immunocompetent subjects, latent toxoplasmosis was considered asymptomatic. However, dozens of studies performed on animals and humans in the past twenty years have shown that it is accompanied by a broad spectrum of specific behavioural, physiological and even morphological changes. In human hosts, the changes often go in the opposite direction in men and women, and are mostly weaker or non-existent in Rh-positive subjects. Methods Here, we searched for the indices of lower endurance of the infected subjects by examining the performance of nearly five hundred university students tested for toxoplasmosis and Rh phenotype in two tests, a weight holding test and a grip test. Results The results confirmed the existence of a negative association of latent toxoplasmosis with the performance of students, especially Rh-negative men, in these tests. Surprisingly, but in an accordance with some already published data, Toxoplasma-infected, Rh-positive subjects expressed a higher, rather than lower, performance in our endurance tests. Discussion Therefore, the results only partly support the hypothesis for the lower endurance of Toxoplasma infected subjects as the performance of Rh-positive subjects (representing majority of population) correlated positively with the Toxoplasma infection.
Immunoglobulin sub-class distribution in bipolar disorder and schizophrenia: potential relationship with latent Toxoplasma Gondii infection
Bengoufa, H. D., Godin, O., Doukhan, R., Guen, E. L.,Daban-Huard, C. , Bennabi, M., Delavest, M., Lepine, J. P., Boukouaci, W., Laouamri,H., Houenou, J., Jamain, S., Richard, J. R. , Lecorvosier, P. , Yolken, R., Rajagopal, K., Leboyer, M., Tamouza, R.
Bmc Psychiatry 2018; 18
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Background: Immune dysfunction could play a significant role in the pathogenesis of bipolar disorder (BD) and schizophrenia (SZ), conditions with an underlying pro-inflammatory state. Studies on humoral immune responses (which reflects antibody mediated fight against pathogens) in schizophrenia and bipolar disorder are sparse and often providing contradictory results. The aim of this study was to assess humoral immunity in a group of stable bipolar disorder and schizophrenia patients compared to controls by determining total Immunoglobulins and IgG subclasses and to assess their association with latent Toxoplasma gondii and/or CMV infection. Methods: 334 subjects (124 BD, 75 SZ and 135 Healthy Controls [HC]) were included and tested for humoral immunity by determining the total immunoglobulins (IgG,A and M) and IgG subclasses (IgG1, IgG2, IgG3, IgG4) and their relationship with latent Toxoplasma gondii infection, an established risk factor for BD and SZ. Results: Although lower levels of IgG, IgG1, IgG2, IgG4 and IgA were found among BD as compared to HC and/or SZ, after adjustment for confounding variables, only low levels of IgG and IgG1 in BD remai- ned significant. Strikingly highest levels of antibodies to T. gondii (but not CMV) infection in BD and SZ were associated with lowest levels of IgG3 and IgG4 levels as compared to controls. Conclusions: Schizophrenia and bipolar disorder patients with latent T. gondii specific infection may be more vulnerable to changes in immuno-inflammatory processes than controls with similar latent infectious state. Simultaneous sequential immunological monitoring both in steady state and active disease phases in the same BD and SZ patients are warranted to understand the role of Toxoplasma gondii latency in these disorders.
Is Toxoplasma gondii infection correlated with nonalcoholic fatty liver disease?- a population-based study
Huang, J. F. , Zhang, H. Y., Liu, S. Y. ,Wang, M. F. .Wan, B. , Velani, B. ., Zhu , Y. Y., Lin, S.
BMC Infectious Diseases 2018; 18: DOI: 10.1186/s12879-018-3547-1
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BackgroundPrevious studies have suggested that Toxoplasma gondii (T. gondii) infection might be associated with fatty liver disease. However, the relationship between non-alcoholic fatty liver disease (NAFLD) and T. gondii infection has not been investigated in a large population. We aimed to study the relationship between those two diseases using a population-based dataset from the United States.MethodsThe data were collected from the third National Health and Nutrition Examination Survey (NHANES III) between 1988 and 1994. Statistical analysis was applied to compare the prevalence of NAFLD in anti-T. gondii antibody-positive participants with antibody-negative ones.ResultsA total of 9465 persons with a mean age of 44.3316.21years, 46.9% of which were males, were included in the final analysis. Their mean BMI was 27.60 +/- 5.96kg/m(2). A total of 2520 participants (26.62%) were positive for the T. gondii antibody. There was an increasing trend of seroprevalence of T. gondii with age (P for trend <0.001). The incidence of NAFLD in the seropositive group was higher than that in the seronegative group (27.10% vs 23.40%, p<0.001). In addition to this, metabolic biomarkers, including serum lipid, fasting blood-glucose, and uric acid were also significantly higher in the seropositive group. However, multivariate analysis revealed that T. gondii infection was not an independent risk factor for NAFLD. Age was independently correlated with both the prevalence of T. gondii and NAFLD.Conclusions Patients with T. gondii infection may have a higher prevalence of NAFLD. Age may have an effect on the increase of NAFLD in the T. gondii seropositive population.
Immunoglobulin sub-class distribution in bipolar disorder and schizophrenia: potential relationship with latent Toxoplasma Gondii infection
Hamdani,N. ,Bengoufa, D. , Godin, O., Doukhan, R.., Le Guen,E., Daban-Huard, C. , Bennabi, M. ,Delavest, M., Lepine, J. P., Boukouaci, W. , Laouamri, H. , Houenou,J., Jamain, S., Richard,J. R. , Lecorvosier, P. , Yolken,R. , Rajagopal, K. , Leboyer, M. , Tamouza, R.
BMC Psychiatry,10.1186/s12888-018-1821-9, Article Number 239
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Background: Immune dysfunction could play a significant role in the pathogenesis of bipolar disorder (BD) and schizophrenia (SZ), conditions with an underlying pro-inflammatory state. Studies on humoral immune responses (which reflects antibody mediated fight against pathogens) in schizophrenia and bipolar disorder are sparse and often providing contradictory results. The aim of this study was to assess humoral immunity in a group of stable bipolar disorder and schizophrenia patients compared to controls by determining total Immunoglobulins and IgG subclasses and to assess their association with latent Toxoplasma gondii and/or CMV infection. Methods: 334 subjects (124 BD, 75 SZ and 135 Healthy Controls [HC]) were included and tested for humoral immunity by determining the total immunoglobulins (IgG,A and M) and IgG subclasses (IgG1, IgG2, IgG3, IgG4) and their relationship with latent Toxoplasma gondii infection, an established risk factor for BD and SZ. Results: Although lower levels of IgG, IgG1, IgG2, IgG4 and IgA were found among BD as compared to HC and/or SZ, after adjustment for confounding variables, only low levels of IgG and IgG1 in BD remai- ned significant. Strikingly highest levels of antibodies to T. gondii (but not CMV) infection in BD and SZ were associated with lowest levels of IgG3 and IgG4 levels as compared to controls. Conclusions: Schizophrenia and bipolar disorder patients with latent T. gondii specific infection may be more vulnerable to changes in immuno-inflammatory processes than controls with similar latent infectious state. Simultaneous sequential immunological monitoring both in steady state and active disease phases in the same BD and SZ patients are warranted to understand the role of Toxoplasma gondii latency in these disorders.
Impact of ApoE genotypes variations on Toxoplasma patients with dementia
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.
Relationship between Toxoplasma gondii seropositivity and acoustic startle response in an inner-city population
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Massa, N. M., Duncan, E., Jovanovic, T., Kerley, K., Weng, L., Gensler, L., Lee, S. S., Norrholm, S., Powers, A., Almli, L. M., Gillespie, C. F., Ressler, K., Pearce, B. D.,
Brain Behavior and Immunity 2017; 61: 176-183
Massa, N. M., Duncan, E., Jovanovic, T., Kerley, K., Weng, L., Gensler, L., Lee, S. S., Norrholm, S., Powers, A., Almli, L. M., Gillespie, C. F., Ressler, K., Pearce, B. D.,
Brain Behavior and Immunity 2017; 61: 176-183
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Toxoplasma gondii (TOXO) is a neuroinvasive protozoan parasite that induces the formation of persistent cysts in mammalian brains. It infects approximately 1.1 million people in the United States annually. Latent TOXO infection is implicated in the etiology of psychiatric disorders, especially schizophrenia (SCZ), and has been correlated with modestly impaired cognition. The acoustic startle response (ASR) is a reflex seen in all mammals. It is mediated by a simple subcortical circuit, and provides an indicator of neural function. We previously reported the association of TOXO with slowed acoustic startle latency, an index of neural processing speed, in a sample of schizophrenia and healthy control subjects. The alterations in neurobiology with TOXO latent infection may not be specific to schizophrenia. Therefore we examined TOXO in relation to acoustic startle in an urban, predominately African American, population with mixed psychiatric diagnoses, and healthy controls. Physiological and diagnostic data along with blood samples were collected from 364 outpatients treated at an inner-city hospital. TOXO status was determined with an ELISA assay for TOXO-specific IgG. A discrete titer was calculated based on standard cut-points as an indicator of seropositivity, and the TOXO-specific IgG concentration served as serointensity. A series of linear regression models were used to assess the association of TOXO seropositivity and serointensity with ASR magnitude and latency in models adjusting for demographics and psychiatric diagnoses (PTSD, major depression, schizophrenia, psychosis, substance abuse). ASR magnitude was 11.5% higher in TOXO seropositive subjects compared to seronegative individuals (p = 0.01). This effect was more pronounced in models with TOXO serointensity that adjusted for sociodemographic covariates (F = 7.41, p = 0.0068; F = 10.05, p = 0.0017), and remained significant when psychiatric diagnoses were stepped into the models. TOXO showed no association with startle latency (t = 0.49, p = 0.63) in an unadjusted model, nor was TOXO associated with latency in models that included demographic factors. After stepping in individual psychiatric disorders, we found a significant association of latency with a diagnosis of PTSD (F = 5.15, p = 0.024), but no other psychiatric diagnoses, such that subjects with PTSD had longer startle latency. The mechanism by which TOXO infection is associated with high startle magnitude is not known, but possible mechanisms include TOXO cyst burden in the brain, parasite recrudescence, or molecular mimicry of a host epitope by TOXO. Future studies will focus on the neurobiology underlying the effects of latent TOXO infection as a potential inroad to the development of novel treatment targets for psychiatric disease.
Evidence of increased exposure to Toxoplasma gondii in individuals with recent onset psychosis but not with established schizophrenia
Yolken, R., Torrey, E.F., Dickerson, F.
PLOS Neglected Tropical Diseases 2017; 10.1371/journal.pntd.0006040
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AB A possible role for Toxoplasma gondii in the etiopathogenesis of schizophrenia is supported by epidemiological studies and animal models of infection. However, recent studies attempting to link Toxoplasma to schizophrenia have yielded mixed results. We performed a nested case-control study measured serological evidence of exposure to Toxoplasma gondii in a cohort of 2052 individuals. Within this cohort, a total of 1481 individuals had a psychiatric disorder and 571 of were controls without a psychiatric disorder. We found an increased odds of Toxoplasma exposure in individuals with a recent onset of psychosis (OR 2.44, 95% Confidence Interval 1.4-4.4, p < .003). On the other hand, an increased odds of Toxoplasma exposure was not found in individuals with schizophrenia or other psychiatric disorder who did not have a recent onset of psychosis. By identifying the timing of evaluation as a variable, these findings resolve discrepancies in previous studies and suggest a temporal relationship between Toxoplasma exposure and disease onset.
A reply to: Do toxoplasma-infected subjects have better leadership skills? Comment on paper “puppet master: possible influence of the parasite toxoplasma gondii on managers and employees”
Houdek, P.
Academy of Management Perspectives 2017; 31: 339-343
Toxoplasma gondii infection and common mental disorders in the Finnish general population
Suvisaari, J., Torniainen-Holm, M., Lindgren, M., Harkanen, T., Yolken, R. H.
Journal of Affective Disorders 2017; 223: 20-25
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Objective: We investigated whether T. gondii seropositivity is associated with 12-month depressive, anxiety and alcohol use disorders and current depressive symptoms and whether inflammation, measured by C-reactive protein (CRP) level, explains these associations.
Method: Health 2000 study (BRIF8901), conducted in years 2000-2001, is based on a nationally representative sample of Finns aged 30 and above, with 7112 participants and 88.6% response rate. DSM-IV depressive, anxiety and alcohol use disorders were assessed with the Composite International Diagnostic Interview and depressive symptoms with the Beck Depressive Inventory (BDI-21). We used logistic regression to investigate the association of T. gondii seropositivity with mental disorders and linear regression with BDI-21 scores.
Results: T. gondii seroprevalence was significantly associated with 12-month generalized anxiety disorder but not with other anxiety, depressive or alcohol use disorders. T. gondii seropositivity was associated with higher BDI-21 scores (beta 0.56, 95% CI 0.12-1.00, P = 0.013) and with having a comorbid depressive and anxiety disorder (OR 1.86, 95% CI 1.16-2.97, P = 0.010). Higher CRP levels were associated with these outcomes and with T. gondii seropositivity, but adjusting for CRP did not change the effect of T. gondii seropositivity.
Limitations: Cross-sectional study design with no information on the timing of T. gondii infection.
Conclusion: T. gondii seropositivity is associated with generalized anxiety disorder, depressive symptoms and comorbid depressive and anxiety disorders, which is not mediated by inflammation.
Is Toxoplasma gondii infection a risk factor for leukemia? An evidence-based meta-analysis
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Huang, Y., Chang, A. S., Wang, J. S., Zeng, X. Q.,
Medical Science Monitor 2016; 22.
Huang, Y., Chang, A. S., Wang, J. S., Zeng, X. Q.,
Medical Science Monitor 2016; 22.
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Background: Possible associations of parasite infection with cancer risk have recently attracted much attention. Published studies concerning the association between Toxoplasma gondii (T. gondii) infection and leukemia risk have generated inconsistent results. In the present study, we aimed to address this topic by conducting a quantitative meta-analysis.
Material/Methods: Relevant publications were searched in electronic databases and eligible studies were rigorously screened and selected. Essential information was extracted and the data were pooled. Subgroup analysis on source of controls and detection target was also performed.
Results: A total of 6 studies that met the inclusion criteria were selected. The overall data show that T. gondii infection might have an association with increased leukemia risk (OR=3.05; 95% CI=1.83-5.08). Similar results were shown in the subgroups regarding source of controls and detection target.
Conclusions: Our results suggest that T. gondii infection might be a risk factor for leukemia, providing new insight into the etiology of leukemia. Future studies with large sample sizes in different geographic areas are needed to confirm this conclusion.
Seroprevalence and serointensity of latent Toxoplasma gondii in a sample of elderly adults with and without Alzheimer disease
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Perry, C. E., Gale, S. D., Erickson, L., Wilson, E., Nielsen, B., Kauwe, J., Hedges, D. W.
Alzheimer Disease and Associated Disorders 2016; 30: 123-126
Perry, C. E., Gale, S. D., Erickson, L., Wilson, E., Nielsen, B., Kauwe, J., Hedges, D. W.
Alzheimer Disease and Associated Disorders 2016; 30: 123-126
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Introduction: Latent infection with Toxoplasma gondii has been associated with behavioral and cognitive changes in animal models and in humans. Early findings have suggested an association between latent toxoplasmosis and Alzheimer disease (AD). On the basis of these factors, we sought to determine whether there is an association between latent toxoplasmosis and AD using a large, well-characterized sample of subjects with AD and age-matched and sex-matched controls without dementia.
Methods: Using ELISA, we determined anti-T. gondii IgG antibody titers in 114 control subjects and in 105 subjects diagnosed with AD through an Alzheimer's Disease Research Center.
Results: There were no group differences between groups in age, ethnicity, or sex. Education and socioeconomic status was slightly higher in the control group. Neither the prevalence of anti-T. gondii IgG antibodies (33% in the nondemented control group compared with 41% in the AD group, P= 0.25) nor log-transformed antibody concentration (106.6 IU/mL in the control group compared with 140.9 IU/mL in the AD group, P= 0.85) differed between the control and AD groups.
Discussion: In this sample, we found neither a higher prevalence of latent toxoplasmosis in the AD group compared with the control group nor differences in serum anti-T. gondii IgG titers between groups.
Is Toxoplasma gondii infection related to brain and behavior impairments in humans? Evidence from a population-representative birth cohort
Sugden, K., Moffitt, T. E., Pinto, L., Poulton, R., Williams, B. S., Caspi, A.
Plos One 2016; 11: ARTN e0148435 10.1371/journal.pone.0148435
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Background
Toxoplasma gondii (T. gondii) is a protozoan parasite present in around a third of the human population. Infected individuals are commonly asymptomatic, though recent reports have suggested that infection might influence aspects of the host's behavior. In particular, Toxoplasma infection has been linked to schizophrenia, suicide attempt, differences in aspects of personality and poorer neurocognitive performance. However, these studies are often conducted in clinical samples or convenience samples.
Methods/Results
In a population-representative birth-cohort of individuals tested for presence of antibodies to T. gondii (N = 837) we investigated the association between infection and four facets of human behavior: neuropsychiatric disorder (schizophrenia and major depression), poor impulse control (suicidal behavior and criminality), personality, and neurocognitive performance. Suicide attempt was marginally more frequent among individuals with T. gondii seropositivity (p = .06). Seropositive individuals also performed worse on one out of 14 measures of neuropsychological function.
Conclusion
On the whole, there was little evidence that T. gondii was related to increased risk of psychiatric disorder, poor impulse control, personality aberrations or neurocognitive impairment.
Inflammatory markers in recent onset psychosis and chronic schizophrenia
Dickerson, F., Stallings, C., Origoni, A., Schroeder, J., Katsafanas, E., Schweinfurth, L., Savage, C., Khushalani, S., Yolken, R.
Schizophrenia Bulletin 2016; 42: 134-141
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Background. Immune markers have been associated with schizophrenia, but few studies have examined multiple markers in both recent onset and chronic schizophrenia patients. Methods. The sample of 588 individuals included 79 with recent onset psychosis, 249 with chronic schizophrenia, and 260 controls. A combined inflammation score was calculated by principal components factor analysis of the levels of C-reactive protein, Pentraxin 3, and IgG antibodies to gliadin, casein, and Saccharomyces cerevisiae measured in blood samples. Inflammation scores among groups were compared by multivariate analyses. Results. The chronic schizophrenia group showed significant elevations in the combined inflammation score compared with controls. The recent onset group surprisingly showed a reduction in the combined inflammation score. Consistent with these findings, the chronic schizophrenia group had significantly increased odds of a combined inflammation score greater than the 75th and the 90th percentile of that of the controls. The recent onset group had significantly increased odds of a combined inflammation score less than the 10th and the 25th percentile level of the controls. Conclusions. The recent onset of psychosis may be associated with inherent deficits in innate immunity. Individuals later in the course of disease may have increased levels of innate immunity. The reasons for these changes are not known with certainty but may be related to compensatory increases as the disease progresses. Longitudinal studies are needed to determine the course of immune abnormalities in schizophrenia and their role in the clinical manifestations of the disorder.
Cognitive deterioration among bipolar disorder patients infected by Toxoplasma gondii is correlated to interleukin 6 levels
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Hamdani, N., Daban-Huard, C., Lajnef, M., Gadel, R., Le Corvoisier, P., Delavest, M., Carde, S., Lepine, J. P., Jamain, S., Houenou, J., Galeh, B., Richard, J. R., Aoki, M., Charron, D., Krishnamoorthy, R., Yolken, R., Dickerson, F., Tamouza, R., Leboyer, M.
Journal of Affective Disorders 2015; 179: 161-166
Hamdani, N., Daban-Huard, C., Lajnef, M., Gadel, R., Le Corvoisier, P., Delavest, M., Carde, S., Lepine, J. P., Jamain, S., Houenou, J., Galeh, B., Richard, J. R., Aoki, M., Charron, D., Krishnamoorthy, R., Yolken, R., Dickerson, F., Tamouza, R., Leboyer, M.
Journal of Affective Disorders 2015; 179: 161-166
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Background: Cognitive deficits are present in a large majority of Bipolar Disorder (BD) patients and known to be a marker of bad prognosis. Because, these deficits encompass several domains and no specific medical treatment seems to be effective, it is important to better understand the mechanisms underlying cognitive deterioration. As Toxoplasma gondii is known to induce the synthesis of pro-inflammatory cytokines such as IL-6, we will explore here the possible role of T. gondii in the cognitive decline observed in BD.
Methods: 42 euthymic BD patients and 36 controls were assessed for episodic verbal memory using the CVLT and for working memory and verbal ability using the WAIS Ill. Patients and controls were also screened for seropositivity to I gondii and evaluated for the levels of IL-fl transcripts.
Results: The seropositivity for I gondii was significantly higher in BD patients as compared to controls (p-0.005). The cognitive deterioration index (Dl) was higher in BD patients (p=5.10 ') and correlated to high IL-6 mRNA expression only among those infected by T gondii (rho-0.43, p-0.01). Among deteriorated patients (defined by scores above 0.10 according to Weschler's definition), the IL-6 mRNA expression was twice greater (p=0.01).
Limitations: Our results are to be interpreted with caution because of our small sample size and the cross-sectional design.
Conclusions: A long-term exposure to inflammation, measured here with IL-6 mRNA expression in T. gonciii infected BD may alter cognitive functioning. IL-6 could thus be a useful predictive marker of cognitive deterioration in BD and may help to design personalized treatment.
Toxoplasma gondii seropositivity and cognitive functions in school-aged children
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Mendy, A., Vieira, E. R., Albatineh, A. N., Gasana, J.
Parasitology 2015; 142: 1221-1227
Mendy, A., Vieira, E. R., Albatineh, A. N., Gasana, J.
Parasitology 2015; 142: 1221-1227
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Toxoplasma gondii (T. gondii) infects one-third of the world population, but its association with cognitive functions in school-aged children is unclear. We examined the relationship between Toxoplasma seropositivity and neuropsychological tests scores (including math, reading, visuospatial reasoning and verbal memory) in 1755 school-aged children 12-16 years old who participated to the Third National Health and Nutrition Examination Survey, using multiple linear regressions adjusted for covariates. Toxoplasma seroprevalence was 7.7% and seropositivity to the parasite was associated with lower reading skills (regression coefficient [beta] = -5.86, 95% confidence interval [CI]: -11.11, -0.61, P = 0.029) and memory capacities (beta = -0.86, 95% CI: -1.58, -0.15, P = 0.017). The interaction between T. gondii seropositivity and vitamin E significantly correlated with memory scores. In subgroup analysis, Toxoplasma-associated memory impairment was worse in children with lower serum vitamin E concentrations (beta = -1.61, 95% CI: -2.44, -0.77, P < 0.001) than in those with higher values (beta = -0.12, 95% CI: -1.23, 0.99, P = 0.83). In conclusion, Toxoplasma seropositivity may be associated with reading and memory impairments in school-aged children. Serum vitamin E seems to modify the relationship between the parasitic infection and memory deficiency.
Interaction between Helicobacter pylori and latent toxoplasmosis and demographic variables on cognitive function in young to middle-aged adults
Gale, S. D., Erickson, L. D., Brown, B. L., Hedges, D. W.
Plos One 2015; 10: UNSP e0116874 10.1371/journal.pone.0116874
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Helicobacter pylori and latent toxoplasmosis are widespread diseases that have been associated with cognitive deficits and Alzheimer's disease. We sought to determine whether interactions between Helicobacter pylori and latent toxoplasmosis, age, race-ethnicity, educational attainment, economic status, and general health predict cognitive function in young and middle-aged adults. To do so, we used multivariable regression and multivariate models to analyze data obtained from the United States' National Health and Nutrition Examination Survey from the Centers for Disease Control and Prevention, which can be weighted to represent the US population. In this sample, we found that 31.6 percent of women and 36.2 percent of men of the overall sample had IgG Antibodies against Helicobacter pylori, although the seroprevalence of Helicobacter pylori varied with sociodemographic variables. There were no main effects for Helicobacter pylori or latent toxoplasmosis for any of the cognitive measures in models adjusting for age, sex, race-ethnicity, educational attainment, economic standing, and self-rated health predicting cognitive function. However, interactions between Helicobacter pylori and race-ethnicity, educational attainment, latent toxoplasmosis in the fully adjusted models predicted cognitive function. People seropositive for both Helicobacter pylori and latent toxoplasmosis - both of which appear to be common in the general population - appear to be more susceptible to cognitive deficits than are people seropositive for either Helicobacter pylori and or latent toxoplasmosis alone, suggesting a synergistic effect between these two infectious diseases on cognition in young to middle-aged adults.
Mortality in schizophrenia: Clinical and serological predictors
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Dickerson, F., Stallings, C., Origoni, A., Schroeder, J., Khushalani, S., Yolken, R.
Schizophrenia Bulletin 2014; 40: 796-803
Dickerson, F., Stallings, C., Origoni, A., Schroeder, J., Khushalani, S., Yolken, R.
Schizophrenia Bulletin 2014; 40: 796-803
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Persons with schizophrenia have a reduced life expectancy largely due to death from natural causes. Factors that have been previously associated with excess mortality include cigarette smoking and antipsychotic medication. The role of other environmental factors such as exposure to infectious agents has been the subject of only limited investigation. We prospectively assessed a cohort of persons with schizophrenia with a clinical evaluation and a blood sample from which antibodies to human herpes viruses and Toxoplasma gondii were measured. Mortality was determined with data from the National Death Index following a period of up to 11 years. We examined the role of demographic, serological, and clinical factors on mortality. A total of 25 (5%) of 517 persons died of natural causes. The standardized mortality ratio was 2.80 (95% CI 0.89, 6.38). After adjusting for age and gender, mortality from natural causes was predicted in separate models by cigarette smoking (relative risk [RR] = 4.66, P = .0029); lower cognitive score (RR = 0.96, P = .013); level of antibodies to Epstein-Barr virus (RR = 1.22, P = .0041) and to Herpes Simplex virus type 1 (RR = 1.19, P = .030); immunologic disease (RR = 3.14, P = .044); and genitourinary disease (RR = 2.70; P = .035). Because cigarette smoking confers an almost 5-fold risk of mortality, smoking cessation is an urgent priority. Having an elevated level of antibodies to Epstein-Barr virus and to Herpes Simplex virus type 1 are also significant predictors of death from natural causes.
The urban risk and migration risk factors for schizophrenia: Are cats the answer?
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Being born in and/or raised in an urban area is a proven risk factor for developing schizophrenia. Migrating from countries such as Jamaica or Morocco to countries such as England or the Netherlands is also a proven risk factor for developing schizophrenia. The transmission of Toxoplasma gondii oocysts to children is reviewed and proposed as a partial explanation for both of these risk factors.
Neonatal antibodies to infectious agents and risk of bipolar disorder: a population-based case-control study
Mortensen, P. B., Pedersen, C. B., McGrath, J. J., Hougaard, D. M., Norgaard-Petersen, B., Mors, O., Borglum, A. D., Yolken, R. H.
Bipolar Disorders 2011; 13: 624-629
The diagnosis of a personality disorder increases the likelihood for seropositivity to Toxoplasma gondii in psychiatric patients
Hinze-Selch, D., Daubener, W., Erdag, S., Wilms, S.
Folia Parasitol (Praha) 2010; 57: 129-135
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Individuals serologically positive for the chronic infection with the parasite Toxoplasma gondii (TG) display certain personality traits differently from uninfected individuals. Experimental data in mice demonstrate that TG infection modulates behaviour. However, psychiatric patients with a personality disorder have not yet been investigated systematically. In our sample containing 896 psychiatric inpatients with the primary diagnoses of schizophrenia, major depression, schizoaffective or bipolar disorder and 214 psychiatrically unaffected controls (same geographic region, sampled during same time period) we analysed for effects of the additional diagnosis of a personality disorder in the patients. Psychiatrically, a patient can meet the criteria of a personality disorder additionally to any of the mentioned primary diagnoses. We applied logistic regression and cross-table statistics, separated groups by the presence/absence of a personality disorder (ICD-10) and adjusted for age between groups. We found that among all patients the additional diagnosis of a personality disorder was significantly associated with TG infection. Furthermore, only in the patients with an additional personality disorder medium titre responses (1:16-1:64) were associated with chronic course and high C-reactive protein (CRP) levels whereas high titre response (>1:64) was associated with a more acute recurrent clinical course. In the older individuals only there was a preponderance of medium titre responses (1:16-1:64) among the patients with personality disorder compared to those without and controls. We conclude that TG infection and the host's response to it make a difference for the diagnosis of a personality disorder. Our data support that TG infection can modulate human behaviour and personality traits.
A possible relationship between Toxoplasma gondii and schizophrenia: A seroprevalence study
Dogruman-Al, F., Aslan, S., Yalcin, S., Kustimur, S., Turk, S.
International Journal of Psychiatry in Clinical Practice 2009; 13: 82-87.
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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.
Selected infectious agents and risk of schizophrenia among US military personnel
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
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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.
Schizophrenia susceptibility genes directly implicated in the life cycles of pathogens: Cytomegalovirus, influenza, herpes simplex, rubella, and Toxoplasma gondii.
Carter CJ.
Schizophrenia Bulletin 2006; 35: 1163-1182
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Over 130 genes have been associated with schizophrenia in genetic studies. None of these has reached a sufficient level of confidence to be accepted as a universal susceptibility gene and problems of replicability suggest that many may be false positives. Nevertheless, these genes can be grouped into distinct families related to glutamate transmission (in particular related to NMDA receptor function), the control of synaptic plasticity, dopaminergic transmission, oxidative stress, glutathione and quinone metabolism and oligodendrocyte viability. These families mirror the processes disrupted in the schizophrenic brain and certain gene families can be linked together to form a clearly defined signalling cascade involved in the phenomenon of NMDA receptor-dependent long-term potentiation and synaptic plasticity, that may be interconnected with oligodendrocyte and oxidative stress-related pathways. Many of the protein products of these genes interact with each other, forming complex integrated networks. Certain high-interest genes (for example DISC1, NRG1, COMT) may exert multiple effects on different areas of these pathways, while others exert more specific effects on certain branches. The convergence of a large number of genes on a definable signaling network raises the possibility of numerous interactions between gene candidates, and suggests that a targeted multigenic pathway approach would be useful in gene association studies. (c) 2006 Elsevier B.V. All rights reserved.
The schizophrenia-rheumatoid arthritis connection: Infectious, immune, or both?
Torrey, E. F. , Yolken, R. H.
Brain Behavior and Immunity 2001; 15: 401-410
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Schizophrenia and rheumatoid arthritis share an impressive number of similarities. Both are chronic, relapsing diseases of unknown etiology. Both became prominent in the early 19th century and have prevalences of approximately 1% in North America and Europe. Both run in families, have pairwise concordance rates of approximately 30% among monozygotic twins, and are more common among individuals born in urban areas. For both diseases, studies have reported greater exposure to cats in childhood than in controls. Both diseases have been associated with similar class II HLA antigens. Both have also been suspected of having infectious etiology, with similar agents-retroviruses, herpesviruses including EBV, and Toxoplasma gondii-having been associated in some cases. Since there is also a well-documented inverse correlation between these two diseases, it is possible that they share a common infectious and/or immune etiology and that once a person gets one of the diseases then they are relatively immune to the other. (C) 2001 Elsevier Science.