risk
The relationship between Toxoplasma gondii IgG antibodies and generalized anxiety disorder and obsessive-compulsive disorder in children and adolescents: a new approach
Akaltun, I., Kara, S. S., Kara, T.,
Nordic Journal of Psychiatry 2019, 72: 57 - 62
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Aim:Toxoplasma gondii may play a role in the development of psychiatric diseases by affecting the brain. The purpose of this study was to examine the relation between serum toxoplasma IgG positivity and obsessive-compulsive disorder (OCD) and generalized anxiety disorder (GAD) in children and adolescents.Method: Sixty patients diagnosed with OCD and 60 patients with GAD presenting to the pediatric psychiatry clinic, together with 60 control group subjects with no psychiatric diagnosis, were included in the study. The patients were administered the State-Trait Anxiety Inventory for Children and the Children's Yale-Brown Obsessive Compulsive Scale. Serum toxoplasma IgG levels were determined from blood specimens collected from the study and control groups. The results were then compared using statistical methods.Results: State and trait anxiety levels were significantly higher in the OCD and GAD patients than in the control group (p=.0001/.0001). Serum toxoplasma IgG levels were positive in 21 (35%) of the OCD patients, 19 (31.7%) of the GAD patients and 6 (10%) of the control group. A significant relation was determined between IgG positivity and GAD (p=.003). IgG-positive individuals were determined to have a 4.171-fold greater risk of GAD compared to those without positivity (4.171[1.529-11.378]) (p=.005). A significant relation was also determined between IgG positivity and OCD (p=.001). IgG-positive individuals were determined to have a 4.846-fold greater risk of OCD compared to those without positivity (4.846[1.789-13.126]) (p=.002).Conclusion: This study shows that serum toxoplasma IgG positivity indicating previous toxoplasma infection increased the risk of GAD 4.171-fold and the risk of OCD 4.846-fold in children and adolescents. Further studies are now needed to investigate the relation between T. gondii infection and GAD/OCD and to determine the pathophysiology involved
The relation between serum Toxoplasma gondii IgG antibody in children and ADHD and its severity
Akaltun, I., Kara, T., Ayaydin, H., Alyanak, B., Beka, H., Agacfidan, A.
Psychiatry and Clinical Psychopharmacology 2019, 29: 326 - 331
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AIM: The purpose of our study was to investigate the relation between serum Toxoplasma gondii IgG antibodies in children and attention deficit hyperactivity disorder (ADHD) and its severity. METHOD: 214 subjects, consisting of 107 children aged 6-18 and diagnosed with ADHD and 107 children with no ADHD or psychiatric pathology were included. Subjects underwent a detailed psychiatric examination based on DSM-V-TR diagnostic criteria, using a data form, the Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL) for School-Aged Children (6-18), the DuPaul ADHD Rating Scale, Parent Rating Scale, the Conners Teacher Rating Scale (CTRS), and the Conners Parent Rating Scale (CPRS). Blood anti-Toxoplasma IgG antibody levels were investigated. The data obtained were then subjected to statistical analysis. RESULTS: T. gondii IgG antibodies were positive in 8 (7.47%) of the case group and positive in 3 (2.8%) of the control group. No statistically significant difference was determined between the case and control groups in terms of T. gondii IgG positivity (p = .215). Higher levels of severe ADHD were determined in Toxoplasma IgG positive patients in the ADHD group compared to Toxoplasma IgG negative subjects, the difference being statistically significant (p = .005). CONCLUSION: No significant differences were determined between the case and control groups in terms of T. gondii IgG positivity and ADHD. However, correlation was determined between ADHD severity and T. gondii IgG positivity. Toxoplasma,
Toxoplasmosis and mental disorders in the Russian Federation (with special reference to schizophrenia)
Stepanova, E. V., Kondrashin, A. V., Sergiev, V. P., Morozova, L. F., Turbabina, N. A., Maksimova, M. S., Romanov, D. V., Kinkulkina, M. A., Lazareva, A. V., Morozov, E. N.
PLoS ONE 2019, 14
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The association of latent toxoplasmosis with mental disorders in general and with schizophrenia in particular was noticed in the mid-1950s. In subsequent years, the role of Toxoplasma gondii was established based on its ability to survive for long periods of time in the nerve cells of the brain. The acute manifestations of the infection include psychopathic symptoms resembling those of schizophrenia. In the former USSR, and in other parts of the world, a number of studies were performed with respect to the association of latent toxoplasmosis and schizophrenia. However, with the dissolution of the USSR at the beginning of the 1990s, studies on the subject were halted due to financial problems and have resumed only recently. The reasons for the resumption of such studies in contemporary Russia are related to the progressively increasing incidence of schizophrenia over the last 25-30 years in the country. According to official data, approximately 550 000 persons reported suffering from the disease in 2014. There are reasons to believe that this is only a fraction of the real burden of the disease. Economically, it cost the state no less than approximately US $10 billion. The purpose of the study was to identify the level of toxoplasmosis seroprevalence in patients with verified diagnoses of schizophrenia in comparison to healthy people in Moscow City and in the Moscow region. A total of 155 persons constituted the patients group and 152 healthy people were in the control group. An integrated approach to the diagnosis and comparison of data from the entire spectrum of serological markers of infection was used, including the detection of specific IgM and the determination of IgG concentrations. It was found that among persons with neuropsychiatric disorders, the incidence of cases with latent toxoplasmosis was higher than in the control group. The effect of toxoplasmosis was significant and similar for men and women. Further statistical analyses revealed that among patients with a diagnosis of schizophrenia, the incidence of latent toxoplasmosis was significantly higher than in the control group. These data are in agreement with the results of similar studies in other countries.
The association between Toxoplasma gondii infection and hypertensive disorders in T2DM patients: a case-control study in the Han Chinese population
Han, Y. J., Nie, L. H., Ye, X. H., Zhou, Z. X., Huang, S. Q., Zeng, C. L., Guo, C. C., Ou, M. L., Xiao, D., Zhang, B. H., Huang, C. C., Ye, X. G., Jing, C. X., Yang, G.
Parasitology Research 2018; 117: 689-695
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Type 2 diabetes mellitus (T2DM) is a major global health problem. The rate of infection with Toxoplasma gondii (T. gondii) is more than one-third of the total world population. The effects of T. gondii infection on the risk of diabetic complications and comorbidities are unclear. This study aims to determine the relationship between T. gondii infection and complications of T2DM in the Han Chinese population. We collected 1580 blood samples from T2DM patients and measured the levels of specific IgG antibodies against T. gondii in the sera of these patients using an ELISA assay. A logistic regression analysis was performed to estimate the effect of T. gondii infection on the complications of T2DM, while adjusting for age, gender, and triglyceride level (TG). We applied the multifactor dimensionality reduction (MDR) method to detect the interactions between T. gondii infections, demographic indexes and biochemical indicators among the different complications. Gender (the odds ratio (OR) = 0.63, 95%CI =0.45-0.89, P = 0.008) and TG level (OR = 0.64, 95%CI =0.45-0.89, P = 0.009) were influencing factors in T. gondii infections. T2DM patients who were infected with T. gondii had a 2.34 times risk of developing hypertension than those patients without T. gondii infection (OR = 2.34, 95%CI = 1.12-4.88, P = 0.024). The multiplicative interaction analysis and the additive interaction analysis did not reveal any evidence of interactive effects on diabetic complications and comorbidities. T. gondii might be a factor associated with hypertension in T2DM patients.
Seroprevalance Anti-Toxoplasma gondii antibodies in children and adolescents with tourette syndrome/chronic motor or vocal tic disorder: A case-control study
Akaltun, I., Kara, T., Kara, S. S., Ayaydin, H.
Psychiatry Research 2018; 263: 154-157
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Toxoplasma gondii infection may be associated with psychiatric disorders due to its neurological effects. The purpose of this study was to investigate the relation between tic disorders in children and adolescents and Anti-Toxoplasma IgG. 43 children diagnosed with Tourette's syndrome(TS) and 87 with chronic motor or vocal tic disorder(CMVTD), and 130 healthy volunteers, all aged 7-18, were enrolled. Anti-Toxoplasma IgG antibody levels obtained from blood specimens were investigated. Toxoplasma IgG positivity was determined in 16(37.2%) of the patients with TS, in 27(31%) of those with CMVTD and in 12(9.2%) members of the control group. Anti-Toxoplasma gondii antibody positivity was 5.827-fold higher in subjects with TS and 4.425-fold higher in subjects with CMVTD compared to the control group. Correlation was determined between a diagnosis of TS or CMVTD and Anti-Toxoplasma gondii antibodies. We think that it will be useful for the neuropsychiatric process associated with Anti-Toxoplasma gondii antibodies to be clarified.
Can offspring sex ratios help to explain the endocrine effects of toxoplasmosis infection on human behaviour?
James, W. H., Grech, V.
Early Human Development 2018; 122: 42-44
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Humans infected with the parasite Toxoplasma gondii display a wide variety of abnormal behaviours, from suicide and depression to stuttering. These behaviours have been seen as so serious as to constitute a public health problem. It is not clear to what extent the parasite is a cause of, or merely a marker for, these behaviours, but there is evidence for both. Some of these behaviours are associated with changes in steroid hormones, that is, estrogen in women and testosterone in men. It is suggested here that these endocrine-related states of infected people may be better understood by studying their offspring sex ratios.
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.
Viral and parasitic pathogen burden and the association with stroke in a population-based cohort
Pearce, B. D.,Bracher, A. , Jones, J. L., Kruszon-Moran, D.
International Journal of Stroke 2018; 13_: 481-495
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Background Higher cumulative burden of viral and bacterial pathogens may increase the risk of stroke, but the contribution of parasitic infections in relation to cumulative pathogen burden and risk of stroke has rarely been examined. Aim To estimate the association of multiple persistent viral and parasitic infections with stroke in a representative sample of adults in the United States. Methods Serological evidence of prior infection was categorized as positive for 0-1, 2, 3, or 4-5 infections based on immunoglobulin G seropositivity to cytomegalovirus, hepatitis A virus, hepatitis B virus, Toxoplasma gondii, and Toxocara spp. in 13,904 respondents from the National Health and Nutrition Examination Survey III. Regression analysis was used to estimate the cross-sectional association between serological evidence of prior infection and history of stroke adjusting for demographic risk factors, and potential mediators of stroke. Results Age-adjusted models that included serological evidence of prior infection to cytomegalovirus, hepatitis A virus, hepatitis B virus, Toxoplasma gondii, and Toxocara spp. showed that adults in the highest serological evidence of prior infection category (4-5 infections) had a higher prevalence of stroke (5.50%, 95% confidence interval 2.44-10.46%) than those in the lowest serological evidence of prior infection categories (1.49%, 95% confidence interval 1.01-2.11%), and a trend test suggested a graded association between serological evidence of prior infection and stroke (p=0.02). In multivariable logistic regression models, the positive association of serological evidence of prior infection with stroke prevalence remained significant after adjustment for other significant risk factors (odds ratio=1.4, p=0.01) but was only significant among those aged 20-59 (odds ratio=2.0, p=0.005) and not among those aged 60-69 (p=0.78) or 70 and older (p=0.43). Conclusion We found support for a connection between serological evidence of prior infection to cytomegalovirus, hepatitis A virus, hepatitis B virus, Toxoplasma gondii, and Toxocara spp. and stroke among those aged 20-59. There may be a need to consider common parasitic infections in addition to viral and bacterial pathogens when calculating serological evidence of prior infection in relation to cerebrovascular disease.
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.
Significance of chronic toxoplasmosis in epidemiology of road traffic accidents in Russian Federation
Stepanova, E. V., Kondrashin, A. V., Sergiev, V. P., Morozova, L. F., Turbabina, N. A., Maksimova, M. S., Brazhnikov, A. I., Shevchenko, S. B., Morozov, E. N.
PLoS ONE 2017;12: 10.1371/journal.pone.0184930
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Studies carried out in Moscow residents have revealed that the prevalence of chronic toxoplasmosis is very close to those in countries of Eastern and Central Europe. Our findings also demonstrated a statistically significant relationship between the rate of traffic accidents and the seroprevalence of chronic toxoplasmosis in drivers who were held responsible for accidents. The latter was 2.37 times higher in drivers who were involved in road accidents compared with control groups. These results suggest that the consequences of chronic toxoplasmosis (particularly a slower reaction time and decreased concentration) might contribute to the peculiarities of the epidemiology of road traffic accidents in the Russian Federation and might interfere with the successful implementation of the Federal Programme named "Increase road traffic safety" . Suggestions for how to address overcome this problem are discussed in this paper.
Prenatal toxoplasmosis antibody and childhood autism
Spann, M. N., Sourander, A., Surcel, H. M., Hinkka-Yli-Salomaki, S., Brown, A. S.
Autism Research 2017; 10: 769-777
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here is evidence that some maternal infections during the prenatal period are associated with neurodevelopmental disorders, such as childhood autism. However, the association between autism and Toxoplasma gondii (T. gondii), an intracellular parasite, remains unclear. The authors examined whether serologically confirmed maternal antibodies to T. gondii are associated with odds of childhood autism in offspring. The study is based on a nested case-control design of a large national birth cohort (N=1.2 million) and the national psychiatric registries in Finland. There were 874 cases of childhood autism and controls matched 1: 1 on date of birth, sex, birthplace and residence in Finland. Maternal sera were prospectively assayed from a national biobank for T. gondii IgM and IgG antibodies; IgG avidity analyses were also performed. High maternal T. gondii IgM antibody was associated with a significantly decreased odds of childhood autism. Low maternal T. gondii IgG antibody was associated with increased offspring odds of autism. In women with high T. gondii IgM antibodies, the IgG avidity was high for both cases and controls, with the exception of three controls. The findings suggest that the relationship between maternal T. gondii antibodies and odds of childhood autism may be related to the immune response to this pathogen or the overall activation of the immune system.
Effects of cumulative herpesviridae and Toxoplasma gondii infections on cognitive function in healthy, bipolar, and schizophrenia subjects
Hamdani, N., Daban-Huard, C.,. Godin, O., Laouamri, H., Jamain, S., Attiba, D., Delavest, M., Lepine, J. P., Le Corvoisier, P., Houenou, J., Richard, J. R., Yolken, R. H., Krishnamoorthy, R., Tamouza, R., Leboyer, M., Dickerson, F. B.
Journal of Clinical Psychiatry 2017, 78: 18-27
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Objective: Schizophrenia and bipolar disorder are associated with cognitive impairment leading to social disruption. While previous studies have focused on the effect of individual infectious exposure, namely, Herpesviridae viruses or Toxoplasma gondii (T gondii), on cognitive functioning, the objective of the present study was to examine the effect of multiple infections on cognitive functioning in patients with schizophrenia and bipolar disorder and in healthy controls.
Methods: Seropositivity to herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), cytomegalovirus (CMV), and T gondii was related to cognitive status among 423 participants (recruited between 2008 and 2014; 138 patients with bipolar disorder, 105 patients with schizophrenia [DSM-IV criteria], and 180 healthy controls) for episodic verbal memory (California Verbal Learning Test), working memory (Wechsler Adult Intelligence Scale, third edition), and premorbid intelligence quotient (National Adult Reading Test).
Results: Seropositivity to and antibody levels of HSV-1 were significantly associated with working memory, which persisted after correction (backward digit span: beta = -0.10 [0.05], chi(2) = 33.89, P = .0001) in the overall sample. This association was particularly strong in the control group (beta = -0.18 [0.08], P = .04, Z = -3.55, P = .0008; corrected P = .012). Further, cumulative exposure to HSV-1, HSV-2, and CMV viruses and T gondii parasite was also associated with lower scores on working memory as measured by backward digit span in the overall sample (Z = 2.86, P = .004; Z = 2.47, P = .01; and Z = 3.35, P = .01, respectively).
Conclusions: Exposures to Herpesviridae and T gondii parasite seem to impact cognitive functioning. Because infections caused by Herpesviridae and/or T gondii parasite are quite common in the (general) population, assessing and confirming the cognitive impairment among those who have cumulative exposures is useful and of interest.
Stability of Toxoplasma gondii: Antibody levels in schizophrenia
Yuksel, P., Kocazeybek, B, Ozdemir, A., Yolken, R. H., Torrey ,E.F.
Schizophrenia Research 2017; 189: 221-222
Latent Toxoplasma infection and higher Toxoplasma gondii immunoglobulin G levels are associated with worse neurocognitive functioning in HIV-infected adults
Bharti, A. R., McCutchan, A., Deutsch, R., Smith, D. M., Ellis, R. J., Cherner, M., Woods, S. P., Heaton, R. K., Grant, I., Letendre, S. L.
Clinical Infectious Diseases 2016; 63: 1655-1660.
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Background. Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist despite suppressive antiretroviral therapy (ART). Because latent Toxoplasma infection (LTI) may adversely impact brain function, we investigated its impact on neurocognitive impairment (NCI) in people living with HIV disease.
Methods. Two hundred sixty-three HIV-infected adults underwent comprehensive neurocognitive assessments and had anti-Toxoplasma gondii immunoglobulin G (anti-Toxo IgG) measured by qualitative and quantitative enzyme-linked immunosorbent assays.
Results. Participants were mostly middle-aged white men who were taking ART (70%). LTI was detected in 30 (11.4%) participants and was associated with a significantly greater prevalence of global NCI (LTI positive [ LTI+]=57% and LTI negative [ LTI-]=34%) (odds ratio, 1.67; 95% confidence interval, 1.17-2.40; P=.017). Deficits were more prevalent in the LTI+ vs the LTI -group in 6 of 7 cognitive domains with statistical significance reached for delayed recall (P<.01). The probability of NCI increased with higher CD4(+) T-cell counts among LTI+ individuals but with lower CD4(+) T-cell counts in LTI-persons. A strong correlation (r=.93) between anti-Toxo IgG levels and global deficit score was found in a subgroup of 9 patients. Biomarkers indicative of central nervous system inflammation did not differ between LTI+ and LTI-participants.
Conclusions. In this cross-sectional analysis, LTI was associated with NCI, especially in those with higher CD4(+) T-cell counts. Longitudinal studies to investigate the role of neuroinflammation and neuronal injury in LTI patients with NCI and trials of anti-Toxoplasma therapy should be pursued.
Association between anti-Toxoplasma gondii antibodies and schizophrenia and psychotic bipolar in patients hospitalized in the psychiatric ward
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.
Latent toxoplasmosis is associated with neurocognitive impairment in young adults with and without chronic HIV infection
Ene, L., Marcotte, T. D., Umlauf, A., Grancea, C., Temereanca, A., Bharti, A., Achim, C. L., Letendre, S., Ruta, S. M.,
Journal of Neuroimmunology 2016; 299: 1-7.
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We evaluated the impact of latent toxoplasmosis (LT) on neurocognitive (NC) and neurobehavioural functioning in young adults with and without chronic HIV infection, using a standardised NC test battery, self-reported Beck Depression Inventory, Frontal System Behavior Scale, MINI-International Neuropsychiatric Interview and risk-assessment battery.
194 young adults (median age 24 years, 48.2% males) with chronic HIV infection (HIV +) since childhood and 51 HIV seronegative (HIV) participants were included. HIV + individuals had good current immunological status (median CD4: 479 cells/mu l) despite a low CD4 nadir (median: 93 cells/mu l). LT (positive anti-Toxoplasma IgG antibodies) was present in one third of participants. The impairment rates in the HIV with and without Toxo were not significantly different (p = 0.17). However, we observed an increasing trend (p < 0.001) in impairment rates with HIV and LT status: HIV -/LT- (6.1%); HIV -/LT+ (22%), HIV +/LT- (31%), HIV +/LT+ (49%). In a multi variable analysis using the entire study group there were main effects on cognition for HIV and also for LT. Within the HIV+ group LT was associated with worse performance globally (p = 0.006), in memory (p = 0.009), speed of information processing (p = 0.01), verbal (p = 0.02) and learning (p = 0.02) domains. LT was not associated with depressive symptoms, frontal systems dysfunction or risk behaviors in any of the groups. HIV participants with lower Toxoplasma antibody concentration had worse NC performance, with higher GDS values (p = 0.03) and worse learning (p = 0.002), memory (p = 0.006), speed of information processing (p = 0.01) T scores. Latent Toxoplasmosis may contribute to NC impairment in young adults, including those with and without chronic HIV infection.
Toxoplasma gondii infection in schizophrenia and associated clinical features
Esshili, A., Thabet, S., Jemli, A., Trifa, F., Mechri, A., Zaafrane, F., Gaha, L., Juckel, G., Babba, H., Jrad, B. B. H.
Psychiatry Research 2016; 245: 327-332
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The belief that latent toxoplasmosis is asymptomatic has been questioned, in particular due to the repeated highlighted link between the Toxoplasma gondii infection and an increased incidence of schizophrenia. However, to understand this relationship, the effect of infection with Toxoplasma gondii on the severity of schizophrenia has been poorly studied. Our work focused on comparing the prevalence of Toxoplasma infection between schizophrenic patients and healthy controls, as well as comparing the clinical features and the demographic characteristics between Toxoplasma-seronegative and Toxoplasma-seropositive patients with schizophrenia. The rate of IgG antibody in the schizophrenia patients was 74.8% compared 53.8% in controls. Patients with schizophrenia had a significantly higher mean of serum IgG antibodies to T. gondii compared to controls. The seropositive male patients had a higher age of disease onset, a higher BPRS score, a greater negative PANSS score and a lower GAF score than the seronegative male patients. These results suggest a higher severity of clinical symptoms in the male patients with schizophrenia. This study provides further evidence to the hypothesis that exposure to Toxoplasma may be a risk factor for schizophrenia. Moreover, toxoplasmosis in men with schizophrenia may lead to more severe negative and cognitive symptoms and a less favorable course of schizophrenia.
Infection and characterization of Toxoplasma gondii in human induced neurons from patients with brain disorders and healthy controls
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
Seroprevalence of Toxoplasma gondii infection among patients with non-schizophrenic neurodevelopmental disorders in Alexandria, Egypt
Shehata AI, Hassanein FI, Abdul-Ghani R
Acta Tropica 2016; 154: 155-159
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Toxoplasma gondii is an opportunistic parasite with neurotropic characteristics that can mediate neurodevelopmental disorders, including mental, behavioral and personality aspects of their hosts. Therefore, the seroprevalence of anti-Toxoplasma antibodies has been studied in patients with different neurological disorders from different localities. On searching online databases, however, we could not find published studies on the seroprevalence of anti-Toxoplasma antibodies among patients with neurodevelopmental disorders in Egypt. Therefore, the present preliminary study was conducted to determine the serological profile of T. gondii infection among patients with non -schizophrenic neurodevelopmental disorders in Alexandria, Egypt. Data and blood samples were collected from 188 patients recruited for the study from four mental rehabilitation centers in the period from July 2014 to March 2015. The overall seropositivity rates of IgM and IgG among patients were 16.5% (31/188) and 50.0% (94/188), respectively. Of the studied patients' characteristics, only age was significantly associated with anti-Toxoplasma IgG seropositivity, with older patients being about twice more likely exposed to infection. However, no statistically significant association was found with IgM. In addition, seropositivity of anti-Toxoplasma IgG, but not IgM, was significantly associated with non-schizophrenic neurodevelopmental disorders; however, neither IgG nor IgM showed a significant association with cognitive impairment as indicated by the intelligence quotient scores.
Seroprevalence of Toxoplasma gondii infection among patients with non-schizophrenic neurodevelopmental disorders in Alexandria, Egypt
Shehata, A. I., Hassanein, F. I., Abdul-Ghani, R.
Acta Tropica 2016; 154: 155-159
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Toxoplasma gondii is an opportunistic parasite with neurotropic characteristics that can mediate neurodevelopmental disorders, including mental, behavioral and personality aspects of their hosts. Therefore, the seroprevalence of anti-Toxoplasma antibodies has been studied in patients with different neurological disorders from different localities. On searching online databases, however, we could not find published studies on the seroprevalence of anti-Toxoplasma antibodies among patients with neurodevelopmental disorders in Egypt. Therefore, the present preliminary study was conducted to determine the serological profile of T. gondii infection among patients with non -schizophrenic neurodevelopmental disorders in Alexandria, Egypt. Data and blood samples were collected from 188 patients recruited for the study from four mental rehabilitation centers in the period from July 2014 to March 2015. The overall seropositivity rates of IgM and IgG among patients were 16.5% (31/188) and 50.0% (94/188), respectively. Of the studied patients' characteristics, only age was significantly associated with anti-Toxoplasma IgG seropositivity, with older patients being about twice more likely exposed to infection. However, no statistically significant association was found with IgM. In addition, seropositivity of anti-Toxoplasma IgG, but not IgM, was significantly associated with non-schizophrenic neurodevelopmental disorders; however, neither IgG nor IgM showed a significant association with cognitive impairment as indicated by the intelligence quotient scores.
Seroprevalence of Toxoplasma gondii infection among patients with non-schizophrenic neurodevelopmental disorders in Alexandria, Egypt
Shehata, A.I., Hassanein, F.I., Abdul-Ghani, R.
Acta Tropica 2016;154: 155-159
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Toxoplasma gondii is an opportunistic parasite with neurotropic characteristics that can mediate neurodevelopmental disorders, including mental, behavioral and personality aspects of their hosts. Therefore, the seroprevalence of anti-Toxoplasma antibodies has been studied in patients with different neurological disorders from different localities. On searching online databases, however, we could not find published studies on the seroprevalence of anti-Toxoplasma antibodies among patients with neurodevelopmental disorders in Egypt. Therefore, the present preliminary study was conducted to determine the serological profile of T. gondii infection among patients with non -schizophrenic neurodevelopmental disorders in Alexandria, Egypt. Data and blood samples were collected from 188 patients recruited for the study from four mental rehabilitation centers in the period from July 2014 to March 2015. The overall seropositivity rates of IgM and IgG among patients were 16.5% (31/188) and 50.0% (94/188), respectively. Of the studied patients' characteristics, only age was significantly associated with anti-Toxoplasma IgG seropositivity, with older patients being about twice more likely exposed to infection. However, no statistically significant association was found with IgM. In addition, seropositivity of anti-Toxoplasma IgG, but not IgM, was significantly associated with non-schizophrenic neurodevelopmental disorders; however, neither IgG nor IgM showed a significant association with cognitive impairment as indicated by the intelligence quotient scores.
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.
Toxoplasmosis Titers and past Suicide Attempts Among Older Adolescents Initiating SSRI Treatment
Coryell, W., Yolken, R., Butcher, B., Burns, T., Dindo, L., Schlechte, J., Calarge, C.
Archives of Suicide Research 2016; 20: 605-613
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Latent infection with toxoplasmosis is a prevalent condition that has been linked in animal studies to high-risk behaviors, and in humans, to suicide and suicide attempts. This analysis investigated a relationship between suicide attempt history and toxoplasmosis titers in a group of older adolescents who had recently begun treatment with an SSRI. Of 108 participants, 17 (15.7%) had a lifetime history of at least one suicide attempt. All were given structured and unstructured diagnostic interviews and provided blood samples. Two individuals (11.9%) with a past suicide attempt, and two (2.1%) without this history, had toxoplasmosis titers >= 10 IU/ml (p = 0.166). Those with a past suicide attempt had mean toxoplasmosis titers that were significantly different (p = 0.018) from those of patients who lacked this history. An ROC analysis suggested a lower optimal threshold for distinguishing patients with and without suicide attempts (3.6 IU/ml) than that customarily used to identify seropositivity. Toxoplasmosis titers may quantify a proneness to suicidal behavior in younger individuals being treated with antidepressants.
Cognitive deterioration among bipolar disorder patients infected by Toxoplasma gondii is correlated to interleukin 6 levels
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.
Immediate rather than delayed memory impairment in older adults with latent toxoplasmosis
Mendy, A., Vieira, E. R., Albatineh, A. N., Gasana, J.
Brain Behavior and Immunity 2015; 45: 36-40
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The neurotropic parasite Toxoplasma gondii infects one third of the world population, but its effect on memory remains ambiguous. To examine a potential relationship of the infection with immediate and delayed memory, a population-based study was conducted in 4485 participants of the Third National Health and Nutrition Examination Survey aged 60 years and older. Serum anti-Toxoplasma IgG antibodies were measured by enzyme immune assay and verbal memory was assessed using the Mini-Mental State Examination and the East Boston Memory Test. The prevalence of latent toxoplasmosis was 41%; in one way analysis of variance, anti-Toxoplasma IgG antibody levels significantly differed across tertiles for immediate (P = 0.006) but not delayed memory scores (P = 0.22). In multinomial logistic regression adjusting for covariates, Toxoplasma seropositivity was associated with lower immediate memory performance (OR: 0.65, 95% CI: 0.44, 0.97 for medium tertile and OR: 0.61, 95% CI: 0.37, 0.98 for highest tertile in reference to the lowest tertile), especially in non-Hispanic Whites (OR: 0.56, 95% CI: 0.36, 0.88 for medium tertile and OR: 0.51, 95% CI: 0.30, 0.87 for highest tertile in reference to the lowest tertile). However, no relationship with delayed memory was observed. In conclusion, latent toxoplasmosis is widespread in older adults and may primarily affect immediate rather than delayed memory, particularly in White Americans.
Flawed analyses undermine proposed relationship between childhood cat ownership and schizophrenia
Wolf, P. J., Hamilton, F. E.
Schizophrenia Research 2015, 168: 596-596
Lack of association between Toxoplasma gondii infection and hypertensive disorders in pregnancy: a case-control study in a Northern Mexican population
Alvarado-Esquivel, C., Vazquez-Alaniz, F., Sandoval-Carrillo, A. A., Salas-Pacheco, J. M., Hernandez-Tinoco, J., Sanchez-Anguiano, L. F., Liesenfeld, O.
Parasites & Vectors 2014; 7
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Background: The outcome of pregnancy is often threatened by hypertension disorders, i.e. eclampsia. Rate of infection with the protozoan parasite Toxoplasma gondii can be as high as 80% in pregnant women, and infection acquired during pregnancy can lead to fetal death. Very little is known about a potential association between infections, i.e. those with Toxoplasma gondii, and hypertensive disorders during pregnancy.
Methods: Through a case-control study design, we investigated the presence of anti-Toxoplasma IgG and anti-Toxoplasma IgM antibodies in 146 pregnant women suffering from hypertensive disorders (cases) and 146 age-matched normotensive pregnant women (controls) attending a public hospital in Durango City, Mexico. Obstetric and blood pressure characteristics from cases and controls were also obtained.
Results: Seroprevalence of anti-Toxoplasma IgG antibodies and IgG titers did not differ significantly in controls (8/146; 5.5%) and cases (9/146; 6.2%). Anti-Toxoplasma IgM antibodies were found in 2 (1.2%) controls and none of the cases. Seroprevalence of T. gondii in controls (5.5%) was similar to seroprevalences found in patients with mild preeclampsia (4/27: 14.8%), severe preeclampsia (5/95: 5.3%), eclampsia (0/16: 0%) and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) (0/8: 0%) (P = 0.23).
Conclusions: Our results suggest that latent infection with T. gondii is not associated with hypertensive disorders in pregnant women in Northern Mexico. Further studies with larger sample sizes are needed to elucidate the association of infection with T. gondii with hypertensive disorders in pregnancy.
Differences in some developmental features between Toxoplasma gondii-seropositive and seronegative school children
Mizgajska-Wiktor, H., Jarosz, W., Andrzejewska, I., Krzykala, M., Janowski, J., Kozlowska, M.
Folia Parasitologica 2013; 60: 416-424
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Knowledge about the influence of latent toxoplasmosis on development and general biological condition of children is scant and thus the aim of the present study was to investigate these aspects in some detail. We compare school children in rural area seropositive and seronegative to the apicomplexan parasite Toxoplasma gondii (Nicolle et Manceaux, 1908) in terms of their developmental age, body mass and body height, physical fitness and end-of-term grades. Additionally, we evaluated the risk factors of infection with T gondii such as the presence of cats in the household and eating raw meat products. With IFAT and ELISA tests, the prevalence of anti-Toxoplasma antibodies was 41% (190 children examined) and the rate of infection was higher in girls (44%) than in boys (36%). No significant differences were observed in morphological features and physical fitness of examined children. In girls the level of developmental age measured with electrophoretical mobility of nuclei method was significantly higher and school performance significantly lower for those infected with Toxoplasma than for uninfected; this finding was particularly intriguing. Only boys who ate raw meat products were more likely to be seropositive. The study provides some new information on gender differences in reaction to Toxoplasma infection.
Rhesus factor modulation of effects of smoking and age on psychomotor performance, intelligence, personality profile, and health in Czech soldiers
Flegr, J., Geryk, J., Volny, J., Klose, J., Cernochova, D.
Plos One 2012; 7: ARTN e49478 10.1371/journal.pone.0049478
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Background: Rhesus-positive and rhesus-negative persons differ in the presence-absence of highly immunogenic RhD protein on the erythrocyte membrane. This protein is a component of NH3 or CO2 pump whose physiological role is unknown. Several recent studies have shown that RhD positivity protects against effects of latent toxoplasmosis on motor performance and personality. It is not known, however, whether the RhD phenotype modifies exclusively the response of the body to toxoplasmosis or whether it also influences effects of other factors.
Methodology/Principal Findings: In the present cohort study, we searched for the effects of age and smoking on performance, intelligence, personality and self-estimated health and wellness in about 3800 draftees. We found that the positive effect of age on performance and intelligence was stronger in RhD-positive soldiers, while the negative effect of smoking on performance and intelligence was of similar size regardless of the RhD phenotype. The effect of age on four Cattell's personality factors, i.e., dominance (E), radicalism (Q(1)), self-sentiment integration (Q(3)), and ergic tension (Q(4)), and on Cloninger's factor reward dependency (RD) was stronger for RhD-negative than RhD-positive subjects, while the effect of smoking on the number of viral and bacterial diseases was about three times stronger for RhD-negative than RhD-positive subjects.
Conclusions: RhD phenotype modulates the influence not only of latent toxoplasmosis, but also of at least two other potentially detrimental factors, age and smoking, on human behavior and physiology. The negative effect of smoking on health (estimated on the basis of the self-rated number of common viral and bacterial diseases in the past year) was much stronger in RhD-negative than RhD-positive subjects. It is critically needed to confirm the differences in health response to smoking between RhD-positive and RhD-negative subjects by objective medical examination in future studies.
Toxoplasma gondii seropositivity and suicide rates in women
Ling, V. J., Lester, D., Mortensen, P. B., Langenberg, P. W., Postolache, T. T.
Journal of Nervous and Mental Disease 2011; 199: 440-444
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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.
Antibodies to infectious agents and the positive symptom dimension of subclinical psychosis: The TRAILS study
Wang, H., Yolken, R. H., Hoekstra, P. J., Burger, H., Klein, H. C.
Schizophrenia Research 2011; 129: 47-51
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nfections have been suggested to play a role in the etiology of schizophrenia, but the evidence for this has been inconsistent. Schizophrenia patients have an increased risk of infections as a result of hospitalizations or life style factors. Therefore a study on early subclinical manifestations of psychosis in relation to virus infections is warranted. We examined whether serum antibodies against human Herpes viruses and Toxoplasma gondii were associated with subclinical symptoms of psychosis in adolescents.
Data were collected as part of the TRacking Adolescents' Individual Lives Survey (TRAILS) cohort, a large prospective cohort of Dutch adolescents. A total of 1176 participants with an available Community Assessment of Psychic Experiences (CAPE) and an available blood sample were included in this analysis. Solid-enzyme immunoassay methods were used to measure the presence of immunoglobulin G (IgG) antibodies in serum to the Herpes virus family and to T. gondii.
There was no significant association between serologic evidence of infection with human Herpes viruses or T. gondii and the risk of subclinical positive experience of psychosis. Subjects with a positive serological reaction to Epstein-Barr Virus (EBV) had higher scores on the positive dimension of psychosis measured by CAPE (b = 0.03, P = 0.02). This significant association was observed in males, but not in females.
The current study suggests that there is no significant association between serological evidence of infection to human Herpes viruses and positive subclinical experience of psychosis, whereas there was an association between EBV infection and subclinical psychotic symptoms in boys.
The neurotropic parasite Toxoplasma gondii increases dopamine metabolism
Prandovszky, E., Gaskell, E., Martin, H., Dubey, J. P., Webster, J. P., McConkey, G. A.
Plos One 2011; 6: ARTN e23866 10.1371/journal.pone.0023866
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The highly prevalent parasite Toxoplasma gondii manipulates its host's behavior. In infected rodents, the behavioral changes increase the likelihood that the parasite will be transmitted back to its definitive cat host, an essential step in completion of the parasite's life cycle. The mechanism(s) responsible for behavioral changes in the host is unknown but two lines of published evidence suggest that the parasite alters neurotransmitter signal transduction: the disruption of the parasite-induced behavioral changes with medications used to treat psychiatric disease (specifically dopamine antagonists) and identification of a tyrosine hydroxylase encoded in the parasite genome. In this study, infection of mammalian dopaminergic cells with T. gondii enhanced the levels of K+-induced release of dopamine several-fold, with a direct correlation between the number of infected cells and the quantity of dopamine released. Immunostaining brain sections of infected mice with dopamine antibody showed intense staining of encysted parasites. Based on these analyses, T. gondii orchestrates a significant increase in dopamine metabolism in neural cells. Tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, was also found in intracellular tissue cysts in brain tissue with antibodies specific for the parasite-encoded tyrosine hydroxylase. These observations provide a mechanism for parasite-induced behavioral changes. The observed effects on dopamine metabolism could also be relevant in interpreting reports of psychobehavioral changes in toxoplasmosis-infected humans.
Maternal infection and schizophrenia: Implications for prevention
Brown, A. S., Patterson, P. H.
Schizophrenia Bulletin 2011; 37: 284-290
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Accumulating evidence suggests that maternal infection is a risk factor for schizophrenia. Prospective epidemiological studies indicate that maternal influenza, toxoplasmosis, and genital/reproductive infection are associated with this disorder in offspring. Preclinical models of maternal immune activation have supported the neurobiological plausibility of these microbes in schizophrenia. Previous studies suggest that treatment or prophylactic efforts targeting these and other infections could have significant effects on reducing the incidence of schizophrenia, given that they are common in the population and the effect sizes derived from epidemiological studies of these and other microbial pathogens and schizophrenia, to date, are not small. Fortunately, the occurrence of many of these infections can be reduced with relatively practical and inexpensive interventions that are scalable to large populations given adequate resources. Hence, in the present article, we focus on the potential for prevention of schizophrenia by control of infection, using these 3 categories of infection as examples. Lessons learned from previous successful public health efforts targeting these infections, including the relative advantages and disadvantages of these measures, are reviewed
Seroepidemiology of Toxoplasma gondii infection in patients with vision and hearing impairments, cancer, HIV, or undergoing hemodialysis in Durango, Mexico.
Alvarado-Esquivel, C., Liesenfeld, O., Torres-Castorena, A., Estrada-Martinez, S., Urbina-Alvarez, J. D., Ramos-de la Rocha, M., Marquez-Conde, J. A., Dubey, J. P.
Journal of Parasitology 2010; 96: 505-508.
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Toxoplasma gondii infection may cause a variety of symptoms involving virtually all organs. Little is known of the epidemiology of T. gondii infection in different patient groups in Mexico. We sought to determine the prevalence of T. gondii infection and associated epidemiological characteristics in 472 patients in Durango, Mexico. Participants were tested for T. gondii IgG and IgM antibodies. In addition, sociodemographic, clinical, and behavioral characteristics from each participant were obtained. Seroprevalences of T. gondii IgG antibodies were found in 7 (8.2%) of 85 patients with hearing impairment, 5 (10.0%) of 50 patients with hemodialysis, 28 (12.0%) of 234 patients with visual impairment, and 7 (6.8%) of 103 at risk of immunosuppression. In total, 47(10%) of 472 subjects had IgG T. gondii antibodies; 6 (1.3%) of them also had IgM anti T. gondii antibodies. Patients born in Durango State had a significantly lower prevalence of T. gondii infection than patients born in other Mexican states (9.0% vs. 21.4%, respectively: P < 0.05). Multivariate analysis showed that T. gondii infection was significantly associated with consumption of undercooked meat (adjusted odds ratio [OR] = 2.95; 95% confidence interval [CI]: 1.18-7.35) or raw cow's milk (adjusted OR = 2.52; 95% CI: 1.28-4.96), presence of cats at home (adjusted OR = 2.01; 95% CI: 1.06-3.78), raising animals (adjusted OR = 2.44; 95% CI: 1.06-5.63), or eating away from home (adjusted OR = 2.70; 95% CI: 1.03-7.11). In the group of patients with visual impairment, those with reflex impairment had a significantly higher frequency of T. gondii infection than those with normal reflexes (19% vs. 9.4%, respectively: P = 0.04). Results of the present study are the first step in the design of prevention programs to avoid the sequelae of toxoplasmosis.
Toxoplasmosis as a cause for behaviour disorders – overview of evidence and mechanisms
Fekadu A, Shibre T, Cleare AJ.
Folia Parasitologica 2010; 57: 105-113
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Background - There is growing interest in the role of microbial agents in the causation of psychiatric disorders. The neurotropic protozoan parasite Toxoplasma gondii is one of the main candidates and has been associated with various psychiatric conditions, including schizophrenia. Methods - A narrative review of the literature from the main medical databases (Medline, PubMed, PsycINFO), Google Scholar and Google using combinations of applicable terms. Results - T. gondii affects the brain in both the acute and the latent stages of infection causing apparent brain pathologies in infected rodents and both immuno-compromised and immuno-competent humans. In immuno-competent individuals, behavioural disorders are primarily related to the latent stages of the illness. Behavioural/mental disorders that include schizophrenia, mood disorders, personality changes and cognitive impairments may be related to infection with T gondii. Evidence for a behavioural effect of T gondii comes from observational reports in animal models and controlled behavioural analysis in humans. Indirect clues of infection also come from raised seroprevalence or serotitres of antitoxoplasma antibodies among those with mental disorders. The pathophysiologic mechanism through which T gondii may exert its effect is not clear, but direct impact on the brain and changes in neuroimmunomodulation, neurotransmission and some gene-environment interactions are postulated. Conclusion - There is evidence supporting a potential role of T gondii infection in the onset of some behavioural disorders. Confirmation of such a role would prove a significant breakthrough in the search for the aetiology, treatment and prevention of behavioural disorders, such as schizophrenia. However, the associations remain preliminary.
The association of infectious agents and schizophrenia
Krause, D., Matz, J., Weidinger, E., Wagner, J., Wildenauer, A., Obermeier, M., Riedel, M., Muller, N.
World Journal of Biological Psychiatry 2010; 11: 739-743
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Objectives. The influence of infectious agents on the pathogenesis of psychiatric disorders has been discussed for decades. Pre- and postnatal infections are risk factors for schizophrenia. This may be explained by chronic infections or an altered immune status. However most of the studies have only focused on one single pathogen and not on the impact of different infectious agents. We investigated the association between schizophrenia and various neurotophic infectious agents. Methods. A total of 31 schizophrenic patients and 30 healthy matched individuals were included. Antibody titres of cytomegalovirus, herpes simplex virus, Epstein-Barr virus, mycoplasma, chlamydia and toxoplasma were evaluated. For statistical analysis we used Fisher's exact and Wilcoxon test. Results. Significantly elevated positive antibody titres within schizophrenic patients were found only for Chlamydia trachomatis (P=0.005) and a trend to significance for herpes simplex virus (P=0.055). Combining the different agents, schizophrenics had a significantly higher rate of positive titres to infectious agents as compared to controls (P=0.04). Conclusions. The higher prevalence of antibodies within schizophrenic patients emphasizes a possible role of infectious agents in the pathogenesis of schizophrenia. Our data indicates that not one specific agent might be responsible for schizophrenic symptoms but the resulting immune response in the central nervous system.
Psychosis may be associated with toxoplasmosis
Zhu S.
Medical Hypotheses 2009; 73: 799-801.
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Many parasites induce characteristic changes in their host. The effect of Toxoplasma gondii infection on the cerebrum and neuropsychiatric patients has been increasingly emphasized in recent years. T gondii has a high affinity for brain tissue where tachyzoites may form tissue cysts and persist for a life long time. Some psychiatric symptoms such as schizophrenia and mental retardation may be induced by the infection of T gondii. Furthermore, experiments demonstrated that some antipsychotics and mood stabilizers used to treat psychosis displayed the function of inhibiting T. gondii replication. Investigations from various regions in China in psychotic patients support the hypotheses that psychosis may be linked to T gondii infection. (C) 2009 Elsevier Ltd. All rights reserved.
Increased incidence of traffic accidents in Toxoplasma-infected military drivers and protective effect RhD molecule revealed by a large-scale prospective cohort study
Flegr, J., Klose, J., Novotná, M., Berenreitterová, M., Havlíček, J.
Bmc Infectious Diseases 2009; 9: Artn 72 10.1186/1471-2334-9-72
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Background: Latent toxoplasmosis, protozoan parasitosis with prevalence rates from 20 to 60% in most populations, is known to impair reaction times in infected subjects, which results, for example, in a higher risk of traffic accidents in subjects with this life-long infection. Two recent studies have reported that RhD-positive subjects, especially RhD heterozygotes, are protected against latent toxoplasmosis-induced impairment of reaction times. In the present study we searched for increased incidence of traffic accidents and for protective effect of RhD positivity in 3890 military drivers.
Methods: Male draftees who attended the Central Military Hospital in Prague for regular entrance psychological examinations between 2000 and 2003 were tested for Toxoplasma infection and RhD phenotype at the beginning of their 1 to 1.5-year compulsory military service. Subsequently, the data on Toxoplasma infection and RhD phenotype were matched with those on traffic accidents from military police records and the effects of RhD phenotype and Toxoplasma infection on probability of traffic accident was estimated with logistic regression.
Results: We confirmed, using for the first time a prospective cohort study design, increased risk of traffic accidents in Toxoplasma-infected subjects and demonstrated a strong protective effect of RhD positivity against the risk of traffic accidents posed by latent toxoplasmosis. Our results show that RhD-negative subjects with high titers of anti-Toxoplasma antibodies had a probability of a traffic accident of about 16.7%, i.e. a more than six times higher rate than Toxoplasma-free or RhD-positive subjects.
Conclusion: Our results showed that a common infection by Toxoplasma gondii could have strong impact on the probability of traffic accident in RhD negative subjects. The observed effects could provide not only a clue to the long-standing evolutionary enigma of the origin of RhD polymorphism in humans (the effect of balancing selection), but might also be the missing piece in the puzzle of the physiological function of the RhD molecule.
The schizophrenia and Toxoplasma gondii connection: Infectious, immune or both?
Tamer, G. S., Dundar, D., Yalug, I., Caliskan, S., Yazar, S., Aker, A.
Advances in Therapy 2008; 25: 703-709
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Introduction: Recent research has suggested a possible link between toxoplasmic agents and schizophrenia. We aimed to assess this by measuring Toxoplasma gondii-associated antibodies in schizophrenia patients and controls.
Methods: We used a commercially available enzyme-linked immunosorbent assay (ELISA) kit to measure the level of immunoglobulin G (IgG) and IgM antibodies in serum samples from schizophrenia patients (n= 40) and from a group of non-schizophrenic control subjects (n= 37).
Results: Among schizophrenic patients, 16 (40%) showed IgG seropositivity and two (5%) showed IgM seropositivity. Among the control group, five (13.5%) were found have IgG seropositivity and one (2.7%) showed IgM seropositivity. In our study we found that IgG T gondii antibodies were significantly higher in schizophrenia patients compared with controls.
Conclusion: This study supports the theory that toxoplasmic agents may have a role in the aetiology of schizophrenia.