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Toxoplasma gondii & Human Phenotype

Compendium of Known Effects and Ongoing Research

adult schizophrenia

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

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

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

Mental health

Schizophrenia and infections: The eyes have it

January 3, 2017
Torrey, E. F. ,Yolken, R. H.
Schizophrenia Bulletin 2017; 43: 247-252
Click for abstract
The visual tract is prominently involved in schizophrenia, as evidenced by perceptual distortions and a type of nystagmus found in many individuals affected. Genetic explanations for these abnormalities have been suggested. This study proposes an alternate explanation based on infection. Several infectious agents thought to be associated with some cases of schizophrenia are known to cause both infection of the fetus and abnormalities of the eye. Toxoplasma gondii is examined in detail, and rubella, cytomegalovirus, varicellazoster virus, and herpes simplex virus more briefly. Careful ophthalmic assessments, including funduscopy and direct examination of tissues for infectious agents, will clarify the role of such agents in ocular aspects of schizophrenia.

Tagged: adult schizophrenia, cat ownership, congenital toxoplasmosis, gondii, herpes-simplex-virus, infections, movement abnormalities, ocular, ocular toxoplasmosis, psychosis, risk factors, Schizophrenia, smooth-pursuit, toxoplasmosis

Mental health

Maternal T-gondii, offspring bipolar disorder and neurocognition

January 4, 2016
Freedman, D., Bao, Y. Y., Shen, L., Schaefer, C. A., Brown, A. S.
Psychiatry Research 2016, 243: 382-389
Click for abstract
Prenatal exposure to maternal Toxoplasma gondii (T. gondii) IgG antibody titer has been associated previously with an increased risk of offspring schizophrenia (SZ) and cognitive impairment. We examined maternal T gondii, offspring bipolar disorder (BP) and childhood cognition using a population based birth cohort. Maternal sera, drawn in the third trimester, were analyzed for T. gondii IgG antibody titer, and offspring cognition at ages 5 and 9-11 was measured with the Peabody Picture Vocabulary Test (PPVT) and the Raven Matrices (Raven). Raw scores were standardized and the ages combined. Potential cases with BP from the cohort were identified by database linkages. This protocol identified 85 cases who were matched 1:2 to controls. Maternal T. gondii IgG was not associated with the risk of BP in offspring. Neither moderate [HR = 1.43 (CI: 0.49, 4.17)] nor high IgG titer [HR=1.6 [CI: 0.74, 3.48)] were associated with offspring BP. Associations were not observed between maternal T gondii and BP with psychotic features or BP type 1. In addition, maternal T gondii was not associated with childhood cognition. Our study suggests that T. gondii may be specific to SZ among major psychotic disorders, though further studies with larger sample sizes are required. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Tagged: 1st-episode schizophrenia, adult schizophrenia, birth cohort, cognition, cognitive impairment, congenital toxoplasmosis, danish draft-board, infectious agents, mood disorders, neurodevelopment, of-the-literature, ppvt, prenatal exposure, psychotic disorders, raven matrices, spectrum disorder, Toxoplasma gondii

Mental health

Maternal infection and schizophrenia: Implications for prevention

January 10, 2011
Brown, A. S., Patterson, P. H.
Schizophrenia Bulletin 2011; 37: 284-290
Click for abstract
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

Tagged: adult schizophrenia, birth cohort, environment, Epidemiology, genital reproductive infection, herpes-simplex-virus, influenza, influenza epidemic, neurodevelopment, pregnant women, prenatal exposure, respiratory illness, risk, Toxoplasma gondii, toxoplasmosis, united-states

Mental health

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

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

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

Mental health

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

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

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

Mental health

Prenatal infection as a risk factor for schizophrenia

October 30, 2006
Brown AS.
Schizophrenia Bulletin 2006; 32: 200-202
Click for abstract
Accumulating evidence suggests that prenatal exposure to infection contributes to the etiology of schizophrenia. This line of investigation has been advanced by birth cohort studies that utilize prospectively acquired data from serologic assays for infectious and immune biomarkers. These investigations have provided further support for this hypothesis and permitted the investigation of new infectious pathogens in relation to schizophrenia risk. Prenatal infections that have been associated with schizophrenia include rubella, influenza, and toxoplasmosis. Maternal cytokines, including interleukin-8, are also significantly increased in pregnancies giving rise to schizophrenia cases. Although replication of these findings is required, this body of work may ultimately have important implications for the prevention of schizophrenia, the elaboration of pathogenic mechanisms in this disorder, and investigations of gene-environment interactions.

Tagged: adult schizophrenia, Epidemiology, exposure, infection, influenza, prenatal, psychosis, Schizophrenia, virus

Mental health

Infectious agents and gene-environmental interactions in the etiopathogenesis of schizophrenia

October 30, 2006
Yolken RH, Torrey EF
Clinical Neuroscience Research 2006; 6: 97-109.
Click for abstract
Schizophrenia is a pervasive neuropsychiatric disorder with worldwide prevalence. Family and adoption studies indicate a strong genetic component of disease susceptibility. However, epidemiological studies also point to a role for infections and other environmental factors in disease etiology. We review the evidence for a role for infectious agents in the etiopathogenesis of schizophrenia and related disorders, focusing on the apicomplexan parasite Toxoplasma gondii. We discuss the epidemiological evidence for a role for this agent, as well as potential mechanisms of gene-environmental interactions which are consistent with the genetic components of disease susceptibility. We describe how the potential role of infections as causative agents of complex disorders such as schizophrenia are not consistent with classical postulates of causation such as the Koch Postulates, but may be consistent with more modern concepts of how infectious agents can interact with genetic determinants to result in disease in susceptible individuals. We outline the research approaches which are necessary to define associations between infectious agents and complex disorders. The successful association between infectious agents and diseases such as schizophrenia might lead to new methods for treatment and prevention of these devastating disorders. (C) 2006 Association for Research in Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved.

Tagged: adult schizophrenia, bipolar disorder, etiopathogenesis, helicobacter-pylori-infection, human endogenous retroviruses, in-vivo, nervous-system infections, recent-onset schizophrenia, Schizophrenia, simplex-virus type-1, Toxoplasma gondii, viral encephalitis

Mental health

Infectious agents and gene-environmental interactions in the etiopathogenesis of schizophrenia

March 26, 2006
Yolken, R. H., Torrey, E. F.
Clinical Neuroscience Research 2006; 6: 97-109
Click for abstract
Schizophrenia is a pervasive neuropsychiatric disorder with worldwide prevalence. Family and adoption studies indicate a strong genetic component of disease susceptibility. However, epidemiological studies also point to a role for infections and other environmental factors in disease etiology. We review the evidence for a role for infectious agents in the etiopathogenesis of schizophrenia and related disorders, focusing on the apicomplexan parasite Toxoplasma gondii. We discuss the epidemiological evidence for a role for this agent, as well as potential mechanisms of gene-environmental interactions which are consistent with the genetic components of disease susceptibility. We describe how the potential role of infections as causative agents of complex disorders such as schizophrenia are not consistent with classical postulates of causation such as the Koch Postulates, but may be consistent with more modern concepts of how infectious agents can interact with genetic determinants to result in disease in susceptible individuals. We outline the research approaches which are necessary to define associations between infectious agents and complex disorders. The successful association between infectious agents and diseases such as schizophrenia might lead to new methods for treatment and prevention of these devastating disorders. (C) 2006 Association for Research in Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved.

Tagged: adult schizophrenia, bipolar disorder, etiopathogenesis, helicobacter-pylori-infection, human endogenous retroviruses, in-vivo, nervous-system infections, recent-onset schizophrenia, Schizophrenia, simplex-virus type-1, Toxoplasma gondii, viral encephalitis

Mental health

Infection and mental illness: Do bugs make us batty?

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

Mental health

Maternal infections and subsequent psychosis among offspring

November 7, 2001
Buka, S.L., Tsuang, M.T., Torrey, E.F., Klebanoff, M.A., Bernstein, D., Yolken, R.H.
ArchGenPsychiatry 2001 Nov;58(11):1032-7 2001
Click for abstract
Background: We tested the hypothesis that maternal infections during pregnancy are associated with the subs equent development of schizophrenia and other psychoses in adulthood. Methods: We conducted a nested case-control study of 27 adults with schizophrenia and other psychotic illnesses and 54 matched unaffected control subjects (matched for sex, ethnicity, and date of birth) from the Providence, RI, cohort of the Collaborative Perinatal Project. We retrieved stored blood samples that had been obtained from these mothers at the end of pregnancy. These samples were analyzed for total class-specific immunoglobulins and for specific antibodies directed at recognized perinatal pathogens capable of affecting brain development. Results: Maternal levels of IgG and IgM class immunoglobulins before the mothers were delivered of their neonates were significantly elevated among the case series (t=3.06, P=.003; t=2.93, P=.004, respectively, for IgG and IgM immunoglobulin-albumin ratios). Secondary analyses indicated a significant association between maternal antibodies to herpes simplex virus type 2 glycoprotein gG2 and subsequent psychotic illness (matched t test=2.43, P=.02). We didn't find significant differences between case and control mothers in the serum levels of IgA class immunoglobulins, or in specific IgG antibodies to herpes simplex Virus type 1, cytomegalovirus, Toxoplasma gondii, rubella virus, human parvovirus B19, Chlamydia trachomatis, or human papillomavirus type 16. Conclusions: The offspring of mothers with elevated levels of total IgG and IgM immunoglobulins and antibodies to herpes simplex virus type 2 are at increased risk for the development of schizophrenia and other psychotic illnesses in adulthood.

Tagged: adult schizophrenia, bipolar disorder, collaborative perinatal project, encephalitis, follow-up, herpes-simplex-virus, influenza, pregnancy, prenatal exposure, type-2

Mental health

Topics

  • Behavior 105
  • Cognitive functions 64
  • Mental health 439
  • Morphology 6
  • Motor functions 10
  • Personality 36
  • Physical health 134
  • Reproduction 36
  • Reviews 40
  • Sensory functions 3
  • Uncategorized 2

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Recent articles

  • Mortality Patterns of Toxoplasmosis and Its Comorbidities in Tanzania: A 10-Year Retrospective Hospital-Based Survey February 6, 2020
  • The role of latent toxoplasmosis in the aetiopathogenesis of schizophrenia–the risk factor or an indication of a contact with cat? February 6, 2020
  • The Association between Toxoplasma gondii Infection and Risk of Parkinson’s Disease: A Systematic Review and Meta-Analysis February 6, 2020

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