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Toxoplasma gondii & Human Phenotype

Compendium of Known Effects and Ongoing Research

cerebrospinal fluid

Exposure to perinatal infections and bipolar disorder: A systematic review

May 24, 2016
Barichello, T., Badawy, M., Pitcher, M. R., Saigal, P., Generoso, J. S., Goularte, J. A., Simoes, L. R., Quevedo, J., Carvalho, A. F.
Curr Mol Med 2016; 16: 106-118
Click for abstract
Bipolar disorder (BD) is a debilitating psychiatric disorder and a growing global public health issue. Notwithstanding BD has been conceptualized as a neuroprogressive illness, there are some evidences to suggest a role for neurodevelopmental pathways in the patho-etiology of this disorder. Evidences on the associations between perinatal infections and risk for bipolar disorder have been inconsistent across studies. Here, we performed a systematic review of observational studies on the relationship between exposure to perinatal pathogens and bipolar disorder. A computerized literature search of the PubMed, Embase, and PsyINFO databases till January 31st, 2015 was performed. Twenty-three studies ultimately met inclusion criteria. Studies investigated exposure to several pathogens namely Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Herpes simplex virus-1 (HSV-1), Herpes simplex virus-2 (HSV-2), Human herpesvirus 6 (HHV-6), Toxoplasma gondii, Influenza, and Varicella zoster virus (VZV). Overall, studies provided mixed evidences. Thus, contrary to schizophrenia, the role of perinatal infections as risk factors for BD remain inconclusive. Larger studies with a prospective design would be necessary to elucidate the role of previous exposure to infectious agents as a potential risk factor for BD.

Tagged: antibodies, bipolar disorder, cerebrospinal fluid, cognitive impairment, cytomegalovirus, herpes, herpes-simplex encephalitis, individuals, influenza, maternal infection, metaanalysis, psychiatric patients, Schizophrenia, systematic review, Toxoplasma gondii, toxoplasma gondii infection

Mental healthReproductionReviews

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

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

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

Mental health

Inflammatory molecular signature associated with infectious agents in psychosis

October 9, 2014
Hayes, L. N., Severance, E. G., Leek, J. T., Gressitt, K. L., Rohleder, C., Coughlin, J. M., Leweke, F. M., Yolken, R. H., Sawa, A.
Schizophrenia Bulletin 2014; 40: 963-972
Click for abstract
Schizophrenia (SZ) is a devastating mental condition with onset in young adulthood. The identification of molecular biomarkers that reflect illness pathology is crucial. Recent evidence suggested immune and inflammatory cascades in conjunction with infection may play a role in the pathology. To address this question, we investigated molecular changes in cerebrospinal fluid (CSF) from antipsychoticnaive patients with SZ and at risk mental status for psychosis (ARMS), in comparison with healthy controls (HCs). We measured 90 analytes using a broad multiplex platform focusing on immune and inflammatory cascades then selected 35 with our quality reporting criteria for further analysis. We also examined Toxoplasma gondii (TG) and herpes simplex virus 1 antibody levels in CSF. We report that expression of 15 molecules was significantly altered in the patient groups (SZ and ARMS) compared with HCs. The majority of these molecular changes (alpha-2-macroglobulin [alpha 2M], fibrinogen, interleukin-6 receptor [IL-6R], stem cell factor [SCF], transforming growth factor alpha [TGF alpha], tumor necrosis factor receptor 2 [TNFR2], IL-8, monocyte chemotactic protein 2 [MCP-2/CCL8], testosterone [for males], angiotensin converting enzyme [ACE], and epidermal growth factor receptor) were consistent between SZ and ARMS patients, suggesting these may represent trait changes associated with psychotic conditions in general. Interestingly, many of these analytes (alpha 2M, fibrinogen, IL-6R, SCF, TGF alpha, TNFR2, IL-8, MCP-2/CCL8, and testosterone [for males]) were exacerbated in subjects with ARMS compared with subjects with SZ. Although further studies are needed, we optimistically propose that these molecules may be good candidates for predictive markers for psychosis from an early stage. Lastly, reduction of IL-6R, TGF alpha, and ACE was correlated with positivity of TG antibody in the CSF, suggesting possible involvement of TG infection in the pathology.

Tagged: antibodies, at risk mental status, biomarker, cerebrospinal fluid, exposure, immune activation, inflammation, metaanalysis, pathways, prenatal infection, recent-onset schizophrenia, risk factors, Schizophrenia, simplex-virus 1, Toxoplasma gondii

Mental health

Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel

October 10, 2013
Li, Y. Z., Weber, N. S., Fisher, J. A., Yolken, R. H., Cowan, D. N., Larsen, R. A., Niebuhr, D. W.
Schizophrenia Research 2013; 151: 36-42
Click for abstract
Introduction: Multiple studies have documented immune activation in many individuals with schizophrenia suggesting that antigens capable of generating a prolonged immune response may be important environmental factors in many cases of this disorder. While existing studies have found single-agent associations of antibodies to food and neurotropic infectious agents with schizophrenia, a simultaneous examination of multiple agents may shed light on agent interactions or possible etiopathogenic pathways. Methods: We used traditional regression and novel statistical techniques to examine associations of single and combined infectious and food antigens with schizophrenia. We tested 6106 serum samples from 855 cases and 1165 matched controls. Results: Higher antibody levels to casein were borderline significant in the prediction of schizophrenia (HR = 1.08,p = 0.06). Study participants with higher cytomegalovirus (CMV) lgG antibody levels had a reduced risk of developing schizophrenia (HR = 0.90; p = 0.02). While lgG antibodies to gliadin, Toxoplasma gondii, vaccinia, measles, and human herpesvirus-6 (HHV-6) showed no significant independent associations with schizophrenia, the increase in antibody levels to several combinations of agents, to include casein, measles, CMV, T gondii and vaccinia, was predictive of an 18-34% increase in the risk of developing schizophrenia. Conclusion: Certain patterns of antibodies, involving some agents, were predictive of developing schizophrenia, with the magnitude of association rising when the level of antibodies increased to two or more agents. A heightened antibody response to a combination of several infectious food antigens might be an indicator of an altered immune response to antigenic stimuli

Tagged: autoimmune diseases, biomarker, bipolar disorder, case-control, cerebrospinal fluid, cytomegalovirus, herpes-simplex, immune-response, psychosis, sero-epidemiology, serum-levels, t-cells, Toxoplasma gondii

Mental health

Toxoplasma gondii immunoglobulin G antibodies and nonfatal suicidal self-directed violence

October 11, 2012
Zhang, Y. F., Traskman-Bendz, L., Janelidze, S., Langenberg, P., Saleh, A., Constantine, N., Okusaga, O., Bay-Richter, C., Brundin, L., Postolache, T. T.
Journal of Clinical Psychiatry 2012; 73: 1069-1076
Click for abstract
Objective: The primary aim was to relate Toxoplasma gondii seropositivity and serointensity to scores on the self-rated Suicide Assessment Scale (SUAS-S). Another aim was to reevaluate the previously reported positive association between T gondii serointensity and a history of nonfatal suicidal self-directed violence. Method: This cross-sectional, observational study compared T gondii serointensity and seropositivity in plasma from 54 adult suicide attempters (inpatients at Lund University Hospital, Lund, Sweden) and 30 adult control subjects (randomly selected from the municipal population register in Lund, Sweden) recruited between 2006 and 2010.The potential of patients and controls for self-directed violence was evaluated with the SUAS-S. Psychiatric diagnoses were made according to DSM-IV criteria. Plasma samples were tested for immunoglobulin G antibodies to T gondii, cytomegalovirus, and herpes simplex virus type 1. Data were analyzed using multivariable logistic regression to investigate the association between T gondii serointensity or seropositivity and a history of nonfatal suicidal self-directed violence; multivariable linear regression was used to explore the relationship between T gondii serointensify or seropositivity and the SUAS-S. Both regression models included sex, age, and body mass index as covariates. Results: Seropositivity of T gondii (adjusted odds ratio [OR]=7.12; 95% CI, 1.66-30.6; P=.008) and serointensity of T gondii (adjusted OR=2.01; 95% CI, 1.09-3.71; P=.03) were positively associated with a history of nonfatal suicidal self-directed violence. Seropositivity of T gondii was associated with higher SUAS-S scores, a relationship significant for the whole sample (P=.026), but not for suicide attempters only. No significant associations with other pathogens were identified. Conclusions: These results are consistent with previous reports on the association between T gondii infection and nonfatal suicidal self-directed violence. Confirming these results in future large longitudinal studies and including suicide as an outcome may lead to novel individualized approaches in suicide prevention. J Clin Psychiatry 2012;73 (8):1069-1076 (c) Copyright 2012 Physicians Postgraduate Press, Inc.

Tagged: assessment scale, Cerebral toxoplasmosis, cerebrospinal fluid, depression scale, interferon-gamma, latent toxoplasmosis, personality changes, quinolinic acid, traffic accidents, united-states

BehaviorMental health

Herpesviruses and Toxoplasma gondii in orbital frontal cortex of psychiatric patients

October 30, 2003
Conejero-Goldberg, C., Torrey, E.F., Yolken, R.H.
Schizophrenia Research 2003; 60: 65-69.
Click for abstract
Herpes simplex virus (HSV), Epstein-Barr virus (EMV), cytomegalovirus (CW), and human herpesvirus-6 (HHV-6) are viruses capable of establishing latency. All of these infect the CNS and have been detected in human postmortem brains. Toxoplasma gondii is a protozoan organism which can reactivate in the brains of previously infected immunocompromised individuals. To screen for the presence of herpesviruses and T gondii in postmortem orbital frontal brain samples from patients with schizophrenia, affective disorders, and controls, we used nested-polymerase chain reaction (n-PCR)/sequencing. We identified HGV-6B sequences in 2/51 postmortem brain samples but no sequences from other herpesviruses, We did not detect sequences of T gondii in the postmortem brains. Additional studies including ones directed at the sensitive detection of viral nucleic acids in multiple brain regions should be directed at confirming or excluding a role for viruses and protozoa in the etiology of these disorders, (C) 2002 Elsevier Science B.V. All rights reserved.

Tagged: bipolar disorder, cerebrospinal fluid, cytomegalo-virus, DNA, first-episode schizophrenia, herpes-simplex-virus, herpesvirus, nucleic-acid sequences, orbital frontal cortex, pcr, polymerase chain-reaction, postmortem, Schizophrenia, sclerosis brain-tissue, search, Toxoplasma gondii

Mental health

Topics

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

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Recent articles

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  • 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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