cytomegalovirus – Toxoplasma gondii & Human Phenotype

Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders

January 31, 2020
Burgdorf, K. S., Trabjerg, B. B., Pedersen, M. G., Nissen, J., Banasik, K., Pedersen, O. B., Sorensen, E., Nielsen, K. R., Larsen, M. H., Erikstrup, C., Bruun-Rasmussen, P., Westergaard, D., Thorner, L. W., Hjalgrim, H., Paarup, H. M., Brunak, S., Pedersen, C. B., Torrey, E. F., Werge, T., Mortensen, P. B., Yolken, R. H., Ullum, H.
Brain Behavior and Immunity 2019, 79: 152 - 158

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Viral and parasitic pathogen burden and the association with stroke in a population-based cohort

February 12, 2018
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.

Effects of cumulative herpesviridae and Toxoplasma gondii infections on cognitive function in healthy, bipolar, and schizophrenia subjects

January 3, 2017
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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Temporal cognitive decline associated with exposure to infectious agents in a population-based, aging cohort

October 29, 2016
Nimgaonkar, V. L., Yolken, R. H., Wang, T. X., Chang, C. C. H., McClain, L., McDade, E., Snitz, B. E., Ganguli, M
Alzheimer Disease & Associated Disorders 2016; 30: 216-222

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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

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Infectious disease burden and cognitive function in young to middle-aged adults

January 4, 2016
Gale, S. D., Erickson, L. D., Berrett, A., Brown, B. L., Hedges, D. W.
Brain Behavior and Immunity 2016, 52: 161-168

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Seroprevalence of Toxoplasma gondii in spontaneous abortions in pregnant women

January 10, 2015
Anubhuti, Roy, R. R., Mittra, J. P., Begum, S. J.
Journal of Evolution of Medical and Dental Sciences-Jemds 2015; 4: 6763-6768

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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

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Difference of neuro- and immunomodulatory steroids and selected hormone and lipid concentrations between Toxoplasma-free and Toxoplasma-infected schizophrenia patients

September 27, 2014
Flegr, J., Hampl, R., Bicíková, M., Ripova, D., Mohr, P.
Neuroendocrinology Letters 2014; 35: 20-27

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OBJECTIVES : Toxoplasma gondii , the protozoan parasite infecting about 30% population worldwide, is suspected to be the etiological agent of certain form of schizophrenia disease. To x o p l a s m a is known to change levels of certain neu- rotransmitters, cytokines and several hormones in both infected animals and humans. A common feature of toxoplasmosis and schizophrenia is a disorder of immune system. METHODS: Here we studied the levels of five neuro- and immunomodulatory steroids, selected hormones and lipids in sera of 173 schizophrenia patients. RESULTS: To x o p l a s m a infected schizophrenia patients expressed only insignifi- cantly lower concentration of neuro- and immunomodulatory DHEA metabo- lites. Infected women had higher concentration of glucose while infected men had higher concentration of cholesterol and LDL cholesterol. No significant effect of human cytomegalovirus infection on the concentration of the above parameters was observed. The difference in the concentration of DHEA metabolites faded with the decrease of the concentration of anti- To x o p l a s m a IgG antibodies (i.e. with the duration of To x o p l a s m a infection) while the difference in the concentra- tion of cholesterol and LDL-cholesterol increased with the decrease of the con- centration of anti- To x o p l a s m a IgG antibodies. The prevalence of toxoplasmosis in male (53.2%) but not female (29.8%) schizophrenia patients was unusually high in comparison with prevalence of toxoplasmosis in a general population. CONCLUSION: Our results provided an explanation for seemingly decreasing prevalence of toxoplasmosis in schizophrenia patients observed in current studies (increased concerns about the rights of patients result- ing in absence of non-cooperative To x o p l a s m a -positive patients in the study population) and suggest possible explanation for reported positive correlation between prevalence of toxoplasmosis and incidence of cardio- vascular diseases (accelerated atherosclerotic develop- ment due to increased level of cholesterol and LDL in To x o p l a s m a infected humans).

Role of infectious agents in the carcinogenesis of brain and head and neck cancers

October 10, 2013
Alibek K, Kakpenova A, Baiken Y.
Infectious agents and cancer 2013; 8

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This review concentrates on tumours that are anatomically localised in head and neck regions. Brain cancers and head and neck cancers together account for more than 873,000 cases annually worldwide, with an increasing incidence each year. With poor survival rates at late stages, brain and head and neck cancers represent serious conditions. Carcinogenesis is a multi-step process and the role of infectious agents in this progression has not been fully identified. A major problem with such research is that the role of many infectious agents may be underestimated due to the lack of or inconsistency in experimental data obtained globally. In the case of brain cancer, no infection has been accepted as directly oncogenic, although a number of viruses and parasites are associated with the malignancy. Our analysis of the literature showed the presence of human cytomegalovirus (HCMV) in distinct types of brain tumour, namely glioblastoma multiforme (GBM) and medulloblastoma. In particular, there are reports of viral protein in up to 100% of GBM specimens. Several epidemiological studies reported associations of brain cancer and toxoplasmosis seropositivity. In head and neck cancers, there is a distinct correlation between Epstein-Barr virus (EBV) and nasopharyngeal carcinoma (NPC). Considering that almost every undifferentiated NPC is EBV-positive, virus titer levels can be measured to screen high-risk populations. In addition there is an apparent association between human papilloma virus (HPV) and head and neck squamous cell carcinoma (HNSCC); specifically, 26% of HNSCCs are positive for HPV. HPV type 16 was the most common type detected in HNSCCs (90%) and its dominance is even greater than that reported in cervical carcinoma. Although there are many studies showing an association of infectious agents with cancer, with various levels of involvement and either a direct or indirect causative effect, there is a scarcity of articles covering the role of infection in carcinogenesis of brain and head and neck cancers. We review recent studies on the infectious origin of these cancers and present our current understanding of carcinogenic mechanisms, thereby providing possible novel approaches to cancer treatment.

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

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Prevalence of anti-Toxoplasma antibodies in patients with autoimmune diseases

October 11, 2012
Shapira, Y., Agmon-Levin, N., Selmi, C., Petrikova, J., Barzilai, O., Ram, M., Bizzaro, N., Valentini, G., Matucci-Cerinic, M., Anaya, J. M., Katz, B. S. P., Shoenfeld, Y.
Journal of Autoimmunity 2012; 39: 112-116

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The identification of etiological factors in the induction of autoimmunity has remained elusive despite an enormous effort at dissection of the molecular structure of the target antigens and effector mechanisms. One characteristic feature of autoantigens is their repetitive structure as well as their conservation and evolution. Toxoplasma (T.)gondii is a primitive protozoan. We hypothesized that patients with autoimmune disease would have broad reactions against Toxoplasma antigens based on autoantigen conservation. To address this issue, we assessed serologic evidence of reactivity to Toxoplasma gondii along with a large profile of autoantibodies in patients with various autoimmune diseases (AID). We included sera of 1514 patients with 11 different AID collected from referral centers in Europe and Latin America as well as from 437 geographically matched controls, for the prevalence of anti Toxoplasma antibodies (ATxA) IgG and IgM and serum autoantibodies utilizing the BioPlex 2200 system (Bio- Rad Laboratories, USA). Serum ATxA IgG were positive in 42% of patients with AID versus 29% of controls (p < 0.0001). Among Europeans, ATxA IgG were associated with anti-phospholipid syndrome (APS; p < 0.0001), cryoglobulinemia (p < 0.0001), ANCA-associated vasculitides (p < 0.01), autoimmune thyroid diseases (p < 0.0001), systemic sclerosis (SSc; p < 0.0001) and rheumatoid arthritis (RA; p < 0.0001). Of note, Latin American RA sera exhibited similar frequency of ATxA IgG as controls. ATxA IgM were more prevalent in European patients with APS (p < 0.01), SSc (p < 0.05) and inflammatory bowel disease (IBD, p < 0.05) than in controls. Further, in AID patients the presence of ATxA correlated with autoantibodies characteristic of APS (anti-cardiolipin, B2GPI, complex of cardiolipin- B2GPI, prothrombin, phosphatydilethanolamine), and of SSc (anti-centromere, Scl-70). Our findings suggest that T. gondii may contribute to the pathogenesis of AID. This interaction may depend on or explain observed geoepidemiological variance in AID. (C) 2012 Elsevier Ltd. All rights reserved.

Neonatal antibodies to infectious agents and risk of bipolar disorder: a population-based case-control study

October 16, 2011
Mortensen, P. B., Pedersen, C. B., McGrath, J. J., Hougaard, D. M., Norgaard-Petersen, B., Mors, O., Borglum, A. D., Yolken, R. H.
Bipolar Disorders 2011; 13: 624-629

Are some cases of psychosis caused by microbial agents? A review of the evidence

October 26, 2008
Yolken RH, Torrey EF
Molecular Psychiatry 2008; 13: 470-479

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Probable neuroimmunological link between Toxoplasma and cytomegalovirus infections and personality changes in the human host

September 26, 2005
Novotná, M., Hanusova, J, Klose J., Preiss, M., Havlicek, J., Roubalová, K., Flegr, J.
BMC Infectious Diseases 2005; 5: 54

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Background: Recently, a negative association between Toxoplasma -infection and novelty s eeking was reported. The authors suggested that changes of pers onality trait were caused by manipula tion activity of the parasite, aimed at increasing the probability of tr ansmission of the parasite from an intermedia te to a definitive host . They also suggested that low novelty seeking indicated an in creased level of the neurot ransmitter dopamine in the brain of infected subjects, a phenomenon already observ ed in experimentally infected ro dents. However, the changes in personality can also be just a byproduct of any neurotropic infection . Moreover, the association between a pe rsonality trait and the toxoplasmosis can even be caused by an independent correlation of both the probability of Toxoplasma -infection and the personality trait with the third factor, namely with th e size of living place of a subject. To test these two alternative hypotheses, we studied the influence of another neurotropic pathogen, the cyto megalovirus, on the personali ty of infected subjects, and reanalyzed the original data after the effect of the potential confounder, the si ze of living plac e, was controlled. Methods: In the case-control study, 533 conscr ipts were tested for to xoplasmosis and presence of anti-cytomegalovirus antibodies and their novelty se eking was examined with Cloninger's TCI questionnaire. Possible association between the two infections and TCI dimensions was analyzed. Results: The decrease of novelty seeking is as sociated also with cytomegalovirus infe ction. After the size of living place was controlled, the effect of to xoplasmosis on novelty seeking increased. Si gnificant difference in novelty seeking was observed only in the largest city, Prague. Conclusion: Toxoplasma and cytomegalovirus probably induce a decrease of novelty seeking. As the cytomegalovirus spreads in population by direct contact (not by predation as with Toxoplasma ), the observed changes are the byproduct of brain infections rather than the result of manipulation activity of a parasite . Four independent line s of indirect evidence, namely direct measurement of neurotransmi tter concentration in mice, the nature of behavioral changes in rodents, the nature of personality changes in humans, and the observed association between schizophren ia and toxoplasmosis, suggest that the changes of dopamine concentration in brain coul d play a role in behavioral changes of infected hosts.

Antibodies to infectious agents in individuals with recent onset schizophrenia

March 26, 2004
Leweke, F. M., Gerth, C. W., Koethe, D., Klosterkotter, J., Ruslanova, I., Krivogorsky, B., Torrey, E. F., Yolken, R. H.
European Archives of Psychiatry and Clinical Neuroscience 2004; 254: 4-8

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