THE SCHIZOPHRENIA AND TOXOPLASMA GONDIII CONNECTION

Adv Ther. 2008 Jul;25(7):703-9.

The schizophrenia and Toxoplasma gondii connection: infectious, immune or both?
Tamer GS, Dundar D, Yalug I, Caliskan S, Yazar S, Aker A.

Kocaeli University, Medical Faculty, Department of Clinical Microbiology, Kocaeli, Turkey. guldensonmez@hotmail.com

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

CONCLUSIONS: This study supports the theory that toxoplasmic agents may have a role in the aetiology of schizophrenia.

PMID: 18563312 [PubMed - indexed for MEDLINE]

NEUROPSYCHIATRIC DISEASE AND TOXOPLASMA GONDII INFECTION

Neuroimmunomodulation. 2009;16(2):122-33. Epub 2009 Feb 11.
Neuropsychiatric disease and Toxoplasma gondii infection.

Henriquez SA, Brett R, Alexander J, Pratt J, Roberts CW.
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow, UK.

Toxoplasma gondii infects approximately 30% of the world's population, but causes overt clinical symptoms in only a small proportion of people. In recent years, the ability of the parasite to manipulate the behaviour of infected mice and rats and alter personality attributes of humans has been reported. Furthermore, a number of studies have now suggested T. gondii infection as a risk factor for the development of schizophrenia and depression in humans. As T. gondii forms cysts that are located in various anatomical sites including the brain during a chronic infection, it is well placed anatomically to mediate these effects directly. The T. gondii genome is known to contain 2 aromatic amino acid hydroxylases that potentially could directly affect dopamine and/or serotonin biosynthesis. However, stimulation of the immune response has also recently been associated with mood and behavioural alterations in humans, and compounds designed to alter mood, such as fluoxetine, have been demonstrated to alter aspects of immune function. Herein, the evidence for T.-gondii-induced behavioural changes relevant to schizophrenia and depression is reviewed. Potential mechanisms responsible for these changes in behaviour including the role of tryptophan metabolism and the hypothalamic-pituitary-adrenal axis are discussed. Copyright (c) 2009 S. Karger AG, Basel.

PMID: 19212132 [PubMed - indexed for MEDLINE]

TOXOPLASMA GONDII INFECTION

Korean J Parasitol. 2009 Jun;47(2):125-30. Epub 2009 May 27.

Seroprevalence of Toxoplasma gondii infection and characteristics of seropositive patients in general hospitals in Daejeon, Korea.

Shin DW, Cha DY, Hua QJ, Cha GH, Lee YH.
Department of Infection Biology, Research Institute for Medical Science, College of Medicine, Chungnam National University, Daejeon, Korea.

To figure out the epidemiological status and relevance with other diseases in toxoplasmosis, we checked serum IgG antibody titers of 1,265 patients and medical records of seropositive patients. Seropositive rates were 6.6% by latex agglutination test (LAT) and 6.7% by ELISA. No significant differences were detected between sexes and age groups. The peak seroprevalence was detected in the 40-49-year-old age group. According to clinical department, Toxoplasma-positive rates were high in patients in psychiatry, ophthalmology, health management, emergency medicine, and thoracic surgery. Major coincidental diseases in seropositive cases were malignant neoplasms, diabetes mellitus, arthritis, chronic hepatitis B, chronic renal diseases, schizophrenia, and acute lymphadenitis, in the order of frequency. In particular, some patients with chronic hepatitis B and malignant neoplasms had high antibody titers. These results revealed that the seroprevalence of toxoplasmosis in a general hospital-based study was similar to that in a community-based study, and T. gondii seropositivity may be associated with neoplasms, diabetes, and other chronic infections.

PMID: 19488418 [PubMed - indexed for MEDLINE]

TOXOPLASMA GONDI IN MOTHERS AND RISK OF PSYCHOSIS AMONG ADULT OFFSPRING

Microbes Infect. 2009 Nov;11(13):1011-8. Epub 2009 Jul 26.

Serological pattern consistent with infection with type I Toxoplasma gondii in mothers and risk of psychosis among adult offspring.
Xiao J, Buka SL, Cannon TD, Suzuki Y, Viscidi RP, Torrey EF, Yolken RH.

The Stanley Division of Developmental Neurovirology, Johns Hopkins School of Medicine, 600 N. Wolfe Street, 1105 Blalock, Baltimore, MD 21287-4933, USA.

Previous studies have shown that maternal antibodies to Toxoplasma measured during pregnancy are associated with an increased risk of schizophrenia and other psychoses in adult offspring. Recently, it has been recognized that different genotypes of Toxoplasma have distinct neuropathogenic potential. The objective of this study was to investigate whether parasite genotype is a contributing factor to disease risk. We have developed an enzyme-linked immunosorbent assay (ELISA) that uses polymorphic polypeptides specific to the three clonal parasite lineages and derived from three dense granule antigens, GRA5, GRA6 and GRA7. We used this assay to measure type-specific antibodies in the sera from 219 pregnant women whose children developed schizophrenia and affective psychotic illnesses in adult life, and 618 matched unaffected control mothers from three cohorts of the Collaborative Perinatal Project. We found that the offspring of mothers with a serological pattern consistent with Toxoplasma type capital I, Ukrainian infection were at significantly increased risk for the development of psychoses as compared with the matched unaffected control mothers (odds ratio=1.94; 95% confidence interval=1.08-3.46; p=0.03). The risk was particularly elevated for affective psychoses (OR=5.24; 95% CI=1.67-16.5; p=0.005). In contrast, we did not find an association between maternal antibodies to other genotypes and risk of psychoses in the offspring. These findings suggest an influence of the parasite genotype on increased risk of psychosis and provide further support for a substantive role of Toxoplasma in the etiology of psychosis.

PMID: 19638313 [PubMed - in process]

SCHIZOPHRENIA AND TOXOPLASMOSIS

Med Sci (Paris). 2009 Aug-Sep;25(8-9):687-91.

[Schizophrenia and toxoplasmosis]
[Article in French]
Dion S, Barbe PG, Leman S, Camus V, Dimier-Poisson I.

Université François Rabelais de Tours, INRA , France. sarah.dion@univ-tours.fr

Schizophrenia is one of the most severe and disabling psychiatric disease that affects about 1 % of the adult worldwide population. Aetiology of schizophrenia is still unknown but genetic and environmental factors are suspected to play a major role in its onset. Recent epidemiologic studies indicate that infectious agents may contribute to some cases of schizophrenia. In particular, several epidemiological, behavioural and neurochemical studies suggested the existence of an association between schizophrenia and past history of primo-infection by the Toxoplasma gondii. However, they are some limitations for this hypothesis among which the lack of correlation between the geographic distribution of both diseases and of direct evidence for the presence of the parasite in schizophrenic patients. Nevertheless the identification of physiopathological mechanisms related to the parasite could provide a better comprehension to the outcome of schizophrenia. Studies on the link between toxoplasmosis and schizophrenia may provide interesting data for the diagnosis and the development of new treatments for this disorder.

PMID: 19765381 [PubMed - indexed for MEDLINE]

TOXOPLASMA GONDI AND SCHIZOPHRENIA

Toxoplasma gondii and Schizophrenia

E. Fuller Torrey* and Robert H. Yolken†*Stanley Medical Research Institute, Bethesda, Maryland, USA; and †Johns Hopkins University Medical Center, Baltimore, Maryland, USA

Suggested citation for this article: Torrey EF, Yolken RH. Toxoplasma gondii and schizophrenia.

Emerg Infect Dis [serial online] Nov 2003 [date cited]. Available from: URL: http://www.cdc.gov/ncidod/EID/vol9no11/03-0143.htm

Recent epidemiologic studies indicate that infectious agents may contribute to some cases of schizophrenia. In animals, infection with Toxoplasma gondii can alter behavior and neurotransmitter function. In humans, acute infection with T. gondii can produce psychotic symptoms similar to those displayed by persons with schizophrenia. Since 1953, a total of 19 studies of T. gondii antibodies in persons with schizophrenia and other severe psychiatric disorders and in controls have been reported; 18 reported a higher percentage of antibodies in the affected persons; in 11 studies the difference was statistically significant. Two other studies found that exposure to cats in childhood was a risk factor for the development of schizophrenia. Some medications used to treat schizophrenia inhibit the replication of T. gondii in cell culture. Establishing the role of T. gondii in the etiopathogenesis of schizophrenia might lead to new medications for its prevention and treatment.

Schizophrenia is a pervasive neuropsychiatric disease of uncertain cause that affects approximately 1% of the adult population in the United States and Europe. An increased occurrence of schizophrenia in family members of affected persons suggests that genetic factors play a role in its etiology, and some candidate predisposing genes have been identified. Environmental factors are also important. Epidemiologic studies, for example, have established that winter-spring birth, urban birth, and perinatal and postnatal infection are all risk factors for the disease developing in later life. These studies have rekindled an interest in the role of infectious agents in schizophrenia, a concept first proposed in 1896 (1). This review focuses on evidence specifically linking infection with Toxoplasma gondii to the etiology of some cases of schizophrenia.

T. gondii is an intracellular parasite in the phylum Apicomplexa. Its life cycle can be completed only in cats and other felids, which are the definitive hosts. However, T. gondii also infects a wide variety of intermediate hosts, including humans. In many mammals, T. gondii is known to be an important cause of abortions and stillbirths and to selectively infect muscle and brain tissue. A variety of neurologic symptoms, including incoordination, tremors, head-shaking, and seizures, have been described in sheep, pigs, cattle, rabbits, and monkeys infected with T. gondii (2).
Humans may become infected by contact with cat feces or by eating undercooked meat. The importance of these modes of transmission may vary in different populations (3). Individual response to Toxoplasma infection is determined by immune status, timing of infection, and the genetic composition of the host and the organism (4).

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PSYCHOSIS CAUSED BY MICROBIAL AGENTS?

Mol Psychiatry. 2008 May;13(5):470-9. Epub 2008 Feb 12.

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

Yolken RH, Torrey EF.

The Stanley Laboratory of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University Medical Center, Baltimore, MD 21287-4933, USA. yolken@mail.jhmi.edu

The infectious theory of psychosis, prominent early in the twentieth century, has recently received renewed scientific support. Evidence has accumulated that schizophrenia and bipolar disorder are complex diseases in which many predisposing genes interact with one or more environmental agents to cause symptoms. The protozoan Toxoplasma gondii and cytomegalovirus are discussed as examples of infectious agents that have been linked to schizophrenia and in which genes and infectious agents interact. Such infections may occur early in life and are thus consistent with neurodevelopmental as well as genetic theories of psychosis. The outstanding questions regarding infectious theories concern timing and causality. Attempts are underway to address the former by examining sera of individuals prior to the onset of illness and to address the latter by using antiinfective medications to treat individuals with psychosis. The identification of infectious agents associated with the etiopathogenesis of schizophrenia might lead to new methods for the diagnosis, treatment and prevention of this disorder.

PMID: 18268502 [PubMed - indexed for MEDLINE]