A Controlled Prospective Study of Toxoplasma gondii Infection in Individuals With Schizophrenia: Beyond Seroprevalence

The Centre for Intergrative Psychiatry, Department of Psychiatry and Psychotherapy, Christian-Albrecht-University, Niemannsweg 147, D-24105 Kiel, Germany.
Schizophrenia Bulletin (Impact Factor: 8.61). 06/2007; 33(3):782-8. DOI: 10.1093/schbul/sbm010
Source: PubMed

ABSTRACT Toxoplasma gondii (TG) infection has been reported to be more frequent in schizophrenia. The interaction of the lifelong persisting parasite with the host's immune system involves T-cell/interferon-gamma-induced degradation of tryptophan and provides a challenge to the host well beyond a possible role in the etiology of schizophrenia. The hypothesis we tested in this study was that TG infection may be more frequent (serofrequency) and/or more intense (serointensity) in patients with schizophrenia or major depression compared with psychiatrically healthy controls. In addition, these measures are associated with the clinical course. We did a cross-sectional, prospective investigation of individuals with schizophrenia (n = 277) and major depression (n = 465) admitted to our department (2002-2005) and of healthy controls (n = 214), with all groups adjusted for age and geographic home region. Serofrequency was comparable between the groups, but serointensity was significantly higher in the patients. In individuals with schizophrenia, serointensity was significantly positively associated with C-reactive protein levels and leukocyte counts, and first-episode patients yielded significantly higher serotiters. Immunomodulatory medication was associated with decreased serotiters. In addition, the route of infection appears to differ between patients and controls. Thus, our results support increased host responses to TG infection in the patients, as well as increased titers in first-episode patients with schizophrenia; this may relate to the shifted T-helper 1/2 status described in these patients. Therefore, we suggest that TG infection, particularly in individuals with schizophrenia, is an important environmental factor in the interaction between psychiatric vulnerability, genetic background, immunomodulation, and the neurotransmitter systems.

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Available from: Walter Däubener, Oct 27, 2014
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    • "It has been estimated that up to one third of the world’s population has been infected by T. gondii with an endemicity from around 10% to 70% [1,3-5] and the prevalence is higher in warm and humid areas [6-8]. In several studies, patients with schizophrenia were found to have a higher tendency of T. gondii infection [9-12], but there has been no conclusive correlation between T. gondii infection and psychiatric disease [13]. "
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    ABSTRACT: Toxoplasmosis is one of the most common parasitic zoonoses. The seroprevalence of Toxoplasma gondii infection in humans varies widely worldwide. Detection of Toxoplasma-specific antibodies has been a gold standard method for both epidemiological investigation and clinical diagnosis. Genetic investigation indicated that there is a wide distribution of different genome types or variants of the parasite prevalent in different areas. Thus the reliability of using antigens from parasites of a single genome type for diagnosis and epidemiology purposes needs to be extensively evaluated. In this study, the prevalence of T. gondii infection among 880 clinically healthy individuals in China was systematically tested using crude soluble native antigens and purified recombinant antigens of type I and II T. gondii. The T. gondii-specific IgG and IgM in the sera was further confirmed using commercial Toxoplasmosis Diagnosis Kits and Western blot assays. The sero-prevalence of T. gondii-specific IgG detected with crude native Type I and type II antigens was 12.2% and 11.3% respectively. Whereas the overall prevalence was more than 20% when combined with the results obtained with recombinant tachyzoite and bradyzoite antigens. There was an obvious variation in immune-recognition of parasite antigens among the individuals studied. The general prevalence of anti-T. gondii IgG in the study population was likely much higher than previously reported. The data also suggested that there is more genetic diversity among the T. gondii isolates in China. Further, combination of recombinant antigens with clear immuno-recognition will be able to generate more sensitive diagnostic results than those obtained with crude antigens of T. gondii tachyzoites.
    Parasites & Vectors 08/2013; 6(1):241. DOI:10.1186/1756-3305-6-241 · 3.25 Impact Factor
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    • "Nevertheless, alterations in the levels of key neurotransmitters, however brief, may be crucial in the development of serious disorders . It is known that dysfunction of the dopamine system is implicated in schizophrenia, other psychotic disorders and Parkinson's disease (Amin et al., 1992; Lodge and Grace, 2008; Siuta et al., 2010; Zhu, 2009), which may account for numerous data suggesting a relationship between the occurrence of certain disorders and T. gondii seroprevalence (Alvarado-Esquivel et al., 2006; Hinze-Selch et al., 2007; Miman et al., 2010; Torrey et al., 2007; Torrey and Yolken, 2003; Yolken et al., 2009). The most intriguing question is, however, how universal the T. gondii behavior alterations really are in wild animals and how specific they are with regard to other pathogens attacking the CNS. "
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    ABSTRACT: The protozoan parasite Toxoplasma gondii has the ability to alter intermediate host behavior, most impressively the natural aversion to cat scent, to favor the predation by the definitive host. However, the underlying mechanism of the observed phenomenon still remains unknown. Since changes in the neurotransmitter level are postulated as a possible contributing factor, the aim of this work was to assess the monoamine systems activity in specified brain regions involved in the natural defense behaviors, emotion evaluation, and motor and sensory stimuli integration in experimentally T. gondii infected mice compared to uninfected controls. Taking into account the natural differences between genders, the experiments were carried out on both male and female mice. Our results revealed statistically significant changes in all tested monoamine systems with regard to both gender and time after T. gondii invasion. Acute toxoplasmosis was accompanied by a decrease in noradrenergic system activity in females and its slight increase in some brain areas of males. Acute invasion also induced a rise in serotonin system activity, mostly in males. The most striking observation was an increase in the dopamine release noted in acutely infected males. We discuss our results in terms of their possible contribution to T. gondii-induced intermediate host behavior alterations and parasite transmission and with regard to postulated relationship between T. gondii seroprevalence and occurrence of certain disorders such as schizophrenia in humans.
    Experimental Parasitology 10/2012; 133(1). DOI:10.1016/j.exppara.2012.10.005 · 1.86 Impact Factor
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    • ".1 1 10 100 Odds Ratio Legend 1 Previous Studies Wende 1956 Caglieris 1958 Cook Derrick 1961 Yegerov 1962 Berengo1966 Garrido & Redondo 1968 Cui 1984 Lu 1990 Zhang 1994 Wang 1995 Lian 1996 Li 1999 Mia & Ding 1999 Gu 2001 Yolken 2001 Lu 2002 Torrey & Yolken 2003 Leweke 2004 Gallo 2005 Schwarz 2005 Dickerson 2005 Wang 2006 Tankuksel 2010 Ave 2 New Studies Zhu 2003 Xu 2005 El Sahn 2005 Sun 2005 Cetinkaya 2007 Hinze-Selch 2007 Tamer 2008 Dogruman-Al 2009 Sarael-Sahnesaraei 2009 Yuksel 2010 Daryani 2010 Hamidinejat 2010 Liu 2011 Tedla 2011 Alvarado-Esquival 2011 Ave Total Group Combined 1 Previous Studies 2 New Studies Fig. 1 "
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    ABSTRACT: The failure to find genes of major effect in schizophrenia has refocused attention on nongenetic, including infectious factors. In a previous study, antibodies to Toxoplasma gondii were found to be elevated in 23 studies of schizophrenia (OR 2.73; 95% CI 2.10-3.60). The current study replicates this finding with 15 additional studies (OR 2.71; 95% CI 1.93-3.80) and compares this with other identified schizophrenia risk factors. The highest risk factors are having an affected mother (relative risks [RR] 9.31; 95% CI 7.24-11.96), father (RR 7.20; 95% CI 5.10-10.16), or sibling (RR 6.99; 95% CI 5.38-9.08) or being the offspring of immigrants from selected countries (RR 4.5; 95% CI 1.5-13.1). Intermediate risk factors, in addition to infection with T. gondii, include being an immigrant from and to selected countries (RR 2.7; 95% CI 2.3-3.2), being born in (RR 2.24; 95% CI 1.92-2.61) or raised in (RR 2.75; 95% CI 2.31-3.28) an urban area, cannabis use (OR 2.10-2.93; 95% CI 1.08-6.13), having minor physical anomalies (OR 2.23; 95% CI 1.42-3.58), or having a father 55 or older (OR 2.21-5.92; 95% CI 1.46-17.02). Low-risk factors include a history of traumatic brain injury (OR 1.65; 95% CI 1.17-2.32), sex abuse in childhood (OR 1.46; 95% CI 0.84-2.52), obstetrical complications (OR 1.29-1.38; 95% CI 1.00-1.84), having a father 45 or older (OR 1.21-1.66; 95% CI 1.09-2.01), specific genetic polymorphisms (OR 1.09-1.24; 95% CI 1.06-1.45), birth seasonality (OR 1.07-1.95; 95% CI 1.05-2.91), maternal exposure to influenza (RR 1.05; 95% CI 0.98-1.12), or prenatal stress (RR 0.98-1.00; 95% CI 0.85-1.16).
    Schizophrenia Bulletin 03/2012; 38(3):642-7. DOI:10.1093/schbul/sbs043 · 8.61 Impact Factor
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