V. Studies of T. gondii Antibodies in Schizophrenia

V. Studies of T. gondii Antibodies in Schizophrenia

§ Studies of antibodies in individuals who have schizophrenia

The first study of antibodies against T. gondii carried out on individuals with psychoses was done by Kozar in Poland in 1953 using a skin test. This was followed by other studies in East Germany in 1956, Czechoslovakia in 1957, Bulgaria in 1962, and Russia in 1962. In the early 1980s, Chinese researchers became aware of this research and subsequently became the leading researchers on the prevalence of T. gondii antibodies in schizophrenia.

Since Kozar’s original study, there have been at least 54 similar studies. A 2007 review of 42 of these studies included a meta-analysis of 23 of them in which the odds ratio of having T. gondii antibodies with a diagnosis of schizophrenia was OR 2.73. In other words, if a person has been infected with T. gondii, he/she has a 2.7 times greater chance of having schizophrenia than if the person had not been infected (Torrey EF, Bartko JJ, Lun Z-R et al., Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis, Schizophr Bull 2007;33:729–736).

Since the publication of this review, at least 12 other studies have been completed. Of the 54 total studies, all except 5 reported that the individuals with schizophrenia and other psychoses had a higher prevalence of antibodies to T. gondii than the controls.

Studies of antibodies in individuals prior to the onset of schizophrenia

In a study of military personnel, serum specimens were available from periods of up to 11 years prior to the onset of schizophrenia. The serum of 180 individuals with schizophrenia and 532 matched (3:1) controls were assessed for IgG antibodies to T. gondii and other infectious agents. Among those with schizophrenia, significantly increased levels of antibodies were seen prior to the onset of illness (hazard ratio = 1.24, p<0.01), maximal in the 6 months prior to onset but seen as early as 3 years prior to the onset (Niebuhr DW, Millikan AM, Cowan DN et al., Selected infectious agents and risk of schizophrenia among U.S. military personnel, Am J Psychiatry 2008;165:99–106).

In another study, antibodies against T. gondii were assessed in 105 young individuals who were thought to be at “ultra-high risk” for developing schizophrenia because of their early symptoms and behavior. Among the 105, 18 had antibodies to T. gondii, and “being Toxoplasma-positive was significantly associated with more severe positive psychotic symptoms, and more severe psychiatric symptoms in general” (Amminger GP, McGorry PD, Berger GE et al., Antibodies to infectious agents in individuals at ultra-high risk for psychosis, Biol Psychiatry 2007;61:1215–1217).

Studies of antibodies in newborn children who later develop schizophrenia

In Denmark, Mortensen et al. obtained sera (from blood collected for PKU analysis) on 71 individuals who developed schizophrenia prior to age 18 (early-onset cases) and matched controls (2:1). T. gondii IgG antibodies were increased in cases compared to controls (p=0.045; OR=1.79) (Mortensen PB, Nørgaard-Pedersen B, Waltoft BL et al., Toxoplasma gondii as a risk factor for early-onset schizophrenia: analysis of filter paper blood samples obtained at birth, Biol Psychiatry 2007;61:688–693).

§ Studies of antibodies in maternal sera from late in pregnancy

Brown et al. assessed antibodies to T. gondii in 63 women who gave birth to individuals (cases) who later developed schizophrenia, schizoaffective disorder, or schizophrenia spectrum disorders. They used 123 matched controls. Among the cases, the incidence of high IgG antibody titres was significantly increased (p=0.051; OR 2.61) (Brown AS, Schaefer CA, Quesenberry CP et al., Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring, Am J Psychiatry 2005;162:767–773).

§ Do antibodies to T. gondii remain detectable over many years?

It has been widely assumed that once a person is exposed to T. gondii they will remain antibody-positive for life. However, no long-term study has been done on this question in humans. In 1941, Dr. Albert Sabin reported that in his experiments on monkeys, “it has been observed that convalescent monkeys may lose their antibodies as early as six weeks after infection” (Sabin AB, Toxoplasmic encephalitis in children, JAMA 1941;116:801–807). There are also suggestions from human studies that seropositivity is not lifelong; in one study, the mean duration of seropositivity was 40 years (Van Druten H, Van Knapen F, Reintjes A, Epiemiologic implications of limited-duration seropositivity after toxoplasma infection, Am J Epidemiol 1990;132:169–180).

Current SMRI-funded research in this area

§ David Niebuhr et al., Walter Reed Army Institute of Research. Enlarged sample of sera from military personnel with schizophrenia and matched controls.

§ Preben Mortensen et al., University of Aarhus, Denmark. Enlarged sample of sera samples from newborn children.

§ Huiling Wang et al., University of Wuhan, China. Antibody studies of university students who develop schizophrenia, with serum collected when they begin university, prior to the onset of their illness.

§ Faith Dickerson et al., Sheppard Pratt Hospital. T. gondii antibodies in individuals with first-episode schizophrenia.

§ Silke Bachmann et al., University of Halle, Germany. T. gondii antibodies in individuals with first-episode schizophrenia.

§ Steven Buka, Brown University, et al. Antibody studies of third-trimester sera of mothers who gave birth to children who developed schizophrenia and analysis of T. gondii strain differences.

§ Yasuhiro Suzuki et al., University of Kentucky. Analysis of T. gondii antigens recognized by IgG antibodies to tachyzoites, but not bradyzoites, in the brain.