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Antibodies to Toxoplasma gondii in Patients with Schizophrenia: A Meta-Analysis

Posted on 21 Feb 2007
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In our Forum discussion "journal club" series, the editors of Schizophrenia Bulletin or Schizophrenia Research provide access to the full text of a recent article. A short introduction by a journal editor gets us started, and then it's up to our readers to share their ideas and insights, questions, and reactions to the selected paper. So read on"

 

Torrey EF, Bartko JJ, Lun ZR, Yolken RH. Antibodies to Toxoplasma gondii in Patients With Schizophrenia: A Meta-Analysis.Schizophr Bull. 2006 Nov 3.

 

Background Text
by Gunvant Thaker, Maryland Psychiatric Research Center, and Associate Editor, Schizophrenia Bulletin

In an upcoming issue of Schizophrenia Bulletin, Torrey, Bartko, Lun, and Yolken report results from a meta-analysis of studies examining association between antibodies to Toxoplasma gondii and schizophrenia. One of the unique aspects of the meta-analysis is that the authors include all available datasets, including many that were published in languages other than English. The analysis includes studies from 17 countries, many from Eastern Europe and China, and only six studies had been written in English. This attempt to include all available datasets is one of the methodological strengths of the meta-analysis carried out by Torrey and colleagues. The results suggest that schizophrenia patients are more than two times likely to have antibodies to T. gondii than the comparison subjects (odds ratio of 2.79). However, these studies are not informative about the timing of infection that contributed to the development of the disorder. Previous studies that noted associations between schizophrenia and other infections such as influenza suggested exposure during the prenatal period, usually at the beginning of the second trimester, being the critical time. Almost all of the studies reviewed by Torrey and colleagues examined antibodies to T. gondii in patients who already had developed the illness. Findings in the first episode cohorts are reassuring and suggest that the exposure likely occurred prior to the onset of the psychotic symptoms. Authors also cite publications that implicate maternal T. gondii infection in the etiology of schizophrenia. This raises the question whether the presence of antibodies in adults reflects prenatal infection, or whether postnatal infection with T. gondii is also a risk factor.

This is an interesting report identifying another environmental risk factor for schizophrenia with public health implications of reducing the risk. However, the meta-analysis also raises several questions. The evidence provided by meta-analysis is indirect, supporting an association but raising the question: Is it causal? Robert Schwarcz and Christopher Hunter speculate that the answer is yes, and in an accompanying "At Issue" piece provide a plausible causal pathway involving astrocyte-derived kynurenic acid. Schwarcz and Hunter review the recent literature that suggests that there is massive astrocyte activation and dramatic increase in the brain content of kynurenic acid in animals infected with T. gondii. Furthermore, data suggest that elevation of brain kynurenic acid levels play a role in the pathophysiology of schizophrenia. The same issue of Schizophrenia Bulletin includes findings from two new studies that further confirm a link between schizophrenia and T. gondii (Dickerson et al., 2007; Mortensen et al., 2007).

The next question is: when is the exposure critical in causing the harm? This is relevant for public health goals of reducing risk, as well as for therapeutic strategies in individual patients. If the prenatal period is the critical vulnerable time for the exposure to have any effect, then treatment against T. gondii in adulthood will be ineffective. What are the underlying mechanisms by which exposure to T. gondii leads to schizophrenia vulnerability, and how do these interact with other risk factors, including genetic factors? These are some of the questions that will need to be addressed, and hopefully will draw comments and discussion from other readers.