Toxoplasma Infection Linked to Schizophrenia

Deborah Brauser

August 19, 2011

August 19, 2011 — Toxoplasma gondii infection is associated with subsequent development of schizophrenia spectrum disorders, new research suggests.

In a prospective cohort study of more than 45,000 women in Denmark who had recently given birth, those with the highest levels of T gondii–specific IgG antibodies were almost twice as likely to develop this psychiatric disorder as women with low levels.

"Based on the findings, it seems advisable to take natural precautions to avoid T gondii infection," lead author Marianne Giørtz Pederson, MSc, from the National Center for Register-Based Research at Aarhus University, Denmark, told Medscape Medical News.

In an accompanying editorial, Alan S. Brown, MD, MPH, from the New York State Psychiatric Institute in New York City, Columbia University College of Physicians and Surgeons, and Department of Epidemiology at the Mailman School of Public Health, writes that the study suggests that "environmental exposures may play a more important role in the etiopathogenesis of schizophrenia" than previously assumed.

"The promise of this work is underscored by the fact that many infectious exposures and other environmental insults are treatable and preventable," he added.

The study is published in the August issue of the American Journal of Psychiatry.

Evaluating Risk

According to the researchers, T gondii is an intracellular parasite, and infections are predominantly caused by eating undercooked meat or consuming oocysts from infected cat feces through contact with a contaminated litterbox.

"Several studies based on clinical samples have found an association between [T gondii] infection and schizophrenia, but the result has never been replicated in a prospective cohort study," said Ms. Pederson.

"I have a general research interest in risk factors for schizophrenia and hope that gaining insight can help in preventing new cases of the disorder," she added.

The investigators sought not only to determine whether the infection increased risk for schizophrenia in mothers but also whether or not the risk depended on IgG antibody level.

They evaluated data on 45,609 women from a Danish population-based study who had their IgG antibody levels measured in conjunction with giving birth between 1992 and 1995. All women were followed up to 2008 through links with the Danish Psychiatric Central Register.

Mechanism Still Unknown

Results showed a T gondii prevalence rate of 26.8% at time of delivery. Both higher maternal age and lower degree of urbanization at delivery were associated with higher infection prevalence (35.15% for those older than 35 years, 30.69% for those from rural areas).

A total of 246 of all participants developed a schizophrenia spectrum disorder during the follow-up period.

Although there was a significantly increased risk for schizophrenia spectrum disorders associated with T gondii infection, when the participants were subdivided according to IgG level, only those with the highest level were found to have a significantly higher risk of developing these disorders (relative risk, 1.73; 95% confidence interval [CI], 1.12 – 2.62 compared with mothers with the lowest level).

Adjusting for family psychiatric history, age at delivery, and residency location had little impact on these findings.

T gondii IgG level was also associated with a greater relative risk for schizophrenia itself (1.68; 95% CI, 0.77 – 3.46), although this was not deemed statistically significant. A total of 80 women went on to develop this disorder.

"Future studies should elucidate the mechanisms underpinning [these associations] — for example, whether there is a direct effect of T gondii–specific IgG antibodies on the central nervous system, whether the effect is mediated through inflammatory mechanisms, and whether there is interaction with gene variants," write the researchers.

Ms. Pederson said she plans to next investigate the importance of the strains and stages of T gondii for the risk for schizophrenia.

"I also want to investigate whether there is an association between [this] infection and other mental disorders," she added.

The study was supported by a grant from the Stanley Medical Research Institute. Although one study author reports having received unrestricted research grants from Lundbeck, the other investigators, including Ms. Pederson, and Dr. Brown have disclosed no relevant financial relationships.

Am J Psychiatry. 2011;168:814-821, 764-766. Abstract Editorial

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