Does Parasite Play Role in Schizophrenia Etiology?

The case continues to build that the parasite Toxoplasma gondii is linked with some cases of schizophrenia.

In 2005 Alan Brown, M.D., an associate professor of clinical psychiatry and clinical epidemiology at the New York State Psychiatric Institute, and colleagues reported that serum antibodies taken from pregnant women 40 years earlier suggested a link between the parasite and the development of schizophrenia in their offspring (Psychiatric News, May 6, 2005).

And now Australian scientists have not only found that some young people acquiring schizophrenia possessed antibodies to T. gondii, but that such possession could be linked with the severity of their psychosis symptoms. The lead scientist was G. Paul Amminger, M.D., an associate professor of child and adolescent psychiatry at the University of Melbourne. Results appeared in the May 15 Biological Psychiatry.

“This is an interesting study,” Brown told Psychiatric News. “A strength of the study is the fact that prodromal subjects are included, suggesting that lifestyle factors that co-exist with schizophrenia or other psychotic disorders don't explain the finding.”

Amminger and his coworkers studied 105 young adults (average age 19) who were at very high risk of acquiring schizophrenia because of genetic risk plus a decrease in functioning, attenuated psychotic symptoms, or limited intermittent psychotic symptoms.

Subjects were evaluated for psychotic symptoms and their severity. Blood samples were also taken from each subject and sent to the Stanley Laboratory of Developmental Neurobiology in Baltimore to determine whether they contained antibodies to various infectious agents such as herpes simplex virus type 1, herpes simplex virus type 2, cytomegalovirus, Epstein-Barr virus, or the T. gondii parasite.

Seventy-two percent of subjects tested positive for Epstein-Barr virus; 48 percent for cytomegalovirus, 42 percent for herpes simplex virus Type 1, 31 percent for herpes simplex virus Type 2, and 17 percent for T. gondii.

Amminger and his coworkers then evaluated whether there was a connection between the severity of subjects' psychotic symptoms and having antibodies to any of these infectious agents. The answer was yes only for T. gondii and Epstein-Barr virus. Having antibodies to the parasite was significantly associated with more severe psychotic symptoms, while testing positive for Epstein-Barr antibodies was significantly associated with less severe ones.

The reason why Epstein-Barr-positive subjects had less severe symptoms than the other subjects is not clear, the scientists said. But they believe that their findings add to the argument that T. gondii is implicated in certain cases of schizophrenia.

The question then is when the parasitic infection is acquired. The researchers believe that it is probably a pre-existing infection, perhaps going back to the prenatal state. One reason is because of the research by Brown and colleagues cited above. Another is because they could find a significant link only between IgG antibodies to T. gondii and psychotic symptoms, not between IgM antibodies to T. gondii and such symptoms. Whereas an IgG antibody response may reflect either an active or reactivated infection, an IgM antibody only mirrors a recent one.

Amminger and his group are now attempting to see whether they can replicate their results in another cohort of subjects. They are also following their current cohort to determine whether T. gondii infection is truly involved in the transition from a pre-schizophrenia state to a full-blown case of the disorder in certain very-high-risk individuals. If a causal link is established, Amminger told Psychiatric News, then it would provide a rationale to determine whether antimicrobial drugs effective against T. gondii, such as trimethoprim-sulfamethoxazole or azithromycin, might be able to keep subthreshold psychotic symptoms from developing into full-blown schizophrenia.

The investigation was funded by the Stanley Medical Research Institute; National Health and Medical Research Council in Canberra, Australia; Janssen-Cilag, Australia; and the Karl-Hermann Spitzy Award by Bayer, Austria.

An abstract of “Antibodies to Infectious Agents in Individuals at Ultra-High Risk for Psychosis” is posted at<www.journals.elsevierhealth.com/periodicals/bps/article/PIIS000632230601273x/ab...>.▪