Targeting infection seen as prevention, treatment for schizophrenia

As research mounts that the root of this mental illness could be infectious in nature, scientists want to use this knowledge to treat and prevent it.

By Victoria Stagg Elliott — Posted Feb. 11, 2008

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The infections that studies have associated with schizophrenia actually might cause this mental illness, and a better understanding of the phenomenon could lead to new therapies and ways to prevent its development, according to a pair of papers published last month in The American Journal of Psychiatry.

One, produced by Sweden's Karolinska Institute in Stockholm, found that children hospitalized for mumps or cytomegalovirus infection were more likely to have psychotic illnesses, including schizophrenia, as adults. Prior studies have shown that in utero exposure to such viruses, particularly those that attack the central nervous system, also can have this effect.

Experts say this recent study highlights the importance of vaccinations and reducing the risk of infection when a young brain is developing.

"The environment is more important in schizophrenia than we previously thought, and we need to be vigilant in preventing these illnesses," said Alan S. Brown, MD, MPH. He wrote an accompanying editorial and is an associate professor of clinical psychiatry and epidemiology at the Columbia University College of Physicians and Surgeons in New York.

The other study from researchers at the Walter Reed Army Institute of Research in Silver Spring, Md., and Johns Hopkins University School of Medicine in Baltimore found that infection with Toxoplasma gondii, a parasite transmitted by cats and farm animals, preceded the emergence of schizophrenic symptoms. Numerous previous studies have linked the two, and the authors say although it is still not conclusive, these data are one step closer to confirming that infection as a possible cause.

"Until now, the only thing we could say is that some people with schizophrenia also had been infected with Toxoplasma at some point, but we couldn't tease out which came first," said Robert Yolken, MD, one of the authors. He is also a professor of pediatrics and director of the Stanley Division of Developmental Neurovirology at Johns Hopkins. "We're not quite there with cause, but, with our current study, we were able to show that infection came first."

A possible target

Those investigating this relationship also see it as a possible treatment target. For instance, the Stanley Medical Research Institute, a nonprofit organization in Chevy Chase, Md., that funded part of the work for this paper, is establishing a project in China to test the possibility.

Investigators there are randomizing people with schizophrenia and infected with this parasite to receive artemisinin, an anti-malarial drug that is believed to work against T. gondii. The institute chose China because this drug is widely available in that country. They hope that this medication will ameliorate the symptoms of schizophrenia, providing relief to patients as well as further evidence that the parasite is a cause of this mental illness.

"If [this recent study] was proof that T. gondii was a cause, we could all go home. It did show that infectious agents are possible causes that need to be taken very seriously," said E. Fuller Torrey, MD, the SMRI's executive director.

But those who care for patients with schizophrenia say many questions will need to be answered before this suspicion becomes a reality. It has long been proven that people with this mental illness are more likely to have antibodies to T. gondii. Evidence is growing that it may be a cause, but it's unclear whether schizophrenia results from active infection or is an eventual result of damage caused by an earlier encounter with the bug. If the latter scenario proves true, an antiparasitic medication would do little good.

"It's very important work," said William Carpenter, MD, professor of psychiatry and pharmacology at the University of Maryland School of Medicine. "They could show that T. gondii has direct involvement. If this drug does not have an effect, it doesn't disprove the association but would show that schizophrenia is not caused by active infection."

Experts say studies also are needed to determine how triggers combine to create this mental illness, because not all with this parasitic infection will go on to develop it.

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Parasitic infection before schizophrenia?

Objective: Determine if infection with Toxoplasma gondii, a parasite with a well-established association with schizophrenia, occurs before the development of this mental illness.

Method: Researchers analyzed serum samples taken before and after a schizophrenia diagnosis from 180 military personnel who were discharged because of this disease. They were compared with 532 healthy controls.

Results: Infection with this parasite at all time points increased the risk of schizophrenia by 24%. Carrying this bug six months before a diagnosis increased the risk by 55%.

Conclusions: Toxoplasma gondii increases the risk of schizophrenia, and infection may occur before this mental illness develops.

Source: The American Journal of Psychiatry, January

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External links

"The Risk for Schizophrenia From Childhood and Adult Infections," The American Journal of Psychiatry, January (link)

"Selected Infectious Agents and Risk of Schizophrenia Among U.S. Military Personnel," abstract, The American Journal of Psychiatry, January (link)

"Infections in the CNS During Childhood and the Risk of Subsequent Psychotic Illness: A Cohort Study of More Than One Million Swedish Subjects," abstract, The American Journal of Psychiatry, January (link)

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