Studies of mice and rats infected by T. gondii have shown risky behavior changes, including an attraction to the smell of cat urine that makes them vulnerable to attacks. These findings may have parallels in behavioral changes in people, from schizophrenia to depression and reflex impairment.
"That's somewhat unusual, because other parasites don't have that [dopamine]," said Sarven Sabunciyan, Yolken's colleague at Hopkins. After all, microbes have no brains.
But in higher animals with nervous systems, dopamine is a neurotransmitter with important roles in regulating behavior. Some anti-psychotic drugs used to treat schizophrenia work by blocking dopamine action in the brain.
Link to mental illness
Medical students have long been told that mental illness and infectious disease were separate fields.
"I was taught they had nothing to do with each other," said Duckworth, at NAMI. But then he'd encounter a Lyme disease patient with something resembling psychosis, or an AIDS patient with depressive symptoms. "I think it's intuitively possible. After my experience with AIDS patients, I can think, 'Why not?' "
Recent studies have found that a variety of viral infections, early in life, appear to carry risks of brain changes.
In May, Hopkins researcher David J. Schretien published a study suggesting that some brain changes and cognitive symptoms in schizophrenics may be caused or worsened by exposure to a herpes simplex virus. A 2005 Czech study found evidence of personality changes in humans infected by another herpes virus called cytomegalovirus. And numerous studies have suggested that flu infections during pregnancy may increase a child's risk of schizophrenia and autism.
Evidence that T. gondii infections may be a cause of schizophrenia, while not yet conclusive, is growing, Yolken said. A review of past studies, published last year by Yolken and Torrey, collected a variety of intriguing correlations. For example: People with schizophrenia have a higher prevalence of T. gondii antibodies in their blood. There are unusually low rates of schizophrenia and toxoplasmosis in countries where cats are rare, and unusually high rates in places where eating uncooked meat is customary. And some adults with toxoplasmosis show psychotic symptoms similar to schizophrenia.
Studies have linked a history of toxoplasmosis with increased rates of other mental changes, too, including bipolar disorders and depression. A 2002 study in the Czech Republic noted slowed reflexes in Toxoplasma-positive people and found links between the infection and increased rates of auto accidents.
A University of Maryland study last year found that people with mood disorders who attempt suicide had higher levels of T. gondii antibodies than those who don't try to take their own lives. Still, the links between schizophrenia and toxoplasmosis are not simple. For example, most people infected with T. gondii never become schizophrenic. And not all schizophrenics have been exposed to toxoplasma.
Yolken believes additional factors, such as an unlucky combination of genes, are probably needed to produce schizophrenia among Toxoplasma-infected people. The parasite's DNA may also be important, since some strains are known to cause more disease.
Studies have also suggested that the timing of the infection — early in life when the brain is developing — and the place in the brain where the cysts settle, may be important, he said.
But once the T. gondii cysts are established, how might medical science find and kill, or at least silence them?
Yolken said that while T. gondii cysts are invisible to the immune system, they are not totally passive. Inside the cysts, the microbes are alive, sensing their environment, periodically trying to break out, multiply and form more dopamine-making cysts. The flare-ups probably occur when the host's immune system is weakened by illness or stress.
Scientists believe these "reactivations" of the infection could explain the emergence or worsening of cognitive symptoms as people with schizophrenia reach adolescence and young adulthood.
Researchers have also noted that toxoplasmosis is similar to malaria in its persistence in the body, its flare-ups, and its ability to hide from the immune system, Yolken said. So Sabunciyan and researchers elsewhere are investigating whether anti-malarial drugs might work against T. gondii cysts.
Sabunciyan has reported promising results with a class of anti-malarial drugs, called artemisinins, which appear to be effective at killing T. gondii in tissue cultures. "The next step is to do that in animals," Yolken said.
If it works in animals, that would raise hopes for a toxoplasmosis treatment for people, and perhaps, one day, some relief for people with schizophrenia.
Link Between Schizophrenia, Cat Parasite Studied
Hopkins scientists explore toxoplasmosis and schizophrenia connection.
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