Parasites and Us: Who is in Control?


by Christine Ottery

October, 2012

We would all like to think we are the masters and mistresses of our own minds. But what if there were a parasite dwelling in our brains with the power to manipulate our behavior, without our even being aware of it? Scarily like science fiction, but research in recent years suggests that the parasite Toxoplasma gondii, which can live in our brains, has links to such psychiatric conditions as suicide attempts and schizophrenia.

The parasite usually enters the body in undercooked meat, unwashed vegetables, or unclean water, but it always traces back to cat feces. T. gondii can infect our muscles and brain, and can lie ‘dormant’ in cyst form or be actively replicating. This infection is particularly dangerous for people with low immunity, such as people with AIDS or undergoing cancer treatment, and also for the development of unborn babies (You can read about safety measures at http://www.cdc.gov/parasites/toxoplasmosis/)

About one-third of people globally are infected by toxoplasma. In parts of Europe, infection rates are as high as 90 percent, but in the United States, the average rate of infection falls between 10 percent and 20 percent. No one knows what if any proportion of people might experience psychiatric symptoms connected with the parasite.

In July this year, though, a large epidemiological study published in the Archives of General Psychiatry found a strong link between suicide attempts in women who were infected with T. gondii.

“What we found in this cohort study is that there is a 50 percent increase in the rate of suicide attempts in women—in mothers—who are Toxoplasma gondii positive,” says Teodor Postolache, the senior author of the paper, an associate professor of psychiatry and director of the mood and anxiety program at the University of Maryland School of Medicine.

This is the first prospective study confirming a link between T. gondii and suicide attempts. Women in the study were tested for the presence of antibodies against the parasite before they attempted suicide rather than after; this is a stronger study type than retrospectively testing suicide attempters, as it could be argued that people with psychiatric problems are more vulnerable to infection through poor hygiene.

Nevertheless, it is still uncertain whether the chicken or egg comes first. Could potential suicide attempters be more at risk of catching T. gondii or does infection with the parasite sometimes cause the urge to commit suicide?

The correlation between the parasite and people potentially attempting suicide has been reinforced by the publication in August of a small study in the Journal of Clinical Psychiatry  looking at the level of T. gondii antibodies in people at risk of attempting suicide. “In our study we found that if you are positive for the parasite, you are seven times more likely to attempt suicide,” says Lena Brundin, co-lead on the study, who is based at Michigan State University.

T. gondii has also has a long-standing link to schizophrenia. Robert Yolken at Johns Hopkins University Medical Center and E. Torrey at Stanley Medical Research Institute found a strong correlation between the two when carrying out meta-analyses of other studies, the latest of which was published in 2012 in the Schizophrenia Bulletin.

 “There have also been various prospective studies now where individuals are looked at before the onset of schizophrenia," Yolken says. "So for the timing in at least some of the cases, clearly the toxoplasma came before the psychiatric problem.”

Postolache’s group has also reported an increase in T. gondii antibodies in people who have schizophrenia, a similar finding to an independent group of researchers in Turkey. However, it is uncertain what role T. gondii might have in the development of schizophrenia.

“The rate of toxoplasma is fairly high and the behaviors we recognize—schizophrenia and suicide—are fortunately reasonably rare,” says Yolken, “There are many people with schizophrenia that are not toxoplasma infected. It's an interesting question why some people do and some people don't: it probably has to do with the underlying genetics of the person and of the toxoplasma.”

But schizophrenia and the risk of suicide attempt are not the only behaviors that have been linked to T. gondii. People who carry the parasite also can display over-impulsive behavior. A Czech group of researchers led by Jaroslav Flegr at the Charles University in Prague have conducted some interesting but small studies into a possible link between being toxoplasma positive and car accidents. These findings have been independently replicated by a Turkish group of researchers, but need further study in larger groups.

The possible correlation suggests either a change in spatial-motor perception or a more impulsive behavior. Stanford neuroscientist Robert Sapolsky says: “It has been impossible to choose between them [the alternate explanations]  … two different groups have now shown that Toxo makes people with depression more likely to impulsively commit suicide... it's more about overcoming that hard-wired inhibition against leaping off a bridge, pulling a trigger... So I think the suicide literature strongly supports the "disinhibition" explanation for the car accidents.”

 

Why?

So, T. gondii could be playing a role in suicide attempts, schizophrenia, and even car accidents. How might the parasite be causing mental disorders and changes in behavior?

A few viable mechanisms have been explored.The most-stablished theory is that T. gondii produces dopamine and disrupts the brain’s own dopamine production.

Glenn McConkey, a parasitologist at the University of Leeds, has been working on the genome analysis of T. gondii. In a study in Plos One in 2009, McConkey and his team described how T. gondii has a gene that makes tyrosine hydroxylase, which produces L-DOPA. “This is what is made into dopamine in the brain,” says McConkey. Furthermore, a 2011 study also in Plos One suggests that when model neurons are infected with the parasite they become filled with dopamine.

Sapolsky, who has been involved in studies finding that infected rats are less adverse to cats, says: “the attraction that Toxo can generate for cats is right in the realm of things that dopamine helps mediate.” He adds: “blocking dopamine receptors blocks the behavioral effects of toxo... but a lot more is needed to implicate dopamine further.”

Other recent studies have explored the possible role of the immune system in causing changes in the brain that affect behavior. One such theory is that an immune system reaction to the parasite can change behavior.

“It is unclear but there could be long-term consequences of a chronic toxoplasma infection," says Chris Hunter, an immunologist at the University of Pennsylvania. "There could be an immune response early on that sets it up, that then has long-lasting consequences, such as schizophrenia.” Hunter cautions that this is complicated, because any kind of infection or stress could play a part in influencing behavior. “For instance, during pregnancy, if there is a life-changing event for the mother the likelihood of the infant having schizophrenia is increased—that could be toxoplasma, another infection, or it could also be the death of a relative” or some other external event.

Brundin has also focusing on the immune system as a possible explanation for the link between suicide attempts and the parasite, after observing that there were higher levels of low-grade inflammation in the cerebrospinal fluid of people who were suicidal and infected with a ‘dormant’ T. gondii compared to those that were clinically depressed. The accepted dogma has been that in the cyst stage, the parasite does not do damage, but this research suggests that the parasite can cause inflammation over time.

“The metabolites that produce inflammation, they are harmful for the cells, and they are actually triggering the glutamate system in the brain, so they are acting in a neurotransmitter level,” says Brundin, “the theory is that this inflammation is what is causing the feelings of suicidality or symptoms of depression in patients.”

“The immune/inflammation angle is a newer one in the field,” comments Sapolsky, “but I think that it is likely to play a fairly indirect role as well. The inflammatory changes seen with chronic toxo infection are of a type that can lead to changes in serotonin, GABA and glutamate signaling in the brain, so that opens up a million ways in which behavior may be altered.”

So which is the better theory? McConkey points out that model neurons are flooded with dopamine in the absence of an immune system, so this mechanism for altering behavior can stand alone. Yolken concedes: “In humans we really don’t know yet. In animals I think both are going on. Schizophrenia and suicide are both very complicated behaviors - I am sure there are multiple pathways and the immune system is probably involved as well.”

Both the dopamine and immune system mechanisms open up future opportunities for the treatment for people if their symptoms are related to T. gondii. Current treatments only help prevent the replication of toxoplasma in the active stage, or help prevent transmission to a fetus (you can ask to be tested in the US and UK if you are pregnant; the test is not done routinely). Although work is being done to create experimental drugs by Yolken’s group and others, new treatments are a long way off, the experts agree, and the most important thing for now is prevention, just in case.