Part 1: Is there a relationship between parasitic infections and psychosis?
The antics of Tom and Jerry have entertained us for years. The chaos created by the cunning mouse and the persistent cat provides much-needed comic relief from everyday life. The cat chasing the mouse, the mouse sassing the cat. But what gave Jerry the guts to chase Tom every once in awhile? Is this so far from reality – is it possible for mice to lose their fear for cats? Short answer: Yes, it is possible.
Now imagine this. A little rodent scampers about your yard, keeping a wary eye out for your pet cat. Along the way, the mouse becomes infected with the cunning Toxoplasma gondii parasite. T. gondii is no ordinary parasite, it can only reproduce inside the gut of cats. And it evolved a very interesting mechanism to achieve this goal. This parasite takes over the master controls for the rodent and strangely enough the rodent all of a sudden loses its fear for your cat. It even becomes attracted to the smell of cat urine [1]! You can imagine the fate of our little rodent friend.
Now T. gondii is inside feline intestines and can complete its life cycle. After being excreted into your garden soil and tracked into the house, or being excreted into a litter box, which you now have to empty, this sly little parasite can infect you. What happens next? It depends…but it is possible that you may start behaving like our rodent friend with increased attraction to cat urine (yes bizzare but makes evolutionary sense for the parasite), increased risk of traffic and workplace accidents, personality changes, and more [1].
Cats & Schizophrenia
Cats have increased in popularity and account for 90 million pets in the United States [2]. They are host to, and can transmit, the protozoan Toxoplasma gondii oocysts to humans via feces in cat litter, contact with surfaces used for food preparation, gardens/soil, and sandboxes, etc [2,3].
Now cats aren’t the only risk factor for infection with Toxoplasma, but they are the host that allows for the protozoa to complete its life cycle. A study of pregnant women in France identified pet cats, poor hand hygiene and undercooked meat as risk factors for Toxoplasmosis [4]. The reason to be concerned with this population is that there is a 20-50% chance of transferring Toxoplasma to the fetus [2]. All three of these risk factors can be reduced with proper prevention, including alterations in the handling of pet cats such as keeping them indoors, proper litter disposal and gardening with gloves on [2].
Cats, Toxoplasma and Schizophrenia
Before we get into the more specific aspects of Toxoplasma and schizophrenia, here some things to consider:
An increased childhood exposure to cats (but not dogs) [5].
Toxoplasmic chorioretinitis due to congenital infection occurs around ages 20-30, which are the ages around which schizophrenia appears [6].
Winter and spring births, which coincides with peak seasons for “Toxo” infection [5].
Some antipsychotic drugs also have antitoxoplasmic activity [5–8].
Can Schizophrenia be a Sexually Transmitted Disease?
The gender differences in the age at onset of schizophrenia are only significant when looking at those with T. gondii infections. Men are more likely to become infected at an early age. Women on the other hand can get infected in early childhood, but also around the ages of 25-30 [7]. The hypothesis is that this second wave of infection is caused by unprotected sex with an infected male [7,9].
Why might this be beneficial to the parasite? Well in rodents, infected male are more attractive mates to uninfected females, probably through the parasite’s ability to increase testosterone levels (helps explain the decreased fear to natural predators), and this allows for another route of transmission [1,10]. Increased luteinizing hormone receptors and testosterone levels have also been found in infected human males, but not females [1,8]. The decreased fear may also be associated with structural changes found in the brain, specifically the basolateral amygdala in rodents with latent infections [8].
Prenatal Environment
Patients with schizophrenia and their mothers are almost three times more likely to possess antibodies to T. gondii than control populations [5]. These results are likely an underestimation, since people with severe cases of schizophrenia are less like to be able to volunteer for clinical studies [7].
The antibodies in these studies were associated with previous infection rather than active infection. This suggests that the patient is not in the initial stages of infection during the onset of schizophrenia, but in an inflammatory stage of tachyzoite proliferation involving inflammatory cytokines (signalling molecules) [6].
Now it is interesting to note that another study looking specifically at neonatal heel-prick blood samples for people who later developed schizophrenia has found elevated maternally-derived antibodies [11]. What could cause elevated T. gondii antibodies in the mother? Perhaps a pet cat? The authors propose that these levels may be a marker of how likely the infant is to be exposed to T. gondii at home [11].
Neonatal antibodies may indicate environmental risk levels, but is there a better indicator of actual infection? The prevalence of T. gondii infection in schizophrenia increases to 12.9 times the rate in control populations when more sensitive tests are performed [12].
In order to avoid exposure to T. gondii during pregnancy various researchers recommend the following in regards to cats [2–4,13]:
wearing gloves when handling soil or cleaning up cat litter
having someone else handle cat litter if possible
cleaning litter boxes daily
feeding cats cooked food or dried commercial food
keeping cats indoors
avoiding new or stray cats
Other precautions include ensuring that meat is properly cooked, freezing meat before cooking it, washing all fruits, vegetables and cooking utensils thoroughly, and covering children’s sandboxes [2–4,13].
In my next post I will discuss genetic factors that relate to schizophrenia, and how some of these “genetic” factors may still be explained by T. gondii infection.
References:
Webster, J. P., Kaushik, M., Bristow, G. C. & McConkey, G. a. Toxoplasma gondii infection, from predation to schizophrenia: can animal behaviour help us understand human behaviour? J. Exp. Biol. 216, 99–112 (2013).
Dabritz, H. A. & Conrad, P. A. Cats and Toxoplasma: implications for public health. Zoonoses Public Health 57, 34–52 (2010).
Torda, A. Are cats really the source? 30, 743–748 (2001).
Baril, L. et al. Risk factors for Toxoplasma infection in pregnancy: a case-control study in France. Scand. J. Infect. Dis. 31, 305–9 (1999).
Torrey, E. F., Bartko, J. J., Lun, Z. R. & Yolken, R. H. Antibodies to Toxoplasma gondii in patients with schizophrenia: A meta-analysis. Schizophr. Bull. 33, 729–736 (2007).
Carruthers, V. B. & Suzuki, Y. Effects of Toxoplasma gondii infection on the brain. Schizophr. Bull. 33, 745–751 (2007).
Flegr, J. Schizophrenia and Toxoplasma gondii: an undervalued association? Expert Rev. Anti. Infect. Ther. 13, 817–820 (2015).
Elsheikha, H. M., Büsselberg, D. & Zhu, X.-Q. The known and missing links between Toxoplasma gondii and schizophrenia. Metab. Brain Dis. 31, 749–59 (2016).
Flegr, J., Klapilová, K. & Kaňková, S. Toxoplasmosis can be a sexually transmitted infection with serious clinical consequences. Not all routes of infection are created equal. Med. Hypotheses 83, 286–9 (2014).
Vyas, A. Review: Parasite-augmented mate choice and reduction in innate fear in rats infected by Toxoplasma gone. J. Exp. Biol. 216, 120–126 (2013).
Mortensen, P. B. et al. Toxoplasma gondii as a Risk Factor for Early-Onset Schizophrenia: Analysis of Filter Paper Blood Samples Obtained at Birth. Biol. Psychiatry 61, 688–693 (2007).
Omar, A. et al. Seropositivity and serointensity of Toxoplasma gondii antibodies and DNA among patients with schizophrenia. Korean J. Parasitol. 53, 29–34 (2015).
Prevention, C.-C. for D. C. and. CDC - Toxoplasmosis - Prevention & Control.
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