Abstract
Toxoplasma gondii is a parasite that affects about 20–80% of the global population. Chronic infection with toxoplasma, also called latent infection, has largely been considered to be asymptomatic with minimal to no clinical effects or sequelae. Though there is now clear evidence in animal models and mounting evidence in humans that latent toxoplasmosis can have various effects on behavior, personality, cognition, and even psychiatric conditions. In this chapter, we will explore the role latent toxoplasmosis plays in the behavior of animals and humans, and discuss the possible mechanisms for the observed effects.
Keywords
- toxoplasmosis
- animal behavior
- human behavior
- personality
- cognition
- mechanism
- neuropsychiatric conditions
1. Introduction
Since its discovery in 1908, there has been curiosity about the interplay between toxoplasmosis, behavioral changes, personality changes, and cognitive changes in both animals and humans. Toxoplasmosis is one of the most common parasites globally. After primary infection with toxoplasmosis, it lives in a latent form usually in the nervous system and muscle tissues of the host. Animal studies demonstrate that latent infection with toxoplasmosis can have effects on the behavior and overall performance of animals. Human studies also suggest that latent toxoplasmosis infection affects personality, behavior, and cognition, and likely plays a role in the development of psychiatric conditions, particularly schizophrenia. It is hypothesized that modification of the host behavior helps to promote transmission of the parasite. Through multiple intricate experiments, the mechanisms of how latent infection affects behavior and psychomotor performance are felt to be largely driven by altered levels of dopamine. It has been also been postulated that humans with certain blood groups who are infected with
2. Effect of toxoplasma on different hosts
2.1 Cats as the definitive hosts of toxoplasma
2.2 Effect of toxoplasma on infected mice and rats
Early studies looking at behavioral changes in rodents noted a decreased learning capacity and impaired memory. Piekarski et al. performed maze experiments with rats and mice who were infected with
Cats are immediately attracted to moving and exposed objects, thus it would behoove
Webster et al. then performed a series of experiments assessing the effects of
Webster et al. then went on to test the correlation and relationship between parasite transmission and load with rat behavioral changes. He sought to understand two things: (1) whether parasites with indirect life cycles, will influence the activity of the intermediate host, increasing the likelihood of transmission and (2) whether the change in observed activity would be an increase in activity rather than a decrease. The authors used four groups of mice: one group were wild brown rats infected with naturally occurring parasites, another was a hybrid of wild and laboratory rats that were experimentally infected with
One of the most profound effects of
2.3 Large animals
Recently, mild red foxes have been demonstrated to show uncharacteristic behavior which has been classified as Dopey Fox Syndrome (DFS). These behaviors include an apparent lack of fear, increased affection, constant pacing, facial muscle twitching, and anorexia. Conditions such as encephalitis as well as visual abnormalities and/or blindness which are consistent with
There is a suggestion that the effects of
3. Toxoplasmosis effect on human personality and behavior
3.1 Role of toxoplasma on human behavior and personality
Toxoplasmosis is known to affect the activity of rodents, though there are also well-established studies implicating an association between Toxoplasmosis and human behavioral changes. Toxoplasmosis in humans can be in three forms: congenital, acute, or chronic. Several studies outline the devasting effects Toxoplasmosis can have on a fetus, ranging from hydrocephalus, chorioretinitis, and intracranial calcifications to fetal demise. Reduced intellection function has been reported in approximately 6–9% of children with congenital toxoplasmosis [6, 17, 18, 19]. Acute infection has been associated with psychosis confusion, aphasia, and other space-occupying neurologic symptoms [20, 21]. There has been increasing interest in the role that chronic or latent infection has on human personality and behavior.
Flegr et al. performed some of the early studies looking at the role latent toxoplasmosis plays in personality changes. One of his first studies looked at the correlation between serologic evidence of
Prolonged reaction time secondary to latent toxoplasmosis has been well established in rodents, though there is increasing data highlighting this same phenomenon of impaired psychomotor performance in humans. One such study was performed by Flagr et al. where increased human activity was associated with increased traffic accidents. The authors conducted a retrospective study assessing the association between toxoplasmosis infection and traffic accidents. The participants included 146 who experienced a traffic accident to 446 persons in the general population. While the seroprevalence of toxoplasmosis varied by age, latent toxoplasmosis was significantly higher in the traffic accident set (
3.2 The role of toxoplasma on neuropsychiatric conditions
Since the 1950s, it was noted that the prevalence of toxoplasmosis among psychiatric patients, especially patients with schizophrenia, was unusually high, implicating that
3.3 Toxoplasma and neurodegenerative diseases
These findings led to further investigation into the effect
However, two recent meta-analyses demonstrated an association between
The varying results found in studies could in part be explained by
4. Mechanisms of toxoplasma affect human behavior
4.1 Mechanism of action for cognitive effects of toxoplasma
Dopamine is a neurotransmitter that is directly involved in the regulation of cognitive processes. It has been demonstrated that
Dopamine is produced in two steps from its precursor tyrosine. In the first step, tyrosine hydroxylase (TH) converts tyrosine into L-DOPA. In the second step, DOPA decarboxylase converts L-DOPA into dopamine. Any increase in the conversion of tyrosine to L-DOPA will result in increased dopamine synthesis. This is important because Gaskell et al. discovered that the genome of
Further evidence that dopaminergic signaling is indeed the most likely cause of
Indirect mechanisms of action of
4.2 Role of rhesus blood group
The effect of toxoplasmosis on personality and performance may also be in part secondary to a specific Rh blood type. Several studies that have been performed on pregnant women and military personnel have shown that RhD blood group positivity, especially in RhD heterozygotes, protects against various effects of latent toxoplasmosis [48, 49, 50, 51]. Novotná et al. and Flegr et al. both noted in their respective studies that Rh-positive subjects, and RhD-positive heterozygotes, in particular, were protected against latent toxoplasmosis-induced impairment of reaction times [48, 50]. Flegr et al. also noted in a prospective study that included nearly 4000 military drivers, that Rh-negative
Flegr et al. further assess the association between toxoplasmosis and the personality of RhD-negative and RhD-positive subjects. The study included 502 male soldiers of Czech nationality who underwent several tests including the N-70 questionnaire, the NEO-PI-R questionnaire, the Wiener Matrizen-Test (WMT) test of intelligence, and the OTIS test intelligence. The authors noted that
In contrast to the findings in this study, an earlier study performed on University students noted differing results. In that study, there was no difference in expression of neuroticism between
5. Conclusions
There is an abundant amount of data that supports Toxoplasmosis affects the behavior of animals, particularly rodents, and increasing data that supports humans also experience a variety of aberrant behaviors, personality shifts, decreased level of cognition, and development of psychiatry conditions secondary to the latent toxoplasmosis infection. However, there are a few limitations that should be considered when interpreting the data presented. It cannot be confirmed that human behavioral manipulation increases the efficiency of Toxoplasmosis transmission from intermediate to definitive hosts. Clinical trial data establishing the causality of Toxoplasmosis and behavioral modifications are lacking. It is also possible that some of the identified associations represent a trait that increases the risk of Toxoplasmosis, rather than a result of Toxoplasmosis. The extensive heterogeneity seen in the human population could influence the observed effect size in studies. Additionally, there could be synergistic effects of a third unknown agent or factor contributing to the effects of Toxoplasmosis. Despite these limitations,
Acknowledgments
The authors’ research activities are supported, in part, by grants from the National Institutes of Health/National Center for Advancing Translational Sciences (NCATS) (TL1TR002382, UL1TR002378).
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