Most cited article - PubMed ID 23126494
Differences in onset of disease and severity of psychopathology between toxoplasmosis-related and toxoplasmosis-unrelated schizophrenia
Over the past three turbulent decades, research has profoundly reshaped our understanding of chronic Toxoplasma gondii infection-traditionally regarded as harmless in immunocompetent individuals-unveiling its surprising impact on human health, performance, and behavior. This review emphasizes the effects of chronic Toxoplasma infection on physical and mental health, cognitive performance, and behavioral changes, highlighting key findings from studies investigating these domains, with a particular focus on both ultimate and proximate mechanisms underlying the observed effects. To this end, the primary focus will be on human studies; however, animal model studies will also be thoroughly considered when necessary and appropriate, to provide context and additional important information. Research demonstrates that chronic Toxoplasma infection may contribute to a broad spectrum of physical health issues. Ecological studies have revealed correlations between toxoplasmosis prevalence and increased morbidity and mortality from various conditions, including cardiovascular diseases, neurological disorders, and certain cancers. Large-scale cross-sectional studies have further shown that infected individuals report a higher incidence of numerous health complaints and diagnosed diseases, suggesting a significant impact on overall physical well-being. In addition to physical health, lifelong Toxoplasma infection (subclinical toxoplasmosis) has been implicated in cognitive impairments and behavioral changes. Studies have reported associations between infection and poorer performance in areas such as reaction time, processing speed, working memory, and executive function. Many of these behavioral changes likely relate to worsened health and a shift towards a "fast life history strategy." These cognitive deficits can have significant implications for daily functioning and performance. Furthermore, the role of Toxoplasma infection in the development or exacerbation of mental health disorders has been extensively investigated. Meta-analyses, ecological studies, and large-scale observational studies have demonstrated associations between Toxoplasma infection and an increased risk of disorders such as schizophrenia and obsessive-compulsive disorder. While the precise mechanisms underlying these associations remain under investigation, research suggests that neuroinflammation and alterations in neurotransmitter systems are likely to play a role. Far from being harmless, subclinical toxoplasmosis is increasingly recognized as a hidden factor influencing human health, behavior, and cognitive performance-with implications that extend well beyond the individual to public health at large. Further research is warranted to elucidate the complex interplay between Toxoplasma infection, host physiology, and the development of various physical, cognitive, behavioral, and mental health conditions.
- Keywords
- OCD, RhD, Rhesus D antigen, autism, evolution, intelligence, manipulation hypothesis, mental health, parasite, schizophrenia, subclinical toxoplasmosis, testosterone,
- Publication type
- Journal Article MeSH
- Review MeSH
Latent infection with Toxoplasma gondii (Nicolle et Manceaux, 1908) has been repeatedly correlated with behavioural and physiological changes in both humans and animals. While classically regarded as a parasite transmitted via ingestion or vertical (transplacental) transmission, accumulating evidence suggests that sexual transmission may also contribute to its epidemiology. This review explores the hypothesis that some behavioural effects of toxoplasmosis - especially those related to attraction, sexual activity, and mate choice - may have evolved to facilitate sexual transmission of the parasite. We summarise findings from animal models and human studies that show modified sexual preferences, altered sexual activity, enhanced attractiveness in infected individuals, and elevated prevalence of T. gondii in groups exhibiting high sexual activity or non-traditional sexual behaviour patterns. Particular attention is given to the role of testosterone, which may mediate both behavioural changes and reproductive consequences, such as shifts in offspring sex ratios and fertility outcomes. Direct detection of the parasite in semen and evidence of transmission through insemination in non-human species further support the plausibility of this route. The observed behavioural effects may also intersect with mechanisms previously thought to enhance predation risk, such as altered fear responses to felid odours. Taken together, these findings point to the possibility that sexual transmission, while likely secondary in humans, may have played a more substantial role in the evolutionary history and current ecology of T. gondii than previously appreciated. This perspective also provides an alternative interpretative framework for understanding the broad spectrum of phenotypic changes associated with latent toxoplasmosis. Further interdisciplinary research is required to clarify the relative contribution of sexual transmission to the parasite's life cycle and to assess its implications for public health and theory of host-parasite coevolution.
- Keywords
- manipulation, parasite manipulation., review, sexual behaviour, sexually transmitted diseases, testosterone, toxoplasmosis,
- MeSH
- Host-Parasite Interactions * MeSH
- Humans MeSH
- Sexual Behavior MeSH
- Toxoplasma * physiology MeSH
- Toxoplasmosis * transmission parasitology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
In this article, I recount the journey of discovering the effects of latent toxoplasmosis on human psychology, behaviour, morphology, and health as I observed it from the closest perspective over the past 30+ years, during which our laboratory has been intensely focused on this research. I trace how we moved from the initial observations of differences between infected and uninfected individuals in certain personality traits to the systematic study of similar differences in behaviour, both in the laboratory and in everyday life, as well as in physiological and even morphological traits. This eventually led us to investigate the causal relationships behind these observed associations and their molecular basis. I describe some of the unexpected discoveries our research revealed - whether it was the impact of toxoplasmosis on the human sexual index, the prenatal and postnatal development, the sexual preferences and behaviour, the modulatory effect of blood Rh factor on toxoplasmosis, or the discovery of sexual transmission of toxoplasmosis. In exploring whether the toxoplasmosis-associated effects were merely side effects of an ongoing latent infection, we gradually uncovered that seemingly asymptomatic toxoplasmosis has profound (and certainly not positive) effects on the mental and physical health of infected individuals. The article also includes three separate boxes that discuss some key methodological challenges we encountered along the way, such as how to distinguish the effect of infection from mere statistical association, or how to differentiate parasitic manipulation from a simple side effect.
- Keywords
- Rh factor, Toxoplasma, behaviour, chronic toxoplasmosis, dopamine, manipulation, mental health, morbidity, parasite., personality, physical health, schizophrenia, sex ratio, testosterone,
- MeSH
- History, 20th Century MeSH
- History, 21st Century MeSH
- Humans MeSH
- Sexual Behavior MeSH
- Toxoplasmosis * psychology physiopathology parasitology MeSH
- Animals MeSH
- Check Tag
- History, 20th Century MeSH
- History, 21st Century MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Historical Article MeSH
- Review MeSH
Infection by the parasite Toxoplasma, which affects about 33% of world population, is associated with an increased risk of several mental health disorders, the most strongly with schizophrenia. It is unknown whether schizophrenia is associated with this infection the most strongly, or whether this association has just been the most intensively studied for historical reasons. We used the data from 6,367 subjects tested for toxoplasmosis who took part in an internet survey to search for associations of these infections with 24 mental health disorders and evidence of otherwise impaired mental health. The typical symptom associated with toxoplasmosis was anxiety, and the typical toxoplasmosis-associated disorders were autism (OR = 4.78), schizophrenia (OR = 3.33), attention deficit hyperactivity disorder (OR = 2.50), obsessive compulsive disorder (OR = 1.86), antisocial personality disorder (OR = 1.63), learning disabilities (OR = 1.59), and anxiety disorder (OR = 1.48). Toxoplasmosis could play a substantial role in the etiopathogenesis of mental health disorders and its association with schizophrenia is the second strongest association, after autism.
- Keywords
- Toxoplasma, etiology, infection hypothesis, mental health, prevalence, psychiatric diseases, risk factors,
- Publication type
- Journal Article MeSH
BACKGROUNDS: The prevalence of toxoplasmosis is higher in schizophrenics than in the general population. It has been suggested that certain symptoms of schizophrenia, including changes in olfactory functions, are in fact symptoms of toxoplasmosis that can be easily detected in schizophrenics only due to the increased prevalence of toxoplasmosis in this population. Schizophrenics have impaired identification of odors and lower sensitivity of odor detection, however, no information about these parameters of non-schizophrenic Toxoplasma-infected subjects is available. METHODS: Here we searched for differences in olfactory functions between 62 infected and 61 noninfected non-schizophrenic subjects using the case-controls experimental design. RESULTS: The infected men scored better than the non-infected controls in the standard odor-identification test. The infected women rated all smells as more intensive while the infected men rated nearly all smells as less intensive. Infected women rated the pleasantness of the smell of the cat urine as higher than the non-infected women and the opposite was true for the men-in contrast, higher pleasantness of odor in infected men and lower in infected women were observed and described in the 2011 study. Toxoplasmosis, Rh, and toxoplasmosis-Rh interaction were not associated with the rated pleasantness of the smell of other stimuli. However, our sample contained only 17 Rh negative men and 30 Rh negative women. Therefore, all results concerning the main effects of Rh factor and the interaction with Rh factor must be considered only preliminary. CONCLUSIONS: Our results suggest that latent toxoplasmosis is associated with changes in the olfactory functions in humans; however, the observed changes differ from those observed in schizophrenics.
- MeSH
- Adult MeSH
- Cats MeSH
- Rh-Hr Blood-Group System metabolism MeSH
- Humans MeSH
- Young Adult MeSH
- Urine MeSH
- Odorants MeSH
- Schizophrenia metabolism parasitology physiopathology MeSH
- Case-Control Studies MeSH
- Toxoplasma pathogenicity MeSH
- Toxoplasmosis metabolism physiopathology MeSH
- Animals MeSH
- Check Tag
- Adult MeSH
- Cats MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Rh-Hr Blood-Group System MeSH
The parasite Toxoplasma needs to get from its intermediate hosts, e.g. rodents, to its definitive hosts, cats, by predation. To increase the probability of this occurrence, Toxoplasma manipulates the behavior of its hosts, for example, by the demethylation of promoters of certain genes in the host's amygdala. After this modification, the stimuli that normally activate fear-related circuits, e.g., the smell of a cat in mice, or smell of leopards in chimpanzees, start to additionally co-activate sexual arousal-related circuits in the infected animals. In humans, the increased attraction to masochistic sexual practices was recently observed in a study performed on 36,564 subjects. Here I show that lower rather than higher attraction to sexual masochism and submissiveness among infected subjects is detected if simple univariate tests instead of multivariate tests are applied to the same data. I show and discuss that when analyzing multiple effects of complex stimuli on complex biological systems we need to use multivariate techniques and very large data sets. We must also accept the fact that any single factor usually explains only a small fraction of variability in the focal variable.
- Keywords
- BDSM, Toxoplasmosis, big data, complex systems, epigenetics, manipulation, multivariate statistics, parasitism, sexual behavior, violence,
- Publication type
- Journal Article MeSH
BACKGROUND: A recent study performed on 1.3 million patients showed a strong association between being bitten by a cat and probability of being diagnosed with depression. Authors suggested that infection with cat parasite Toxoplasma could be the reason for this association. METHOD: A cross sectional internet study on a non-clinical population of 5,535 subjects was undertaken. RESULTS: The subjects that reported having been bitten by a dog and a cat or scratched by a cat have higher Beck depression score. They were more likely to have visited psychiatrists, psychotherapists and neurologists in past two years, to have been previously diagnosed with depression (but not with bipolar disorder). Multivariate analysis of models with cat biting, cat scratching, toxoplasmosis, the number of cats at home, and the age of subjects as independent variables showed that only cat scratching had positive effect on depression (p = 0.004). Cat biting and toxoplasmosis had no effect on the depression, and the number of cats at home had a negative effect on depression (p = 0.021). CONCLUSIONS: Absence of association between toxoplasmosis and depression and five times stronger association of depression with cat scratching than with cat biting suggests that the pathogen responsible for mood disorders in animals-injured subjects is probably not the protozoon Toxoplasma gondii but another organism; possibly the agent of cat-scratched disease - the bacteria Bartonella henselae.
- MeSH
- Bartonella henselae physiology MeSH
- Depression microbiology MeSH
- Cats MeSH
- Humans MeSH
- Multivariate Analysis MeSH
- Cat-Scratch Disease microbiology MeSH
- Cross-Sectional Studies MeSH
- Dogs MeSH
- Animals MeSH
- Check Tag
- Cats MeSH
- Humans MeSH
- Male MeSH
- Dogs MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: About 30% of people on Earth have latent toxoplasmosis. Infected subjects do not express any clinical symptoms, however, they carry dormant stages of parasite Toxoplasma for the rest of their life. This form of toxoplasmosis is mostly considered harmless, however, recent studies showed its specific effects on physiology, behaviour and its associations with various diseases, including psychiatric disorders such as schizophrenia. Individuals who suffer from schizophrenia have about 2.7 times higher prevalence of Toxoplasma-seropositivity than controls, which suggests that some traits characteristic of schizophrenic patients, including the sex difference in schizophrenia onset, decrease of grey matter density in specific brain areas and modification of prepulse inhibition of startle reaction could in fact be caused by toxoplasmosis for those patients who are Toxoplasma-seropositive. METHODOLOGY/PRINCIPAL FINDINGS: We measured the effect of prepulse inhibition/facilitation of the startle reaction on reaction times. The students, 170 women and 66 men, were asked to react as quickly as possible to a startling acoustic signal by pressing a computer mouse button. Some of the startling signals were without the prepulse, some were 20 msec. preceded by a short (20 msec.) prepulse signal of lower intensity. Toxoplasma-seropositive subjects had longer reaction times than the controls. Acoustic prepulse shorted the reaction times in all subjects. This effect of prepulse on reaction times was stronger in male subjects and increased with the duration of infection, suggesting that it represented a cumulative effect of latent toxoplasmosis, rather than a fading out after effect of past acute toxoplasmosis. CONCLUSIONS: Different sensitivity of Toxoplasma-seropositive and Toxoplasma-seronegative subjects on effect of prepulses on reaction times (the toxoplasmosis-prepulse interaction) suggested, but of course did not prove, that the alternations of prepulse inhibition of startle reaction observed in schizophrenia patients probably joined the list of schizophrenia symptoms that are in fact caused by latent toxoplasmosis.
- MeSH
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Reaction Time MeSH
- Schizophrenic Psychology MeSH
- Schizophrenia immunology parasitology physiopathology MeSH
- Sex Factors MeSH
- Toxoplasma physiology MeSH
- Toxoplasmosis immunology parasitology physiopathology psychology MeSH
- Reflex, Startle physiology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH