Most cited article - PubMed ID 23433494
How and why Toxoplasma makes us crazy
The amyloid cascade hypothesis, focusing on pathological proteins aggregation, has so far failed to uncover the root cause of Alzheimer's disease (AD), or to provide an effective therapy. This traditional paradigm essentially explains a mechanism involved in the development of sporadic AD rather than its cause. The failure of an overwhelming majority of clinical studies (99.6%) demonstrates that a breakthrough in therapy would be difficult if not impossible without understanding the etiology of AD. It becomes more and more apparent that the AD pathology might originate from brain infection. In this review, we discuss a potential role of bacteria, viruses, fungi, and eukaryotic parasites as triggers of AD pathology. We show evidence from the current literature that amyloid beta, traditionally viewed as pathological, actually acts as an antimicrobial peptide, protecting the brain against pathogens. However, in case of a prolonged or excessive activation of a senescent immune system, amyloid beta accumulation and aggregation becomes damaging and supports runaway neurodegenerative processes in AD. This is paralleled by the recent study by Alam and colleagues (2022) who showed that alpha-synuclein, the protein accumulating in synucleinopathies, also plays a critical physiological role in immune reactions and inflammation, showing an unforeseen link between the 2 unrelated classes of neurodegenerative disorders. The multiplication of the amyloid precursor protein gene, recently described by Lee and collegues (2018), and possible reactivation of human endogenous retroviruses by pathogens fits well into the same picture. We discuss these new findings from the viewpoint of the infection hypothesis of AD and offer suggestions for future research.
- MeSH
- Alzheimer Disease * metabolism MeSH
- Amyloid beta-Peptides metabolism MeSH
- Amyloid beta-Protein Precursor metabolism MeSH
- Anti-Bacterial Agents therapeutic use MeSH
- Anti-Infective Agents * metabolism MeSH
- Humans MeSH
- Brain pathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Amyloid beta-Peptides MeSH
- Amyloid beta-Protein Precursor MeSH
- Anti-Bacterial Agents MeSH
- Anti-Infective Agents * MeSH
The article is a perspective on utilization of microorganisms and chemosignals in studying human economic behavior. Research in biological roots of economic development has already confirmed that parasitic pressure influenced the creation and development of cultural norms and institutions. However, other effects of microorganisms on human groups and individual decision-making and behavior are heavily understudied. The perspective discusses how parasitic infections, sexually transmitted organisms and microbiota (i.e., "human holobiont") could causally influence risk-seeking behavior, impulsivity, social dominance, empathy, political views and gender differences. As a case study, the parasite Toxoplasma gondii and its influence on economic preferences, personal characteristics and human appearance are examined. I also briefly review how chemosignals influence decision-making, particularly in the social preferences domain. I mention some predictions that arise from the paradigm of economic holobiont for the economic science. The conclusion summarizes limitations of the discussed findings and the stated speculations.
- Keywords
- Toxoplasma gondii, chemosignaling, economics, microbiota, parasites, risk preferences, social preferences, time preferences,
- Publication type
- Journal Article MeSH
Latent infection with Toxoplasma gondii has repeatedly been shown to be associated with behavioral changes that are commonly attributed to a presumed increase in dopaminergic signaling. Yet, virtually nothing is known about its effects on dopamine-driven reward processing. We therefore assessed behavior and event-related potentials in individuals with vs. without latent toxoplasmosis performing a rewarded control task. The data show that otherwise healthy young adults with latent toxoplasmosis show a greatly diminished response to monetary rewards as compared to their non-infected counterparts. While this selective effect eliminated a toxoplasmosis-induced speed advantage previously observed for non-rewarded behavior, Toxo-positive subjects could still be demonstrated to be superior to Toxo-negative subjects with respect to response accuracy. Event-related potential (ERP) and source localization analyses revealed that this advantage during rewarded behavior was based on increased allocation of processing resources reflected by larger visual late positive component (LPC) amplitudes and associated activity changes in the right temporo-parietal junction (BA40) and left auditory cortex (BA41). Taken together, individuals with latent toxoplasmosis show superior behavioral performance in challenging cognitive control situations but may at the same time have a reduced sensitivity towards motivational effects of rewards, which might be explained by the presumed increase in dopamine.
- MeSH
- Dopamine metabolism MeSH
- Adult MeSH
- Evoked Potentials MeSH
- Cognition physiology MeSH
- Humans MeSH
- Young Adult MeSH
- Reward * MeSH
- Antibodies, Protozoan metabolism MeSH
- Auditory Cortex MeSH
- Case-Control Studies MeSH
- Toxoplasma immunology MeSH
- Toxoplasmosis metabolism psychology 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
- Names of Substances
- Dopamine MeSH
- Antibodies, Protozoan MeSH
The protozoan Toxoplasma gondii infects about one-third of the world's population. The consumption of raw meat, contact with cats, contact with soil, and ingestion of food or water contaminated with soil are considered to be the most important sources of infection. Still in most women who were infected during pregnancy, no definitive source of infection is found. In 2014-2016, independent sources of T. gondii infection were searched for by gathering epidemiological data from 1865 (519 infected) responders. Touching garden soil (odds ratio (OR) 3·14, 95% confidence interval (CI) 1·3-6·35), sustaining cat-related injuries (OR 2·16, 95% CI 1·25-3·74), and eating improperly washed root vegetables (OR 1·71, 95% CI 1·02-2·87), but not risky sexual behavior (OR 1·22, 95% CI 0·79-1·90), were the predictors of infection. The seroprevalence of T. gondii infection had been increasing up to ages 35-50 in men and ages 50-54 in women. Past those ages, seroprevalence of toxoplasmosis has been decreasing. This suggests that the natural decrease of anamnestic antibodies concentrations over time leads to positivity-to-negativity seroconversion in many subjects. If this is true, then the prevalence of T. gondii infection in a general population and its potential impacts on public health could be much larger than generally believed.
- Keywords
- Cats, STD, Toxoplasmosis, dogs, pets, risk factors, sexually transmitted diseases, zoonosis,
- MeSH
- Adult MeSH
- Cats MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Prevalence MeSH
- Surveys and Questionnaires MeSH
- Dogs MeSH
- Risk-Taking * MeSH
- Risk Factors MeSH
- Aged MeSH
- Seroepidemiologic Studies MeSH
- Sexual Behavior * MeSH
- Toxoplasma physiology MeSH
- Toxoplasmosis, Animal epidemiology parasitology MeSH
- Toxoplasmosis epidemiology parasitology MeSH
- Age Factors MeSH
- Animals MeSH
- Check Tag
- Adult MeSH
- Cats MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Dogs MeSH
- Aged MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic epidemiology MeSH
- Slovakia epidemiology 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: Past research linked Toxoplasma gondii (TG) infection in humans with neurological and mental disorders (e.g., schizophrenia, Alzheimer's disease and attention disorders), irregularities of the dopaminergic and testosterone system, and increased likelihood of being involved in traffic accidents. METHODOLOGY/PRINCIPAL FINDINGS: We test for an association between TG infection and financial decision-making (DM) using a case-control design in a sample of female Czech students (n = 79). We estimate each subject's risk attitude and loss aversion using an experimental economic task involving real monetary incentives. We find no significant evidence that either measure of decision-making is associated with TG infection. CONCLUSION: We were unable to find evidence of an association between TG infection and financial decision-making in females.
- MeSH
- Adult MeSH
- Financial Management * MeSH
- Rh-Hr Blood-Group System genetics immunology MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Risk-Taking * MeSH
- Decision Making MeSH
- Sex Factors MeSH
- Case-Control Studies MeSH
- Toxoplasmosis complications diagnosis MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Rh-Hr Blood-Group System MeSH
- Rho(D) antigen MeSH Browser
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
BACKGROUND: Toxoplasmosis is becoming a global health hazard as it infects 30-50% of the world human population. Clinically, the life-long presence of the parasite in tissues of a majority of infected individuals is usually considered asymptomatic. However, a number of studies show that this 'asymptomatic infection' may also lead to development of other human pathologies. AIMS OF THE STUDY: The purpose of the study was to collect available geoepidemiological data on seroprevalence of toxoplasmosis and search for its relationship with mortality and disability rates in different countries. METHODS AND FINDINGS: Prevalence data published between 1995-2008 for women in child-bearing age were collected for 88 countries (29 European). The association between prevalence of toxoplasmosis and specific disease burden estimated with age-standardized Disability Adjusted Life Year (DALY) or with mortality, was calculated using General Linear Method with Gross Domestic Product per capita (GDP), geolatitude and humidity as covariates, and also using nonparametric partial Kendall correlation test with GDP as a covariate. The prevalence of toxoplasmosis correlated with specific disease burden in particular countries explaining 23% of variability in disease burden in Europe. The analyses revealed that for example, DALY of 23 of 128 analyzed diseases and disease categories on the WHO list showed correlations (18 positive, 5 negative) with prevalence of toxoplasmosis and another 12 diseases showed positive trends (p<0.1). For several obtained significant correlations between the seroprevalence of toxoplasmosis and specific diseases/clinical entities, possible pathophysiological, biochemical and molecular explanations are presented. CONCLUSIONS: The seroprevalence of toxoplasmosis correlated with various disease burden. Statistical associations does not necessarily mean causality. The precautionary principle suggests however that possible role of toxoplasmosis as a triggering factor responsible for development of several clinical entities deserves much more attention and financial support both in everyday medical practice and future clinical research.
- MeSH
- Asymptomatic Diseases epidemiology MeSH
- Accidents, Traffic statistics & numerical data MeSH
- Gross Domestic Product MeSH
- Internationality * MeSH
- Quality-Adjusted Life Years MeSH
- Humans MeSH
- Prevalence MeSH
- Suicide statistics & numerical data MeSH
- Seroepidemiologic Studies MeSH
- Toxoplasmosis blood epidemiology mortality transmission MeSH
- Humidity MeSH
- Geography MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH