Toxoplasma Infection and Its Sequential Impact on Physical Health, Stress, and Anxiety: A Large Cross-Sectional Study Testing the Stress-Coping Hypothesis

Abstract

Introduction

Latent toxoplasmosis, affecting approximately one-third of people worldwide, was once thought to be asymptomatic. However, studies in the last three decades have revealed that it can cause significant psychological and behavioral changes in humans. The observation that the behavioral impacts of toxoplasmosis manifest in opposite directions in men and women has led to the development of the Stress-Coping Hypothesis. This hypothesis posits that health degradation from toxoplasmosis results in chronic stress, with gender-specific coping strategies explaining the divergent behavioral responses observed between men and women.

Methods

This study, conducted on 1,768 individuals who had previously been tested for toxoplasmosis or borreliosis, sought to examine this hypothesis through a survey that included the Perceived Stress Scale and the State-Trait Anxiety Inventory.

Results

Confirmed poorer health, higher stress, and anxiety levels among Toxoplasma -infected participants. Path analysis showed that toxoplasmosis directly negatively impacts physical health, which in turn directly increases stress and anxiety among infected individuals, thereby negatively affecting cognitive performance. This pattern was not seen with borreliosis, serving as a negative control, underscoring the unique impact of toxoplasmosis on human physical health, well-being, and cognition.

Conclusions

Our findings strongly suggest that the cognitive impairments associated with toxoplasmosis are primarily side effects of chronic stress resulting from the compromised health of infected individuals.

Key Points

Chronic stress mediates the negative effects of toxoplasmosis on cognition, stemming from the impaired health of infected individuals.

This effect was not observed with the negative control, borreliosis.

Our results support the side effects hypothesis and contradict the parasite manipulation hypothesis.

This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/14127021.

Does the introduction explain the objective of the research presented in the preprint? Yes The introduction provides an overview of Toxoplasmosis and Toxoplasma gondii in connection to the effects of infection. The introduction emphasizes personality change and increased anxiety that results from Toxoplasma infection. The authors also mention a sex difference in the manifestations of the Toxoplasma personality changes and stress-coping methods. However, most of the studies that support the conclusions about Toxoplasma infection effects were written by the same few authors, some of which also authored this study. There is a significant amount of self-citation in covering the background evidence. This over-reliance on self-citation is a big concern regarding the scientific rigor and validity of the study results.

Are the methods well-suited for this research? Highly inappropriate Method #1: Snowball sampling - often can introduce sampling bias and lacks generalizability or representativeness. Given that the research questions of the study seeks to validate the "Stress Coping Hypothesis" and the conclusions draw on these results to generalize to a larger population of toxoplasma infected individuals, a more objective sampling method should have been utilized. The authors do not explain why they decided to proceed in this manner (e.g. perhaps it may be appropriate if they were exploring a subset of a population to obtain qualitative data rather than looking for generalizable trends) Additionally, given that recruitment was done online through Facebook, which is a limited sample base that could again introduce bias to those who have internet/social media access that are seeking out information regarding this particular illness. This is not standard/best practices when trying to answer the given research question. More objective and informed recruitment criteria should be used, perhaps recruiting from a clinical sample. Method #2: Questionnaire-based data - given that these symptoms are self-reported based on two standardized questionnaires for screening, only associative assumptions can be drawn. Further validation with a clinical staff (or diagnostic tool) would be a better method to utilize for the claims. Additionally, using questionnaires to elicit self-reported status of a clinical diagnosis (e.g. toxoplasmosis infection) is not considered standard/best practices; a serological test is widely available for confirmation, therefore limiting the validity of the clinical status of the recruited participants. They do discuss the rationale for why this path was not utilized in "discussions", though it is reliant on self-citation, which as mentioned previously is problematic in establishing an accurate basis for research design. Method #3: Statistical analyses - univariate and multivariate analysis, Path analysis, and Shapiro-Wilk test - requesting additional peer review to further assess the appropriateness of these statistical tools would be helpful, given that the data gathered using the sampling method specified above is not ideal to answer this research question.

Are the conclusions supported by the data? Highly unsupported Some parts of the conclusion are overreaching and not reflected in the results. Conclusions drawn from the results rely on self-reported data of toxoplasma infection rather than a more objective measure, such as laboratory test results, introducing the risk of false-reporting of infection status (and it is not standard/best practice). Although the study uses path analysis to control for factors such as age and sex, there are other unaccounted confounding factors that affect stress and anxiety including the study taking place during the COVID-19 pandemic, a time of high stress and anxiety. The conclusion states that toxoplasmosis impacts physical health, which leads to increased stress and anxiety, thereby negatively affecting their cognitive performance is overreaching as the data relies on cross-sectional data, making it difficult to infer this causal and temporal relationship. Furthermore, the p-values found in the results of the study are varied as there are p-values greater than 0.05, making the results not statistically significant.

Are the data presentations, including visualizations, well-suited to represent the data? Neither appropriate and clear nor inappropriate and unclear They follow some elements of accessibility best practices and communicate the results and patterns. However, the visual representations chosen are not the best or clearest ones to use for this kind of data; for example, the box plots used in figure 2 all appear very similar, therefore it is hard to know what type of data they are trying to illustrate; the caption does not go into detail, or note whether there is any significance; a different visual that can ascertain differences (perhaps a bar graph, or a descriptive table) may be more helpful.

How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research? Very unclearly The findings of the study are highly unsupported by the methods and results, with the significance overstated. The authors state that age, sex, and Borrelia infection correlate to increased Toxoplasma incidence. Additionally, they claim that anxiety and stress are significantly heightened in a Toxoplasma infection. This then is connected to the Stress-Coping hypothesis, as the authors conclude that physical health is significantly impacted by Toxoplasma, which leads to increased stress and anxiety. In the discussion, however, the limitations of the study are mostly overlooked in consideration of the validity of the findings. Moreover, the discussion confirms the findings as in alignment with previous research in this area; however, many of these studies were done by authors of the present study. The authors fail to address the following gaps in their research methodology and conclusions, and need to apprise in their manuscript why the following non-best practices were utilized: - Self-reporting laboratory test of toxoplasmosis and borreliosis were not confirmed by serological testing in this study - The study took place during the pandemic, where there was already heightened stress and anxiety; they did not account for this in data analysis - The study utilized self-selection of participants through online/social media recruiting rather than more balanced recruitment through a clinical sample

Is the preprint likely to advance academic knowledge? Not likely The study provides potential insight into self-reported toxoplasma status and one's health, which is worth exploring in a qualitative sense to better understand this population. However, the findings of this study are concerning in that the methodology is not appropriate with misleading reports using overreaching conclusions, which is a potentially harmful addition to the scientific misinformation regarding latent toxoplasmosis. The authors continuously allude to toxoplasma infection and its correlation to self-reported anxiety, though the status of infection is not validated, and the Stress-Coping hypothesis is mired in conflict of interest as it is self-cited and created by the same authors that are looking to validate it.

Would it benefit from language editing? Yes There were minor grammatical errors, but there are complex sentences as well as redundant information that could be simplified to improve reader clarity. For example, the complex sentence "The public health impact of toxoplasmosis on the whole population could be substantial. On average, about one-third of the population is infected with toxoplasmosis. Given that its prevalence increases with age, it is likely that more than half of the population in older age groups are infected. " can be simplified to "The public health impact of toxoplasmosis could be significant, as approximately one-third of the population is infected on average. Since the infection rate increases with age, it's likely that more than half of older adults are affected." as the term "population" is reduced.

Would you recommend this preprint to others? No, it's of low quality or is majorly flawed

Is it ready for attention from an editor, publisher or broader audience? No, it needs a major revision The authors could adjust their claims to reflect the findings, which is that self-reported status of toxoplasma infection could be correlated with higher self-reported anxiety. Additionally, the authors would need to find other evidence in literature that may be supportive of their initial claims and hypotheses as the paper is over-reliant on self citations. However, as the paper stands, the claims are unsupported with their findings and wrought with issues such as significant conflict of interest and misinformation.

Competing interests

The authors declare that they have no competing interests.

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