Epigenetic Manipulation of Psychiatric Behavioral Disorders Induced by Toxoplasma gondii.

Toxoplasma gondii is known to have a complex life cycle and infect almost all kinds of warm-blooded animals around the world. The brain of the host could be persistently infected by cerebral cysts, and a variety of psychiatric disorders such as schizophrenia and suicide have been reported to be related with latent toxoplasmosis. The infected animals showed fear reduction and a tendency to be preyed upon. However, the mechanism of this "parasites manipulation" effects have not been elucidated. Here, we reviewed the recent infection prevalence of toxoplasmosis and the evidence of mental and behavioral disorders induced by T. gondii and discussed the related physiological basis including dopamine dysregulation and gamma-aminobutyric acid (GABA) pathway and the controversial opinion of the necessity for cerebral cysts existence. Based on the recent advances, we speculated that the neuroendocrine programs and neurotransmitter imbalance may play a key role in this process. Simultaneously, studies in the evaluation of the expression pattern of related genes, long noncoding RNAs (lncRNAs), and mRNAs of the host provides a new point for understanding the mechanism of neurotransmitter dysfunction induced by parasite manipulation. Therefore, we summarized the animal models, T. gondii strains, and behavioral tests used in the related epigenetic studies and the responsible epigenetic processes; pinpointed opportunities and challenges in future research including the causality evidence of human psychiatric disorders, the statistical analysis for rodent-infected host to be more vulnerable preyed upon; and identified responsible genes and drug targets through epigenetics.

An investigation into the association between latent toxoplasmosis and suicide attempts among adolescents.

INTRODUCTION: There have been several studies investigating the association between Toxoplasma gondii seropositivity and psychiatric disorders although there is insufficient data on causality. Suicide, depression, and anxiety disorders have been especially investigated in this regard. In this study, we aimed to investigate whether there is any causal association between Toxoplasma gondii seropositivity and suicide attempts in adolescents. METHODOLOGY: This is a case-control study conducted between January and December 2019. A total of 27 adolescents who had attempted suicide and were aged between 12 and 18 years were included in the study. 26 age and sex ratio matched healthy volunteers were taken as the control group. A possible association between suicide attempts and Toxoplasma gondii serology (IgM and IgG) was investigated.. RESULTS: The suicide attempt group consisted of 17 females and 10 males. The mean age was 15.9 ± 1.4 (13.5-17.9) years. Toxoplasma gondii IgG seropositivity was 3.7% (1/27) in the suicide attempt group and 3.8% (1/26) in the control group. There was no significant association between the suicide attempt group and the control group in terms of the presence of Toxoplasma gondii IgG antibodies (p > 0.05). CONCLUSION: Our study is one of the few studies examining the association between Toxoplasma gondii seropositivity and suicide attempts in adolescents yet we did not find any significant association. Further evidence is needed to clarify this controversial issue.

Toxoplasma gondii: AnUnderestimated Threat?

Traditionally, the protozoan parasite Toxoplasma gondii has been thought of as relevant to public health primarily within the context of congenital toxoplasmosis or postnatally acquired disease in immunocompromised patients. However, latent T.gondii infection has been increasingly associated with a wide variety of neuropsychiatric disorders and, more recently, causal frameworks for these epidemiological associations have been proposed. We present assimilated evidence on the associations between T.gondii and various human neuropsychiatric disorders and outline how these may be explained within a unifying causal framework. We argue that the occult effects of latent T.gondii infection likely outweigh the recognised overt morbidity caused by toxoplasmosis, substantially raising the public health importance of this parasite.

Infection with Toxoplasma gondii increases the risk of psychiatric disorders in Taiwan: a nationwide population-based cohort study.

This study aimed to evaluate associations between toxoplasmosis and psychiatric disorders in Taiwan based on the National Health Insurance Research Database, Taiwan (1997-2013). Patients newly diagnosed with toxoplasmosis formed the case group (n = 259), and the control group included propensity-score matched patients without toxoplasmosis (n = 1036). The primary outcome was incidence of psychiatric disorders. Cox proportional hazards regression and stratified analyses were performed to examine risk of developing specific psychiatric disorders between patients with and without toxoplasmosis. Patients with toxoplasmosis had significantly higher incidence of psychiatric disorders than those without toxoplasmosis (P = 0.016). A significant difference was found in numbers of psychiatric disorders between the two groups during 14 years of follow-up (log-rank P < 0.001). Those with toxoplasmosis had significantly higher risk of bipolar disorder [adjusted hazard ratio (aHR = 3.60, 95% confidence interval (CI) = 2.07, 7.26), depression (aHR = 4.94, 95% CI = 2.15, 11.80) and anxiety (aHR = 5.36, 95% CI = 2.98, 25.88), but no significant between-group differences were found for schizophrenia and other psychiatric disorders. In conclusion, the present nationwide population-based analysis revealed that Toxoplasma gondii infection in Taiwan significantly increases the risk for developing bipolar disorder, depression and anxiety, but not for schizophrenia and other psychiatric disorders.

Neurocognitive and neuropsychiatric effects of toxocariasis.

Caused by the neuroinvasive nematodes Toxocara canis and Toxocara cati, human toxocariasis has a worldwide distribution with seroprevalence in humans associated with low socioeconomic status and low educational attainment. Third-stage Toxocara larvae can invade human tissues, including the brain and spine, where they can result in encephalitis, meningitis, and inflammation. Toxocara infection in animal models has been associated with cognitive and behavioural changes. In humans, preliminary cross-sectional research suggests that Toxocara seropositivity is associated with worse cognitive function in children and adults. Additional preliminary cross-sectional findings suggest associations between Toxocara seropositivity and neuropsychiatric function, including schizophrenia and neurologic conditions such as epilepsy. Given the widespread distribution of human toxocariasis and early evidence suggesting that it can be associated with cognitive and neuropsychiatric function in humans, additional research regarding the effects of toxocariasis on the human brain is required.

Toxoplasma-induced Behavioral Changes: An Aspecific Consequence of Neuroinflammation.

A key strategy that many parasites use to facilitate transmission involves behavioral modification of their hosts. Toxoplasma gondii has been taken as an example for this strategy. A recent study by Boillat et al. reported that attraction to predator odor following Toxoplasma infection is not specific to felines.

Infection with Trichomonas vaginalis increases the risk of psychiatric disorders in women: a nationwide population-based cohort study.

BACKGROUND: Trichomonas vaginalis is a protozoan parasite that causes trichomoniasis and annually infects approximately 276 million people worldwide. We observed an ambiguously higher probability of trichomoniasis in patients from the psychiatric department of Tri-Service General Hospital. Herein, we aimed to investigate the association between trichomoniasis and the risk of developing psychiatric disorders. METHODS: The nationwide population-based study utilized the database of the National Health Insurance (NHI) programme in Taiwan. A total of 46,865 subjects were enrolled in this study from 2000-2013, comprising 9373 study subjects with trichomoniasis and 37,492 subjects without trichomoniasis as the control group. Cox proportional hazards regression analysis was performed to calculate the hazard ratio (HR) of psychiatric disorders during the 14 years of follow-up. RESULTS: Of the study subjects with trichomoniasis, 875 (9.34%) developed psychiatric disorders compared with 1988 (5.30%) in the control group (P < 0.001). The adjusted hazard ratio (aHR) of overall psychiatric disorders in the study subjects was 1.644 (95% confidence interval, CI: 1.514-1.766; P < 0.001). More specifically, the study subjects had a higher risk for developing an individual psychiatric disorder, including depression, anxiety, bipolar disorder, schizophrenia and substance abuse. Although metronidazole treatment reduced the risk for developing several subgroups of psychiatric disorders, significant reduction was detected for depression only. Furthermore, refractory trichomoniasis (trichomoniasis visits ≥ 2) enhanced the risk of psychiatric disorders. CONCLUSIONS: We show herein that T. vaginalis infection increases the overall risk for psychiatric disorders. The novel role of T. vaginalis in developing psychiatric disorders deserves more attention, and the control of such a neglected pathogen is of urgent public health importance.

From inflammatory reactions to neurotransmitter changes: Implications for understanding the neurobehavioral changes in mice chronically infected with Toxoplasma gondii.

Toxoplasma gondii is a protozoan parasite that can cause a latent infection in the central nervous system, leading to neurobehavioral abnormalities in the host. However, the mechanism underlying these changes remains relatively unexplored. In this study, we detected behavioral changes, pathological injury, secretion of neurotransmitters and related signal pathway in mice infected by T. gondii using behavioral test, histopathology, immunofluorescence staining, western blotting, HPLC and real time PCR. Mice showed neurobehavioral disturbances two months after infection with T. gondii. Histopathology revealed the activation of astrocytes and microglia, apoptosis of neurons and decreases in synapses in the brain of infected mice. Excessive secretion of cytokines and chemokines was detected in the brains of mice infected by T. gondii compared to uninfected mice. Furthermore, T. gondii infection led to abnormalities in neurotransmitters and the activation of NF-κB and dopamine (DA) signaling pathways in the infected mice. In conclusion, excessive activation of the inflammation in the brain could induce neuronal apoptosis in mice chronically infected with T. gondii. Dysregulation of the dopaminergic neurotransmitter could provide an explanation of neurobehavioral disorders in infected hosts.

Toxoplasmosis: A pathway to neuropsychiatric disorders.

Toxoplasma gondii is an obligate intracellular parasite that resides, in a latent form, in the human central nervous system. Infection with Toxoplasma drastically alters the behaviour of rodents and is associated with the incidence of specific neuropsychiatric conditions in humans. But the question remains: how does this pervasive human pathogen alter behaviour of the mammalian host? This fundamental question is receiving increasing attention as it has far reaching public health implications for a parasite that is very common in human populations. Our current understanding centres on neuronal changes that are elicited directly by this intracellular parasite versus indirect changes that occur due to activation of the immune system within the CNS, or a combination of both. In this review, we explore the interactions between Toxoplasma and its host, the proposed mechanisms and consequences on neuronal function and mental health, and discuss Toxoplasma infection as a public health issue.

Neurological complications in patients with Plasmodium vivax malaria from Karachi, Pakistan.

BACKGROUND: Malaria remains an endemic disease in Pakistan with an estimated healthcare burden of 1.6 million cases annually, with Plasmodium vivax accounting for 67% of reported cases. P. vivax is the most common species causing malaria outside of Africa, with approximately 13.8 million reported cases worldwide. METHOD: We report a series of P. vivax cases with cerebral involvement that presented at Aga Khan University Hospital, Karachi, Pakistan. RESULTS: The majority of the patients presented with high-grade fever accompanied by projectile vomiting and abnormal behaviour, seizures, shock and unconsciousness. Seven of 801 patients with P. vivax monoinfection presented or developed cerebral complications. P. vivax infections were diagnosed based on peripheral smears and rapid diagnostic testing. CONCLUSION: P. vivax infection can lead to severe complications, although not with the frequency of Plasmodium falciparum infection. Current cases highlight an increasing trend of cerebral complications caused by P. vivax.

Toxoplasma gondii infection and behavioral outcomes in humans: a systematic review.

Studies suggest that the protozoan Toxoplasma gondii can disturb human behavior. This study aimed to systematically review the scientific literature on the possible associations between Toxoplasma gondii infection and neurobehavioral abnormalities in humans. We reviewed and summarized the studies published since 1990. The descriptors used were related to T. gondii infection and behavioral outcomes in humans; the main databases of the medical literature were accessed. The results of eight original articles published between 1994 and 2016 were evaluated and described. The most common serological method was the enzyme immunoassay. Most of the researchers used validated instruments for behavioral evaluation. Seven studies reported some association between the prevalence of anti-T. gondii antibodies and some altered behavioral aspects in adult humans; these studies focused on adult population in Europe and the USA. The most reported behavioral deviations are related to greater impulsivity and aggressiveness. There are very few studies on this subject, which present some limitations for inference and conclusions: most were cross-sectional studies, with a small sample size and in similar populations. Investigations with a larger sample size of different population groups should be performed to evaluate multiple factors.

Intestinal worms eating neuropsychiatric disorders? Apparently so.

A number of factors in Western society, including inflammatory diets, sedentary lifestyles, vitamin D deficiency and chronic psychological stress, are known to induce inflammation and to be associated with neuropsychiatric disorders. One factor that is emerging as a potential inflammation inducing factor is biota depletion, or loss of biodiversity from the ecosystem of the human body as a result of industrialization. Originally known as the "hygiene hypothesis", biota alteration theory describes the effects of biota alteration on the human immune system. Work on this topic has pinpointed depletion of helminths as a key loss to the body's ecosystem in Western society, and suggests that some exposure to helminths, ubiquitous prior to the modern era, may be necessary for normal immune system development. Socio-medical studies of humans "self-treating" with helminths as well as limited studies in animal models strongly suggest that helminth therapy may be a productive approach toward treating a range of neuropsychiatric disorders, including chronic fatigue, migraine headaches, depression and anxiety disorders. However, helminth therapy faces some daunting hurdles, including the lack of a financial incentive for development, despite a tremendous potential market for the organisms. It is argued that benevolent donation for early trials as well as changes in regulatory policy to accommodate helminth therapy may be important for the field to develop. It is hoped that future success with some high-profile trials can propel the field, now dominated more by self-treatment than by clinical trials, forward into the main stream of medicine.

Engendered Responses to, and Interventions for, Shame in Dissociative Disorders: A Survey and Experimental Investigation.

This study examined shame and responses to it in adult dissociative disorder (DD; n = 24) and comparison psychiatric (n = 14) samples. To investigate how helpful different therapeutic responses are after shame disclosures in therapy, participants heard two vignettes from "mock" patients disclosing a) shame and b) surprise. Participants rated the helpfulness of five potential responses. Interventions covered withdrawing from the affect (withdrawal focused) to feeling it (feeling focused), with other interventions on cognitions (cognitive focused), management strategies (management focused), and previous experiences (history focused). The DD sample reported higher characterological and bodily shame, and more shame avoidance and withdrawal. There was no difference across groups for intervention ratings. For shame, interventions focused on feelings, cognitions, or previous shame experiences were deemed most helpful, but this was qualified by experiencing dissociation while hearing the script, where the history intervention was reported less helpful. Exposure to shame while monitoring dissociation should accompany therapy for DDs.

Leishmania amazonensis infection induces behavioral alterations and modulates cytokine and neurotrophin production in the murine cerebral cortex.

Neurological symptoms have been associated with Leishmania infection, however little is known about how the nervous system is affected in leishmaniasis. This work aimed to analyze parasitic load, production of cytokines/neurotrophins in the prefrontal cortex and behavioral changes in BALB/c mice infected with Leishmania amazonensis. At 2 and 4months post-infection, infected mice showed a decrease in IFN-γ, IL-1, IL-6, IL-4, IL-10 cytokines and BDNF and NGF neurotrophins in prefrontal cortex associated with increased anxiety behavior. Parasite DNA was found in brain of all animals at 4months post-infection, when the levels of IBA-1 (activated macrophage/microglia marker) and TNF-α was increased in the prefrontal cortex. However TNF-α returned to normal levels at 6months post-infection suggesting a neuroprotective mechanism.

Under seize: neurocysticercosis in an immigrant woman and review of a growing neglected disease.

Neurocysticercosis (NCC) is a significantly neglected tropical disease and, with increasing globalisation, a notable emerging infection in the developed world. We describe a case of ventricular NCC in a 22-year-old Mexican-American woman with a history of seizures, who presented with 2 weeks of headaches and intermittent fevers progressing to altered mental status and vomiting. Initial imaging revealed a cystic mass at the posteroinferior aspect of the third ventricle superior to the aqueduct of Sylvius, calcifications scattered throughout the parenchyma, and enlargement of the lateral and third ventricles. Initial laboratories were unrevealing and serum investigations for Taenia solium antibody were negative, but T. solium antibody was subsequently returned positive from cerebrospinal fluid. This case highlights important issues regarding the clinical presentation, diagnostic evaluation and treatment of NCC relevant to providers not only in areas with endemic disease but, importantly, in locales with diverse immigrant populations.

Prevalence of intestinal parasites among patients of a Ghanaian psychiatry hospital.

BACKGROUND: Neglected tropical diseases are of major concern to sub-Saharan African countries. Though efforts to monitor the prevalence and control are in place, these are mostly restricted to groups within the population. This study was performed to determine the prevalence among patients of a Ghanaian psychiatric hospital and find out whether there is a reason for active monitoring in this population. METHODS: A cross-sectional study was performed to determine the prevalence of intestinal parasites among patients of a Ghanaian psychiatric hospital. Stool samples were collected and analyzed in addition to data. RESULTS: Of the 111 patients studied, asymptomatic carriage of parasites was 13.5 % and was higher in males (18.8 %) than in females (4.8 %). Carriage of parasites decreased with age but increase with duration of admission. CONCLUSION: This is the first report of parasitic pathogens among patients of a psychiatric institution in Ghana. The data shows that there are risks of transmission of infectious diseases via the oral route hence, the need for regular monitoring and intervention is emphasized.

The validity of the multi-informant approach to assessing child and adolescent mental health.

Child and adolescent patients may display mental health concerns within some contexts and not others (e.g., home vs. school). Thus, understanding the specific contexts in which patients display concerns may assist mental health professionals in tailoring treatments to patients' needs. Consequently, clinical assessments often include reports from multiple informants who vary in the contexts in which they observe patients' behavior (e.g., patients, parents, teachers). Previous meta-analyses indicate that informants' reports correlate at low-to-moderate magnitudes. However, is it valid to interpret low correspondence among reports as indicating that patients display concerns in some contexts and not others? We meta-analyzed 341 studies published between 1989 and 2014 that reported cross-informant correspondence estimates, and observed low-to-moderate correspondence (mean internalizing: r = .25; mean externalizing: r = .30; mean overall: r = .28). Informant pair, mental health domain, and measurement method moderated magnitudes of correspondence. These robust findings have informed the development of concepts for interpreting multi-informant assessments, allowing researchers to draw specific predictions about the incremental and construct validity of these assessments. In turn, we critically evaluated research on the incremental and construct validity of the multi-informant approach to clinical child and adolescent assessment. In so doing, we identify crucial gaps in knowledge for future research, and provide recommendations for "best practices" in using and interpreting multi-informant assessments in clinical work and research. This article has important implications for developing personalized approaches to clinical assessment, with the goal of informing techniques for tailoring treatments to target the specific contexts where patients display concerns. (PsycINFO Database Record

[The classifying criteria for the evaluation of the severity of the harm to health in the case of development of psychic health problems associated with HIV infection].

The objective of the present study was to develop the classifying criteria for the evaluation of the severity of the harm inflicted to human health that resulted in the development of mental disorders in response to subsequent HIV infection. The analysis of the available information about a rise in the prevalence of HIV infection and the high frequency of associated psychic disorders among the infected subjects gave evidence of the importance of this problem and the necessity to improve the existing statutory and legislative basis underlying the regulation of activities in this field. The scientifically substantiated criteria for the expert assessment of the severity of the harm to human health are proposed taking into consideration the clinical manifestations of psychic disorders.

Toxoplasma gondii exposure in patients suffering from mental and behavioral disorders due to psychoactive substance use.

BACKGROUND: Toxoplasma gondii infection has been associated with psychiatric diseases. However, there is no information about the link between this infection and patients with mental and behavioral disorders due to psychoactive substance use. METHODS: We performed a case-control study with 149 psychiatric patients suffering from mental and behavioral disorders due to psychoactive substance use and 149 age- and gender-matched control subjects of the general population. We searched for anti-T. gondii IgG and IgM antibodies in the sera of participants by means of commercially available enzyme-linked immunoassays. Seroprevalence association with socio-demographic, clinical and behavioral characteristics in psychiatric patients was also investigated. RESULTS: Anti-T. gondii IgG antibodies were present in 15 (10.1%) of 149 cases and in 14 (9.4%) of 149 controls (P=1.0). Anti-T. gondii IgM antibodies were found in 11 (7.4%) of the 149 cases and in 16 (10.7%) of the 149 controls (P=0.31). No association of T. gondii exposure with socio-demographic characteristics of patients was found. Multivariate analysis of clinical and behavioral characteristics of cases showed that T. gondii seropositivity was positively associated with consumption of opossum meat (OR=10.78; 95% CI: 2.16-53.81; P=0.003) and soil flooring at home (OR=11.15; 95% CI: 1.58-78.92; P=0.01), and negatively associated with suicidal ideation (OR=0.17; 95% CI: 0.05-0.64; P=0.008). CONCLUSIONS: Mental and behavioral disorders due to psychoactive substance use do not appear to represent an increased risk for T. gondii exposure. This is the first report of a positive association of T. gondii exposure with consumption of opossum meat. Further studies to elucidate the role of T. gondii infection in suicidal ideation and behavior are needed to develop optimal strategies for the prevention of infection with T. gondii.