Toxoplasmosis in Treatment-Resistant Obsessive-Compulsive Disorder Patients.

BACKGROUND AND OBJECTIVES: The current study was done to evaluate the relationship between T. gondii and obsessive-compulsive disorder (OCD) as well as prevalence rate of toxoplasmosis in treatment-resistant patients with OCD in comparison with treatment-sensitive patients with OCD. METHODS: A total of 180 subjects were selected, including 90 patients with OCD and 90 control participants. Immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies against T. gondii were measured by the enzyme-linked immunosorbent assay (ELISA) technique. Detection of acute and chronic toxoplasmosis was carried out using the ELISA IgG avidity. In addition, the presence of this parasite in blood was detected using the nested-polymerase chain reaction (PCR) method. RESULTS: Regarding T. gondii IgG antibodies 42 (46.7%) and 17 (18.9%) cases were detected in the patients and controls, respectively (P = 0.000). Also, 16 (17.8%) and 5 (5.6%) cases were positive for B1 gene in patients and controls, respectively (P = 0.018). The antibodies were found to be related to risk of OCD [OR (95% CI) = 3.71 (1.88-7.30); P < 0.001]. Moreover, out of 90 patients, 35 and 55 cases were resistant and sensitive to treatment, respectively, so that 24 (68.6%) out of 35 and 18 (32.7%) out of 55 were positive for the antibodies (P = 0.01) as well as 11 (31.4%) out of 35 and 5 (9.1%) out of 55 were positive for B1 gene (P = 0.010). The antibodies were also associated with risk of resistance to treatment in patients with OCD [OR (95% CI) = 3.81 (1.42-10.17); P = 0.008]. CONCLUSION: Our findings showed that toxoplasmosis was more frequent in patients with OCD than the control group. In addition, prevalence rate of toxoplasmosis in treatment-resistant patients with OCD was significantly more than that in treatment-sensitive patients with OCD.

Relationship between toxoplasmosis and obsessive compulsive disorder: A systematic review and meta-analysis.

BACKGROUND: A few studies investigated the relationship between toxoplasmosis and mental disorders, such as obsessive compulsive disorder (OCD). However, the specific nature of the association between Toxoplasma gondii (T. gondii) infection and OCD is not yet clear. The aim of this study was to collect information on the relationship between OCD and toxoplasmosis and assess whether patients with toxoplasmosis are prone to OCD. METHODS: For the purpose of this study, 6 major electronic databases and the Internet search engine Google Scholar were searched for the published articles up to July 30th, 2018 with no restriction of language. The inverse variance method and the random effect model were used to combine the data. The values of odds ratio (OR) were estimated at 95% confidence interval (CI). RESULTS: A total of 9 case-control and 3 cross-sectional studies were included in our systematic review. However, 11 of these 12 articles were entered into the meta-analysis containing 9873 participants, out of whom 389 were with OCD (25.96% positive for toxoplasmosis) and 9484 were without OCD (17.12% positive for toxoplasmosis). The estimation of the random effect model indicated a significant common OR of 1.96 [95% CI: 1.32-2.90]. CONCLUSION: This systematic review and meta-analysis revealed that toxoplasmosis could be as an associated factor for OCD (OR = 1.96). However, further prospective investigations are highly recommended to illuminate the underlying pathophysiological mechanisms of T. gondii infection in OCD and to better investigate the relationship between OCD and T. gondii infection.

Toxoplasma-infected subjects report an Obsessive-Compulsive Disorder diagnosis more often and score higher in Obsessive-Compulsive Inventory.

BACKGROUND: Latent toxoplasmosis, the life-long presence of dormant stages of Toxoplasma in immunoprivileged organs and of anamnestic IgG antibodies in blood, affects about 30% of humans. Infected subjects have an increased incidence of various disorders, including schizophrenia. Several studies, as well as the character of toxoplasmosis-associated disturbance of neurotransmitters, suggest that toxoplasmosis could also play an etiological role in Obsessive-Compulsive Disorder (OCD). METHODS: The aim of the present cross-sectional study performed on a population of 7471 volunteers was to confirm the association between toxoplasmosis and OCD, and toxoplasmosis and psychological symptoms of OCD estimated by the standard Obsessive-Compulsive Inventory-Revised (OCI-R). RESULTS: Incidence of OCD was 2.18% (n=39) in men and 2.28% (n=83) in women. Subjects with toxoplasmosis had about a 2.5 times higher odds of OCD and about a 2.7 times higher odds of learning disabilities. The incidence of 18 other neuropsychiatric disorders did not differ between Toxoplasma-infected and Toxoplasma-free subjects. The infected subjects, even the OCD-free subjects, scored higher on the OCI-R. LIMITATIONS: Examined subjects provided the information about their toxoplasmosis and OCD statuses themselves, which could result in underrating the strength of observed associations. CONCLUSIONS: The results confirmed earlier reports of the association between toxoplasmosis and OCD. They also support recent claims that latent toxoplasmosis is in fact a serious disease with many impacts on quality of life of patients.

Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis.

OBJECTIVE: To perform a meta-analysis on studies reporting prevalence of Toxoplasma gondii (T. gondii) infection in any psychiatric disorder compared with healthy controls. Our secondary objective was to analyze factors possibly moderating heterogeneity. METHOD: A systematic search was performed to identify studies into T. gondii infection for all major psychiatric disorders versus healthy controls. Methodological quality, publication bias, and possible moderators were assessed. RESULTS: A total of 2866 citations were retrieved and 50 studies finally included. Significant odds ratios (ORs) with IgG antibodies were found in schizophrenia (OR 1.81, P < 0.00001), bipolar disorder (OR 1.52, P = 0.02), obsessive-compulsive disorder (OR 3.4, P < 0.001), and addiction (OR 1.91, P < 0.00001), but not for major depression (OR 1.21, P = 0.28). Exploration of the association between T. gondii and schizophrenia yielded a significant effect of seropositivity before onset and serointensity, but not IgM antibodies or gender. The amplitude of the OR was influenced by region and general seroprevalence. Moderators together accounted for 56% of the observed variance in study effects. After controlling for publication bias, the adjusted OR (1.43) in schizophrenia remained significant. CONCLUSION: These findings suggest that T. gondii infection is associated with several psychiatric disorders and that in schizophrenia reactivation of latent T. gondii infection may occur.

[Toxoplasma gondii: a potential role in the genesis of psychiatric disorders]. / Toxoplasma gondii : un rôle potentiel dans la genèse de troubles psychiatriques. Une revue systématique de la littérature.

INTRODUCTION: Toxoplasma gondii is the most common protozoan parasite in developed nations. Up to 43% of the French population may be infected, depending on eating habits and exposure to cats, and almost one third of the world human's population may be infected. Two types of infection have been described: a congenital form and an acquired form. Although the medical profession treats these latent cases as asymptomatic and clinically unimportant, results of animal studies and recent studies of personality profiles, behavior, and psychomotor performance have led to reconsider this assumption. PRECLINICAL DATA: Among rats: parasite cysts are more abundant in amygdalar structures than those found in other regions of the brain. Infection does not influence locomotion, anxiety, hippocampal-dependent learning, fear conditioning (or its extinction) and neophobia in rats. Rats' natural predator is the cat, which is also T. gondii's reservoir. Naturally, rats have an aversion to cat urine, but the parasite suppresses this aversion in rats, thus influencing the infection cycle. Tachyzoites may invade different types of nervous cells, such as neurons, astrocytes and microglial cells in the brain, and Purkinje cells in cerebellum. Intracellular tachyzoites manipulate several signs for transduction mechanisms involved in apoptosis, antimicrobial effectors functions, and immune cell maturation. Dopamine levels are 14% higher in mice with chronic infections. These neurochemical changes may be factors contributing to mental and motor abnormalities that accompany or follow toxoplasmosis in rodents and possibly in humans. Moreover, the antipsychotic haloperidol and the mood stabilizer valproic acid most effectively inhibit Toxoplasma growth in vitro with synergistic activity. CLINICAL DATA: The effects of the parasite are not due to the manipulation in an evolutionary sense but merely due to neuropathological or neuroimmunological effects of the parasite's presence. Toxoplasmosis and schizophrenia: epidemiological studies point to a role for toxoplasmosis in schizophrenia's etiology, probably during pregnancy and early life, this association being congruent with studies in animal models indicating that animal exposures of the developing brain to infectious agents or immune modulating agents can be associated with behavioral changes that do not appear until the animal reaches full maturity. Psychiatric patients have increased rates of toxoplasmic antibodies, the differences between cases and controls being greatest in individuals who are assayed near the time of the onset of their symptoms. The increase of dopamine in the brain of infected subjects can represent the missing link between toxoplasmosis and schizophrenia. Toxoplasmosis and Obsessive Compulsive Disorder (OCD): the seropositivity rate for anti-T. gondii IgG antibodies among OCD patients is found to be significantly higher than the rate in healthy volunteers. Infection of basal ganglia may be implicated in the pathogenesis of OCD among Toxoplasma seropositive subjects. Toxoplasmosis and personality: infected men appear to be more dogmatic, less confident, more jealous, more cautious, less impulsive and more orderly than others. Conversely, infected women seem warmest, more conscientious, more insecure, more sanctimonious and more persistent than others. It is possible that differences in the level of testosterone may be responsible for the observed behavioral differences between Toxoplasma-infected and Toxoplasma-free subjects. CONCLUSION: In the future two major avenues for research seem essential. On one hand, prospective studies and research efforts must still be carried out to understand the mechanisms by which the parasite induces these psychiatric disorders. On the other hand, it has not yet been demonstrated that patients with positive toxoplasmic serology may better respond to haloperidol's or valproic acid's antiparasitic activity. These results may appear as a major issue in the drug's prescribing choices and explain variability in response to the treatment of patients with schizophrenia that is not explained by the genetic polymorphism.

Is there any role of Toxoplasma gondii in the etiology of obsessive-compulsive disorder?

Obsessive-compulsive disorder (OCD) is a common psychiatric illness. Although the aetiology of OCD is still unknown, the family-genetic data show that familial forms of OCD may be associated with a specific genetic susceptibility. Recent investigations have associated development of OCD with infectious illness. Toxoplasmic encephalitis (TE) is a common presentation of Toxoplasma gondii infection of the central nervous system (CNS). The most commonly affected CNS region in TE is the cerebral hemisphere, followed by the basal ganglia, cerebellum and brain stem. The basal ganglia has been implicated in the development of OCD. Therefore, in this study, it was aimed to investigate a possible association between Toxoplasma infection and OCD. We selected 42 patients with OCD and 100 healthy volunteers, and investigated the sero-positivity rate for anti-Toxoplasma IgG antibodies by Enzyme Linked Immunosorbent Assay (ELISA). The sero-positivity rate for anti-T. gondii IgG antibodies among OCD patients (47.62%) was found to be significantly higher than the rate in healthy volunteers (19%). This is the first report to examine a potential association between Toxoplasma infection and OCD. The main finding of the present study is an increased level of IgG antibodies to T. gondii in OCD patients when compared with the level in healthy controls. There might be a causal relationship between chronic toxoplasmosis and the aetiology of OCD.

A combined marble burying-locomotor activity test in mice: a practical screening test with sensitivity to different classes of anxiolytics and antidepressants.

Over the last decades, the inhibition of spontaneous burying of glass marbles by mice has been used as an index of anxiolytic drug action in the so-called marble burying test. Indeed, acute administration of rapid-onset (e.g. diazepam) and slow-onset (e.g. fluoxetine) anxiolytics inhibit marble burying. However, non-anxiolytic compounds such as classical antipsychotics also reduce marble burying thus suggesting that the predictive validity of this procedure for anxiety may be limited. In the present study, after having selected a strain of mice (C57BL/6J) that showed spontaneous avoidance of glass marbles, we tried to improve the predictive validity of the marble burying test for anxiety by measuring locomotor activity during the marble burying test and--if needed--in control experiments by using a videotracking system. Twenty-four reference compounds were tested including anxiolytics, anxiogenics, antidepressants, antipsychotics and other classes. By comparing marble burying scores with locomotor measures, we found that, based on our criteria, most of the anxiolytics and antidepressants selectively inhibited marble burying in contrast to most of the other compounds (e.g. haloperidol, morphine). Two putative anxiolytics, i.e. the nociceptin orphanin FQ peptide receptor agonist Ro 64-6198 and the metabotropic glutamate 5 receptor antagonist 2-methyl-6-(phenylethynyl)pyridine, also showed a selective profile. We propose this modified procedure, requiring only a limited number of animals, as a valuable screening test for the detection of compounds having anxiolytic effects.

Performance of clinician versus self-report measures to identify obsessive-compulsive disorder in children and adolescents.

OBJECTIVE: The aim of this study was to study agreement between clinician-rated measures and self-report measures previously used in epidemiologic studies to identify obsessive-compulsive disorder (OCD) in youth and to determine the adequacy of self-report measures as screening instruments. METHOD: Leyton Obsessional Inventory-Child Version (LOI-CV) survey form self-report and Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) clinician-report measures were compared in a sample of 81 OCD-affected youths diagnosed using structured diagnostic interviews and the best-estimate method. Sensitivities and agreement between tests are determined for different cutoff scores. RESULTS: The LOI-CV survey form total (item+interference) score is correlated with KSADS-E OCD severity (r=0.37, p=0.001) but not clinician-rated GAF scores (r=-0.18, p=0.12). LOI-CV survey form sensitivities at cutoff scores of 15, 20, 25, and 30 are 55%, 36%, 28%, and 19%, respectively. CY-BOCS scores are correlated with subject-rated interview severity (p<0.001) and clinician-rated GAF scores (por=0.03), but correlate with the CY-BOCS compulsion subscore. CONCLUSIONS: The clinician-rated CY-BOCS measure using parent and child reporting performs superiorly to the subject-rated LOI-CV measure using child reporting to identify pediatric OCD in a clinically referred population. Because self-report measures have been used in epidemiological studies, youth OCD prevalence rates may be higher than previously reported.