Associations between Toxoplasma gondii seropositivity and psychopathological manifestations in schizophrenic patients: A single-center study from Ecuador.

BACKGROUND: Schizophrenia, a complex neuropsychiatric disorder, is believed to be influenced by various factors including environmental exposures. A potential environmental factor is the infection by the obligate intracellular parasitic protozoan, Toxoplasma gondii which affects neurotransmitter levels, which could potentially exacerbate, trigger symptoms of schizophrenia or make them worst. OBJECTIVE: To investigate the association between Toxoplasma gondii seropositivity and psychopathological presentation in persons with schizophrenia in Ecuador. METHODS: This study was conducted at the Neuroscience Institute of Guayaquil, Ecuador. Among 368 inpatients, 104 were selected based on specific inclusion and exclusion criteria. Descriptive statistics captured patient characteristics and mental health outcomes. Logistic regression models estimated the effect of toxoplasmosis on various mental health outcomes, controlling for demographic and health-related variables. RESULTS: 86.5% of participants were seropositive for toxoplasmosis. Toxoplasma-seropositive schizophrenic patients had a lower risk of depression but a significantly higher risk of disorientation. The most prevalent mental health outcomes were Language Impairments (70.2%) and Bizarre Behavior (76.0%). CONCLUSION: Our findings suggest that Toxoplasma gondii seropositivity may have specific effects on mental functions in schizophrenic patients, particularly reducing the risk of depression but increasing the risk of disorientation. Further studies are required to clarify these associations and the potential underlying mechanisms.

Relationship between Toxoplasma gondii seropositivity and schizophrenia in the Lebanese population: potential implication of genetic polymorphism of MMP-9.

BACKGROUND: Toxoplasma multiplication and its persistence into the brain cause a local neuroinflammatory reaction, resulting synthesis of neurotransmitters involved in neurological disorders, especially schizophrenia. The Matrix metallopeptidase 9 (MMP-9) protein can play a major role in this neuroinflammation. It can promote extravasation and migration of infected immune cells into the brain. The objectives of this study are to determine the possible association between schizophrenia and toxoplasmosis and highlight the existence of gene polymorphism encoding MMP-9 protein's in patients presented both schizophrenia and toxoplasmosis. METHODS: A case-control study was conducted on 150 patients with schizophrenia (case group), and 150 healthy persons (control group). Groups were matched with age, gender, and place of residence. The survey was conducted using a questionnaire and a serological profile assay for specific IgG and IgM antibodies against T. gondii. Reverse transcription-polymerase chain reaction (RT-PCR) of gene polymorphism encoding MMP-9 was performed on 83 cases selected randomly. RESULTS: Data show a significant association between toxoplasmosis (IgM+/IgG+ serological profile) and schizophrenia. Significant effects of raw meat consumption and contact with cats have been associated with the occurrence of schizophrenia. RT-PCR shows the presence of muted allele of MMP-9 gene in selected cases whose present T. gondii serological profile IgM+/IgG+ and IgM-/IgG+ respectively. CONCLUSION: Toxoplasmosis may be one of the etiological causes of schizophrenia, and MMP-9 gene polymorphism could be involved in the occurrence mechanism of this pathology following Toxoplasma infection.

Toxoplasmosis and behavioural changes.

Nearly one-third of the planet's population is affected by Toxoplasma gondii infection. In ophthalmology, toxoplasmosis is even considered to be the most common cause of posterior uveitis of infectious origin. Humans are only an intermediate host and T. gondii needs to infect cats for its sexual reproduction. All the elements increasing the risk of predation by the definitive host are then favourable to the parasite. Numerous experimental animal model studies have shown that T. gondii infection is associated with predatory risk behaviours such as an attraction of infected mice to cat urine. Infection with the parasite is associated with a demethylation of the promoters of certain genes in the cerebral amygdala of the intermediate hosts, modifying dopaminergic circuits associated with fear. Similarly, T. gondii has been linked to behavioural changes in humans. Toxoplasma infection is classically associated with the frequency of schizophrenia, suicide attempts or "road rage". A more recent study shows that toxoplasma infection prevalence was a consistent, positive predictor of entrepreneurial activity. Fear of failure would be less important in infected individuals, who are more willing than others to start their own business. These elements shed interesting light on behaviours and their possible relationship with toxoplasmosis, which is generally considered benign in adults.

Lack of circulating toxoplasma gondii DNA in seropositive patients with bipolar or schizophrenia spectrum disorders.

Toxoplasmosis has been previously associated with an increased risk of having Schizophrenia or Bipolar disorder in several epidemiological studies. The aim of this observational, cross-sectional study was to examine the seroprevalence of Toxoplasma infection in a cohort of Italian psychiatric inpatients and to verify the presence of circulating Toxoplasma gondii DNA in the seropositive subjects. Sixty-three patients affected by bipolar or schizoaffective disorders according to DSM-5 criteria were enrolled. The presence of Toxoplasma infection was firstly examined using an indirect serological method (ELFA), and three different direct PCR-based methods were performed to detect circulating DNA in the seropositive patients. The seroprevalence of infection was 28.6%, with a significant association between higher age and the infection status. PCR, nested-PCR and Real-Time PCR revealed no positive samples for Toxoplasma gondii. This result is in contrast with recent data from case-control studies that detected parasite genome in patients with different neuropsychiatric diagnosis without clinical evidence of acute toxoplasmosis. Our findings are to be interpreted with caution, because of the small sample size, the heterogeneity of enrolled patients and the observational nature of the study. Further studies are needed to better define the clinical features correlated to the seropositive status in neuropsychiatric patients.

Seroprevalence and Manifestations of Ocular Toxoplasmosis in Patients with Schizophrenia.

PURPOSE: Recent studies have linked infectious agents such as Toxoplasma gondii to schizophrenia. We investigated the seroprevalence of T. gondii and conducted ophthalmologic examinations in schizophrenia patients and controls to identify lesions suggestive of ocular toxoplasmosis. METHODS: During 2015 and 2016, 34 schizophrenia patients and 85 healthy controls underwent ophthalmologic examination and anti-T. gondii IgG and IgM antibody measurements by chemiluminescence. RESULTS: Schizophrenia patients had a higher prevalence of anti-T. gondii IgG positivity than controls (91.18% [95% confidence interval (CI), 77.04%-96.95%] vs. 70.59% [95% CI, 60.18%-79.21%]; p = 0.017). Anti-T. gondii IgM antibodies (acute form) were not detected in any patient. One (3%) schizophrenic patient and two (2.4%) control patients presented fundoscopic scarring. CONCLUSION: The seropositivity rate was significantly higher among schizophrenia patients than among controls (p = 0.017). There was no association between the presence of fundoscopic scarring and schizophrenia (p = 1.000).

Latent toxoplasmosis and olfactory functions of Rh positive and Rh negative subjects.

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.

Immunoglobulin sub-class distribution in bipolar disorder and schizophrenia: potential relationship with latent Toxoplasma Gondii infection.

BACKGROUND: Immune dysfunction could play a significant role in the pathogenesis of bipolar disorder (BD) and schizophrenia (SZ), conditions with an underlying pro-inflammatory state. Studies on humoral immune responses (which reflects antibody mediated fight against pathogens) in schizophrenia and bipolar disorder are sparse and often providing contradictory results. The aim of this study was to assess humoral immunity in a group of stable bipolar disorder and schizophrenia patients compared to controls by determining total Immunoglobulins and IgG subclasses and to assess their association with latent Toxoplasma gondii and/or CMV infection. METHODS: 334 subjects (124 BD, 75 SZ and 135 Healthy Controls [HC]) were included and tested for humoral immunity by determining the total immunoglobulins (IgG,A and M) and IgG subclasses (IgG1, IgG2, IgG3, IgG4) and their relationship with latent Toxoplasma gondii infection, an established risk factor for BD and SZ. RESULTS: Although lower levels of IgG, IgG1, IgG2, IgG4 and IgA were found among BD as compared to HC and/or SZ, after adjustment for confounding variables, only low levels of IgG and IgG1 in BD remai- ned significant. Strikingly highest levels of antibodies to T. gondii (but not CMV) infection in BD and SZ were associated with lowest levels of IgG3 and IgG4 levels as compared to controls. CONCLUSIONS: Schizophrenia and bipolar disorder patients with latent T. gondii specific infection may be more vulnerable to changes in immuno-inflammatory processes than controls with similar latent infectious state. Simultaneous sequential immunological monitoring both in steady state and active disease phases in the same BD and SZ patients are warranted to understand the role of Toxoplasma gondii latency in these disorders.

Neuroimaging investigations of dorsal stream processing and effects of stimulus synchrony in schizophrenia.

Impairments in auditory and visual processing are common in schizophrenia (SP). In the unisensory realm visual deficits are primarily noted for the dorsal visual stream. In addition, insensitivity to timing offsets between stimuli are widely reported for SP. The aim of the present study was to test at the physiological level differences in dorsal/ventral stream visual processing and timing sensitivity between SP and healthy controls (HC) using MEG and a simple auditory/visual task utilizing a variety of multisensory conditions. The paradigm included all combinations of synchronous/asynchronous and central/peripheral stimuli, yielding 4 task conditions. Both HC and SP groups showed activation in parietal areas (dorsal visual stream) during all multisensory conditions, with parietal areas showing decreased activation for SP relative to HC, and a significantly delayed peak of activation for SP in intraparietal sulcus (IPS). We also observed a differential effect of stimulus synchrony on HC and SP parietal response. Furthermore, a (negative) correlation was found between SP positive symptoms and activity in IPS. Taken together, our results provide evidence of impairment of the dorsal visual stream in SP during a multisensory task, along with an altered response to timing offsets between presented multisensory stimuli.

Latent toxoplasma infection in real-world schizophrenia: Results from the national FACE-SZ cohort.

OBJECTIVE: Latent Toxoplasma infection has been associated with widespread brain immune activation, increased blood brain barrier permeability, neural disruption, increased dopamine release in dopaminergic neurons, with NMDA activation and with schizophrenia (SZ) onset risk. Toxoplasma has been suggested to be a source of chronic low-grade inflammation and this inflammation has been associated with cognitive impairment in SZ. The objective of the present study were (i) to determine if latent Toxoplasma infection was associated with specific clinical features in stabilized SZ subjects, with cognitive impairment and with increased low-grade peripheral inflammation and (ii) to determine if Treatments with Anti-Toxoplasmic Activity (TATA) were associated with improved outcomes in subjects with latent Toxoplasma infection. METHODS: A comprehensive 2 daylong clinical and neuropsychological battery was administered in 250 SZ subjects included between 2015 and 2017 in the national FondaMental Expert Center (FACE-SZ) Cohort. Solid phase-enzyme microplate immunoassay methods were used to measure IgG class of antibodies to T. gondii in blood sample. Latent Toxoplasma infection was defined by T. gondii IgG ratio ≥0.8, equivalent to ≥10 international units. Chronic peripheral inflammation was defined by highly sensitive C reactive protein blood level ≥ 3 mg/L. RESULTS: Latent Toxoplasma infection has been found in 184 (73.6%) of this national multicentric sample. In the multivariate analyses, latent Toxoplasma infection has been significantly associated with higher PANSS negative (aOR = 1.1 [1.1-1.1], p = 0.04) and excitement subscores (aOR = 1.3 [1.1-1.6], p = 0.01), with two specific symptoms (i.e., reference delusion (aOR = 3.6 [1.2-10.6] p = 0.01) and alogia (aOR = 16.7 [2.0-134.7], p = 0.008)) and with chronic low-grade peripheral inflammation (27.2% vs. 7.6%, aOR = 3.8 [1.4-10.3], p = 0.004). Extrapyramidal symptoms remained significantly associated with latent Toxoplasma infection. On the opposite, no significant association of latent Toxoplasma infection with age, gender, age at SZ onset, suicide behavior or cognitive deficits has been found in these models (all p > 0.05). TATA were associated with lower depressive symptoms (aOR = 0.8[0.7-0.9], p = 0.01), and with lower rates of chronic peripheral inflammation (20.9% vs. 48.6%, aOR = 3.5 [1.5-7.9], p = 0.003) but not with higher cognitive scores (p > 0.05). CONCLUSION: The present findings suggest that Toxoplasma is almost 3 times more frequent in SZ population compared to general population in France. The potential cerebral underpinnings of the association of latent Toxoplasma infection and the above-mentioned outcomes have been discussed. Future studies should confirm that TATA may be effective to reduce Toxoplasma-associated depressive symptoms and low-grade peripheral inflammation.

Relationship between toxoplasmosis and schizophrenia: A review.

A growing body of evidence suggests a correlation between schizophrenia and exposure to infectious agents. The majority of studied cases concerns the infection caused by T. gondii, an obligatory intracellular parasite that infects about 1/3 of the entire human population, according to the available data. The acute stage of the disease, predominantly short-lived and transient, transforms into the latent and chronic phase in which the parasite localizes within tissue cysts, mainly in the central nervous system. The chronic toxoplasmosis, primarily regarded as benign and asymptomatic, might be responsible, in light of current scientific evidence, for a vast array of neuropsychiatric symptoms. Numerous epidemiological case-control studies show a higher prevalence of T. gondii infestation in individuals with various psychiatric and behavior disorders, including schizophrenia. This paper tends to review the relevant studies that demonstrate links between schizophrenia and T. gondii infestation, of which the latter may be acquired in different developmental phases. Apart from epidemiological correlation studies, some papers on other associations were also presented, describing putative patophysiological mechanisms that might be at least partly responsible for chronic infection-induced neuromediator disturbances, together with morphological and functional alterations, e.g., low-grade neuroinflammation, which are likely to induce psychopathological symptoms. Toxoplasmosis is only one of the putative infectious agents that derange correct brain growth and differentiation, alongside genetic and environmental factors. All of them may lead eventually to schizophrenia. A better knowledge of infection mechanisms and its influence on neurobiochemical and neuropathological pathways may enable more efficient therapy and the prevention of this devastating disease.

Association of Toxoplasma gondii infection with schizophrenia and its relationship with suicide attempts in these patients.

OBJECTIVES: To investigate the association between schizophrenia and Toxoplasma gondii, and to assess the association of infection with suicide attempts and age of onset of schizophrenia in these patients. METHODS: Case-control study Fars Province, southern Iran. Cases were individuals with psychiatric diagnosis of schizophrenia as per Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Controls were healthy blood donors, frequency-matched with patients according to age and sex. For the detection of IgG antibodies, enzyme-linked immunosorbent assay (ELISA) was used. Data about demographic information in all subjects and duration of illness and history of suicide attempts in patients with schizophrenia were collected using a brief questionnaire and hospital records. Chi-square test and multivariable logistic regression were used for statistical analyses. RESULTS: Among 99 cases, 42 individuals (42%) were positive for T. gondii antibody, vs. 41 (27%) among 152 controls (OR = 2, 95% CI: 1.2-3.4, P = 0.012). We compared the suicide attempts in patients with schizophrenia based on their T. gondii serologic status. There was a lower rate of suicide attempts in seropositive male patients than seronegative ones (OR = 0.3, 95% CI: 0.1-0.97, P = 0.04). Age of onset of schizophrenia did not differ between T. gondii-infected and non-infected patients. CONCLUSIONS: These findings may have implications for schizophrenia and suicide prevention programmes. However, clearly further studies are required to confirm them.

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.

Infection and inflammation in schizophrenia and bipolar disorder.

The present study investigated the relationship between exposure to infectious agents and inflammation markers in individuals with schizophrenia (SZ), bipolar disorder (BP), and controls without a psychiatric disorder. We measured plasma levels of antibodies and innate immune markers and correlated them with clinical symptoms and cognitive function. In both SZ and BP, we found an increase in soluble CD14, and in BP an increase in C-reactive protein, IgM class antibodies against cytomegalovirus (CMV), and IgG class antibodies against herpes simplex virus 2. Furthermore in BP, we observed a negative relationship between IgG antibodies against CMV and scores for cognitive function.

Toxoplasma gondii infection and schizophrenia: an inter-kingdom communication perspective.

PURPOSE OF REVIEW: The apicomplexan protozoan Toxoplasma gondii has a striking predilection for infecting the central nervous system and has been suggested as a risk factor for schizophrenia. Here, we address some of the mechanisms by which T. gondii achieves this by manipulating signaling pathways of the host brain cells. RECENT FINDINGS: Recent years have brought notable progress in the understanding of how the opportunistic parasite T. gondii establishes a successful infection in mammalian brain by secreting effector molecules that manipulate multiple cell functions. Many pathways involved in this inter-kingdom signaling, such as dopaminergic, GABAergic and kynurenine pathways, also have key roles in the development of schizophrenia. More understanding of T. gondii-brain cell interaction holds the key to unlocking the mystery of T. gondii-mediated schizophrenia pathogenesis. SUMMARY: T. gondii usurps a variety of host signaling pathways to ensure physiological adaptation, evasion of host immune defense systems, and efficient replication. A detailed knowledge of T. gondii signaling molecules involved in this cross-kingdom communication with host brain cells will probably provide novel means of pharmacologically manipulating host cellular pathways to promote efficient elimination of the parasite and may permit the development of new schizophrenia-modifying therapeutics.

The known and missing links between Toxoplasma gondii and schizophrenia.

Toxoplasma gondii, an intracellular protozoan parasite, has a striking predilection for infecting the Central Nervous System and has been linked to an increased incidence of a number of psychiatric diseases. Several in vitro and in vivo studies have shown that T. gondii infection can affect the structure, bioenergetics and function of brain cells, and alters several host cell processes, including dopaminergic, tryptophan-kynurenine, GABAergic, AKT1, Jak/STAT, and vasopressinergic pathways. These mechanisms underlying the neuropathology of latent toxoplasmosis seem to operate also in schizophrenia, supporting the link between the two disorders. Better understanding of the intricate parasite-neuroglial communications holds the key to unlocking the mystery of T. gondii-mediated schizophrenia and offers substantial prospects for the development of disease-modifying therapies.

Is there any role of latent toxoplasmosis in schizophrenia disease?

BACKGROUND: A large number of studies have hypothesized that Toxoplasma gondii is a potentially relevant etiological factor in some cases of schizophrenia. By contrast, some studies have disproved this association. The aim of this study was to investigate whether latent toxoplasmosis has any role in schizophrenia disease. Additionally, the association between T. gondii and subtypes of schizophrenia, and the impacts of toxoplasmosis on psychopathology were examined in the study. METHODS: A total of 85 patients with schizophrenia and 60 healthy volunteers were included in this prospective study. Immunoglobulin G (IgG) antibody to T. gondii was examined by enzyme-linked immune-sorbent assay method. RESULTS: Seropositivity rates were 43.5% for the patients with schizophrenia and 43.3% for the healthy controls (odds ratio: 1.008, 95% confidence interval: 0.517-1.964, p = 0.981).There was no significant difference in T. gondii IgG positivity between the schizophrenia and control groups with respect to sex and age. The difference in seroprevalence of T. gondii IgG antibodies among the schizophrenia subtypes was not statistically significant (p = 0.934). No significant difference was found in Positive and Negative Syndrome Subscales between Toxoplasma-infected and Toxoplasma-free patients. CONCLUSION: In the study area with a high prevalence of T. gondii, no association between toxoplasmosis and schizophrenia was detected. These findings showed that toxoplasmosis has no role in the risk of schizophrenia disease.

Chronic Toxoplasma gondii in Nurr1-null heterozygous mice exacerbates elevated open field activity.

Latent infection with Toxoplasma gondii is common in humans (approximately 30% of the global population) and is a significant risk factor for schizophrenia. Since prevalence of T. gondii infection is far greater than prevalence of schizophrenia (0.5-1%), genetic risk factors are likely also necessary to contribute to schizophrenia. To test this concept in an animal model, Nurr1-null heterozygous (+/-) mice and wild-type (+/+) mice were evaluate using an emergence test, activity in an open field and with a novel object, response to bobcat urine and prepulse inhibition of the acoustic startle response (PPI) prior to and 6 weeks after infection with T. gondii. In the emergence test, T. gondii infection significantly decreased the amount of time spent in the cylinder. Toxoplasma gondii infection significantly elevated open field activity in both +/+ and +/- mice but this increase was significantly exacerbated in +/- mice. T. gondii infection reduced PPI in male +/- mice but this was not statistically significant. Aversion to bobcat urine was abolished by T. gondii infection in +/+ mice. In female +/- mice, aversion to bobcat urine remained after T. gondii infection while the male +/- mice showed no aversion to bobcat urine. Antibody titers of infected mice were a critical variable associated with changes in open field activity, such that an inverted U shaped relationship existed between antibody titers and the percent change in open field activity with a significant increase in activity at low and medium antibody titers but no effect at high antibody titers. These data demonstrate that the Nurr1 +/- genotype predisposes mice to T. gondii-induced alterations in behaviors that involve dopamine neurotransmission and are associated with symptoms of schizophrenia. We propose that these alterations in murine behavior were due to further exacerbation of the altered dopamine neurotransmission in Nurr1 +/- mice.

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.