Differences in onset of disease and severity of psychopathology between toxoplasmosis-related and toxoplasmosis-unrelated schizophrenia.

OBJECTIVE: Toxoplasmosis is a lifelong parasitic disease that appears to be associated to schizophrenia. However, no distinguishing attributes in Toxoplasma-infected schizophrenia patients have been described as yet. METHOD: We searched for differences in symptom profile, cognitive performance and treatment response between 194 Toxoplasma-free and 57 (22.7%) Toxoplasma-infected schizophrenia patients treated in Prague Psychiatric Centre between 2000 and 2010. RESULTS: Infected and non-infected patients differed in severity of symptoms (P = 0.032) measured with the Positive and Negative Symptom Scale (PANSS). Infected patients scored higher in positive subscale of PANSS, but not in the general and negative subscales. Infected men scored higher also in Total PANSS score, and negative, reality distortion, disorganisation and cognitive scores. Higher PANSS scores of positive, negative and disorganised psychopathology were associated with the lower titres of anti-Toxoplasma antibodies suggesting that psychopathology deteriorates with duration of parasitic infection. Infected patients remained about 33 days longer in hospital during their last admission than uninfected ones (P = 0.003). Schizophrenia started approximately 1 year earlier in infected men and about 3 years later in infected women, no such difference was observed in uninfected subjects. CONCLUSION: Latent toxoplasmosis in schizophrenia may lead to more severe positive psychopathology and perhaps less favourable course of schizophrenia.

Toxoplasma gondii and cognitive deficits in schizophrenia: an animal model perspective.

Cognitive deficits are a core feature of schizophrenia. Epidemiological evidence indicates that microbial pathogens may contribute to cognitive impairment in patients with schizophrenia. Exposure to Toxoplasma gondii (T. gondii) has been associated with cognitive deficits in humans. However, the mechanisms whereby the parasite impacts cognition remain poorly understood. Animal models of T. gondii infection may aid in elucidating the underpinnings of cognitive dysfunction. Here, we (1) overview the literature on the association of T. gondii infection and cognitive impairment, (2) critically analyze current rodent models of cognitive deficits resulting from T. gondii infection, and (3) explore possible mechanisms whereby the parasite may affect cognitive function.

Congenital infection of mice with Toxoplasma gondii induces minimal change in behavior and no change in neurotransmitter concentrations.

We examined the effect of maternal Toxoplasma gondii infection on behavior and the neurotransmitter concentrations of congenitally infected CD-1 mice at 4 and 8 wk of age when latent tissue cysts would be present in their brains. Because of sex-associated behavioral changes that develop during aging, infected female mice were compared with control females and infected male mice were compared with control males. Only the short memory behavior (distance between goal box and first hole investigated) of male mice congenitally infected with T. gondii was significantly different (P < 0.05) from that of uninfected control males at both 4 and 8 wk by using the Barnes maze test. The other parameters examined in the latter test, i.e., functional observational battery tests, virtual cliff, visual placement, and activity tests, were not significantly different (P > 0.05) at 4 and 8 wk. Concentrations of neurotransmitters and their metabolites (dopamine; 3,4-dihydroxyphenylacetic acid; homovanillic acid; norepinephrine; epinephrine; 3-methoxy-4-hydroxyphenylglycol; serotonin; and 5-hydroxyindoleacetic acid) in the frontal cortex and striatum were not different (P > 0.05) between infected and control mice at 8 wk of age. The exact mechanism for the observed effect on short-term memory in male mice is not known, and further investigation may help elucidate the molecular mechanisms associated with the proposed link between behavioral changes and T. gondii infection in animals. We were not able, however, to confirm the widely held belief that changes in neurotransmitters result from chronic T. gondii infection of the brain.

Dopamine stimulates propagation of Toxoplasma gondii tachyzoites in human fibroblast and primary neonatal rat astrocyte cell cultures.

Toxoplasma gondii is an obligate intracellular parasite often found in the brain of humans. Research has shown a correlation between prevalence of antibody titers to T. gondii and psychological illness in humans. Recent studies indicate that individuals seropositive for T. gondii antibodies are more likely to develop psychotic disorders including schizophrenia, which is associated with changes in the dopamine neurotransmitter system. Dopamine in the brain may play a role in proliferation, chemoattraction, infection efficiency, or stage conversion of T. gondii . Because tachyzoites are the first developmental stage to reach the brain, the present study was conducted to determine the effects of dopamine on their development in vitro. In human fibroblast host cells, dopamine was added at either 100 nM or 250 nM to cell culture media, and the numbers of tachyzoites produced at 48 hr were determined and compared to vehicle-treated controls. An increase of tachyzoite numbers and increased destruction in cell monolayer were observed at both concentrations of dopamine. Dopamine used at 250 nM caused a significant (P < 0.05) increase in tachyzoites counts compared to controls. Dopamine antagonists (10 µM) did not significantly alter dopamine-stimulated tachyzoite production in human fibroblasts. In primary neonatal rat astrocyte cell cultures, dopamine (200 µM) significantly (P < 0.05) increased numbers of intracellular tachyzoites after 24 hr. The role that this increase plays in tachyzoite production under the stimulus of dopamine in the modulation of neural infection in humans awaits further studies.

Brain parasites and suicide.

In a sample of 20 European nations, the prevalence of the brain parasite Toxoplasma gondii was positively associated with national suicide rates for men and women.

Trimethoprim as adjuvant treatment in schizophrenia: a double-blind, randomized, placebo-controlled clinical trial.

Various infectious agents, such as Toxoplasma gondii, have been hypothesized to be potentially relevant etiological factors in the onset of some cases of schizophrenia. We conducted a randomized, double-blind, placebo-controlled treatment trial in an attempt to explore the hypothesis that the symptoms of schizophrenia may be related to infection of the central nervous system with toxoplasma gondii. Systematically selected patients with ongoing and at least moderately severe schizophrenia from Butajira, in rural Ethiopia, were randomly allocated to trimethoprim or placebo, which were added on to participants' regular antipsychotic treatments. Trial treatments were given for 6 months. The Positive and Negative Syndrome Scale (PANSS) was used to assess outcome. Ninety-one patients were included in the study, with 80 cases (87.9%) positive for T. gondii immunoglobulin G antibody. Seventy-nine subjects (87.0%) completed the trial. The mean age of subjects was 35.3 (SD = 8.0) years, with a mean duration of illness of 13.2 (SD = 6.7) years. Both treatment groups showed significant reduction in the overall PANSS score with no significant between-group difference. In this sample of patients with chronic schizophrenia, trimethoprim used as adjuvant treatment is not superior to placebo. However, it is not possible to draw firm conclusion regarding the etiological role of toxoplasmosis on schizophrenia based on this study because the timing and the postulated mechanisms through which toxoplasmosis produces schizophrenia are variable.

Toxoplasma gondii antibody titers and history of suicide attempts in patients with recurrent mood disorders.

Toxoplasma gondii (T.gondii) is an obligate intracellular protozoan parasite infecting one-third of the world population, residing relatively silently in the brain of the immunocompetent host. We hypothesized that T.gondii seropositivity and serointensity are associated with having a history of attempting suicide and, in those attempting suicide, a greater number of attempts. T.gondii seropositivity and antibody titers were compared between (a) patients with recurrent mood disorders with history of suicide attempt (99 individuals) versus (b) patients with recurrent mood disorders without history of suicide attempt (119 individuals), and (c) healthy controls (39 individuals). Diagnosis was made using the Structured Clinical Interview for DSM-IV. Statistical methods included chi square, analysis of variance, and linear and logistic regression analyses. Suicide attempters had higher T.gondii antibody titers than nonsuicide attempters (p = 0.004). The logistic regression analysis revealed a predictive association between titers of anti- T.gondii antibodies and history of suicide attempt with OR = 1.55 (1.14-2.12), p = 0.006. No significant relationship was found between T.gondii seropositivity and suicide attempt status, number of prior suicide attempts, and recurrent mood disorder diagnosis. Although preliminary and bearing replication, this is the first report, to our knowledge, of an association between attempting suicide and T. gondii.

A controlled prospective study of toxoplasma gondii infection in individuals with schizophrenia: beyond seroprevalence.

Toxoplasma gondii (TG) infection has been reported to be more frequent in schizophrenia. The interaction of the lifelong persisting parasite with the host's immune system involves T-cell/interferon-gamma-induced degradation of tryptophan and provides a challenge to the host well beyond a possible role in the etiology of schizophrenia. The hypothesis we tested in this study was that TG infection may be more frequent (serofrequency) and/or more intense (serointensity) in patients with schizophrenia or major depression compared with psychiatrically healthy controls. In addition, these measures are associated with the clinical course. We did a cross-sectional, prospective investigation of individuals with schizophrenia (n = 277) and major depression (n = 465) admitted to our department (2002-2005) and of healthy controls (n = 214), with all groups adjusted for age and geographic home region. Serofrequency was comparable between the groups, but serointensity was significantly higher in the patients. In individuals with schizophrenia, serointensity was significantly positively associated with C-reactive protein levels and leukocyte counts, and first-episode patients yielded significantly higher serotiters. Immunomodulatory medication was associated with decreased serotiters. In addition, the route of infection appears to differ between patients and controls. Thus, our results support increased host responses to TG infection in the patients, as well as increased titers in first-episode patients with schizophrenia; this may relate to the shifted T-helper 1/2 status described in these patients. Therefore, we suggest that TG infection, particularly in individuals with schizophrenia, is an important environmental factor in the interaction between psychiatric vulnerability, genetic background, immunomodulation, and the neurotransmitter systems.

Effects of toxoplasma on human behavior.

Although latent infection with Toxoplasma gondii is among the most prevalent of human infections, it has been generally assumed that, except for congenital transmission, it is asymptomatic. The demonstration that latent Toxoplasma infections can alter behavior in rodents has led to a reconsideration of this assumption. When infected human adults were compared with uninfected adults on personality questionnaires or on a panel of behavioral tests, several differences were found. Other studies have demonstrated reduced psychomotor performance in affected individuals. Possible mechanisms by which T. gondii may affect human behavior include its effect on dopamine and on testosterone.

[Neurological manifestations of HIV-infection in the era of highly active antiretroviral therapy (HAART)]. / Neurologische Manifestationen der HIV-Infektion in der Ara der hochaktiven antiretroviralen Therapie (HAART).

After the introduction of highly active antiretroviral therapy (HAART) in 1996 the neurological manifestations of human immunodeficiency virus (HIV-1)-infection did not decline in incidence and prevalence like the other complications of immunodeficiency; in contrast, due to the longer survival times of HAART treated HIV-1-positive individuals, prevalence of virus associated neurological disease increased during the last years, as international studies underline. Therefore, clinicians and HIV-therapists should be able to diagnose HIV-1-associated neurological disease even in early stages. This article describes symptoms and signs, neuro-imaging and cerebrospinal fluid findings as well as therapy options in primary HIV-1-associated neurological disease like encephalo- and myelopathy and polyneuropathy. Furthermore, those opportunistic infections, caused by bacteria, viruses other than HIV and parasites emerging with manifest immunodeficiency and remaining to be relevant in the HAART era are presented from diagnostic, differential-diagnostic and therapeutic points of view. An extra paragraph describes the interaction of HAART with neurological/psychiatric standard therapies.

Central nervous system toxoplasmosis in the AIDS patient.

Toxoplasmosis is a central nervous system infection commonly occurring in persons with HIV disease. The disease can manifest as encephalitis and cause neurological damage. The author presents an overview of the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of toxoplasmosis. The nurse's role in the management of patients diagnosed with the disease is discussed, including doing comprehensive, on-going assessments, providing education, and addressing quality-of-life issues.

[Clinico-functional correlations in the evaluation of the development of children with perinatal lesions of the central nervous system during the first 6 months of life]. / Kliniko-funktsional'nye korreliatsii v otsenke razvitiia detei pervogo polugodiia zhizni s perinatal'nym porazheniem TsNS.

The purpose of the work was to design a model of the screening estimation of the psychomotor development of the child with perinatal CNS derangement seen in the first half-year of life since the neonatal period. Use was made of noninvasive diagnostic methods, available for examination both under in- and outpatient conditions. Complex analysis of the health status of the child with perinatal CNS pathology made every month of life according to the screening program allows one to decide the problem of the intensity of morphofunctional disorders of the brain and of the methods of choosing treatment and corrective measures.