Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The exact mechanisms of action of some antipsychotics and mood stabilizers have not been elucidated. Response to these medications can vary among individuals. Recent studies indicate that infection with the parasite Toxoplasma gondii may contribute to the symptoms of schizophrenia in some individuals. We investigated commonly used antipsychotic and mood stabilizing medications for their ability to inhibit the replication of this organism. We employed a system for testing compounds for in vitro activity against T. gondii. Human fibroblasts (HFF) were treated with test compounds and then exposed to Toxoplasma that has been genetically modified to express cytoplasmic beta-galactosidase. Inhibition by the drugs was determined by spectrophotometric analysis of colorimetric reactions. We tested 12 neuroleptic compounds and found that of these, the antipsychotic haloperidol and the mood stabilizer valproic acid most effectively inhibit Toxoplasma growth in vitro. Valproic acid inhibited the parasite at a concentration below that found in the cerebrospinal fluid and blood of individuals being treated with this medication and displayed synergistic activity with haloperidol and with trimethoprim, an antibiotic commonly used to treat Toxoplasma infections.Several medications used to treat schizophrenia and bipolar disorder have the ability to inhibit the in vitro replication of T. gondii.
...
PMID:Drugs used in the treatment of schizophrenia and bipolar disorder inhibit the replication of Toxoplasma gondii. 1283 20

Toxoplasma gondii infects about 30% of the human population. Common sources of infection are oocysts in cat faeces contaminating drinking water or unwashed vegetables, undercooked meat containing tissue cysts, and organ transplants from infected donors containing tissue cysts. However, very often, it is not possible to identify any potential source of infection in mothers of children with congenital toxoplasmosis. Here we present a hypothesis suggesting that toxoplasmosis is transmitted from infected men to noninfected women during unprotected sexual intercourse, which can result in the most serious form of disease, congenital toxoplasmosis. Arguments for the hypothesis: (1) Toxoplasma tachyzoites are present in the seminal fluid and tissue of the testes of various animals including humans. In some species infection of females by artificial insemination with semen from infected males has been observed. (2) Up to two thirds of Toxoplasma infections in pregnant women cannot be explained by the known risk factors. (3) Prevalence of toxoplasmosis in women in child-bearing age covaries with the incidence of sexually transmitted diseases in particular countries. (4) In some countries, an increased incidence of toxoplasmosis has been reported in women (but not men) aged 25-35 years. This second peak of infection could be associated with women having regular unprotected sex after marriage. (5) Toxoplasmosis triggers schizophrenia in predisposed subjects. Onset of schizophrenia is about 2-3 years earlier in men than in women. However, this difference in the onset can be found only between Toxoplasma-infected patients. The increased onset of schizophrenia in infected women could be associated with the already mentioned second peak of toxoplasmosis incidence. (6) The prevalence of toxoplasmosis decreases in developed countries in last 20 years. This trend could be a result of decrease in promiscuity and increase in safe sex practices, both associated with the AIDS pandemics. (7) In women, probability of being Toxoplasma-infected correlates positively with the amount of unprotected sex with the child's father before the conception. Evidence against the hypothesis: Questionnaire study showed negative association between Toxoplasma infection and the number of earlier partners with whom the woman had unprotected sex. If our hypothesis turns out to be true, then sexual route of transmission, even if rare, could be responsible for a large part of cases of congenital toxoplasmosis. Women should be warned that having unprotected sex with men of positive or unknown toxoplasmosis status should be avoided during pregnancy.
...
PMID:Toxoplasmosis can be a sexually transmitted infection with serious clinical consequences. Not all routes of infection are created equal. 2498 6

It is increasingly evident that the brain is not truly an immune privileged site and that cells of the central nervous system are sensitive to the inflammation generated when the brain is fighting off infection. Among the many microorganisms that have access to the brain, the apicomplexan protozoan Toxoplasma gondii has been one of the most studied. This parasite has been associated with many neuropsychiatric disorders including schizophrenia. This article provides a comprehensive review of the status of Toxoplasma research in schizophrenia. Areas of interest include (1) the limitations and improvements of immune-based assays to detect these infections in humans, (2) recent discoveries concerning the schizophrenia-Toxoplasma association, (3) findings of Toxoplasma neuropathology in animal models related to schizophrenia pathogenesis, (4) interactions of Toxoplasma with the host genome, (5) gastrointestinal effects of Toxoplasma infections, and (6) therapeutic intervention of Toxoplasma infections.
...
PMID:Toxoplasma gondii: Biological Parameters of the Connection to Schizophrenia. 2988 80