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Environmental toxicants are thought to play a major role in the pathogenesis of Parkinson’s disease. In reviewing the literature on heavy metals known to be toxicants, we noted several recent studies on mercury suggesting a possible role in the etiology of some cases of this disease. We therefore undertook a review of this association, focusing especially on peer-reviewed articles to avoid the bias inherent in much of the literature regarding mercury. For most people, our contemporary exposure to mercury comes from dental amalgam tooth restorations and from eating fish contaminated with mercury. In both cases, mercury is known to get into the brain in utero and at all ages. It remains in the brain for many years and is known to produce permanent neuropsychological deficits. Mercury toxicity can produce tremors and other Parkinsonian clinical symptoms. It can also produce neurochemical and neuropathological changes similar to those found in Parkinson’s disease, including the loss of dopamine neurons, degeneration of tubulin and axons, dysfunction of mitochondria, and the aggregation of alpha-synuclein. Relatively few studies have assessed mercury in parkinsonian patients, but almost all reported a statistically significant association. Published studies suggest some promising leads in the relationship between mercury exposure and Parkinson’s disease. However, studies of patients are relatively few, and the need for research is clear. A search of Parkinsonian research studies currently funded by the US National Institutes of Health, Parkinson’s Foundation, and the Michael J Fox Foundation yielded no studies on mercury. We believe such studies should be supported.

A unique array-based pathogen chip has been developed for the detection of viral RNA or DNA relevant to pathologies of the central nervous system. A total of 715 unique oligonucleotides (60-mer) representing approximately 100pathogens were designed based on open reading frames (ORFs)from highly conserved and heterogenic regions within viral families. In addition, viral genes reflecting different stages of pathogen infection were also included to potentially define the stage of the viral infection. Viruses (double-stranded DNA, double- or single-stranded RNA, delta, retroid), parasites, and bacteria were included. Test samples labeled with Cy™5 were examined by cohybridization with a reference RNA, labeled with Cy3, to the pathogen microarray chip. Good reproduc-ibility of experiments was observed, based on data generated from duplicate hybridizations and duplicate spots on the microarray platform. A viral transcript detection sensitivity of 1 ×103 plaque-forming units (pfus) was achieved using selected cell lines and viruses. These findings suggest that the array-based platform described here is capable of detecting a broad spectrum of viruses in a single assay with relatively high sensitivity, specificity, and reproducibility. This method may be used to provide evidence of viral infection in postmortem tissue from psychiatric patients as well as a wide range of other diagnostic categories.

Recent epidemiologic studies indicate that infectious agents may contribute to some cases of schizophrenia. In animals, infection with Toxoplasma gondii can alter behavior and neurotransmitter function. In humans, acute infection with T. gondii can produce psychotic symptoms similar to those displayed by persons with schizophrenia. Since 1953, a total of 19 studies of T. gondii antibodies in persons with schizophrenia and other severe psychiatric disorders and in controls have been reported; 18 reported a higher percentage of antibodies in the affected persons; in 11 studies the difference was statistically significant. Two other studies found that exposure to cats in childhood was a risk factor for the development of schizophrenia. Some medications used to treat schizophrenia inhibit the replication of T. gondii in cell culture. Establishing the role of T. gondii in the etiopathogenesis of schizophrenia might lead to new medications for its prevention and treatment.

A possible role for Toxoplasma gondii in the etiopathogenesis of schizophrenia is supported by epidemiological studies and animal models of infection. However, recent studies attempting to link Toxoplasma to schizophrenia have yielded mixed results. We performed a nested case-control study measured serological evidence of exposure to Toxoplasma gondii in a cohort of 2052 individuals. Within this cohort, a total of 1481 individuals had a psychiatric disorder and 571 of were controls without a psychiatric disorder. We found an increased odds of Toxoplasma exposure in individuals with a recent onset of psychosis (OR 2.44, 95% Confidence Interval 1.4-4.4, p < .003). On the other hand, an increased odds of Toxoplasma exposure was not found in individuals with schizophrenia or other psychiatric disorder who did not have a recent onset of psychosis. By identifying the timing of evaluation as a variable, these findings resolve discrepancies in previous studies and suggest a temporal relationship between Toxoplasma exposure and disease onset.