THE EPIDEMIOLOGY OF SEVERE PSYCHIATRIC DISORDERS: IS IT TIME TO PUT THE CAT OUT?
E. Fuller Torrey, M.D., Stanley Foundation Research Programs, Bethesda, MD
It is known that some infectious agents can cause brain diseases indistinguishable from schizophrenia and manic-depressive illness. Epidemiological aspects, including winter-spring birth, urban birth, and migration as risk factors, are also compatible with an infectious cause. Pet cats are known to carry many infectious agents that can be transmitted to humans; two studies have demonstrated that individuals with schizophrenia and manic-depressive illness as compared to well controls have had greater exposure to cats in childhood. Toxoplasmosis is especially interesting because it has been reported to affect personality traits and to occasionally cause schizophrenia-like symptoms. Toxoplasmosis has also been found to affect neurotransmitters in animal studies. Furthermore, antipsychotic drugs are known to “have lethal effects on protozoa.” Most importantly, increased antibodies to toxoplasmosis have been found in the sera of individuals with schizophrenia and manic-depressive illness. The critical variable whether toxoplasmosis causes these illnesses may be the timing of the primary infection.
STANLEY LABORATORY STUDIES OF SCHIZOPHRENIA AND BIPOLAR DISORDER
Michael B. Knable, Stanley Foundation Research Programs, Bethesda, MD
A brief overview of the Stanley Foundation Neuropathology Consortium and of drug trials supported by the Stanley Foundation will be given.. The Stanley Foundation Neuropathology Consortium, which contains samples from patients with schizophrenia, bipolar disorder, non-psychotic depression, and normal controls (n=15 per group), is a tissue resource available to qualified researchers around the world. To date, tissue has been sent to more than 80 laboratories. A summary of results obtained in the prefrontal cortex will be given. Between 1997 and 2000 data were returned from 14 laboratories with 69 separate data sets. These data sets were analysed in an integrative fashion and revealed 17 abnormal markers in at least one disease. These markers pertained to a variety of neural systems and processes including neuronal plasticity, neurotransmission, signal transduction, inhibitory interneuron function and glial cells. Schizophrenia was associated with the largest number of abnormalities, many of which were also present in bipolar disorder. Major depression was associated with relatively few abnormalities. The majority of the abnormal findings represented a decline in function. This summary suggests that the major psychiatric diseases are characterized by a widespread, but variable failure in gene expression that effects many cellular phenotypes. Such a constellation of findings may be best explained by a global insult such as infection hypoxia, malnutrition, or a failure of homeobox gene organization.
Through our various programs the Stanley Foundation is encouraging proposals for new clinical trials. We are currently supporting 96 different clinical trials without our Research Grants, Research Centers, Schizophrenia Network and Bipolar Network. These programs will be described briefly.
MOLECULAR SYSTEMATICS OF TOXOPLASMA GONDII AND RELATED COCCIDIA: EXPANDING THE RANGE OF DISTINGUISHING CHARACTERS FOR TAXONOMY, SYSTEMATICS AND DIAGNOSTICS
John R. Barta, Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada
Within the group of apicomplexan parasites broadly recognized as the coccidian, there is a limited range of morphological characters that can be used to distinguish species and even fewer characters that one can use to infer evolutionary relationships. For this reason, molecular data, most notably sequences associated with the ribosomal RNA gene, have been used increasingly to infer relationships among species and strains. The use of small subunit ribosomal DNA sequences clearly demonstrate some well-supported clades within the coccidian: 1) the eimeriid coccidian including Eimeria and Cyclospora species as well as some avian Isospora species (those possessing Stieda bodies and refractile bodies); 2) the isosporoid coccidian including species in the genera Toxoplasma, Neospora, Frenkelia, Hammondia and Saracocystis as well as some Isospora species (those lacking Stieda bodies and refractile bodies). Within the latter clade, there appear to be two sub-clades that are comprised of 1) Sarcocystis and Frenkelia species; and 2) Toxoplasma, Neospora and Isospora species. Recent observations suggest that Cryptosporidium species, long considered to be “unusual” coccidian, are only distantly related to the coccidian and may be most closely related to the gregarines that infect invertebrates. Molecular systematics has been instrumental in expanding the range of characters are available for inferring relationships among apicomplexan taxa. As an adjunct to morphological characters, sequence data allow us to better understand the evolutionary history of this group of parasites and thereby erect a well-supported taxonomic framework that reflects these historical relationships. Importantly, the predictive nature of such a framework can aid the search for therapeutic compounds (e.g. via shared biochemical pathways) and highlight organisms that should be tested for cross-reactivity in immunological or molecular diagnostic methods (e.g. use of the closest relatives to assess test specificity).