Development of a blood-based molecular biomarker test for identification of schizophrenia before disease onset.

Recent research efforts have progressively shifted towards preventative psychiatry and prognostic identification of individuals before disease onset. We describe the development of a serum biomarker test for the identification of individuals at risk of developing schizophrenia based on multiplex immunoassay profiling analysis of 957 serum samples. First, we conducted a meta-analysis of five independent cohorts of 127 first-onset drug-naive schizophrenia patients and 204 controls. Using least absolute shrinkage and selection operator regression, we identified an optimal panel of 26 biomarkers that best discriminated patients and controls. Next, we successfully validated this biomarker panel using two independent validation cohorts of 93 patients and 88 controls, which yielded an area under the curve (AUC) of 0.97 (0.95-1.00) for schizophrenia detection. Finally, we tested its predictive performance for identifying patients before onset of psychosis using two cohorts of 445 pre-onset or at-risk individuals. The predictive performance achieved by the panel was excellent for identifying USA military personnel (AUC: 0.90 (0.86-0.95)) and help-seeking prodromal individuals (AUC: 0.82 (0.71-0.93)) who developed schizophrenia up to 2 years after baseline sampling. The performance increased further using the latter cohort following the incorporation of CAARMS (Comprehensive Assessment of At-Risk Mental State) positive subscale symptom scores into the model (AUC: 0.90 (0.82-0.98)). The current findings may represent the first successful step towards a test that could address the clinical need for early intervention in psychiatry. Further developments of a combined molecular/symptom-based test will aid clinicians in the identification of vulnerable patients early in the disease process, allowing more effective therapeutic intervention before overt disease onset.

Pezizalean mycorrhizas and sporocarps in ponderosa pine (Pinus ponderosa) after prescribed fires in eastern Oregon, USA.

Post-fire Pezizales fruit commonly in many forest types after fire. The objectives of this study were to determine which Pezizales appeared as sporocarps after a prescribed fire in the Blue Mountains of eastern Oregon, and whether species of Pezizales formed mycorrhizas on ponderosa pine, whether or not they were detected from sporocarps. Forty-two sporocarp collections in five genera (Anthracobia, Morchella, Peziza, Scutellinia, Tricharina) of post-fire Pezizales produced ten restriction fragment length polymorphism (RFLP) types. We found no root tips colonized by species of post-fire Pezizales fruiting at our site. However, 15% (6/39) of the RFLP types obtained from mycorrhizal roots within 32 soil cores were ascomycetes. Phylogenetic analyses of the 18S nuclear ribosomal DNA gene indicated that four of the six RFLP types clustered with two genera of the Pezizales, Wilcoxina and Geopora. Subsequent analyses indicated that two of these mycobionts were probably Wilcoxina rehmii, one Geopora cooperi, and one Geopora sp. The identities of two types were not successfully determined with PCR-based methods. Results contribute knowledge about the above- and below-ground ascomycete community in a ponderosa pine forest after a low intensity fire.

Endemic human plague in New Mexico: risk factors associated with infection.

A retrospective case-control study was conducted to identify risk factors, other than contact with infected animal tissues, for infection caused by Yersinia pestis in non-Indian residents of areas with endemic sylvatic plague in New Mexico. The study group consisted of 16 persons who had bacteriologically confirmed cases of plague in the period 1975-1976 and 45 controls who were matched by age, sex, and location of residence. Participants were questioned about outdoor activities, environmental conditions in and around the home, procedures of pet care, exposure to animals and insects, and medical history. The availability of harborage and food sources for wild rodents as a result of human activity in the immediate home environment was associated with risk of infection. Failure to take steps to control fleas on dogs and cats also appeared to be a possible risk factor. No other significant differences were found between patients and controls. Plague in New Mexico appears to result primarily from entry of the reservoir host into the habitat of the human rather than from entry of the human into the sylvatic habitat of the reservoir host.

Epidemiologic and clinical features of an outbreak of bubonic plague in New Mexico.

An outbreak of seven cases of bubonic plague in New Mexico was investigated. Clinical features were studied and correlated with field studies in an attmept to determine the source of infection in patients with indefinite histories of exposure. Most patients presented with fever, malaise, and an acute painful lymphadenitis (bubo). One death occurred in a patient with bubonic-septicemic plague complicated by meningitis due to Yersinia pestis. All patients lived in rural or semirural areas, and most had been in the general vicinity of their usual residence during the six days prior to onset of symptoms. The outbreak was associated with probable epizootics in rodents in two different areas of the state. One case was traced to direct hand contact with plague-infected rabbits. One patient developed insect bites after sleeping in the same bed with a flea-infested cat. Three of the other five patients had insect bites, presumably flea bites, but none of the five recalled contact with rodents or rabbits. Four of the five, however, had been in contact with dogs or cats that were later shown to have titers of antibody to Y. pestis. These findings provide further support for the hypothesis that contact with domestic dogs and cats may result in direct or indirect transmission of Y. pestis to humans.

Bubonic plague from exposure to a rabbit: a documented case, and a review of rabbit-associated plague cases in the United States.

A 62-year-old woman developed bubonic plague with an epitrochlear bubo one to two days after skinning two cottontail rabbits. The implicated rabbits were later recovered from the patient's freezer, and Yersinia pestis was isolated from marrows of both rabbits. Although human plague cases in the United States have occasionally been traced to exposure to wild rabbits, this is the first documentation of plague infection in the actual rabbits to which the patient was exposed. All reported cases of rabbit-associated plague in the United States were then reviewed. Eight cases were characterized by direct exposure to rabbit tissues. Seven of the eight cases occurred in adult males who had hunted rabbits during winter months in plague-endemic areas. These patients had upper extremity buboes, and the case-fatality ration for the group was 50%. Three other cases in which rabbit exposure was indirect or its role less clear, were also analyzed.

Bubonic plague from direct exposure to a naturally infected wild coyote.

An 11-year-old boy developed axillary bubonic plague and plague meningitis 3 days after skinning a dead coyote near Albuquerque, New Mexico. The coyoto carcass was recovered 10 days later, and Yersinia pestis was isolated from spleen and marrow of the animal. This is the first report of human plague from exposure to a coyote. A review of experimental and epidemiologic studies suggests that severe plague infection in members of the family Canidae is unusual, and that the risk of acquiring plague from direct contact with coyote tissues is minimal. Nevertheless, certain precautions are outlined for persons working with wild coyotes.