We describe the validation of a serum-based test developed by Rules-Based Medicine which can be used to help confirm the diagnosis of schizophrenia. In preliminary studies using multiplex immunoassay profiling technology, we identified a disease signature comprised of 51 analytes which could distinguish schizophrenia (n = 250) from control (n = 230) subjects. In the next stage, these analytes were developed as a refined 51-plex immunoassay panel for validation using a large independent cohort of schizophrenia (n = 577) and control (n = 229) subjects. The resulting test yielded an overall sensitivity of 83% and specificity of 83% with a receiver operating characteristic area under the curve (ROC-AUC) of 89%. These 51 immunoassays and the associated decision rule delivered a sensitive and specific prediction for the presence of schizophrenia in patients compared to matched healthy controls.

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.

An early and accurate diagnosis has the potential to delay or even prevent the onset of BD. This study demonstrates the potential utility of a biomarker panel as a diagnostic test for BD.

The present results suggest that there are distinct serum alterations that occur before clinical manifestation of schizophrenia and bipolar disorder. These findings could lead to development of diagnostic tests to help clinical psychiatrists identify and classify vulnerable patients early in the disease process, allowing for earlier and more effective therapeutic intervention.

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Knowledge of the risks of comorbid psychiatric and general medical conditions is critical both for clinicians and for patients with schizophrenia. Closer attention to prevention, early diagnosis, and treatment of comorbid conditions may decrease associated morbidity and mortality and improve prognosis among patients with schizophrenia.

Findings from previous studies of herpes family viruses and schizophrenia have been inconsistent. Our study is based on a larger population than most previous studies and used serum specimens collected before onset of illness. This study adds to the body of knowledge and provides testable hypotheses for follow-on studies.

The study of effects associated with human exposure to repeated low-level blast during training or operations of select military occupational specialties (MOS) challenges medical science because acute negative effects that might follow such exposures cannot be expected to be clear or prevalent. Any gross effects from such occupational blast exposure on health or performance should be expected to have been already identified and addressed by affected military units through changes to their standard training protocols. Instead, effects, if any, should be expected to be incremental in nature and to vary among individuals of different susceptibilities and exposure histories. Despite the challenge, occupational blast-associated effects in humans are emerging in ongoing research. The purpose of the present study was to examine medical records for evidence of blast-associated effects that may have clinical significance in current standard of care. We hypothesized that populations exposed to blast by virtue of their military occupation would have poorer global medical outcomes than cohorts less likely to have been occupationally exposed. Records from a population of 50,254 service members in MOSs with a high likelihood of occupational blast exposure were compared to records from a matched cohort of 50,254 service members in MOSs with a lower likelihood of occupational blast exposure. These two groups were compared in hospitalizations, outpatient visits, pharmacy, and disability ratings. The clearest finding was higher risk among blast-exposed MOSs for ambulatory encounters for tinnitus, with adjusted risk ratios of 1.19 (CI 1.03-1.37), 1.21 (CI 1.16-1.26), and 1.31 (CI 1.18-1.45) across career time points. Other hypothesized effects (i.e., neurological outcomes) were smaller and were associated with acute exposure. This study documents that service members in occupations that likely include repeated exposure to blast are at some increased risk for neurosensory conditions that present in medical evaluations. Other hypothesized risks from occupational exposure may manifest as symptomology not visible in the medical system or current standard of care. Separate studies, observational and epidemiological, are underway to evaluate further the potential for occupational risk, but the evidence presented here may indicate near-term opportunities to guide efforts to reduce neurosensory risk among exposed service members.