title: Biomarker Case-Detection and Prediction with Potential for Functional Psychosis Screening: Development and Validation of a Model Related to Biochemistry, Sensory Neural Timing and End Organ Performance.
abstract: The Mental Health Biomarker Project aimed to discover case-predictive biomarkers for functional psychosis. In a retrospective, cross-sectional study, candidate marker results from 67 highly characterized symptomatic participants were compared with results from 67 gender- and age-matched controls. Urine samples were analyzed for catecholamines, their metabolites, and hydroxylpyrolline-2-one, an oxidative stress marker. Blood samples were analyzed for vitamin and trace element cofactors of enzymes in catecholamine synthesis and metabolism pathways. Cognitive, auditory, and visual processing measures were assessed using a simple 45-min, office-based procedure. Receiver operating curve (ROC) and odds ratio analysis discovered biomarkers for deficits in folate, vitamin D and B6 and elevations in free copper to zinc ratio, catecholamines and the oxidative stress marker. Deficits were discovered in peripheral visual and auditory end-organ function, intracerebral auditory and visual processing speed and dichotic listening performance. Fifteen ROC biomarker variables were divided into five functional domains. Through a repeated ROC process, individual ROC variables, followed by domains and finally the overall 15 set model, were dichotomously scored and tallied for abnormal results upon which it was found that ≥3 out of 5 abnormal domains achieved an area under the ROC curve of 0.952 with a sensitivity of 84% and a specificity of 90%. Six additional middle ear biomarkers in a 21 biomarker set increased sensitivity to 94%. Fivefold cross-validation yielded a mean sensitivity of 85% for the 15 biomarker set. Non-parametric regression analysis confirmed that ≥3 out of 5 abnormally scored domains predicted >50% risk of caseness while 4 abnormally scored domains predicted 88% risk of caseness; 100% diagnostic certainty was reached when all 5 domains were abnormally scored. These findings require validation in prospective cohorts and other mental illness states. They have potential for case-detection, -screening, -monitoring, and -targeted personalized management. The findings unmask unmet needs within the functional psychosis condition and suggest new biological understandings of psychosis phenomenology.
authors.affiliation: The University of Adelaide, Adelaide, SA, Australia; Youth in Mind Research Institute, Norwood, SA, Australia; The Queen Elizabeth Hospital, Woodville, SA, Australia; Basil Hetzel Institute for Translational Health Research, Woodville, SA, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Fryar-Williams
authors.affiliation: The University of Adelaide , Adelaide, SA , Australia.
authors.forename: Jörg E
authors.initials: JE
authors.lastname: Strobel
keywords: biomarkers; case detection; case prediction; mental illness; model; psychosis; schizoaffective; schizophrenia