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

Stephanie Fryar-Williams, Jörg E. Strobel

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Article number48
Number of pages17
JournalFrontiers in Psychiatry
Volume7
Issue numberApril
DOIs
Publication statusPublished - 14 Apr 2016
Externally publishedYes

Bibliographical note

Copyright: © 2016 Fryar-Williams and Strobel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Keywords

  • Biomarkers
  • Case detection
  • Case prediction
  • Mental illness
  • Model
  • Psychosis
  • Schizoaffective
  • Schizophrenia

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