Validation of oxidative stress assay for schizophrenia.

Journal: Schizophrenia research
PMID:

Abstract

Accumulating evidence implicates oxidative stress in a range of diseases, yet no objective measurement has emerged that characterizes the global nature of oxidative stress. Previously, we reported a measurement that employs the moderately strong oxidant iridium (Ir) to probe the oxidative damage in a serum sample and reported that in a small study (N = 15) the Ir-reducing capacity assay could distinguish schizophrenia from healthy control groups based on their levels of oxidative stress. Here, we used a larger sample size to evaluate the Ir-reducing capacity assay to assess its ability to discriminate the schizophrenia (N = 73) and healthy control groups (N = 45). Each serum sample was measured (in triplicate) at three different times that were separated by several weeks. The Intraclass Correlation Coefficient (ICC = 0.69) for these repeated measurements indicates the assay detects stable components in the sample (i.e., it is not detecting transient reactive species or air-oxidizable serum components). Correlations between the Ir-reducing capacity assay and independently-measured total serum protein levels (r = +0.74, p < 2.2 × 10) suggest the assay is detecting information in the protein pool. For cross-validation of the discrimination ability, we used machine learning and receiver operating characteristic (ROC) analysis. After adjusting for potential confounders (age and smoking status), an area under the curve (AUC) of ROC curve was calculated to be 0.89 (p = 9.3 × 10). In conclusion, this validation indicates the Ir-reducing capacity assay provides a simple global measure of oxidative stress, and further supports the hypothesis that oxidative stress is linked with schizophrenia.

Authors

  • Eunkyoung Kim
    Institute for Bioscience & Biotechnology Research, University of Maryland, College Park, MD 20742, USA.
  • Zoe Keskey
    Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
  • Mijeong Kang
    Institute for Bioscience & Biotechnology Research, University of Maryland, College Park, MD 20742, USA.
  • Christopher Kitchen
    Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
  • William E Bentley
    Department of Chemical and Biomolecular Engineering , University of Maryland , College Park , MD 20742 , USA . Email: sraghava@umd.edu.
  • Shuo Chen
    Department of Thoracic Surgery Beijing Chao-Yang Hospital Affiliated Capital Medical University Beijing China.
  • Deanna L Kelly
    Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
  • Gregory F Payne
    Institute for Bioscience & Biotechnology Research, University of Maryland, College Park, MD 20742, USA. Electronic address: gpayne@umd.edu.