Redox Dysregulation in Schizophrenia Revealed by in vivo NAD+/NADH Measurement

Schizophr Bull. 2017 Jan;43(1):197-204. doi: 10.1093/schbul/sbw129. Epub 2016 Sep 24.


Balance between the redox pair of nicotinamide adenine dinucleotides (oxidized NAD+ and reduced NADH), reflects the oxidative state of cells and the ability of biological systems to carry out energy production. A growing body of evidence suggests that an "immuno-oxidative" pathway including oxidative stress, mitochondrial dysfunction, neuroinflammation, and cell-mediated immune response may contribute to disruptions in brain activity in schizophrenia (SZ). The aim of this study is to assess possible redox imbalance in SZ patients by using a novel in vivo 31P MRS technique. The participants included 40 healthy controls, 21 chronic SZ, 13 first-episode (FE) SZ, and 18 FE bipolar disorder (BD) patients (as a psychiatric control group). All participants initially underwent structural imaging at a 3 Tesla (3 T) and 31P MRS measurements were performed on a 4 T MR scanner. NAD+ and NADH components were determined by nonlinear least-square fitting of the model simulated spectra; these incorporated prior chemical shift and coupling constant information to in vivo resonances obtained from 31P MRS experiments. We found a significant reduction in the NAD+/NADH ratio in chronically ill SZ patients compared to a matched healthy control group, and in FE SZ patients compared to both a matched FE BD patient group and a matched healthy control group. These findings provide evidence for redox imbalance in the brain in all phases of SZ, potentially reflecting oxidative stress.

Keywords: 31P MRS; NAD+ and NADH; oxidative stress; redox state; schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Bipolar Disorder / diagnostic imaging
  • Bipolar Disorder / metabolism*
  • Humans
  • Magnetic Resonance Spectroscopy / methods*
  • NAD / metabolism*
  • Oxidation-Reduction
  • Oxidative Stress*
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / metabolism*


  • NAD