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

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

Author information

1
McLean Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA.
2
Psychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA.
3
Program for Neuropsychiatric Research, McLean Hospital, Harvard Medical School, Belmont, MA.
4
Behavioral Psychopharmacology Research Laboratory, McLean Hospital, Harvard Medical School, Belmont, MA.
5
The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, P. R. China.
6
West China Brain Research Center, West China Hospital, Sichuan University, Chengdu, P. R. China.
7
McLean Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA; fdu@mclean.harvard.edu.

Abstract

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

PMID:
27665001
PMCID:
PMC5216857
DOI:
10.1093/schbul/sbw129
[Indexed for MEDLINE]
Free PMC Article

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