Redox Dysregulation in Schizophrenia Revealed by in vivo NAD+/NADH Measurement.
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 vivo31P 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) and31P 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 from31P 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.
McLean Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA.|Psychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA.
Sang-Young
SY
Kim
Program for Neuropsychiatric Research, McLean Hospital, Harvard Medical School, Belmont, MA.
Bruce M
BM
Cohen
McLean Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA.|Psychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA.
Xi
X
Chen
McLean Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA.|Behavioral Psychopharmacology Research Laboratory, McLean Hospital, Harvard Medical School, Belmont, MA.
Scott E
SE
Lukas
Psychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA.
Ann K
AK
Shinn
Psychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA.
A Cagri
AC
Yuksel
The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, P. R. China.|West China Brain Research Center, West China Hospital, Sichuan University, Chengdu, P. R. China.
Tao
T
Li
McLean Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA; fdu@mclean.harvard.edu.|Psychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA.
Fei
F
Du
Psychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA.
Dost
D
Öngür
D000328:Adult; D001714:Bipolar Disorder / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism*
D009243:NAD
31P MRS; NAD+ and NADH; oxidative stress; redox state; schizophrenia
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