Brain bioenergetics and redox state measured by 31P magnetic resonance spectroscopy in unaffected siblings of patients with psychotic disorders

SCHIZOPHRENIA RESEARCH

卷:187

Article

Chouinard, Virginie-Anne^1,2  Kim, Sang-Young^1,2  Valeri, Linda^2,3  Yuksel, Cagri^1,2  Ryan, Kyle P.¹  Chouinard, Guy^4,5  Cohen, Bruce M.^1,2  Du, Fei^1,2  Ongur, Dost^1,2 

[1] McLean Hosp, Psychot Disorders Div, 115 Mill St, Belmont, MA 02178 USA

[2] Harvard Med Sch, Dept Psychiat, Boston, MA USA

[3] McLean Hosp, Lab Psychiat Biostat, 115 Mill St, Belmont, MA 02178 USA

[4] McGill Univ, Clin Pharmacol Program, Montreal, PQ, Canada

[5] Univ Montreal, Mental Hlth Inst Montreal, Montreal, PQ, Canada

关键词: Unaffected relatives;    Schizophrenia;    Bipolar disorder;    P-31 magnetic resonance spectroscopy;    Energy metabolism;    Oxidative stress;   

DOI  :  10.1016/j.schres.2017.02.024

来源: Elsevier

【 摘 要 】

Background: Brain bioenergetic anomalies and redox dysregulation have been implicated in the pathophysiology of psychotic disorders. The present study examined brain energy-related metabolites and the balance between nicotinamide adenine dinucleotide metabolites (oxidized NAD+ and reduced NADH) using P-31-magnetic resonance spectroscopy (P-31-MRS) in unaffected siblings, compared to first episode psychosis (FEP) patients and healthy controls. Methods: 21 unaffected siblings, 32 FEP patients (including schizophrenia spectrumand affective psychoses), and 21 controls underwent P-31-MRS in the frontal lobe (6 x 6 x 4 cm(3)) on a 4T MR scanner, using custom-designed dual-tuned surface coil with outer volume suppression. Brain parenchymal pH and steady-state metabolite ratios of high energy phosphate compounds were measured. NAD+ and NADH levels were determined using a P-31-MRS fitting algorithm. 13 unaffected sibling-patient pairs were related; other patients and siblings were unrelated. ANCOVA analyses were used to examine P-31-MRS measures, with age and gender as covariates. Results: The phosphocreatine/adenosine triphosphate ratio was significantly reduced in both unaffected siblings and FEP patients, compared to controls. NAD+/NADH ratio was significantly reduced in patients compared to siblings and controls, with siblings showing a reduction in NAD+/NADH compared to controls that was not statistically significant. Compared to patients and controls, siblings showed significantly reduced levels of NAD+. Siblings did not differ from patients or controls on brain pH. Discussion: Our results indicate that unaffected siblings show some, but not all the same abnormalities in brain energy metabolites and redox state as FEP patients. Thus, P-31-MRS studies may identify factors related both to risk and expression of psychosis. (C) 2017 Elsevier B.V. All rights reserved.

【 授权许可】

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