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

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.