Brain bioenergetics and redox state measured by31 P magnetic resonance spectroscopy in unaffected siblings of patients with psychotic disorders

Abstract 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) using31 P-magnetic resonance spectroscopy (31 P-MRS) in unaffected siblings, compared to first episode psychosis (FEP) patients and healthy controls. Methods 21 unaffected siblings, 32 FEP patients (including schizophrenia spectrum and affective psychoses), and 21 controls underwent31 P-MRS in the frontal lobe (6 × 6 × 4 cm3 ) 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 a31 P-MRS fitting algorithm. 13 unaffected sibling-patient pairs were related; other patients and siblings were unrelated. ANCOVA analyses were used to examine31 P-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,31 P-MRS studies may identify factors related both to risk and expression of psychosis.