title: Brain bioenergetics and redox state measured by31P magnetic resonance spectroscopy in unaffected siblings of patients with psychotic disorders.
abstract: 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) using31P-magnetic resonance spectroscopy (31P-MRS) in unaffected siblings, compared to first episode psychosis (FEP) patients and healthy controls.
  
  
  
  21 unaffected siblings, 32 FEP patients (including schizophrenia spectrum and affective psychoses), and 21 controls underwent31P-MRS in the frontal lobe (6×6×4cm3) 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 a31P-MRS fitting algorithm. 13 unaffected sibling-patient pairs were related; other patients and siblings were unrelated. ANCOVA analyses were used to examine31P-MRS measures, with age and gender as covariates.
  
  
  
  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.
  
  
  
  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,31P-MRS studies may identify factors related both to risk and expression of psychosis.
authors.affiliation: Psychotic Disorders Division, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA. Electronic address: vchouinard@mclean.harvard.edu.
authors.forename: Virginie-Anne
authors.initials: VA
authors.lastname: Chouinard
authors.affiliation: Psychotic Disorders Division, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Sang-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Laboratory for Psychiatric Biostatistics, McLean Hospital, Belmont, MA, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Valeri
authors.affiliation: Psychotic Disorders Division, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Cagri
authors.initials: C
authors.lastname: Yuksel
authors.affiliation: Psychotic Disorders Division, McLean Hospital, Belmont, MA, USA.
authors.forename: Kyle P
authors.initials: KP
authors.lastname: Ryan
authors.affiliation: Clinical Pharmacology Program, McGill University, Montreal, Quebec, Canada; Mental Health Institute of Montreal, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Guy
authors.initials: G
authors.lastname: Chouinard
authors.affiliation: Psychotic Disorders Division, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Cohen
authors.affiliation: Psychotic Disorders Division, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Du
authors.affiliation: Psychotic Disorders Division, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Dost
authors.initials: D
authors.lastname: Öngür
mesh_terms: D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D010759:Phosphorus Isotopes; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D011619:Psychotropic Drugs / Q000627:therapeutic use; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D035781:Siblings; D055815:Young Adult
chemical_list: D010759:Phosphorus Isotopes; D011619:Psychotropic Drugs; D009243:NAD
keywords: (31)P magnetic resonance spectroscopy; Bipolar disorder; Energy metabolism; Oxidative stress; Schizophrenia; Unaffected relatives