title: Reproducibility of proton magnetic resonance spectroscopic imaging in patients with schizophrenia.
abstract: Using proton magnetic resonance spectroscopic imaging (1H-MRSI) we found in a previous study a specific pattern of neuronal pathology in patients with schizophrenia as determined by relative loss of signal from N-acetyl-containing compounds (NAA). The purpose of the present study was to assess the reproducibility of the results of 1H-MRSI both in patients with schizophrenia and in normal controls. We studied twice 10 patients and 10 controls on 2 days separated by, on average, 3 months. Reproducibility was assessed with several statistical procedures including ANOVA, coefficients of variation (CVs) and intra-class correlation coefficients (ICC). Patients showed significant reductions of NAA/creatine-phosphocreatine (CRE) and NAA/choline-containing compounds (CHO) selectively in the hippocampal region (HIPPO) and in the dorsolateral prefrontal cortex (DLPFC) on both experimental days. A repeated measures ANOVA showed no effect of time on metabolite ratios in all subjects. CVs were fairly low (especially for NAA/CRE and CHO/CRE) and did not differ significantly between patients and controls. The ICCs of the ROIs reached statistical significance only in a few instances. The present multislice 1H-MRSI study shows that: (1) patients with schizophrenia, when compared as a group to normal controls, show a consistent 1H-MRSI pattern of group differences, i.e., bilateral reductions of NAA/CRE and NAA/CHO in HIPPO and DLPFC; (2)1H-MRSI data in both patients and controls do not show significant changes over this 90-day period; however, absolute metabolite ratios in individuals show low predictability over this time interval; (3) 1H-MRSI data show relatively low variability (as measured by the CVs) both in patients and normal controls, especially for NAA/CRE and CHO/CRE.
authors.affiliation: Clinical Brain Disorders Branch, National Institutes of Health, National Institute of Mental Health, Neurosciences Center at Saint Elizabeths, Washington, DC, USA.
authors.forename: A
authors.initials: A
authors.lastname: Bertolino
authors.forename: J H
authors.initials: JH
authors.lastname: Callicott
authors.forename: S
authors.initials: S
authors.lastname: Nawroz
authors.forename: V S
authors.initials: VS
authors.lastname: Mattay
authors.forename: J H
authors.initials: JH
authors.lastname: Duyn
authors.forename: G
authors.initials: G
authors.lastname: Tedeschi
authors.forename: J A
authors.initials: JA
authors.lastname: Frank
authors.forename: D R
authors.initials: DR
authors.lastname: Weinberger
mesh_terms: D000107:Acetylation; D000328:Adult; D001923:Brain Chemistry / Q000502:physiology; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010725:Phosphocreatine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000473:pathology; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000473:pathology*
chemical_list: D010725:Phosphocreatine; D003401:Creatine; D002794:Choline