Validation of glutathione quantitation from STEAM spectra against edited 1H NMR spectroscopy at 4T: application to schizophrenia

Abstract

Objective: Quantitation of glutathione (GSH) in the human brain in vivo using short echo time 1 H NMR spectroscopy is challenging because GSH resonances are not easily resolved. The main objective of this study was to validate such quantitation in a clinically relevant population using the resolved GSH resonances provided by edited spectroscopy. A secondary objective was to compare several of the neurochemical concentrations quantified along with GSH using LCModel analysis of short echo time spectra in schizophrenia versus control. Materials and Methods: GSH was quantified at 4T from short echo STEAM spectra and MEGA-PRESS edited spectra from identical volumes of interest (anterior cingulate) in ten volunteers. Neurochemical profiles were quantified in nine controls and 13 medicated schizophrenic patients. Results: GSH concentrations as quantified using STEAM, 1.6 ± 0.4 µmol/g (mean ± SD, n = 10), were within error of those quantified using edited spectra, 1.4 ± 0.4 µmol/g, and were not different (p = 0.4). None of the neurochemical measurements reached sufficient statistical power to detect differences smaller than 10% in schizophrenia versus control. As such, no differences were observed. Conclusions: Human brain GSH concentrations can be quantified in a clinical setting using short-echo time STEAM spectra at 4T.

Glutathione and glutamate in schizophrenia: a 7T MRS study

“…Four other studies reported no statistically significant differences in glutathione levels in the posterior medial frontal cortex [23], mPFC [24] or anterior cingulate cortex (ACC) [25,26]. However, two out of the four found a trend toward reduced glutathione in schizophrenia [24,25] and in one, lowered levels of glutathione were associated with negative symptoms [24]. On balance, these studies of predominantly wellestablished cases of schizophrenia indicate a tendency toward reduced glutathione.…”

“…Another recent study reported reduced glutathione only in schizophrenia patients carrying a risk variant of the gene coding for the ratelimiting enzyme in glutathione synthesis [22]. Four other studies reported no statistically significant differences in glutathione levels in the posterior medial frontal cortex [23], mPFC [24] or anterior cingulate cortex (ACC) [25,26]. However, two out of the four found a trend toward reduced glutathione in schizophrenia [24,25] and in one, lowered levels of glutathione were associated with negative symptoms [24].…”

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

“…At a high field, with gain in sensitivity and spectral resolution, direct detection of glutathione and ascorbate at short echo time is possible (e.g. Terpstra et al, 2005Terpstra et al, , 2006. While ascorbate is predominantly in the neuronal compartment (Rice, 2000), glutathione is more concentrated in glia than neurons (Dringen, 2000), both existing under tight homeostatic regulation by synthesis and/or transport through the blood-brain-barrier.…”

Sulforaphane Augments Glutathione and Influences Brain Metabolites in Human Subjects: A Clinical Pilot Study

“…Successful application of MRS has shown alterations in brain glutamate (Glu) and γ-aminobutyric acid (GABA) levels in SZ patients [31-34]. In contrast, the data for GSH have been less consistent [19, 35, 36]. The limited sensitivity of 3-T MRS in detecting GSH levels may be the underlying source of this inconsistency, and studies with 7-T MRS should improve detection and yield more consistent results.…”