Effect of age on gaba1 and glutathione in a pediatric sample

Abstract

BACKGROUND AND PURPOSE: Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the human brain and is implicated in several neuropathologies. Glutathione is a major antioxidant in the brain and is considered a marker of oxidative stress. Several studies have reported age-related declines in GABA levels in adulthood, but the trajectory of both GABA and glutathione during childhood has not been well explored. The aim of this study is to establish how GABA and glutathione vary with age during early development. MATERIALS AND METHODS: Twenty-three healthy children (5.6–13.9 years of age) were recruited for this study. MR imaging/MR spectroscopy experiments were conducted on a 3T MR scanner. A 27-mL MR spectroscopy voxel was positioned in the frontal lobe. J-difference edited MR spectroscopy was used to spectrally edit GABA and glutathione. Data were analyzed using the Gannet software, and GABAþ (GABA þ macromolecules/homocarnosine) and glutathione were quantified using water (GABAþH2O and GlutathioneH2O) and Cr (GABAþ/Cr and glutathione/Cr) as concentration references. Also, the relative gray matter contribution to the voxel volume (GMratio) was estimated from structural images. Pearson correlation coefficients were used to examine the association between age and GABAþH2O (and glutathioneH2O), between age and GABAþ/Cr (and glutathione/Cr), and between age and GMratio. RESULTS: Both GABAþH2O (r ¼ 0.63, P ¼ .002) and GABAþ/Cr (r ¼ 0.48, P ¼ .026) significantly correlated with age, whereas glutathione measurements and GMratio did not. CONCLUSIONS: We demonstrate increases in GABA and no differences in glutathione with age in a healthy pediatric sample. This study provides insight into neuronal maturation in children and may facilitate better understanding of normative behavioral development and the pathophysiology of developmental disorders.