Effect of Age on GABA+ and Glutathione in a Pediatric Sample

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. 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 GABA+ (GABA + macromolecules/homocarnosine) and glutathione were quantified using water (GABA+ and Glutathione ) and Cr (GABA+/Cr and glutathione/Cr) as concentration references. Also, the relative gray matter contribution to the voxel volume (GM ) was estimated from structural images. Pearson correlation coefficients were used to examine the association between age and GABA+ (and glutathione ), between age and GABA+/Cr (and glutathione/Cr), and between age and GM . Both GABA+ ( = 0.63, = .002) and GABA+/Cr ( = 0.48, = .026) significantly correlated with age, whereas glutathione measurements and GM did not. 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.