We hypothesized that glutamatergic signalling is related to pathophysiology of Gilles de la Tourette syndrome (GTS) and investigated glutamatergic metabolism within cortico-striatal regions using 1H-MRS at baseline and during treatment. Absolute metabolite concentrations were calculated with the consideration of voxel compartmentation following frequency and phase drift correction in the time domain. GTS patients exhibited reductions in striatal and thalamic [Glx], which were normalized with treatment and were correlated with clinical severity parameters. Our results implicate glutamatergic metabolism in GTS pathophysiology and indicate a possibly dysfunctional astrocytic-neuronal coupling system, which would have profound effects on the dopaminergic modulation of cortico-striatal input.