Tics severity in Tourette syndrome associated with higher glutamatergic activity in the anterior cingulate cortex

Abstract Tourette syndrome is a neuropsychiatric disorder whose physiopathology is still poorly understood. It involves alterations in the dopaminergic system within the cortico-basal ganglia-thalamo-cortical loops although several hypotheses from the literature implicate the glutamatergic system. Our objective was to study the activity of NMDA receptors in vivo in patients with Tourette syndrome compared to healthy controls. PET imaging was used in patients with Tourette syndrome (n=12) and healthy controls (n=12) with a new radioligand, the [18F]-FNM, which binds to activated NMDA receptors. Clinical and behavioural assessments were also performed on patients to evaluate tics severity (YGTSS), obsessive–compulsive disorder (Y-BOCS), impulsivity (BIS-11) and anxio-depressive state (HAD). PET activity was compared between groups in different regions of interest (ROIs). Correlations were made between PET activity and clinical/behavioural scores in patients with Tourette syndrome. Significant differences in NMDA receptors activity were found between patients with Tourette syndrome and controls in the right and left anterior cingulate cortex (ACC), the right caudate nucleus, the right olfactory cortex, and the left paracentral lobule: patients with Tourette syndrome exhibited higher NMDA receptors activity in these ROIs. Moreover, this hyper-NMDA receptors activity in the ACC correlated positively and significantly with YGTSS scores in patients with Tourette syndrome. Patients with Tourette syndrome showed higher NMDA receptors activity in the ACC, caudate nucleus, paracentral lobule and olfactory cortex. This presumed hyper-glutamatergic activity may indicate a hyper-activation of the direct striatal pathway leading to the onset of tics, in addition to the supposed hypo-activation of the indirect striatal pathway related to hypo-GABAergic state reported in the literature. Tourette syndrome would therefore be associated with an imbalance between excitatory and inhibitory influences within the cortico-basal ganglia-thalamo-cortical circuit.