Phasic dysfunction of dopamine transmission in Tourette's syndrome evaluated with ^99mTc TRODAT-1 imaging

Abstract 

This study investigated the complex dysregulation of the dopaminergic neurotransmitter system in Tourette's syndrome (TS) patients challenged with methylphenidate (MPH). Eight drug-naïve male patients (aged 21–25 years) who met DSM-IV criteria for TS and had a mean disease severity of 25 on the Yale Global Tic Severity Scale were recruited. Brain ^99mTC TRODAT-1 dopamine transporter (DAT) single photon emission computed tomography (SPECT) was performed 5 days before, and 2 h after 10 mg of orally administered MPH. Eight age-matched healthy males served as controls. Repeated measures analysis of variance was used to measure differences in DAT-binding ratios before and after MPH challenge between the TS patients and controls. The DAT-binding ratios decreased significantly after MPH treatment in both groups. However, a significant interaction between group and MPH effects was found only in the right caudate, which was mainly due to a smaller decline of the DAT-binding ratio after MPH in the TS group than in the controls. Such a distinction was not found in the other striatal sub-regions in the two groups. No correlation, however, was observed between the tic severity score and DAT-binding ratio measured from the whole striatum or its sub-regions. The observed change in the DAT-binding ratio might indicate a functional abnormality of the dopaminergic system in the right caudate nucleus of TS patients. Future studies exploring dopamine transmission are thus needed to understand the pathophysiology of TS.

Keywords: Tourette's syndrome, Dopamine transporter, Methylphenidate, ^99mTC TRODAT-1