Differences in dopamine release in Tourette's syndrome and obsessive-compulsive disorder

Objectives Dopaminergic abnormalities in frontal-subcortical circuits have been hypothesized as the underlying pathophysiology in both patients with Tourette's syndrome (TS) and Obsessive-Compulsive Disorder (OCD). Work from our lab showed greater dopamine (DA) release (ΔBP) in the putamen (Singer et al 2002) and ventral striatum (Wong et al 2008) of adults with TS vs. healthy control subjects (HC) after a pharmacologic amphetamine challenge. Additionally, in subjects with both TS and OCD, we found a significant ΔBP increase in the right ventral striatum (Wong et al 2008) compared to controls, suggesting the underlying pathobiology in both disorders is phasic dysfunction of DA transmission.

Methods We expanded this research by examining a further 28 age-matched subjects; 1 HC, 3 subjects with TS, 10 subjects with OCD and 7 subjects with both TS and OCD (making a total of 24 TS subjects). All subjects received two PET scans with high specific activity [11C]raclopride-the 1st scan after IV saline, the 2nd after IV amphetamine, as well as extensive neuropsychological/psychiatric testing. The relative ΔBP was estimated as the percentage change in binding potential (BP_ND).

Results We found a significant differences in: 1) ΔBP between TS and HC in the right ventral striatum (t=-2.749, p=0.010), 2) ΔBP between TS and TS+OCD in the left posterior putamen (t=2.146, p=0.047) and right posterior putamen (t=2.435, p= 0.024). ΔBP in OCD was not significantly different than HC.

Conclusions These results confirm our earlier work and also suggest that there may be regional differences between TS and OCD in terms of DAergic dysfunction. Simultaneous serotonin receptor (5HT_2A) and 5HT transporter (SERT) PET were obtained in 11 of these new subjects, and will be presented, as this is an additional key component of our DA/5HT model.

Research Support R01MH07817