Serotonin Control of Impulsivity in Tourette Disorder

Tourette disorder (TD) is a neurodevelopmental disorder characterized by motor and vocal tics. It is often associated with multiple psychiatric comorbidities involving a high degree of impulsivity such as obsessive-compulsive disorders (OCD), attention-deficit hyperactivity disorders (ADHD), and intermittent explosive disorders (IED). Although a substantial body of clinical studies have emphasized the role of the dopamine system in motor symptoms, little is known about how the serotonergic (5-HT) system modulate both cognitive and affective abilities in TD. Several lines of evidence suggest that different 5-HT receptor subtypes may constitute a crucial factor in the development and maintenance of different symptoms. Because abnormal 5-HT2A receptor bindings have been reported in patients with TD and aripiprazole (drug of first choice) is a 5-HT2A antagonist, we hypothesize that 5-HT2A receptors may play an important role in regulating psychiatric symptoms in TD such as those characterized by impulsive behaviors. To investigate the involvement of 5-HT2A receptors in TD, we propose to perform a multimodal imaging study with 20 adult patients (ON and OFF treatment). Neuroimaging data will be collected with a hybrid system that simultaneously combines the positron emission tomography (PET) and the functional magnetic resonance imaging (fMRI). A highly selective PET radiotracer ([18F]-altanserin) will map 5-HT2A receptor bindings in the whole brain, while fMRI will provide detail information regarding the altered brain activities.