High presynaptic dopaminergic activity in children with Tourette's disorder

Objective: Tourette's disorder is characterized by chronic fluctuating moto r and vocal ties. Despite extensive investigation of the neuropathophysiolo gy of the disorder by a wide array of methodologies, its neurobiochemical s ubstrate is still unclear. Converging evidence, however, suggests a primary role of the dopaminergic system, particularly within the basal ganglia. Me thod: This study examined the integrity of presynaptic dopaminergic functio n in children with Tourette's disorder, using positron emission tomography and the tracer [F-18]fluorodopa (FDOPA). Accumulation of FDOPA in synaptic terminals, a measure of DOPA decarboxylase activity, was quantified in caud ate nucleus, putamen, frontal cortex, and midbrain (i.e., substantia nigra and ventral tegmentum). Results: Subjects with Tourette's disorder showed h igher FDOPA accumulation than controls in the left caudate nucleus (by 25%; p = .03) and right midbrain (by 53%; p = .08). Conclusion: These findings provide evidence of dopaminergic dysfunction in children with Tourette's di sorder which affects both cell nuclei and nerve terminals. Based on the kno wn regulation of DOPA decarboxylase activity by post- and presynaptic recep tors, and by extracellular dopamine concentration, abnormal activity in thi s enzyme may reflect deficits in a variety of functional elements of the do pamine system. The precise mechanism underlying an up-regulation of DOPA de carboxylase activity needs to be identified in future studies.