High presynaptic dopaminergic activity in children with Tourette's disorder.
OBJECTIVE
Tourette's disorder is characterized by chronic fluctuating motor and vocal tics. Despite extensive investigation of the neuropathophysiology of the disorder by a wide array of methodologies, its neurobiochemical substrate is still unclear. Converging evidence, however, suggests a primary role of the dopaminergic system, particularly within the basal ganglia.


METHODS
This study examined the integrity of presynaptic dopaminergic function in children with Tourette's disorder, using positron emission tomography and the tracer [18F]fluorodopa (FDOPA). Accumulation of FDOPA in synaptic terminals, a measure of DOPA decarboxylase activity, was quantified in caudate nucleus, putamen, frontal cortex, and midbrain (i.e., substantia nigra and ventral tegmentum).


RESULTS
Subjects with Tourette's disorder showed higher FDOPA accumulation than controls in the left caudate nucleus (by 25%; p = .03) and right midbrain (by 53%; p = .08).


CONCLUSIONS
These findings provide evidence of dopaminergic dysfunction in children with Tourette's disorder which affects both cell nuclei and nerve terminals. Based on the known regulation of DOPA decarboxylase activity by post- and presynaptic receptors, and by extracellular dopamine concentration, abnormal activity in this enzyme may reflect deficits in a variety of functional elements of the dopamine system. The precise mechanism underlying an up-regulation of DOPA decarboxylase activity needs to be identified in future studies.
Ernst
M
M
Laboratory of Cerebral Metabolism, National Institute of Mental Health, NIH, Bethesda, MD 20892-4030, USA.
Zametkin
A J
AJ
Jons
P H
PH
Matochik
J A
JA
Pascualvaca
D
D
Cohen
R M
RM
D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D017661:Receptors, Presynaptic / Q000378:metabolism*; D012044:Regression Analysis; D014055:Tomography, Emission-Computed; D005879:Tourette Syndrome / Q000000981:diagnostic imaging / Q000378:metabolism*
D005462:Fluorine Radioisotopes; D017661:Receptors, Presynaptic; D004298:Dopamine