Extrastriatal dopaminergic dysfunction in tourette syndrome.
OBJECTIVE
Tourette syndrome (TS) is a neuropsychiatric disorder presenting with tics and a constellation of nonmotor symptoms that includes attention deficit hyperactivity disorder, obsessive-compulsive disorder, and impulse control disorders. Accumulated evidence from pharmacological trials and postmortem analyses suggests that abnormalities of dopaminergic neurotransmission play a key role in the pathogenesis of TS. A substantial body of evidence has also accrued to implicate regions outside the striatum in the generation of tics.


METHODS
We initiated an [11C]FLB 457 positron emission tomography study in conjunction with an amphetamine challenge to evaluate extrastriatal dopamine (DA) D2/D3 receptor binding and DA release in a group of treatment-naive, adult TS patients compared with a group of age- and sex-matched controls.


RESULTS
At baseline, TS patients showed decreased [11C]FLB 457 binding potentials bilaterally in cortical and subcortical regions outside the striatum, including the cingulate gyrus, middle and superior temporal gyrus, occipital cortex, insula, and thalamus. Amphetamine challenge induced DA release in both control and TS subjects bilaterally in many cortical regions; however, in TS patients, regions of increased DA release were significantly more widespread and extended more anteriorly to involve anterior cingulate and medial frontal gyri. Conversely, and in contrast to healthy controls, no significant DA release was noted in the thalami of TS patients.


CONCLUSIONS
These abnormalities of dopaminergic function localize to brain regions previously implicated in TS and suggest a mechanism for the hyperexcitability of thalamocortical circuits that has been documented in the disorder.
Steeves
Thomas D L
TD
Division of Neurology, Toronto Western Hospital, University Health Network, University of Toronto, Ontario, Canada.
Ko
Ji Hyun
JH
Kideckel
David M
DM
Rusjan
Pablo
P
Houle
Sylvain
S
Sandor
Paul
P
Lang
Anthony E
AE
Strafella
Antonio P
AP
D000293:Adolescent; D000328:Adult; D001667:Binding, Competitive; D001931:Brain Mapping / Q000379:methods; D002247:Carbon Isotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D011759:Pyrrolidines; D012457:Salicylamides; D005879:Tourette Syndrome / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
D002247:Carbon Isotopes; D018492:Dopamine Antagonists; D011759:Pyrrolidines; D012457:Salicylamides; C065065:FLB 457; D004298:Dopamine