Striatal [11C]dihydrotetrabenazine and [11C]methylphenidate binding in Tourette syndrome.
OBJECTIVE
Tourette syndrome (TS) is a common neurodevelopmental disorder marked by tics and behavioral comorbidities. Clinical pharmacology suggests that dopaminergic signaling abnormalities are part of the pathophysiology of TS. Prior molecular imaging studies of nigrostriatal dopaminergic terminal markers report conflicting results. Our goal was to characterize the distribution of nigrostriatal dopaminergic terminals in subjects with TS.


METHODS
Thirty-three adult subjects with TS were studied with PET using [11C]dihydrotetrabenazine (DTBZ), a ligand for the type 2 vesicular monoamine transporter, and with [11C] methylphenidate (MP), a ligand for the plasmalemmal dopamine transporter. Subjects were characterized with standard rating instruments for tic severity, obsessive-compulsive behaviors, and attentional deficits.


RESULTS
We found no differences between subjects with TS and control subjects in DTBZ and MP binding in any striatal region. There was no correlation between binding measures and clinical variables. Ventral striatal DTBZ and MP binding distributions in subjects with TS were normal.


CONCLUSIONS
We found no evidence of increased striatal dopaminergic innervation in Tourette syndrome (TS). Discrepancy between our present results and those of other studies may be explained by heterogeneity of TS.
Albin
R L
RL
Geriatrics Research, Education, and Clinical Center, Ann Arbor VAMC, Ann Arbor, MI, USA. ralbin@umich.edu
Koeppe
R A
RA
Wernette
K
K
Zhuang
W
W
Nichols
T
T
Kilbourn
M R
MR
Frey
K A
KA
D000293:Adolescent; D000328:Adult; D001667:Binding, Competitive / Q000502:physiology; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D017729:Presynaptic Terminals / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism / Q000503:physiopathology; D013747:Tetrabenazine / Q000031:analogs & derivatives; D005879:Tourette Syndrome / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000503:physiopathology; D050493:Vesicular Monoamine Transport Proteins / Q000032:analysis / Q000378:metabolism; D055815:Young Adult
D002250:Carbon Radioisotopes; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; D008774:Methylphenidate; C032811:dihydrotetrabenazine; D004298:Dopamine; D013747:Tetrabenazine