Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET.
Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by motor and phonic tics. Obsessive-compulsive disorder (OCD) is often concomitant with TS. Dysfunctional tonic and phasic dopamine (DA) and serotonin (5-HT) metabolism may play a role in the pathophysiology of TS. We simultaneously measured the density, affinity, and brain distribution of dopamine D2 receptors (D2-R's), dopamine transporter binding potential (BP), and amphetamine-induced dopamine release (DA(rel)) in 14 adults with TS and 10 normal adult controls. We also measured the brain distribution and BP of serotonin 5-HT2A receptors (5-HT2AR), and serotonin transporter (SERT) BP, in 11 subjects with TS and 10 normal control subjects. As compared with controls, DA rel was significantly increased in the ventral striatum among subjects with TS. Adults with TS+OCD exhibited a significant D(2)-R increase in left ventral striatum. SERT BP in midbrain and caudate/putamen was significantly increased in adults with TS (TS+OCD and TS-OCD). In three subjects with TS+OCD, in whom D2-R, 5-HT2AR, and SERT were measured within a 12-month period, there was a weakly significant elevation of DA rel and 5-HT2A BP, when compared with TS-OCD subjects and normal controls. The current study confirms, with a larger sample size and higher resolution PET scanning, our earlier report that elevated DA rel is a primary defect in TS. The finding of decreased SERT BP, and the possible elevation in 5-HT2AR in individuals with TS who had increased DA rel, suggest a condition of increased phasic DA rel modulated by low 5-HT in concomitant OCD.
Wong
Dean F
DF
Division of Nuclear Medicine, Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA. dfwong@jhmi.edu
Brasić
James R
JR
Singer
Harvey S
HS
Schretlen
David J
DJ
Kuwabara
Hiroto
H
Zhou
Yun
Y
Nandi
Ayon
A
Maris
Marika A
MA
Alexander
Mohab
M
Ye
Weiguo
W
Rousset
Olivier
O
Kumar
Anil
A
Szabo
Zsolt
Z
Gjedde
Albert
A
Grace
Anthony A
AA
D000328:Adult; D000661:Amphetamine / Q000008:administration & dosage; D001931:Brain Mapping; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000008:administration & dosage; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008962:Models, Theoretical; D009483:Neuropsychological Tests; D009771:Obsessive-Compulsive Disorder / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D020891:Raclopride / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005879:Tourette Syndrome / Q000000981:diagnostic imaging*
D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; D012701:Serotonin; D020891:Raclopride; D000661:Amphetamine; D004298:Dopamine