Mechanisms of Dopaminergic and Serotonergic Neurotransmission in Tourette Syndrome: Clues from an In Vivo Neurochemistry Study with PET

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 33; no. 6; pp. 1239 - 1251
• Main Authors: Wong, Dean F, Brašić, James R, Singer, Harvey S, Schretlen, David J, Kuwabara, Hiroto, Zhou, Yun, Nandi, Ayon, Maris, Marika A, Alexander, Mohab, Ye, Weiguo, Rousset, Olivier, Kumar, Anil, Szabo, Zsolt, Gjedde, Albert, Grace, Anthony A
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.05.2008; Nature Publishing; Nature Publishing Group
• Subjects: Adult; Adult and adolescent clinical studies; Amphetamine - administration & dosage; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Brain Mapping; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine - metabolism; Dopamine Agents - administration & dosage; Dopamine Plasma Membrane Transport Proteins - metabolism; Female; Humans; Magnetic Resonance Imaging; Male; Medical sciences; Medicine; Medicine & Public Health; Models, Theoretical; Neurology; Neuropsychological Tests; Neurosciences; Obsessive-Compulsive Disorder - diagnostic imaging; Organic mental disorders. Neuropsychology; original-article; Pharmacotherapy; Positron-Emission Tomography; Psychiatric Status Rating Scales; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Raclopride - metabolism; Receptors, Dopamine D2 - drug effects; Receptors, Dopamine D2 - metabolism; Serotonin - metabolism; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Tourette Syndrome - diagnostic imaging; Tourette's syndrome; brain imaging; serotonin; neurochemistry; dopamine; PET; Nervous system diseases; Dopamine; Serotonin; Central nervous system; Catecholamine; Cerebral disorder; Encephalon; In vivo; Imaging; Central nervous system disease; Neurotransmitter; Medical imagery; Gilles de la Tourette syndrome; Degenerative disease; Mechanism of action; Neurotransmission; Emission tomography
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/sj.npp.1301528

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 D 2 receptors (D 2 -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-HT 2A receptors (5-HT 2A R), 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 D 2 -R, 5-HT 2A R, and SERT were measured within a 12-month period, there was a weakly significant elevation of DA rel and 5-HT 2A 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-HT 2A R 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.