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-HT_2A receptors (5-HT_2AR), 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 D₂-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-HT_2AR, 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_2AR 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.