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 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-HT2A receptors (5HT(2A)R), and serotonin transporter (SERT) BP, in 11 subjects with TS and 10 normal control subjects. As compared with controls, DArel 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 DArel and 5-HT2ABP, 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 DArel 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 DArel, suggest a condition of increased phasic DArel modulated by low 5-HT in concomitant OCD.