Dopaminergic activity in Tourette syndrome and obsessive-compulsive disorder

Abstract

Tourette syndrome (TS) and obsessive-compulsive disorder (OCD) both are neuropsychiatric disorders associated with abnormalities in dopamine neurotransmission. Aims of this study were to quantify striatal D2/3 receptor availability in TS and OCD, and to examine dopamine release and symptom severity changes in both disorders following amphetamine challenge. Changes in [(11)C]raclopride binding potential (BP(ND)) were assessed using positron emission tomography before and after administration of d-amphetamine (0.3 mg kg(-1)) in 12 TS patients without comorbid OCD, 12 OCD patients without comorbid tics, and 12 healthy controls. Main outcome measures were baseline striatal D2/3 receptor BP(ND) and change in BP(ND) following amphetamine as a measure of dopamine release. Voxel-based analysis revealed significantly decreased baseline [(11)C]raclopride BP(ND) in bilateral putamen of both patient groups vs. healthy controls, differences being more pronounced in the TS than in the OCD group. Changes in BP(ND) following amphetamine were not significantly different between groups. Following amphetamine administration, tic severity increased in the TS group, which correlated with BP(ND) changes in right ventral striatum. Symptom severity in the OCD group did not change significantly following amphetamine challenge and was not associated with changes in BP(ND). This study provides evidence for decreased striatal D2/3 receptor availability in TS and OCD, presumably reflecting higher endogenous dopamine levels in both disorders. In addition, it provides the first direct evidence that ventral striatal dopamine release is related to the pathophysiology of tics.

Functional neuroimaging in Tourette syndrome: recent perspectives

“…54 With regard to the dopaminergic system, studies have shown contradictory results. Decreased dopamine receptor binding was found in patients with TS (both striatal 61 and extrastriatal 62 ). Steeves et al 62 has found reductions in dopamine receptor binding in the frontal cortex and thalamus.…”

“…33 In an MRS study, it was shown that the GABA concentration in SM1 correlated negatively with motor tic severity. 53 Amphetamineinduced dopamin release in the ventral striatum was related to increased tic severity in one PET study, 61 while another PET study did not find any correlations between the TS-related metabolic covariance pattern (with increased activity bilaterally in premotor cortex and cerebellum, associated with relative reductions in striatum and orbitofrontal cortices) and severity of tics. 58 During voluntary movement control measured with MEG, larger amplitudes were inversely correlated with motor tic frequency and severity, 39 while another MEG study found ipsilateral motor cortical inhibition to be inversely related with tic severity.…”

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

“…The defining symptoms of TS are motor and phonic tics, defined as sudden, repetitive, nonrhythmic, involuntary or semiinvoluntary movements or utterances that involve discrete muscle groups. Tics fluctuate and are exacerbated by stress (3)(4)(5) and by acute challenge with prodopaminergic drugs (6). Individuals with TS also often have deficits in fine motor control (7,8), procedural learning (9), and sensorimotor gating (10,11).…”

Association between genetic variants related to glutamatergic, dopaminergic and neurodevelopment pathways and white matter microstructure in child and adolescent patients with obsessive–compulsive disorder

“…Atypical antipsychotics and dopaminergic agents can reduce or exacerbate OCD symptoms, respectively (Bokor and Anderson, 2014). The few reports on DA receptor binding in OCD consistently show decreased DA receptor availability (Denys et al, 2013, Perani et al, 2008 supporting the hypothesis of chronically increased dopaminergic activity in the disorder, which has been recently observed in different brain regions including left and right cerebellum of OCD patients (Hsieh et al, 2014).…”