Brief reportDopamine D1 receptor binding in the striatum of patients with obsessive–compulsive disorder
Introduction
Obsessive–compulsive disorder (OCD) is a chronic anxiety disorder characterised by recurrent obsessions and compulsions aimed at reducing the distress caused by obsessional thinking. The lifetime prevalence of OCD may be as high as 2.5% (Weissman et al., 1994). The course is frequently chronic with up to half of patients experiencing continuous symptoms over a 30 year period (Skoog and Skoog, 1999). The illness may severely affect the quality of life of sufferers and their families.
The aetiology of OCD is not known however the prevailing theory suggests a role for the neurotransmitter serotonin. This is largely based on the efficacy of serotonin reuptake inhibitors (SRIs) in the disorder. High doses are required over a prolonged period to achieve most therapeutic gains. Further evidence for a serotonergic abnormality in OCD is conflicted (Westenberg et al., 2007).
The major competing neurotransmitter theory of OCD proposes a role for dopamine. Functional neuroimaging studies of patients with OCD at rest and during symptom provocation have consistently reported increased activity in regions associated with cortico–striatal–thalamo–cortical circuits. In particular, a loop involving orbitofrontal cortex (OFC) and cingulate gyrus, striatum (caudate nucleus and putamen), globus pallidus and thalamus has been implicated (Saxena et al., 1998). Within the “OCD loop”, dopamine acting at D1 and D2 receptors in the striatum has been suggested to have a modulatory role (Saxena et al., 1998). Previous studies have suggested there is a downregulation of dopamine D2 receptors in OCD patients compared with controls (Denys et al., 2004, Moresco et al., 2006) however no studies have yet reported on changes in the D1 receptor system in OCD patients.
In this study, we used positron emission tomography (PET) to investigate the binding of [11C]-SCH23390, a dopamine D1 antagonist ligand, in striatum of drug-free patients with OCD compared to healthy controls.
Section snippets
Subjects
Seven drug-free subjects (4 male, 3 female) with a mean age of 40.0 ± 13.9 years (mean ± 1 SD) (range 24–65 years) meeting DSM-IV criteria for the diagnosis of obsessive–compulsive disorder were referred by psychiatrists for the study (Table 1) The diagnosis was confirmed using the Anxiety Disorders Interview Schedule for DSMIV. Two OCD patients were medication-naïve, three had not received SRI treatment for over 18 months, one patient was medication-free for 4 weeks and one patient was
Results
The mean binding potential (BP) of [11C]-SCH23390 to D1 receptors is presented in Fig. 1. Binding potentials in the caudate (summed total) of OCD patients was significantly reduced compared with normal controls (0.59 ± 0.06 vs 0.88 ± 0.06, t = 2.67, p < 0.05). Lateralised binding potentials to D1 receptors in caudate were also reduced in OCD patients compared with healthy controls (Left: 0.66 ± 0.09 vs 0.93 ± 0.07, t = 2.34, p < 0.05, Right: 0.52 ± 0.09 vs 0.85 ± 0.07, t = 2.80, p < 0.05). Similarly a reduced BP to D1
Discussion
We report reduced BP of [11C]-SCH23390 to dopamine D1 receptors in the caudate nucleus (right and left side) and putamen (right and left side) of patients with OCD compared with healthy controls. A widely accepted neuroanatomical model proposed to account for the functional neuroimaging findings in OCD suggests involvement of the cortico–striatal–thalamic pathways (Saxena et al., 1998). Direct and indirect pathways within the loops have been suggested to have opposite effects on the activation
Role of funding source
This project was funded from in-house resources, Austin Health, Heidelberg, Australia.
Conflict of interest
All authors declare there are no conflicts of interest in the publication of this study.
Acknowledgements
Nil.
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