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Original

Frontal-subcortical circuits in obsessive-compulsive disorder: Role of the dopamine D1 receptor

, , , , , , , , & show all
Page A49 | Published online: 06 Jul 2009
 

Abstract

Obsessive-Compulsive Disorder (OCD) is increasingly being recognized as a neurobiological disorder. Serotonergic mechanisms have been proposed on the basis of a partial response of patients to drugs which block the neuronal uptake of serotonin. Further evidence for a serotonergic abnormality is lacking. The major competing theory in the pathophysiology of OCD involves the neurotransmitter dopamine. OCD symptoms are frequently found in neuropsychiatric disorders involving the dopamine rich regions of the basal ganglia, dopamine agonists worsen OCD, peripheral models of central dopaminergic function are abnormal in OCD, urinary excretion of HVA is elevated and neurophysiological studies suggest dopamine-related gating abnormalities in OCD. The Dopamine D1 receptor is implicated in OCD following the finding of specific spatial working memory abnormalities in a series of neuropsychological studies. Spatial working memory is known to depend on the integrity of D1 receptor function in the Dorso-lateral Prefrontal Cortex (DLPFC) of primates. This study aims to examine the role of dopamine in patients with OCD and in particular to test the hypothesis that there is an up-regulation of dopamine D1 receptors in the DLPFC which correlates with spatial working memory deficits in OCD.

Methods: Three OCD patients and one normal control underwent Positron Emission Tomography (PET) following intravenous injection of the D1 antagonist PET ligand SCH23390. Reconstructed PET images were co-registered with subject Magnetic Resonance Images (MRI) and regions of interest drawn manually.

Results: Mean binding of 11C-SCU 23390 in the DLPFC and OFC of 3 OCD patients was greater than normal control patient.

Conclusion: Preliminary results suggest increased D1 binding in selected frontal cortex regions in patients with OCD.

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