Martijn Figee1, Pelle de Koning2, Sanne Klaassen2, Nienke Vulink2, Mariska Mantione2, Pepijn van den Munckhof3, Richard Schuurman3, Guido van Wingen2, Thérèse van Amelsvoort4, Jan Booij5, Damiaan Denys6. 1. Department of Psychiatry, Academic Medical Center, Amsterdam; Brain Imaging Center, Academic Medical Center, Amsterdam. Electronic address: m.figee@amc.nl. 2. Department of Psychiatry, Academic Medical Center, Amsterdam. 3. Department of Neurosurgery, Academic Medical Center, Amsterdam. 4. Department of Psychiatry, Academic Medical Center, Amsterdam; Department of Psychiatry and Psychology, Maastricht University, Maastricht. 5. Brain Imaging Center, Academic Medical Center, Amsterdam; Department of Nuclear Medicine, Academic Medical Center, Amsterdam. 6. Department of Psychiatry, Academic Medical Center, Amsterdam; Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
Abstract
BACKGROUND: Obsessive-compulsive disorder is a chronic psychiatric disorder related to dysfunctional dopaminergic neurotransmission. Deep brain stimulation (DBS) targeted at the nucleus accumbens (NAc) has recently become an effective treatment for therapy-refractory obsessive-compulsive disorder, but its effect on dopaminergic transmission is unknown. METHODS: We measured the effects of NAc DBS in 15 patients on the dopamine D2/3 receptor availability in the striatum with [(123)I]iodobenzamide ([(123)I]IBZM) single photon emission computed tomography. We correlated changes in [(123)I]IBZM binding potential (BP) with plasma levels of homovanillic acid (HVA) and clinical symptoms. RESULTS: Acute (1-hour) and chronic (1-year) DBS decreased striatal [(123)I]IBZM BP compared with the nonstimulated condition in the putamen. BP decreases were observed after 1 hour of stimulation, and chronic stimulation was related to concurrent HVA plasma elevations, implying DBS-induced dopamine release. BP decreases in the area directly surrounding the electrodes were significantly correlated with changes in clinical symptoms (45% symptom decrease). CONCLUSIONS: NAc DBS induced striatal dopamine release, which was associated with increased HVA plasma levels and improved clinical symptoms, suggesting that DBS may compensate for a defective dopaminergic system.
BACKGROUND:Obsessive-compulsive disorder is a chronic psychiatric disorder related to dysfunctional dopaminergic neurotransmission. Deep brain stimulation (DBS) targeted at the nucleus accumbens (NAc) has recently become an effective treatment for therapy-refractory obsessive-compulsive disorder, but its effect on dopaminergic transmission is unknown. METHODS: We measured the effects of NAc DBS in 15 patients on the dopamine D2/3 receptor availability in the striatum with [(123)I]iodobenzamide ([(123)I]IBZM) single photon emission computed tomography. We correlated changes in [(123)I]IBZM binding potential (BP) with plasma levels of homovanillic acid (HVA) and clinical symptoms. RESULTS: Acute (1-hour) and chronic (1-year) DBS decreased striatal [(123)I]IBZMBP compared with the nonstimulated condition in the putamen. BP decreases were observed after 1 hour of stimulation, and chronic stimulation was related to concurrent HVA plasma elevations, implying DBS-induced dopamine release. BP decreases in the area directly surrounding the electrodes were significantly correlated with changes in clinical symptoms (45% symptom decrease). CONCLUSIONS: NAc DBS induced striatal dopamine release, which was associated with increased HVA plasma levels and improved clinical symptoms, suggesting that DBS may compensate for a defective dopaminergic system.
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