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Dopamine D1 receptor binding in the striatum of patients with obsessive–compulsive disorder

Abstract Background Obsessive–compulsive disorder (OCD) is a chronic anxiety disorder of unknown aetiology. Psychopharmacological studies have suggested a role for the neurotransmitter serotonin however further evidence for serotonin in the aetiology of OCD is conflicted. The authors used positron e...

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Published in:Journal of affective disorders 2009-04, Vol.114 (1), p.321-326
Main Authors: Olver, James S, O'Keefe, Graeme, Jones, Gareth R, Burrows, Graham D, Tochon-Danguy, Henri J, Ackermann, Uwe, Scott, Andrew, Norman, Trevor R
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container_start_page 321
container_title Journal of affective disorders
container_volume 114
creator Olver, James S
O'Keefe, Graeme
Jones, Gareth R
Burrows, Graham D
Tochon-Danguy, Henri J
Ackermann, Uwe
Scott, Andrew
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description Abstract Background Obsessive–compulsive disorder (OCD) is a chronic anxiety disorder of unknown aetiology. Psychopharmacological studies have suggested a role for the neurotransmitter serotonin however further evidence for serotonin in the aetiology of OCD is conflicted. The authors used positron emission tomography (PET) to examine the binding of the dopamine D1 receptor antagonist [11 C]-SCH23390 to D1 receptors in the striatum of drug-free OCD patients compared with healthy controls. Methods Seven drug-free patients (two drug naïve) with OCD and seven age, gender and education matched healthy controls underwent positron emission tomography with [11 C]-SCH23390. Binding Potentials (BP) at D1 receptors were calculated for the caudate nucleus and putamen. Correlations between BP values for basal ganglia regions and clinical measures were performed in OCD patients. Results The BP for [11 C]-SCH23390 at D1 receptors in OCD patients was significantly reduced in both caudate nucleus (0.59 ±0.06 vs 0.88 ± 0.06, p < 0.05) and putamen (0.89 ± 0.06 vs 1.14 ± 0.06, p < 0.05) compared with healthy controls. No correlations were found between D1 BP and symptom measures. Limitations The main limitations of this study are the small sample size and the PET methodology which does not allow for disaggregation of Bmax and Kd values for D1 receptor binding of [11 C]-SCH23390. Conclusions The finding of downregulation of D1 receptors in the striatum of OCD patients suggests increased nigrostriatal dopaminergic drive in OCD. If confirmed, this finding provides support for trials of novel treatments in OCD based on dopaminergic system blockade.
doi_str_mv 10.1016/j.jad.2008.06.020
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Psychopharmacological studies have suggested a role for the neurotransmitter serotonin however further evidence for serotonin in the aetiology of OCD is conflicted. The authors used positron emission tomography (PET) to examine the binding of the dopamine D1 receptor antagonist [11 C]-SCH23390 to D1 receptors in the striatum of drug-free OCD patients compared with healthy controls. Methods Seven drug-free patients (two drug naïve) with OCD and seven age, gender and education matched healthy controls underwent positron emission tomography with [11 C]-SCH23390. Binding Potentials (BP) at D1 receptors were calculated for the caudate nucleus and putamen. Correlations between BP values for basal ganglia regions and clinical measures were performed in OCD patients. Results The BP for [11 C]-SCH23390 at D1 receptors in OCD patients was significantly reduced in both caudate nucleus (0.59 ±0.06 vs 0.88 ± 0.06, p &lt; 0.05) and putamen (0.89 ± 0.06 vs 1.14 ± 0.06, p &lt; 0.05) compared with healthy controls. No correlations were found between D1 BP and symptom measures. Limitations The main limitations of this study are the small sample size and the PET methodology which does not allow for disaggregation of Bmax and Kd values for D1 receptor binding of [11 C]-SCH23390. Conclusions The finding of downregulation of D1 receptors in the striatum of OCD patients suggests increased nigrostriatal dopaminergic drive in OCD. If confirmed, this finding provides support for trials of novel treatments in OCD based on dopaminergic system blockade.</description><identifier>ISSN: 0165-0327</identifier><identifier>EISSN: 1573-2517</identifier><identifier>DOI: 10.1016/j.jad.2008.06.020</identifier><identifier>PMID: 18706700</identifier><identifier>CODEN: JADID7</identifier><language>eng</language><publisher>Oxford: Elsevier</publisher><subject>Adult ; Adult and adolescent clinical studies ; Aged ; Anxiety disorders. 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Psychopharmacological studies have suggested a role for the neurotransmitter serotonin however further evidence for serotonin in the aetiology of OCD is conflicted. The authors used positron emission tomography (PET) to examine the binding of the dopamine D1 receptor antagonist [11 C]-SCH23390 to D1 receptors in the striatum of drug-free OCD patients compared with healthy controls. Methods Seven drug-free patients (two drug naïve) with OCD and seven age, gender and education matched healthy controls underwent positron emission tomography with [11 C]-SCH23390. Binding Potentials (BP) at D1 receptors were calculated for the caudate nucleus and putamen. Correlations between BP values for basal ganglia regions and clinical measures were performed in OCD patients. Results The BP for [11 C]-SCH23390 at D1 receptors in OCD patients was significantly reduced in both caudate nucleus (0.59 ±0.06 vs 0.88 ± 0.06, p &lt; 0.05) and putamen (0.89 ± 0.06 vs 1.14 ± 0.06, p &lt; 0.05) compared with healthy controls. No correlations were found between D1 BP and symptom measures. Limitations The main limitations of this study are the small sample size and the PET methodology which does not allow for disaggregation of Bmax and Kd values for D1 receptor binding of [11 C]-SCH23390. Conclusions The finding of downregulation of D1 receptors in the striatum of OCD patients suggests increased nigrostriatal dopaminergic drive in OCD. If confirmed, this finding provides support for trials of novel treatments in OCD based on dopaminergic system blockade.</description><subject>Adult</subject><subject>Adult and adolescent clinical studies</subject><subject>Aged</subject><subject>Anxiety disorders. 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Neuroses</topic><topic>Benzazepines - pharmacokinetics</topic><topic>Biological and medical sciences</topic><topic>Carbon Radioisotopes</topic><topic>Case-Control Studies</topic><topic>Caudate Nucleus - diagnostic imaging</topic><topic>Caudate Nucleus - metabolism</topic><topic>Dopamine Antagonists - pharmacokinetics</topic><topic>Down-Regulation</topic><topic>Female</topic><topic>Humans</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Mood disorders</topic><topic>Obsessive-Compulsive Disorder - diagnostic imaging</topic><topic>Obsessive-Compulsive Disorder - metabolism</topic><topic>Obsessive-compulsive disorders</topic><topic>Positron-Emission Tomography</topic><topic>Psychiatric Status Rating Scales</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. 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Psychopharmacological studies have suggested a role for the neurotransmitter serotonin however further evidence for serotonin in the aetiology of OCD is conflicted. The authors used positron emission tomography (PET) to examine the binding of the dopamine D1 receptor antagonist [11 C]-SCH23390 to D1 receptors in the striatum of drug-free OCD patients compared with healthy controls. Methods Seven drug-free patients (two drug naïve) with OCD and seven age, gender and education matched healthy controls underwent positron emission tomography with [11 C]-SCH23390. Binding Potentials (BP) at D1 receptors were calculated for the caudate nucleus and putamen. Correlations between BP values for basal ganglia regions and clinical measures were performed in OCD patients. Results The BP for [11 C]-SCH23390 at D1 receptors in OCD patients was significantly reduced in both caudate nucleus (0.59 ±0.06 vs 0.88 ± 0.06, p &lt; 0.05) and putamen (0.89 ± 0.06 vs 1.14 ± 0.06, p &lt; 0.05) compared with healthy controls. No correlations were found between D1 BP and symptom measures. Limitations The main limitations of this study are the small sample size and the PET methodology which does not allow for disaggregation of Bmax and Kd values for D1 receptor binding of [11 C]-SCH23390. Conclusions The finding of downregulation of D1 receptors in the striatum of OCD patients suggests increased nigrostriatal dopaminergic drive in OCD. If confirmed, this finding provides support for trials of novel treatments in OCD based on dopaminergic system blockade.</abstract><cop>Oxford</cop><pub>Elsevier</pub><pmid>18706700</pmid><doi>10.1016/j.jad.2008.06.020</doi><tpages>6</tpages></addata></record>
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source ScienceDirect Journals
subjects Adult
Adult and adolescent clinical studies
Aged
Anxiety disorders. Neuroses
Benzazepines - pharmacokinetics
Biological and medical sciences
Carbon Radioisotopes
Case-Control Studies
Caudate Nucleus - diagnostic imaging
Caudate Nucleus - metabolism
Dopamine Antagonists - pharmacokinetics
Down-Regulation
Female
Humans
Magnetic Resonance Imaging
Male
Medical sciences
Middle Aged
Mood disorders
Obsessive-Compulsive Disorder - diagnostic imaging
Obsessive-Compulsive Disorder - metabolism
Obsessive-compulsive disorders
Positron-Emission Tomography
Psychiatric Status Rating Scales
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Putamen - diagnostic imaging
Putamen - metabolism
Receptors, Dopamine D1 - metabolism
Young Adult
title Dopamine D1 receptor binding in the striatum of patients with obsessive–compulsive disorder
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