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Serotonin 2A receptors in obsessive-compulsive disorder: a positron emission tomography study with [11C]MDL 100907.

ABSTRACT: Serotonergic abnormalities are hypothesized to contribute to obsessive-compulsive disorder (OCD). This study used positron emission tomography with the radioligand [11C]MDL 100907 to examine whether the distribution of serotonin 2A (5-HT(2A)) receptors is altered in OCD.Nineteen OCD subjects, free of psychiatric medications and depression, and 19 matched healthy subjects underwent positron emission tomography scans following injection of [11C]MDL 100907. Total distribution volumes were derived by kinetic analysis using the arterial input function. Two measures of 5-HT(2A) availability were computed: the ratio at equilibrium of specifically bound radiotracer either to nondisplaceable radiotracer in tissue (BP(ND)) or to unmetabolized tracer in arterial plasma (BP(p)). Groups were compared using a region of interest (ROI) analysis and voxelwise analysis of spatially normalized parametric maps. ROIs included cortical (orbitofrontal, dorsolateral prefrontal, medial prefrontal, anterior cingulate, temporal, parietal, occipital, and insular cortex) and limbic (entorhinal cortex, parahippocampal gyrus, and medial temporal lobe) regions.No significant group differences were observed in [11C]MDL 100907 BP(ND) or BP(p) in the ROIs or in the voxelwise analysis of BP(ND) maps. There was a significant correlation in the orbitofrontal cortex between [11C]MDL 100907 binding and age of onset, with earlier age of onset associated with higher binding.Adults with OCD are not characterized as a group by major changes in 5-HT(2A) availability in cortical or limbic brain regions. Further research is warranted to examine potential differences in 5-HT(2A) availability between early- and late-onset OCD and to assess 5-HT(2A) function in relation to other neurotransmitter systems implicated in OCD.

SUBMITTER: Simpson HB

PROVIDER: S-EPMC3951757 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Serotonin 2A receptors in obsessive-compulsive disorder: a positron emission tomography study with [11C]MDL 100907.

Simpson Helen Blair HB Slifstein Mark M Bender James J Xu Xiaoyan X Hackett Elizabeth E Maher Michael J MJ Abi-Dargham Anissa A

Biological psychiatry 20111101 9

<h4>Background</h4>Serotonergic abnormalities are hypothesized to contribute to obsessive-compulsive disorder (OCD). This study used positron emission tomography with the radioligand [11C]MDL 100907 to examine whether the distribution of serotonin 2A (5-HT(2A)) receptors is altered in OCD.<h4>Methods</h4>Nineteen OCD subjects, free of psychiatric medications and depression, and 19 matched healthy subjects underwent positron emission tomography scans following injection of [11C]MDL 100907. Total ...[more]

PMID: 21855857

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Project description:BackgroundThe pathophysiology of bipolar disorder (BD) remains largely unknown despite it causing significant disability and suicide risk. Serotonin signaling may play a role in the pathophysiology, but direct evidence for this is lacking. Treatment of the depressed phase of the disorder is limited. Previous studies have indicated that positron emission tomography (PET) imaging of the serotonin 1A receptor (5HT1AR) may predict antidepressant response.MethodsA total of 20 participants with BD in a current major depressive episode and 16 healthy volunteers had PET imaging with [11C]CUMI-101, employing a metabolite-corrected input function for quantification of binding potential to the 5HT1AR. Bipolar participants then received an open-labeled, 6-week clinical trial with a selective serotonin reuptake inhibitor (SSRI) in addition to their mood stabilizer. Clinical ratings were obtained at baseline and during SSRI treatment.ResultsPretreatment binding potential (BPF) of [11C]CUMI-101 was associated with a number of pretreatment clinical variables within BD participants. Within the raphe nucleus, it was inversely associated with the baseline Montgomery Åsberg Rating Scale (P = .026), the Beck Depression Inventory score (P = .0023), and the Buss Durkee Hostility Index (P = .0058), a measure of lifetime aggression. A secondary analysis found [11C]CUMI-101 BPF was higher in bipolar participants compared with healthy volunteers (P = .00275). [11C]CUMI-101 BPF did not differ between SSRI responders and non-responders (P = .907) to treatment and did not predict antidepressant response (P = .580). Voxel-wise analyses confirmed the results obtained in regions of interest analyses.ConclusionsA disturbance of serotonin system function is associated with both the diagnosis of BD and its severity of depression. Pretreatment 5HT1AR binding did not predict SSRI antidepressant outcome.The study was listed on clinicaltrials.gov with identifier NCT02473250.

Dataset Information

Serotonin 2A receptors in obsessive-compulsive disorder: a positron emission tomography study with [11C]MDL 100907.

Publications

Serotonin 2A receptors in obsessive-compulsive disorder: a positron emission tomography study with [11C]MDL 100907.

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