E Kim1, O D Howes2, J W Park3, S N Kim3, S A Shin4, B-H Kim5, F E Turkheimer6, Y-S Lee7, J S Kwon3. 1. Department of Neuropsychiatry,Seoul National University Bundang Hospital,Gyeonggi-do,Korea. 2. Psychiatric Imaging,Medical Research Council Clinical Sciences Centre,Imperial College London,Hammersmith Hospital Campus,London,UK. 3. Department of Psychiatry,Seoul National University College of Medicine,Seoul,Korea. 4. Department of Biomedical Sciences,Seoul National University,Seoul,Korea. 5. Department of Clinical Pharmacology and Therapeutics,Kyung Hee University College of Medicine and Hospital,Seoul,Korea. 6. King's College London, Institute of Psychiatry,London,UK. 7. Department of Nuclear Medicine,Seoul National University College of Medicine,Seoul,Korea.
Abstract
BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic, relapsing mental illness. Selective serotonin reuptake inhibitors block serotonin transporters (SERTs) and are the mainstay of treatment for OCD. SERT abnormalities are reported in drug-free patients with OCD, but it is not known what happens to SERT levels during treatment. This is important as alterations in SERT levels in patients under treatment could underlie poor response, or relapse during or after treatment. The aim of the present study was first to validate a novel approach to measuring SERT levels in people taking treatment and then to investigate SERT binding potential (BP) using [11C]DASB PET in patients with OCD currently treated with escitalopram in comparison with healthy controls. METHOD: Twelve patients and age- and sex-matched healthy controls were enrolled. The patients and healthy controls underwent serial PET scans after administration of escitalopram and blood samples for drug concentrations were collected simultaneously with the scans. Drug-free BPs were obtained by using an inhibitory E max model we developed previously. RESULTS: The inhibitory E max model was able to accurately predict drug-free SERT BP in people taking drug treatment. The drug-free BP in patients with OCD currently treated with escitalopram was significantly different from those in healthy volunteers [Cohen's d = 0.03 (caudate), 1.16 (putamen), 1.46 (thalamus), -5.67 (dorsal raphe nucleus)]. CONCLUSIONS: This result extends previous findings showing SERT abnormalities in drug-free patients with OCD by indicating that altered SERT availability is seen in OCD despite treatment. This could account for poor response and the high risk of relapse in OCD.
BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic, relapsing mental illness. Selective serotonin reuptake inhibitors block serotonin transporters (SERTs) and are the mainstay of treatment for OCD. SERT abnormalities are reported in drug-free patients with OCD, but it is not known what happens to SERT levels during treatment. This is important as alterations in SERT levels in patients under treatment could underlie poor response, or relapse during or after treatment. The aim of the present study was first to validate a novel approach to measuring SERT levels in people taking treatment and then to investigate SERT binding potential (BP) using [11C]DASB PET in patients with OCD currently treated with escitalopram in comparison with healthy controls. METHOD: Twelve patients and age- and sex-matched healthy controls were enrolled. The patients and healthy controls underwent serial PET scans after administration of escitalopram and blood samples for drug concentrations were collected simultaneously with the scans. Drug-free BPs were obtained by using an inhibitory E max model we developed previously. RESULTS: The inhibitory E max model was able to accurately predict drug-free SERT BP in people taking drug treatment. The drug-free BP in patients with OCD currently treated with escitalopram was significantly different from those in healthy volunteers [Cohen's d = 0.03 (caudate), 1.16 (putamen), 1.46 (thalamus), -5.67 (dorsal raphe nucleus)]. CONCLUSIONS: This result extends previous findings showing SERT abnormalities in drug-free patients with OCD by indicating that altered SERT availability is seen in OCD despite treatment. This could account for poor response and the high risk of relapse in OCD.
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