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Altered serotonin transporter binding potential in patients with obsessive-compulsive disorder under escitalopram treatment: [11C]DASB PET study

Published online by Cambridge University Press:  01 October 2015

E. Kim ,
O. D. Howes ,
J. W. Park ,
S. N. Kim ,
S. A Shin ,
B.-H. Kim ,
F. E. Turkheimer ,
Y.-S. Lee  and
J. S. Kwon
E. Kim
Affiliation:
Department of Neuropsychiatry, Seoul National University Bundang Hospital, Gyeonggi-do, Korea
O. D. Howes
Affiliation:
Psychiatric Imaging, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, London, UK King's College London, Institute of Psychiatry, London, UK
J. W. Park
Affiliation:
Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea
S. N. Kim
Affiliation:
Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea
S. A Shin
Affiliation:
Department of Biomedical Sciences, Seoul National University, Seoul, Korea
B.-H. Kim
Affiliation:
Department of Clinical Pharmacology and Therapeutics, Kyung Hee University College of Medicine and Hospital, Seoul, Korea
F. E. Turkheimer
Affiliation:
King's College London, Institute of Psychiatry, London, UK
Y.-S. Lee
Affiliation:
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea
J. S. Kwon*
Affiliation:
Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea Department of Brain & Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea
*
* Address for correspondence: Professor J. S. Kwon, Department of Psychiatry,Seoul National University College of Medicine & Department of Brain & Cognitive Sciences, College of Natural Science, Seoul National University, 28 Yeongon-dong, Chongno-gu, Seoul 110-744, Korea. (Email: [email protected])
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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 Emax model we developed previously.

Results

The inhibitory Emax 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.

Keywords

Anxiety disordermolecular imagingobsessive-compulsive disorderserotonin transporterSSRI
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 2 , January 2016 , pp. 357 - 366
Copyright
Copyright © Cambridge University Press 2015 

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