title: The serotonin transporter availability in untreated early-onset and late-onset patients with obsessive-compulsive disorder.
abstract: The pathogenetic role of central serotonin transporters (SERT) in obsessive-compulsive disorder (OCD) has been investigated in vivo by positron emission tomography (PET) or single-photon emission computed tomography (SPECT) studies with inconsistent results. This might reflect methodological differences but possibly also the pathophysiological heterogeneity of the disorder, i.e. the age at onset of OCD. The aim of our study was to compare SERT availability in patients with OCD to healthy controls (HC) taking into account the onset type, other factors and covariates (e.g. SERT genotype, age, depression level, gender). We studied 19 drug-naive OCD patients (36±13 yr, eight females) with early onset (EO-OCD, n=6) or with late onset (LO-OCD, n=13), and 21 HC (38±8 yr, nine females) with PET and the SERT-selective radiotracer [11C]DASB. Statistical models indicated that a variety of covariates and their interaction influenced SERT availability measured by distribution volume ratios (DVR). These models revealed significant effects of onset type on DVR with lower values in LO-OCD (starting at age 18 yr) compared to EO-OCD and HC in limbic (e.g. the amygdala), paralimbic brain areas (the anterior cingulate cortex), the nucleus accumbens and striatal regions, as well as borderline significance in the thalamus and the hypothalamus. The putamen, nucleus accumbens and hypothalamus were found with significant interaction between two SERT gene polymorphisms (SERT-LPR and VNTR). These findings suggest that late but not early onset of OCD is associated with abnormally low SERT availability. In part, functional polymorphisms of the SERT gene might determine the differences.
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Germany. swen.hesse@medizin.uni-leipzig.de
authors.forename: Swen
authors.initials: S
authors.lastname: Hesse
authors.forename: Katarina
authors.initials: K
authors.lastname: Stengler
authors.forename: Ralf
authors.initials: R
authors.lastname: Regenthal
authors.forename: Marianne
authors.initials: M
authors.lastname: Patt
authors.forename: Georg-Alexander
authors.initials: GA
authors.lastname: Becker
authors.forename: Annegret
authors.initials: A
authors.lastname: Franke
authors.forename: Heike
authors.initials: H
authors.lastname: Knüpfer
authors.forename: Philipp M
authors.initials: PM
authors.lastname: Meyer
authors.forename: Julia
authors.initials: J
authors.lastname: Luthardt
authors.forename: Ina
authors.initials: I
authors.lastname: Jahn
authors.forename: Donald
authors.initials: D
authors.lastname: Lobsien
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Heinke
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hegerl
authors.forename: Osama
authors.initials: O
authors.lastname: Sabri
mesh_terms: D000328:Adult; D000375:Aging; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D007031:Hypothalamus / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000000981:diagnostic imaging / Q000473:pathology; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011877:Radionuclide Imaging; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D013788:Thalamus / Q000000981:diagnostic imaging / Q000473:pathology; D013997:Time Factors; D055815:Young Adult
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins