title: Occupancy of serotonin transporters in the amygdala by paroxetine in association with attenuation of left amygdala activation by negative faces in major depressive disorder.
abstract: Amygdala hyperactivation in major depressive disorder (MDD) might be attenuated by selective serotonin reuptake inhibitors (SSRIs), but the working mechanism remains unclear. We hypothesized that higher amygdala serotonin transporter (SERT) occupancy by paroxetine results in greater attenuation of amygdala activation by negative facial expressions in MDD patients. We treated fifteen MDD patients (22-55 years) with paroxetine 20-50mg/day. After 6 and 12 weeks, we quantified (1) clinical response (≥50% decrease in Hamilton Depression Rating Scale (HDRS), (2) SERT occupancy in both amygdala measured by repeated [123I]β-CIT single photon emission computed tomography (SPECT), and (3) amygdala activation when viewing fearful and angry (negative) faces with repeated functional MRI scans. Response rates were 4/15 and 9/15 at 6 and 12 weeks, respectively. Attenuation of left amygdala activation was associated with amygdala SERT occupancy (P=0.006) and response (P=0.015). This association may provide a rationale for decreased limbic activity seen during treatment of MDD. It might also explain the rapid decrease in negative attentional bias and amygdala activation caused by SSRIs.
authors.affiliation: Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; University of Groningen, University Medical Center Groningen, Mood and Anxiety Disorders, Department of Psychiatry, Groningen, The Netherlands. Electronic address: H.G.Ruhe@UMCG.NL.
authors.forename: Henricus G
authors.initials: HG
authors.lastname: Ruhé
authors.affiliation: Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: Koster
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Booij
authors.affiliation: Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: van Herk
authors.affiliation: Department of Psychiatry VUMC, Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands.
authors.forename: Aart H
authors.initials: AH
authors.lastname: Schene
mesh_terms: D000328:Adult; D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005149:Facial Expression; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D007457:Iodine Radioisotopes; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000008:administration & dosage / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
chemical_list: D003042:Cocaine; D007457:Iodine Radioisotopes; D017374:Paroxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
keywords: Amygdala; Functional magnetic resonance imaging; Major depressive disorder; Paroxetine; Serotonin transporter; Single photon emission computed tomography