title: Effects of Selective Serotonin Reuptake Inhibitors on Interregional Relation of Serotonin Transporter Availability in Major Depression.
abstract: Selective serotonin reuptake inhibitors (SSRIs) modulate serotonergic neurotransmission by blocking reuptake of serotonin from the extracellular space. Up to now, it remains unclear how SSRIs achieve their antidepressant effect. However, task-based and resting state functional magnetic resonance imaging studies, have demonstrated connectivity changes between brain regions. Here, we use positron emission tomography (PET) to quantify SSRI's main target, the serotonin transporter (SERT), and assess treatment-induced molecular changes in the interregional relation of SERT binding potential (BPND). Nineteen out-patients with major depressive disorder (MDD) and 19 healthy controls (HC) were included in this study. Patients underwent three PET measurements with the radioligand [11C]DASB: (1) at baseline, (2) after a first SSRI dose; and (3) following at least 3 weeks of daily intake. Controls were measured once with PET. Correlation analyses were restricted to brain regions repeatedly implicated in MDD pathophysiology. After 3 weeks of daily SSRI administration a significant increase in SERT BPNDcorrelations of anterior cingulate cortex and insula with the amygdala, midbrain, hippocampus, pallidum and putamen (p< 0.05; false discovery rate, FDR corrected) was revealed. No significant differences were found when comparing MDD patients and HC at baseline. These findings are in line with the clinical observation that treatment response to SSRIs is often achieved only after a latency of several weeks. The elevated associations in interregional SERT associations may be more closely connected to clinical outcomes than regional SERT occupancy measures and could reflect a change in the regional interaction of serotonergic neurotransmission during antidepressant treatment.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna Vienna, Austria.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: James
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna Vienna, Austria.
authors.forename: Pia
authors.initials: P
authors.lastname: Baldinger-Melich
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna Vienna, Austria.
authors.forename: Cecile
authors.initials: C
authors.lastname: Philippe
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna Vienna, Austria.
authors.forename: Georg S
authors.initials: GS
authors.lastname: Kranz
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vanicek
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hahn
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna Vienna, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Gryglewski
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna Vienna, Austria.
authors.forename: Marius
authors.initials: M
authors.lastname: Hienert
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna Vienna, Austria.
authors.forename: Marie
authors.initials: M
authors.lastname: Spies
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna Vienna, Austria.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Traub-Weidinger
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna Vienna, Austria.
authors.forename: Marcus
authors.initials: M
authors.lastname: Hacker
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna Vienna, Austria.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna Vienna, Austria.
authors.forename: Rupert
authors.initials: R
authors.lastname: Lanzenberger
keywords: SSRI; antidepressants; connectivity; depression; network analysis; positron emission tomography; serotonin transporter