Conflict of interest: Without any relevance to this work, S. Kasper declares that he has received grant/research support from Eli Lilly, Lundbeck A/S, Bristol-Myers Squibb, Servier, Sepracor, GlaxoSmithKline, Organon, and has served as a consultant or on advisory boards for AstraZeneca, Austrian Science Found, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lily, Lundbeck A/S, Pfizer, Organon, Sepracor, Janssen, and Novartis, and has served on speakers' bureaus for AstraZeneca, Eli Lilly, Lundbeck A/S, Servier, Sepracor and Janssen. R. Lanzenberger received travel grants or conference speaker honoraria from AstraZeneca, Lundbeck A/S, and Roche Austria. M. Mitterhauser and W. Wadsak received speaker honoraria from Bayer. Parts of this study were presented at the 19th European Psychiatric Association (EPA) Congress, Vienna, the 10th World Congress of Biological Psychiatry (WFSBP), Prague and the 26th Congress of the European College of Neuropsychopharmacology (ECNP), Barcelona.
Attenuated serotonin transporter association between dorsal raphe and ventral striatum in major depression
Version of Record online: 17 JAN 2014
Copyright © 2014 Wiley Periodicals, Inc.
Human Brain Mapping
Volume 35, Issue 8, pages 3857–3866, August 2014
How to Cite
Hahn, A., Haeusler, D., Kraus, C., Höflich, A. S., Kranz, G. S., Baldinger, P., Savli, M., Mitterhauser, M., Wadsak, W., Karanikas, G., Kasper, S. and Lanzenberger, R. (2014), Attenuated serotonin transporter association between dorsal raphe and ventral striatum in major depression. Hum. Brain Mapp., 35: 3857–3866. doi: 10.1002/hbm.22442
Andreas Hahn was recipient of a DOC-fellowship of the Austrian Academy of Sciences at the Department of Psychiatry and Psychotherapy. This study was supported by funds from the Oesterreichische Nationalbank (Anniversary Fund, project numbers: 13214, 13675) to Rupert Lanzenberger and Markus Mitterhauser, and partly by an investigator-initiated and unrestricted research grant from H. Lundbeck A/S, Denmark, to Siegfried Kasper
- Issue online: 8 JUL 2014
- Version of Record online: 17 JAN 2014
- Manuscript Accepted: 25 NOV 2013
- Manuscript Revised: 21 OCT 2013
- Manuscript Received: 16 MAY 2013
- serotonin transporter;
- major depression;
- ventral striatum;
- dorsal raphe nucleus;
- positron emission tomography;
- interregional association
Suffering from anhedonia, patients with major depressive disorder (MDD) exhibit alterations in several parts of the serotonergic neurotransmitter system, which are in turn involved in reward processing. However, previous investigations of the serotonin transporter (SERT) focused on regional differences with varying results depending on the clinical syndrome. Here, we aimed to describe the serotonergic system of MDD patients on a network level by evaluating SERT associations across brain regions. Twenty medication free patients with major depression and 20 healthy controls underwent positron emission tomography using the radioligand [11C]DASB. SERT binding potentials (BPND) were quantified voxel-wise with the multilinear reference tissue model 2. In addition, SERT BPND was extracted from the dorsal raphe nucleus (DRN) as an indicator of midbrain serotonergic neurotransmission. Whole-brain linear regression analysis was applied to evaluate the association of DRN SERT bindings to those in projection areas, which was followed by ANCOVA to assess differences in interregional relationships between patients and controls. Although both groups showed widespread positive correlations, group differences were restricted to decreased SERT associations between the DRN and the ventral striatum (right and left respectively: t = 5.85, P < 0.05 corrected and t = 5.07, P < 0.1 corrected) when comparing MDD patients (R2 = 0.11 and 0.24) to healthy subjects (R2 = 0.72 and 0.66, P < 0.01 and 0.05 corrected). Adjusting for age and sex did not change these findings. This study indicates a disturbed regulation between key regions involved in reward processing via the SERT. Our interregional approach highlights the importance of evaluating pathophysiological alterations on a network level to gain complementary information in addition to regional investigations. Hum Brain Mapp 35:3857–3866, 2014. © 2014 Wiley Periodicals, Inc.