title: White matter microstructure alterations of the medial forebrain bundle in melancholic depression.
abstract: BACKGROUND
  The medial forebrain bundle (MFB) is a key structure of the reward system and connects the ventral tegmental area (VTA) with the nucleus accumbens (NAcc), the medial and lateral orbitofrontal cortex (mOFC, lOFC) and the dorsolateral prefrontal cortex (dlPFC). Previous diffusion tensor imaging (DTI) studies in major depressive disorder point to white matter alterations of regions which may be incorporated in the MFB. Therefore, it was the aim of our study to probe white matter integrity of the MFB using a DTI-based probabilistic fibre tracking approach.
  
  
  METHODS
  22 patients with major depressive disorder (MDD) (12 melancholic-MDD patients, 10 non-melancholic-MDD patients) and 21 healthy controls underwent DTI scans. We used a bilateral probabilistic fibre tracking approach to extract pathways between the VTA and NACC, mOFC, lOFC, dlPFC respectively. Mean fractional anisotropy (FA) values were used to compare structural connectivity between groups.
  
  
  RESULTS
  Mean-FA did not differ between healthy controls and all MDD patients. Compared to healthy controls melancholic MDD-patients had reduced mean-FA in right VTA-lOFC and VTA-dlPFC connections. Furthermore, melancholic-MDD patients had lower mean-FA than non-melancholic MDD-patients in the right VTA-lOFC connection. Mean-FA of these pathways correlated negatively with depression scale rating scores.
  
  
  CONCLUSIONS
  Due to the small sample size and heterogeneous age group comparisons between melancholic and non-melancholic MDD-patients should be regarded as preliminary.
  
  
  CONCLUSIONS
  Our results suggest that the melancholic subtype of MDD is characterized by white matter microstructure alterations of the MFB. White matter microstructure is associated with both depression severity and anhedonia.
authors.affiliation: University Hospital of Psychiatry, University of Bern, Bolligenstrasse 111, 3000 Bern 60, Switzerland. Electronic address: bracht@puk.unibe.ch.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bracht
authors.affiliation: University Hospital of Psychiatry, University of Bern, Bolligenstrasse 111, 3000 Bern 60, Switzerland.
authors.forename: Helge
authors.initials: H
authors.lastname: Horn
authors.affiliation: University Hospital of Psychiatry, University of Bern, Bolligenstrasse 111, 3000 Bern 60, Switzerland.
authors.forename: Werner
authors.initials: W
authors.lastname: Strik
authors.affiliation: University Hospital of Psychiatry, Department of Psychiatric Neurophysiology, University of Bern, Bolligenstrasse 111, 3000 Bern 60, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Federspiel
authors.affiliation: Departments of Radiology and Biomedical Engineering, Northwestern University, Feinberg School of Medicine, 737 N. Michigan Ave Suite 1600, Chicago, IL 60611, USA.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnell
authors.affiliation: University Hospital of Psychiatry, University of Bern, Bolligenstrasse 111, 3000 Bern 60, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Höfle
authors.affiliation: University Hospital of Psychiatry, University of Bern, Bolligenstrasse 111, 3000 Bern 60, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Stegmayer
authors.affiliation: Institute of Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Freiburgstrasse 3010, Bern, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Wiest
authors.affiliation: University Hospital of Psychiatry, Department of Psychiatric Neurophysiology, University of Bern, Bolligenstrasse 111, 3000 Bern 60, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dierks
authors.affiliation: University Hospital of Psychiatry, University of Bern, Bolligenstrasse 111, 3000 Bern 60, Switzerland.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Müller
authors.affiliation: University Hospital of Psychiatry, University of Bern, Bolligenstrasse 111, 3000 Bern 60, Switzerland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Walther
mesh_terms: D000328:Adult; D059445:Anhedonia; D016880:Anisotropy; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000145:classification* / Q000503:physiopathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008474:Medial Forebrain Bundle / Q000473:pathology*; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D012720:Severity of Illness Index
keywords: Anhedonia; Diffusion tensor imaging; Mood disorder; Structural imaging