White matter microstructure alterations of the medial forebrain bundle in melancholic depression

Tobias Bracht*, Helge Horn, Werner Strik, Andrea Federspiel, Susanne Schnell, Oliver Höfle, Katharina Stegmayer, Roland Wiest, Thomas Dierks, Thomas J. Müller, Sebastian Walther

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


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. Limitations 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.

Original languageEnglish (US)
Pages (from-to)186-193
Number of pages8
JournalJournal of Affective Disorders
Issue number1
StatePublished - Feb 2014


  • Anhedonia
  • Diffusion tensor imaging
  • Mood disorder
  • Structural imaging

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health


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