Fronto-limbic disconnection in patients with multiple sclerosis and depression

Mult Scler. 2019 Apr;25(5):715-726. doi: 10.1177/1352458518767051. Epub 2018 Mar 28.


Background: The biological mechanism of depression in multiple sclerosis (MS) is not well understood. Based on work in major depressive disorder, fronto-limbic disconnection might be important.

Objective: To investigate structural and functional fronto-limbic changes in depressed MS (DMS) and non-depressed MS (nDMS) patients.

Methods: In this retrospective study, 22 moderate-to-severe DMS patients (disease duration 8.2 ± 7.7 years), 21 nDMS patients (disease duration 15.3 ± 8.3 years), and 12 healthy controls underwent neuropsychological testing and magnetic resonance imaging (MRI; 1.5 T). Brain volumes (white matter (WM), gray matter, amygdala, hippocampus, thalamus), lesion load, fractional anisotropy (FA) of fronto-limbic tracts, and resting-state functional connectivity (FC) between limbic and frontal areas were measured and compared between groups. Regression analysis was performed to relate MRI measures to the severity of depression.

Results: Compared to nDMS patients, DMS patients (shorter disease duration) had lower WM volume ( p < 0.01), decreased FA of the uncinate fasciculus ( p < 0.05), and lower FC between the amygdala and frontal regions ( p < 0.05). Disease duration, FA of the uncinate fasciculus, and FC of the amygdala could explain 48% of variance in the severity of depression. No differences in cognition were found.

Conclusion: DMS patients showed more pronounced (MS) damage, that is, structural and functional changes in temporo-frontal regions, compared to nDMS patients, suggestive of fronto-limbic disconnection.

Keywords: Multiple sclerosis; cognition; depression; diffusion tensor imaging; functional connectivity; functional magnetic resonance imaging; limbic system; magnetic resonance imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Depression / complications
  • Depression / pathology*
  • Depressive Disorder, Major / pathology
  • Diffusion Tensor Imaging / methods
  • Female
  • Frontal Lobe / pathology*
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Male
  • Middle Aged
  • Multiple Sclerosis / complications
  • Multiple Sclerosis / pathology*
  • Nerve Net / pathology*
  • Retrospective Studies