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.

Original languageEnglish
Pages (from-to)715-726
Publication statusPublished - 1 Apr 2019


  • Journal Article

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