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

Fronto-limbic disconnection in patients with multiple sclerosis and depression

Quinten van Geest  1 , Rosa E Boeschoten  2 , Matthijs J Keijzer  1 , Martijn D Steenwijk  1 , Petra Jw Pouwels  3 , Jos Wr Twisk  4 , Johannes H Smit  2 , Bernard Mj Uitdehaag  4   5 , Jeroen Jg Geurts  1 , Patricia van Oppen  2 , Hanneke E Hulst  1
Affiliations

Fronto-limbic disconnection in patients with multiple sclerosis and depression

Quinten van Geest et al. Mult Scler. 2019 Apr.

Abstract

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.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Q.v.G., R.E.B., M.J.K., M.D.S., J.H.S., J.W.R.T., and P.v.O. have nothing to disclose. P.J.W.P. receives research support from the Dutch MS Research Foundation, grant number 14-876. B.M.J.U. has received personal compensation for consulting from Biogen Idec, Genzyme, Merck Serono, Novartis, and Roche en TEVA. J.J.G.G. serves on the editorial boards of MS Journal, BMC Neurology, MS International and Neurology and the Scientific Advisory Board of the Dutch MS Research Foundation and of MS Academia, Merck Serono, and has served as a consultant for Merck Serono, Biogen Idec, Novartis, Sanofi Genzyme, and Teva Pharmaceuticals. H.E.H. receives research support from the Dutch MS Research Foundation, grant number 12-799, and serves as a consultant for Sanofi Genzyme, Merck Serono, Roche, and Novartis.

Figures

Figure 1.
Figure 1.
Schematic overview of functional connectivity between limbic and frontal regions. All ipsi- and contralateral connections between key limbic and frontal regions were obtained. For each limbic region, its average FC with all frontal areas was calculated, which is represented by the different colors. ACC: anterior cingulate cortex; Amy: amygdala; dlPFC: dorsolateral prefrontal cortex; FC: functional connectivity; Hip: hippocampus; mPFC: medial prefrontal cortex; Thal: thalamus; vPFC: ventral prefrontal cortex.
See this image and copyright information in PMC

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