Microstructural Changes in the Left Mesocorticolimbic Pathway are Associated with the Comorbid Development of Fatigue and Depression in Multiple Sclerosis.
BACKGROUND AND PURPOSE
Lower reward responsiveness has been associated with fatigue in multiple sclerosis (MS). However, association of MS-related fatigue with damage to the mesocorticolimbic reward pathway (superolateral medial forebrain bundle [slMFB]) has not been assessed. We investigated the association of fatigue and depression with slMFB damage in MS patients stratified based on longitudinal fatigue patterns.


METHODS
Patient stratification: 1. Sustained Fatigue (SF): latest two Modified Fatigue Impact Scale (MFIS) ≥ 38 (n = 26); 2. Reversible Fatigue (RF): latest MFIS < 38, and at least one previous MFIS ≥ 38 (n = 25); 3. Never Fatigued (NF): ≥ 5 consecutive MFIS < 38 (n = 42); 4. Healthy Controls (n = 6). Diffusion MRI-derived measures of fractional anisotropy (FA), axial (AD), mean (MD), and radial diffusivity (RD) of the slMFB were compared between the groups. Depression was assessed using the Center for Epidemiologic Studies-Depression Scale (CES-D).


RESULTS
Depressed (CES-D ≥ 16) SF patients showed significantly higher MD and RD than nondepressed SF and RF, and depressed RF patients, and significantly lower FA than nondepressed SF and depressed RF patients in their left slMFB. Depressed SF patients showed significantly higher left slMFB MD and AD than healthy controls.


CONCLUSION
Microstructural changes to the left slMFB may play a role in the comorbid development of fatigue and depression in MS.
['Palotai|Miklos|M|0000-0003-0268-6977', 'Small|Catherine|C|', 'Makris|Nikolaos|N|', 'Somes|Nathaniel G|NG|', 'Pinzon|Alfredo Morales|AM|', 'Rathi|Yogesh|Y|', 'Marzullo|Aldo|A|', 'Levitt|James J|JJ|', 'Bakshi|Rohit|R|0000-0001-8601-5534', 'Chitnis|Tanuja|T|', 'Guttmann|Charles R G|CRG|']
D000328:Adult D016880:Anisotropy D003863:Depression D038524:Diffusion Magnetic Resonance Imaging D005221:Fatigue D005260:Female D006801:Humans D008297:Male D008474:Medial Forebrain Bundle D008875:Middle Aged D009103:Multiple Sclerosis
fatigue depression Multiple sclerosis reward medial forebrain bundle