Abstract Details

Title Monoaminergic Networks Abnormalities Associated with Fatigue and Depression in Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) S19 - MS Biomarkers and Symptom Management (2:12 PM-2:24 PM)

Poster/Presentation
Number 007

Background Fatigue and depression occur in a large proportion of MS patients; however, their pathophysiological correlates are not completely understood. Monoaminergic networks may present both functional and structural damage, which are likely to contribute to both fatigue and depression.

Objective To explore monoaminergic networks abnormalities in multiple sclerosis (MS) patients and their correlation with fatigue and depression by applying a PET-constrained independent component analysis (ICA) approach on resting state functional MRI (RS fMRI) images.

Design/Methods 213 MS patients (mean age=40.6 ± 12.5 years; 94/119 men/women; 153 relapsing-remitting; 60 progressive) and 53 healthy controls (HCs, mean age=39.0 ± 10.4 years; 30/32 men/women) underwent neurological, fatigue, depression and RS fMRI assessment. MS patients with either cognitive impairment assessed through the symbol digit modality test or with disease modifying treatment-associated depression or fatigue were excluded from the study. We extracted patterns of dopamine, noradrenaline- and serotonin-dependent RS fMRI functional connectivity (FC) through ICA, constrained to PET atlases for dopamine, noradrenaline and serotonin transporters, previously obtained in HCs’ brain.

Results MS patients showed abnormalities in all three explored monoaminergic networks, mostly with decreased monoamine-dependent RS fMRI FC in frontal regions and subcortical areas including the cerebellum and thalamus, and increased RS fMRI FC in temporo-parieto-occipital cortical areas, including bilateral precunei vs HCs. MS-related fatigue was associated with decreased dopamine-dependent RS fMRI FC in the left thalamus and left cerebellum, and increased serotonin-dependent RS fMRI FC in the left middle occipital gyrus. MS-related depression was associated with abnormalities involving the three explored monoaminergic networks, resulting in reduced monoamine-dependent RS fMRI FC in the frontal lobe, limbic areas and the precuneus.

Conclusions MS patients are characterised by diffuse monoaminergic networks functional abnormalities. Alterations in these networks provide a new pathological substrates for MS-related fatigue and depression and may suggest putative targets for their treatment.

Authors/Disclosures
Paolo Preziosa (Ospedale San Raffaele) PRESENTER	Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
Maria A. Rocca (Neuroimaging Research Unit)	Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. The institution of Maria Assunta Rocca has received research support from MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
Antonio Carotenuto	Mr. Carotenuto has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Merk, Novartis, Roche and Almirall. The institution of Mr. Carotenuto has received research support from ALMIRALL. The institution of Mr. Carotenuto has received research support from Carotenuto Antonio.
Paola Valsasina	No disclosure on file
Laura Cacciaguerra, MD, PhD (Mayo Clinic)	Dr. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS Celgene. Dr. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIOMEDIA.
	No disclosure on file
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi;. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi- Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.