{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T15:47:28Z","timestamp":1789228048520,"version":"build-2803163510"},"reference-count":44,"publisher":"BMJ","issue":"2","funder":[{"name":"MAGNIMS\/ECTRIMS","award":["MAGNIMS\/ECTRIMS research fellowship; grant n. N\/A"],"award-info":[{"award-number":["MAGNIMS\/ECTRIMS research fellowship; grant n. N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"accepted":{"date-parts":[[2022,10,1]]},"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate monoaminergic network abnormalities in patients with multiple sclerosis (MS) according to their fatigue and depressive status through a positron emission tomography (PET)-based constrained independent component analysis (ICA) on resting state (RS) functional MRI (fMRI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective study, 213 patients with MS (mean age=40.6\u00b112.5 years; 94\/119\u2009men\/women; 153 relapsing-remitting; 60 progressive) and 62 healthy controls (HCs, mean age=39.0\u00b110.4 years; 30\/32\u2009men\/women) underwent neurological, fatigue, depression and RS fMRI assessment. Patterns of dopamine, norepinephrine-related and serotonin-related RS functional connectivity (FC) were derived by ICA, constrained to PET atlases for dopamine, norepinephrine and serotonin transporters, obtained in HCs\u2019 brain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with HCs, patients with MS showed abnormalities in all three explored monoaminergic networks, mostly with decreased RS FC within PET-guided monoaminergic networks in frontal regions and subcortical areas including the cerebellum and thalamus, and increased RS FC in temporo-parieto-occipital cortical areas, including bilateral precunei.<\/jats:p>\n                    <jats:p>MS-related fatigue was associated with decreased RS FC within the PET-guided dopamine network in the left thalamus and left cerebellum, and with increased RS FC within the PET-guided serotonin network in the left middle occipital gyrus. MS-related depression was associated with more distributed abnormalities involving the three explored monoaminergic networks, resulting in overall reduced RS FC in the frontal lobe, limbic areas and the precuneus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with MS present diffuse dysregulation in the monoaminergic networks. Specific alterations in these networks were associated with fatigue and depression, providing a pathological marker for these bothersome symptoms and putative targets for their treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jnnp-2022-330109","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T13:20:41Z","timestamp":1665667241000},"page":"94-101","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Monoaminergic network abnormalities: a marker for multiple sclerosis-related fatigue and depression"],"prefix":"10.1136","volume":"94","author":[{"given":"Antonio","family":"Carotenuto","sequence":"first","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milan, 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