Psychiatric symptoms in multiple sclerosis: a biological perspective on synaptic and network dysfunction.

Psychiatric symptoms frequently occur in multiple sclerosis (MS), presenting with a complex phenomenology that encompasses a large clinical spectrum from clear-cut psychiatric disorders up to isolated psychopathological manifestations. Despite their relevant impact on the overall disease burden, such clinical features are often misdiagnosed, receive suboptimal treatment and are not systematically evaluated in the quantification of disease activity. The development of psychiatric symptoms in MS underpins a complex pathogenesis involving both emotional reactions to a disabling disease and structural multifocal central nervous system damage. Here, we review MS psychopathological manifestations under a biological perspective, highlighting the pathogenic relevance of synaptic and neural network dysfunction. Evidence obtained from human and experimental disease models suggests that MS-related psychiatric phenomenology is part of a disconnection syndrome due to diffuse inflammatory and neurodegenerative brain damage.

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Déclaration de conflit d'intérêts

Competing interests: LB and LP have no conflicts of interest to declare. GM received travel grants from Janssen and Lundbeck (unrelated to the present work). AM received travel grants and writing honoraria from Almirall, Biogen, Merck, Mylan, Novartis, Sanofi Genzyme and Teva. LG participated on advisory boards for, and received writing honoraria and travel grants from Almirall, Biogen, Euroimmun, Fujirebio, Merck, Mylan, Novartis, Roche, Sanofi, Siemens Healthineers and Teva. AT received research support from Lundbeck and served as speaker for Lundbeck and Angelini (unrelated to the present work). MDF participated on advisory boards for and received speaker or writing honoraria, funding for travelling and research support from Alexion, Bayer, Biogen Idec, Sanofi, Siemens Healthineers, Merck, Mylan, Novartis, Roche, Teva and Viatris.