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Review
Psychiatric symptoms in multiple sclerosis: a biological perspective on synaptic and network dysfunction
  1. Giulia Menculini1,
  2. Andrea Mancini2,
  3. Lorenzo Gaetani2,
  4. Laura Bellingacci2,
  5. Alfonso Tortorella1,
  6. Lucilla Parnetti2,
  7. Massimiliano Di Filippo2
  1. 1 Section of Psychiatry, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
  2. 2 Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
  1. Correspondence to Professor Massimiliano Di Filippo, Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, 06123, Italy; massimiliano.difilippo{at}unipg.it

Abstract

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.

  • MULTIPLE SCLEROSIS
  • PSYCHIATRY
  • NEUROIMMUNOLOGY

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Footnotes

  • GM and AM contributed equally.

  • Contributors GM, AM and MDF: review conceptualisation. GM, AM and LG: literature search. GM, AM, LG and LB: writing—original draft. AT, LP and MDF: writing—review and editing.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • 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.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.