Depression is associated with disconnection of neurotransmitter-related nuclei in multiple sclerosis

Matteo Martino, Paola Magioncalda, Mohamed Mounir El Mendili, Amgad Droby, Swetha Paduri, Simona Schiavi, Maria Petracca, Matilde Inglese

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Background: Depression is frequently associated with multiple sclerosis (MS). However, the biological background underlying such association is poorly understood. Objective: Investigating the functional connections of neurotransmitter-related brainstem nuclei, along with their relationship with white matter (WM) microstructure, in MS patients with depressive symptomatology (MS-D) and without depressive symptomatology (MS-nD). Methods: Combined resting-state functional magnetic resonance imaging (fMRI) and diffusion-weighted MRI (dMRI) study on 50 MS patients, including 19 MS-D and 31 MS-nD patients, along with 37 healthy controls (HC). Main analyses performed are (1) comparison between groups of raphe nuclei (RN)-related functional connectivity (FC); (2) correlation between RN-related FC and whole brain dMRI-derived fractional anisotropy (FA) map; and (3) comparison between groups of FA in the RN-related WM area. Results: (1) RN-related FC was reduced in MS-D when compared to MS-nD and HC; (2) RN-related FC positively correlated with FA in a WM cluster mainly encompassing thalamic/basal ganglia regions, including the fornix; and (3) FA in such WM area was reduced in MS-D. Conclusion: Depressive symptomatology in MS is specifically associated to a functional disconnection of neurotransmitter-related nuclei, which in turn may be traced to a distinct spatial pattern of WM alterations mainly involving the limbic network.

Original languageEnglish
Pages (from-to)1102-1111
Number of pages10
JournalMultiple Sclerosis Journal
Issue number7
Publication statusPublished - Jun 2021


  • depression
  • functional connectivity
  • Multiple sclerosis
  • raphe nuclei
  • ventral tegmental area
  • white matter

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


Dive into the research topics of 'Depression is associated with disconnection of neurotransmitter-related nuclei in multiple sclerosis'. Together they form a unique fingerprint.

Cite this