Vortioxetine Improves Brain Glymphatic System Function, Functional Connectivity, and Cognitive Functions in Major...

Area of Science:

• Neuroscience
• Neuroimaging
• Pharmacology

Background:

• Major depressive disorder (MDD) is associated with impaired mood and cognitive function.
• The brain's glymphatic system and functional brain networks are implicated in MDD pathophysiology.
• Vortioxetine is an antidepressant with known effects on mood and cognition.

Purpose of the Study:

• To investigate vortioxetine's effects on glymphatic system function in MDD patients.
• To examine vortioxetine's impact on functional brain network connectivity, specifically the default mode network (DMN).
• To explore the relationship between glymphatic function, DMN connectivity, and cognitive improvements.

Main Methods:

• Recruited 34 MDD patients and 41 healthy controls (HCs).
• Utilized diffusion tensor imaging (DTI) to assess DTI analysis along the perivascular space (DTI-ALPS) index.
• Employed resting-state functional MRI (rs-fMRI) to evaluate functional connectivity (FC) and cognitive assessments (MCCB).

Main Results:

• MDD patients exhibited reduced DTI-ALPS and altered DMN FC (increased PCC-precuneus connectivity) compared to HCs.
• MDD patients showed deficits in attention, learning, social cognition, and global cognition.
• Vortioxetine treatment improved DTI-ALPS, normalized DMN FC, and enhanced cognitive functions in MDD patients.

Conclusions:

• Vortioxetine treatment improves glymphatic system function and DMN connectivity in MDD.
• The restoration of glymphatic function is associated with enhanced brain function and cognitive performance in MDD.
• Findings suggest vortioxetine's therapeutic effects may involve glymphatic system modulation and network restoration.