Glymphatic dysfunction associated with cortisol dysregulation in major depressive disorder

Area of Science:

• Neuroscience
• Psychiatry
• Radiology

Background:

• Cortisol dysregulation is implicated in depression pathophysiology.
• The precise impact of cortisol on brain function requires further elucidation.
• Glymphatic system dysfunction may contribute to neurological disorders.

Purpose of the Study:

• To investigate the relationship between cortisol levels and glymphatic system function in depressed patients.
• To compare glymphatic parameters between depressed individuals and healthy controls.

Main Methods:

• Cross-sectional study of 210 participants (164 depressed, 46 healthy controls).
• Magnetic Resonance Imaging (MRI) assessed choroid plexus (CP) volume, perivascular space (PVS) volume, extracellular-free water (FW), and diffusion tensor imaging along the perivascular space (DTI-ALPS).
• Chemiluminescence measured cortisol levels in a patient sub-cohort; statistical analyses included t-tests and correlation.

Main Results:

• Depressed patients showed significantly higher FW and lower DTI-ALPS compared to healthy controls after adjustments.
• No significant differences in CP volume or PVS fraction were observed between groups.
• Increased FW in depressed patients positively correlated with plasma cortisol levels.

Conclusions:

• Glymphatic system dysfunction, characterized by increased extracellular-free water and reduced DTI-ALPS, is associated with depression.
• Elevated cortisol levels in depressed patients are linked to impaired glymphatic circulation.
• These findings suggest a connection between hormonal imbalance and brain fluid dynamics in depression.