White Matter Alterations Associated with Pro-inflammatory Cytokines in Patients with Major Depressive Disorder

Area of Science:

• Neuroscience
• Psychiatry
• Immunology

Background:

• The neuroinflammatory theory of major depressive disorder (MDD) is gaining traction.
• However, the specific impact of pro-inflammatory cytokines on white matter (WM) integrity in MDD remains largely unexplored.

Purpose of the Study:

• To investigate the relationship between pro-inflammatory cytokines and WM alterations in patients diagnosed with MDD.
• To explore the potential role of specific cytokines, such as TNF-α, in the observed WM changes.

Main Methods:

• Utilized diffusion tensor imaging (DTI) metrics including fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) via Tract-Based Spatial Statistics and FreeSurfer.
• Assessed serum levels of pro-inflammatory cytokines: interleukin (IL)-1β, IL-6, IL-8, interferon-γ, and tumor necrosis factor (TNF)-α.
• Compared 22 MDD patients with 22 healthy controls (HC).

Main Results:

• MDD patients exhibited significantly higher levels of TNF-α and IL-8 compared to HC.
• WM analysis revealed lower FA and higher MD and RD values in multiple WM regions in the MDD group.
• Voxel-wise correlation analysis demonstrated a negative correlation between TNF-α levels and FA, and positive correlations with MD and RD in specific WM tracts, including the corpus callosum and corona radiata.

Conclusions:

• Findings suggest a significant role for TNF-α in mediating WM alterations observed in MDD.
• The results point towards a potential mechanism involving demyelination contributing to white matter damage in depression.