Reduced default mode network functional connectivity in patients with recurrent major depressive disorder

Area of Science:

• Neuroscience
• Psychiatry
• Medical Imaging

Background:

• Major depressive disorder (MDD) is a prevalent and debilitating condition with unclear neuropathophysiology.
• Previous functional brain network studies in MDD often lacked statistical power and used varied analysis methods.

Purpose of the Study:

• To investigate functional connectivity (FC) within the default mode network (DMN) in a large cohort of MDD patients using resting-state fMRI (R-fMRI).
• To address limitations of prior studies by employing a standardized preprocessing protocol and aggregated group analyses from multiple research sites.

Main Methods:

• Utilized resting-state fMRI (R-fMRI) data from the REST-meta-MDD Consortium, comprising 1,300 MDD patients and 1,128 normal controls (NCs) from 25 research groups.
• Standardized local preprocessing followed by aggregated group analyses, focusing on DMN FC comparisons between 848 MDD patients and 794 NCs from 17 sites.
• Exploratory analyses examined FC in other brain networks and associations with clinical variables like episode type, medication usage, duration, and symptom severity.

Main Results:

• Contrary to expectations, a significant decrease in DMN FC was observed in MDD patients compared to NCs.
• FC reduction was specifically found in recurrent MDD, not in first-episode drug-naïve MDD.
• Decreased DMN FC correlated with medication usage and positively with symptom severity in recurrent MDD, but not MDD duration.
• Alterations in visual, sensory-motor, and dorsal attention networks were also detected in MDD.

Conclusions:

• The study confirms the involvement of the DMN in MDD but reveals reduced, not increased, FC within this network.
• Decreased DMN FC appears characteristic of recurrent MDD and associated with treatment and symptom severity.
• Future research should explore whether reduced DMN FC mediates treatment response in MDD.
• All R-fMRI data are publicly available through the R-fMRI Maps Project for further investigation.