Functional connectivity of the default mode network in first-episode drug-naïve patients with major depressive disorder

Jun 20, 2024Journal of affective disorders

Brain network communication in first-time, untreated major depression patients

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Abstract

First-episode drug-naïve patients with MDD showed significantly increased functional connectivity (FC) within the default mode network (DMN).

Increased FC was observed within the overall DMN, as well as in the dorsal and medial DMN subsystems.
Distinct FC patterns were identified for each DMN subsystem when connected to other brain networks.
Increased FC between the core DMN and dorsal DMN subsystems and other networks was associated with more severe depressive symptoms.
Connectivity related to the medial DMN was correlated with memory performance.
Findings may not be generalizable beyond the specific population studied due to the limited sample characteristics.

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BACKGROUND: Alterations in the default mode network (DMN) have been reported in major depressive disorder (MDD), well-replicated robust alterations of functional connectivity (FC) of DMN remain to be established. Investigating the functional connections of DMN at the overall and subsystem level in early MDD patients has the potential to advance our understanding of the physiopathology of this disorder.

METHODS: We recruited 115 first-episode drug-naïve patients with MDD and 137 demographic-matched healthy controls (HCs). We first compared FC within the DMN, within/between the DMN subsystems, and from DMN subsystems to the whole brain between groups. Subsequently, we explored correlations between clinical features and identified alterations in FC.

RESULTS: First-episode drug-naïve patients with MDD showed significantly increased FC within the DMN, dorsal DMN and medial DMN. Each subsystem showed a distinct FC pattern with other brain networks. Increased FC between the subsystems (core DMN, dorsal DMN) and other networks was associated with more severe depressive symptoms, while medial DMN-related connectivity correlated with memory performance.

LIMITATIONS: The relatively large "pure" MDD sample could only be generalized to a limited population. And, atypical asymmetric FCs in the DMN related to MDD might be missed for only left-lateralized ROIs were used to avoid strong correlations between mirrored (right/left) seed regions.

CONCLUSION: These findings suggest patients with early MDD showed distinct patterns of FC alterations throughout DMN and its subsystems, which were related to illness severity and illness-associated cognitive impairment, highlighting their clinical significance.

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Functional connectivity of the default mode network in first-episode drug-naïve patients with major depressive disorder

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