Childhood trauma and frontal-limbic network abnormalities in major depressive disorder: Resting-state functional connectivity and brain network analysis

초록

BACKGROUND: Childhood trauma impacts brain development, increasing vulnerability to Major Depressive Disorder (MDD). The frontal-limbic network, essential for emotion regulation and stress response, is frequently implicated in MDD pathophysiology. This study examined whether childhood trauma is associated with alterations in resting-state functional connectivity (FC) within brain networks involved in emotion regulation in individuals with MDD and healthy controls (HCs). METHODS: A cross-sectional study was conducted with 76 patients with MDD and 97 HCs (aged 19-64 years). Resting-state FC was assessed among 24 predefined regions of interest (ROIs) within brain networks associated within the fronto-limbic circuit. Childhood trauma was quantified using the Childhood Trauma Questionnaire (CTQ). ROI-to-ROI FC and global/regional brain network properties were evaluated. RESULTS: The MDD group demonstrated significant reductions in frontal-limbic FC (e.g., left dorsolateral prefrontal cortex [dlPFC]-left hippocampus, left dlPFC-right pregenual anterior cingulate cortex [ACC], right pregenual ACC-right subgenual ACC). Brain network properties analysis revealed a negative correlation between global efficiency and emotional neglect severity, as well as positive correlations between local efficiency/clustering efficiency and total CTQ scores. Specifically, in the MDD group, the clustering coefficient in the ventromedial prefrontal cortex (vmPFC) was positively associated with emotional neglect, whereas in the HC group, total CTQ scores were positively correlated with the nodal degree of the right subgenual ACC. CONCLUSIONS: Childhood trauma is associated with significant alterations in resting-state FC and brain network properties within the frontal-limbic network in individuals with MDD. These findings highlight a potential neural pathway through which early adversity contributes to MDD pathophysiology. Copyright © 2025 Elsevier B.V. All rights reserved.

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