Regional and interregional brain functional abnormalities in major depressive disorder with childhood maltreatment.

BACKGROUND: Childhood maltreatment (CM) significantly enhances the vulnerability to major depressive disorder (MDD), but the relationship with brain dysfunction remains uncertain. METHODS: We recruited 84 MDD patients (52 with CM, 32 without CM) and 54 healthy controls. Regional brain activity was assessed using amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), degree centrality, and regional homogeneity. The identified abnormal regions were used as seeds for functional connectivity (FC) analysis. We employed partial correlation and moderated mediation to explore the relationships between CM, brain dysfunction, MDD severity, and dysfunctional attitudes. RESULTS: MDD patients with CM had reduced ALFF in the right posterior orbitofrontal cortex (pOFC) and right middle frontal gyrus (MFG) compared to those without CM. In MDD with CM, FC between the right pOFC and core regions within the default mode network (DMN), including the superior medial frontal gyrus (SMFG), angular gyrus, and superior frontal gyrus, was reduced. Meanwhile, the FC between the right MFG and the right superior temporal gyrus, both regions related to Theory of Mind, increased. Additionally, both intra- and inter-regional brain activities were significantly associated with CM and dysfunctional attitudes. In the moderated mediation model, ALFF in the right MFG mediated the relationship between emotional neglect and MDD severity, while dysfunctional attitudes moderated this mediation effect. CONCLUSIONS: Our findings provide evidence for the relationship between MDD and CM, offering insights into the local and interregional brain dysfunction associated with both MDD and CM. CLINICAL TRIAL NUMBER: ChiCTR2300078193, registered in the Chinese Clinical Trial Registry on November 30, 2023.