Abnormal spontaneous activity of regions related to mood regulation mediates the effect of childhood emotional neglect on major depressive disorder

This study investigated the mediating factors between childhood emotional neglect (EN) and major depressive disorder (MDD) and whether combining multi-indicator could help diagnose MDD. Regional homogeneity (ReHo) and clinical features were compared between 33 MDD patients and 36 healthy controls (HC). Mediation analysis was employed to explore whether social support or ReHo mediates the association between EN and MDD. The linear discriminant analysis model was constructed with EN, social support, and ReHo, and applied to distinguish MDD from HC in both primary and replication cohorts. We found that MDD patients experienced severer EN and poorer social support, and exhibited lower ReHo in the left middle occipital gyrus and bilateral postcentral gyrus, and higher ReHo in the right cerebellum crus1. EN could affect MDD directly and indirectly through ReHo in these discrepant brain regions and social support. Combining ReHo values of these four distinct brain regions, EN, and objective support could classify MDD patients from HC, and the 10-fold cross-validation accuracy within-study replication and in the independent cohort was 83.78 % ± 1.49 % and 82.72 % ± 2.22 %, respectively. These findings suggested that childhood EN, social support, and emotional-related regions' ReHo were associated with risks of MDD, providing new insights into the pathological mechanisms underlying MDD.