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.

本研究探讨了儿童情感忽视（EN）与重度抑郁症（MDD）之间的中介因素，以及结合多指标是否有助于诊断MDD。对 33 名 MDD 患者和 36 名健康对照者 (HC) 进行了区域同质性 (ReHo) 和临床特征的比较。采用中介分析来探讨社会支持或 ReHo 是否介导 EN 和 MDD 之间的关联。线性判别分析模型是用 EN、社会支持和 ReHo 构建的，并用于区分原发队列和复制队列中的 MDD 和 HC。我们发现MDD患者经历了更严重的EN和更差的社会支持，并且在左侧枕中回和双侧中央后回表现出较低的ReHo，而在右侧小脑小腿表现出较高的ReHo。EN 可以通过 ReHo 在这些差异的大脑区域和社会支持中直接或间接影响 MDD。结合这四个不同大脑区域的 ReHo 值、EN 和客观支持，可以将 MDD 患者与 HC 进行分类，研究重复内和独立队列中的 10 倍交叉验证准确度分别为 83.78 % ± 1.49 % 和 82.72 % ±分别为 2.22%。这些发现表明，儿童期 EN、社会支持和情绪相关区域的 ReHo 与 MDD 风险相关，为 MDD 的病理机制提供了新的见解。