What question did this study set out to answer?

This study aims to explore how childhood emotional neglect impacts depressive severity through inflammation.

June 14, 2026Open Access

The mediating role of the aggregate index of systemic inflammation between childhood emotional neglect and depressive severity in major depressive disorder: a cross-sectional study

YDYongqi DingCal Humanities XDXiaomei DongCommand Hospital QWQi WangHainan University

Key Points

This study aims to explore how childhood emotional neglect impacts depressive severity through inflammation.
Enrolled 236 patients with major depressive disorder (MDD) for cross-sectional analysis.
Participants completed the Childhood Trauma Questionnaire and Hamilton Depression Rating Scale, and routine blood tests were conducted.
Used hierarchical regression analysis and PROCESS mediation model to evaluate relationships between variables.
MDD patients with childhood trauma had higher inflammatory markers and depressive severity.
Emotional neglect correlated positively with HAMD-24 scores (r = 0.280, p < 0.001) and AISI (r = 0.213, p < 0.001).
AISI partially mediated the relationship between emotional neglect and depressive severity, showing a 28.07% mediation effect.

Abstract

Objective This cross-sectional study aimed to explore the associations among childhood trauma, inflammation and depressive severity, with a particular focus on the mediating role of a peripheral blood inflammatory marker (the Aggregate Index of Systemic Inflammation, AISI) in the relationship between childhood emotional neglect and depressive severity. Methods A total of 236 patients with major depressive disorder (MDD) were enrolled in this study. All participants completed the Childhood Trauma Questionnaire (CTQ) and the 24-item Hamilton Depression Rating Scale (HAMD-24), and underwent routine blood tests. Using Hierarchical regression analysis, after controlling for fixed covariates (age, sex, education level, etc.), separate models were built for each indicator to compare their predictive ability for HAMD-24 scores. The PROCESS mediation model was employed to examine the mediating role of AISI in the relationship between childhood emotional neglect and depressive severity. Results MDD patients with a history of childhood trauma exhibited significantly higher levels of inflammatory markers and depressive severity than those without such a history. Among the dimensions of childhood trauma, emotional neglect exhibited the strongest predictive power for HAMD-24 scores (ΔR² = 0.111, ΔP 0.001, AIC = 1691.663), and among inflammatory markers, AISI demonstrated the strongest predictive power for HAMD-24 scores (ΔR² = 0.230, ΔP 0.001, AIC = 1654.19). Emotional neglect was positively correlated with AISI (r = 0.213, p 0.001) and with HAMD-24 scores (r = 0.280, p 0.001). Furthermore, the inflammatory marker AISI partially mediated the relationship between childhood emotional neglect and depressive severity, with a mediation effect of 28.07%. Conclusion Childhood emotional neglect may be associated with depression severity through alterations in systemic inflammatory responses, supporting inflammation as a plausible mediating mechanism in this pathway. While causal relationships cannot be established, these results highlight the potential value of investigating anti-inflammatory strategies as adjunctive treatments for MDD in future prospective studies.

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