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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

10 June 2026

Ding Y, Dong X, Wang Q, Xu T.

Summary

What the study found

This study discovered that individuals with major depressive disorder who experienced emotional neglect as children tend to have higher levels of systemic inflammation and more severe depressive symptoms. Specifically, an inflammatory blood marker called the Aggregate Index of Systemic Inflammation (AISI) acts as a biological bridge, partially explaining how early-life stress translates into worse mental health outcomes in adulthood.

Key findings

  • Patients with a history of childhood trauma exhibited significantly higher inflammatory markers and more severe depression compared to those without such history.
  • Among all forms of childhood trauma, emotional neglect was the most powerful predictor of the severity of a patient's depression.
  • The AISI inflammatory marker served as the strongest biological indicator for predicting how severe a patient's depressive symptoms would be.
  • Inflammation was found to be a mediating mechanism, accounting for approximately 28% of the relationship between childhood emotional neglect and adult depression levels.

Practical takeaways

For those focused on longevity and mental well-being, these findings suggest that managing systemic inflammation is a critical component of mental health maintenance, especially for those with a history of stress. Prioritizing an anti-inflammatory lifestyle, including a diet rich in antioxidants and omega-3 fatty acids, may help mitigate the biological impact of early-life experiences on current mood and brain health.

Limitations

Because this was a cross-sectional study, it can only show associations and cannot prove that emotional neglect directly causes higher inflammation later in life. Additionally, the research focused exclusively on patients already diagnosed with major depressive disorder, so the results may not apply to the general population.

Abstract

<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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%.<h4>Conclusion</h4>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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