Journal of affective disorders · 2026
The aggregate index of systemic inflammation as peripheral inflammatory markers for first-episode drug-naïve patients with major depressive disorder.
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Wang Qi, Li Li, Yang Binjie, Wang Jiyang, Wei Xiaodong, Shen Yanmei, Wang Yitong, Fan Lin, Wang Shihui, Shao Nan, Ding Yongqi, Gong Lili, Xu Tianchao
Аннотация
OBJECTIVE: This case-control study investigated the utility of routine blood-derived inflammatory markers, particularly the Aggregate Index of Systemic Inflammation (AISI), as peripheral inflammatory indicators in major depressive disorder (MDD), and explored its associations with clinical characteristics and underlying psychological mechanisms.
METHODS: The study enrolled 236 first-episode, drug-naïve MDD patients and 207 age- and sex-matched healthy controls. Blood routine tests were performed, and nine inflammatory indices (AISI, SII, SIRI, NLR, dNLR, MLR, NMLR, PLR, INFLA-score) were calculated. Clinical assessments included the Hamilton Depression Scale (HAMD-24), Snaith-Hamilton Pleasure Scale (SHAPS), and Childhood Trauma Questionnaire (CTQ). Statistical analyses employed ridge logistic regression (to handle multicollinearity), ROC curve analysis (internal validation involved 1000 bootstrapped iterations), correlation analyses, quantile regression, and mediation modeling.
RESULTS: Compared to controls, MDD patients showed elevated levels of AISI, SII, SIRI, NLR, MLR, NMLR, PLR, INFLA-score, and lower lymphocyte counts. Ridge logistic regression identified childhood trauma, HAMD-24 score, and AISI as factors independently associated with MDD. Bootstrap validation confirmed the robustness of this estimate: the mean AUC across 1000 resamples was 0.710, with a 95% CI of [0.662, 0.757]. AISI levels correlated with disease duration, anhedonia, depressive severity, and emotional neglect, with stronger associations observed in severe clinical phenotypes. A chain mediation model revealed that childhood trauma influenced depressive symptoms through three significant indirect paths involving AISI and anhedonia.
CONCLUSION: Systemic inflammation, particularly reflected by the AISI, is significantly altered in first-episode drug-naïve MDD patients and shows potential as an accessible diagnostic biomarker. The findings support an associative pattern where emotional neglect is linked to MDD via inflammation and anhedonia, offering new insights into the potential inflammatory correlates of MDD.
METHODS: The study enrolled 236 first-episode, drug-naïve MDD patients and 207 age- and sex-matched healthy controls. Blood routine tests were performed, and nine inflammatory indices (AISI, SII, SIRI, NLR, dNLR, MLR, NMLR, PLR, INFLA-score) were calculated. Clinical assessments included the Hamilton Depression Scale (HAMD-24), Snaith-Hamilton Pleasure Scale (SHAPS), and Childhood Trauma Questionnaire (CTQ). Statistical analyses employed ridge logistic regression (to handle multicollinearity), ROC curve analysis (internal validation involved 1000 bootstrapped iterations), correlation analyses, quantile regression, and mediation modeling.
RESULTS: Compared to controls, MDD patients showed elevated levels of AISI, SII, SIRI, NLR, MLR, NMLR, PLR, INFLA-score, and lower lymphocyte counts. Ridge logistic regression identified childhood trauma, HAMD-24 score, and AISI as factors independently associated with MDD. Bootstrap validation confirmed the robustness of this estimate: the mean AUC across 1000 resamples was 0.710, with a 95% CI of [0.662, 0.757]. AISI levels correlated with disease duration, anhedonia, depressive severity, and emotional neglect, with stronger associations observed in severe clinical phenotypes. A chain mediation model revealed that childhood trauma influenced depressive symptoms through three significant indirect paths involving AISI and anhedonia.
CONCLUSION: Systemic inflammation, particularly reflected by the AISI, is significantly altered in first-episode drug-naïve MDD patients and shows potential as an accessible diagnostic biomarker. The findings support an associative pattern where emotional neglect is linked to MDD via inflammation and anhedonia, offering new insights into the potential inflammatory correlates of MDD.