Investigating the association between the inflammatory burden index and depressive symptoms in US adults: evidence from the NHANES 2015–2020

Abstract Background and aim Systemic inflammation has been increasingly implicated in the pathogenesis of depressive symptoms. The inflammatory burden index (IBI), which integrates C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR), provides a composite measure of systemic inflammation. This study aimed to examine the association between IBI and depressive symptoms in a nationally representative sample of U.S. adults, with particular focus on potential threshold effects. Methods and results Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), with scores ≥10 indicating clinically relevant depressive symptoms. Because the PHQ-9 captures symptom severity rather than a clinician-diagnosed depressive disorder, we consistently use the term ‘depressive symptoms’ throughout to denote the PHQ-9–defined outcome. Multivariable logistic regression, generalised additive models, and segmented (two-piecewise) logistic regression were used to evaluate associations. Each one-unit increase in ln-IBI was associated with slightly higher odds of depressive symptoms (weighted OR = 1.07; 95% CI 1.02–1.12). Although statistically significant, the magnitude of the association was modest. Participants in the highest IBI quartile had 24% higher odds of depressive symptoms compared to those in the lowest quartile (OR = 1.24; 95% CI 1.02–1.50). A curvilinear trend was observed between ln-IBI and depressive symptoms, with visual evidence of a turning point around ln-IBI = –0.85. Based on two-piecewise logistic regression, an inverse association was noted below this threshold (OR = 0.71; 95% CI 0.51–0.99), while the odds of depressive symptoms increased significantly above it (OR = 1.09; 95% CI 1.04–1.15). Stronger associations were observed in the obesity subgroup (BMI ≥30 kg/m²) and among participants with either low (less than 9th grade) or high (college or above) education levels. Conclusions In this cross-sectional, nationally representative study of U.S. adults, higher IBI was associated with higher odds of depressive symptoms, with an apparent threshold around ln-IBI ≈ −0.85 beyond which the positive association was steeper. These findings support an association between inflammation and depressive symptoms and suggest that IBI may help identify individuals at higher odds of depressive symptoms. However, causality cannot be inferred from this cross-sectional analysis, and prospective studies are needed to establish temporality and evaluate clinical utility.