The inflammatory response contributes to the progression and prognosis of depression. The C-reactive protein-to-lymphocyte ratio (CLR) is increasingly recognized as a promising indicator of systemic inflammatory activity. Yet the relationship between CLR and depression is still uncertain. The conducted study aimed to investigate the potential link between CLR and depression. We analyzed 12,578 participants aged ≥20 years from National Health and Nutrition Examination Survey 1999 to 2010. CLR (C-reactive protein mg/L/lymphocyte × 10 3 /µL) was calculated from fasting blood. Depression was defined as Patient Health Questionnaire-9 ≥ 10. Five sequential logistic models adjusted for demographics, lifestyle and comorbidities; quartile and trend analyses were performed, followed by stratified assessments. Overall depression prevalence was 8.53%. Each 0.1-unit CLR increment was associated with 11% higher odds of depression in the fully adjusted model (odds ratio = 1.11; 95% confidence intervals 1.01–1.22). Participants in the highest CLR quartile showed 36% increased risk versus the lowest quartile (odds ratio = 1.36; 95% confidence intervals 1.10–1.66; P -trend = .004). Findings were consistent across sex, age, education, smoking and metabolic subgroups. Higher CLR, reflecting combined innate activation and adaptive suppression, is significantly and dose-dependently associated with depression. This inexpensive, routinely available biomarker may aid early risk detection and guide anti-inflammatory treatment strategies; prospective studies are needed to confirm causality.
Zhu et al. (2026) studied this question.