The Association Between High-Sensitivity C-Reactive Protein and Depression Symptom Severity among U.S. Adults: A Multivariable Analysis of NHANES Data

Background Systemic inflammation may play a role in depression. This study examined the association between high-sensitivity C-reactive protein (hs-CRP), a well-established biomarker of systemic inflammation, and the severity of depression symptoms as measured by the Patient Health Questionnaire (PHQ-9). Methods Data from the National Health and Nutrition Examination Survey (NHANES) 2015-2023 were utilized. Depression was classified as low (PHQ-9 < 10) and high (PHQ-9 ≥ 10). hs-CRP levels were dichotomized into low (≤ 3 mg/L) and high (> 3mg/L). Logistic regression models were used to analyze the association between hs-CRP and depression symptom severity, adjusting for demographic, socioeconomic, health-related covariates, while considering the NHANES complex sampling design. Results Among 15,525 U.S. adults, elevated hs-CRP levels were significantly associated with high depression symptom severity. hs-CRP > 3mg/L was associated with 26% greater odds of high depression symptom severity (adjusted OR=1.26; 95% CI: 1.04-1.51; p-value=0.018). Other factors associated with greater odds of high depression symptom severity included female sex, younger age (20-39 years), low-income status, unmarried status, tobacco use, multimorbidity, and timing of survey responses in relation to the onset of the COVID-19 pandemic. Exploratory depression symptom-domain analysis showed that hs-CRP was significantly associated with somatic symptom-domain (p-value < 0.001) while not significantly associated with cognitive/affective symptom-domain (p-value=0.056). Conclusion Depression symptom severity is influenced by many demographic, socioeconomic, behavioral, and health-related factors. The study findings support an independent association between elevated hs-CRP and depression symptom severity, and the significance of the association could depend on the specific depression symptom-domain.