Association between C-reactive protein to lymphocyte ratio and depression: A population-based study

Prog Neuropsychopharmacol Biol Psychiatry. 2026 May 23:111750. doi: 10.1016/j.pnpbp.2026.111750. Online ahead of print.

ABSTRACT

BACKGROUND: Emerging biomarkers like the C-reactive protein to lymphocyte ratio (CLR) have been associated with various diseases and may be useful for evaluating depression risk. This study investigates the association between CLR and depression and suicidal ideation, using data from the 2015-2023 of the National Health and Nutrition Examination Survey (NHANES).

METHODS: A population-based study using NHANES data were conducted. A total of 12,868 participants were included. Depressive symptoms and suicidal ideation were assessed using the Patient Health Questionnaire-9 (PHQ-9). The CLR was calculated as the ratio of high-sensitivity C-reactive protein (hs-CRP) and lymphocyte count. Multivariable weighted logistic and linear regression models were employed to assess the relationship between Ln-CLR and depression. Several sensitivity analyses were conducted.

RESULTS: A significant positive association was found between elevated Ln-CLR levels and depressive symptoms, both continuously (OR = 1.12, CI: 1.02-1.22, P = 0.014) and categorically (OR = 1.35, CI: 1.00-1.82, P = 0.047 in the fourth quartile) in the fully adjusted model. Subgroup analyses suggested that the association was stable without interaction. Sensitivity analyses using multiple imputation, suicidal ideation as the outcome and the primitive CLR value as the exposure, further confirmed the robustness of the findings.

CONCLUSION: This study demonstrates a significant association between elevated CLR and an increased risk of depressive symptoms and suicidal ideation, highlighting its potential as a novel and accessible biomarker for the early detection and management of depression.

PMID:42178017 | DOI:10.1016/j.pnpbp.2026.111750