Serum HDL mediates the association between inflammatory predictors and depression risk after the COVID-19 pandemic

This study investigated whether HDL cholesterol mediates the relationship between inflammatory indicators and depression, using post-pandemic data in the context of metabolic disturbances and immune system impairment potentially caused by COVID-19.

This cross-sectional study, using data from the National Health and Nutrition Examination Survey (NHANES), included 5731 participants aged 20 years or older from August 2021 to August 2023. The Patient Health Questionnaire-9 (PHQ-9) assessed depressive symptoms. Multivariable logistic regression, Pearson correlation, and mediation analyses were conducted to evaluate odds ratios and associations between inflammatory indicators and depression.

Correlation analysis revealed significant negative associations between four inflammatory indicators (CRP, C-reactive protein; PC, platelet count; SII, systemic immune-inflammation index; PPN, product of platelet count and neutrophil count) and HDL cholesterol, as well as between HDL cholesterol and depression, while the inflammatory indicators were significantly positively correlated with depression (all p < 0.05). Furthermore, multivariable logistic regression models, adjusted for covariates, demonstrated that elevated levels of these four inflammatory indicators (CRP: adjusted OR = 1.011, CI = 1.003-1.025; PC: OR = 1.002, CI = 1.001-1.004; SII: OR = 1.002, CI = 1.001-1.003; PPN: OR = 1.002, CI = 1.001-1.004) were significantly associated with an increased risk of depression in the total study population. Finally, mediation analysis indicated that HDL cholesterol mediated the presumed causal associations between CRP (6.7-13.2 %), PC (4.5-12.8 %), PPN (4.8-14.9 %), and depression, whereas SII was identified as an independent predictor of depression development.

Targeting HDL cholesterol and inflammatory indicators such as CRP, PC, SII and PPN may provide potential interventions for mitigating depression risk.