The association between high-density lipoprotein cholesterol and depressive symptoms: The moderating role of inflammation

Depression is a serious mental disorder, and growing research focuses on its bidirectional link with cardiovascular health. From this integrative perspective, high-density lipoprotein cholesterol (HDL-C) and C-reactive protein (CRP, a marker of systemic inflammation) can serve as biological substrates linking the two conditions. Previous studies on depression and HDL-C have reported inconsistent findings, likely because depression was often treated as a single condition rather than accounting for its varied symptom dimensions. Furthermore, while inflammation was reported to influence the overall link between HDL-C and depression, its role in specific depressive symptoms remains unclear. Therefore, in this study, we constructed network models to analyze the relationships between HDL-C and depressive symptoms and investigate the moderating effect of CRP levels, using data from the National Health and Nutrition Examination Survey. The results indicated that HDL-C exhibited negative correlations with sadness and psychomotor changes and a positive correlation with low self-esteem. Furthermore, as inflammation levels increased, the associations between HDL-C and both anhedonia and death thoughts tended toward negative correlations, whereas the association with appetite changes shifted toward a positive correlation. Our findings suggest that the relationship between HDL-C and depression is symptom-specific and partially modulated by the inflammatory environment, providing symptom-level evidence for understanding the shared biological basis of depression and cardiovascular disease.