Platelet/high-density lipoprotein cholesterol ratio as a biomarker of depression in individuals with chronic opioid use

Background: The comorbidity of depression and opioid use is increasingly recognized as a significant public health concern. Chronic opioid use can alter biological systems, including lipid metabolism and inflammatory responses, potentially contributing to depressive symptoms. The platelet/high-density lipoprotein cholesterol ratio (PHR) has emerged as a biomarker associated with both cardiovascular and mental health outcomes. This study investigates the relationship between PHR and depression in individuals with chronic opioid use. Methods: A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) (2007-2018). A total of 843 participants with prescription opioid use were included. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), with a score ≥10 indicating clinically significant depression. PHR was calculated from platelet counts and HDL cholesterol levels and categorized into quartiles. Weighted logistic regression and restricted cubic spline regression were employed to evaluate associations and potential nonlinear relationships, adjusting for demographic, socioeconomic, lifestyle, and clinical covariates. Results: Higher PHR quartiles were significantly associated with increased odds of depression, even after full adjustment for confounders (OR for Q3: 3.40; 95% CI: 1.95-5.94; OR for Q4: 4.12; 95% CI: 2.21-7.12). A nonlinear relationship was observed, with depression risk increasing sharply beyond a specific PHR threshold. Subgroup analyses revealed stronger associations in younger participants and those with obesity, with significant interaction effects for age and BMI. Conclusion: Elevated PHR is independently associated with depression in individuals with chronic opioid use, suggesting its potential as a biomarker for identifying at-risk populations. The findings underscore the need to address systemic inflammation and lipid dysregulation as part of integrated mental health care for opioid users.