Serum lipid profiles and risk of depression: a UK Biobank prospective cohort study

Background The relationship between serum lipids and depression is poorly characterized, with existing studies yielding inconsistent results. We aim to prospectively investigate the associations between 11 serum lipid traits and risk of incident depression in a large cohort from the UK Biobank. Methods The primary exposures were baseline serum concentrations of Apolipoprotein A (ApoA), Apolipoprotein B (ApoB), HDL-C, LDL-C, triglyceride, total cholesterol, total esterified cholesterol, total free cholesterol, total choline, total fatty acids, and Lipoprotein A, while the primary outcome was diagnosis of depression. Cox proportional hazards models were used to calculate hazard ratios (HRs). Non-linearity was assessed using restricted cubic splines. Results Over a mean follow-up of 12.3 years, 19,303 participants developed depression among 445,105 participants. In multivariable models, significant inverse associations were observed for ApoB (HR = 0.85, 95% CI = 0.79–0.91), LDL-C (HR = 0.89, 0.86–0.92), and total cholesterol (HR = 0.95, 0.94–0.97), and nominal inverse association for ApoA (HR = 0.91, 0.85–0.98). Quartile analyses showed monotonic decreases in depression risk for each lipid. Restricted cubic spline analyses revealed a U-shaped association for ApoA, indicating elevated depression risk at both extremely low and high concentrations, whereas other lipid traits showed monotonic decreasing relationships. Furthermore, the associations were significantly modified by smoking, with attenuated protective effects among heavy smokers. Conclusion These findings suggest maintaining specific lipid levels within a moderate range may be important for mental health, particularly in conjunction with healthy lifestyle factors.