Jin Zhi, Luo Qiang, Sun Xueqing, Ge Guangzhi, Song Yihang, Shi Yongfeng
Department of Neurology, Shanghai Fifth People's Hospital, Fudan University, Shanghai City, China; Center of Community-Based Health Research, Fudan University, Shanghai City, China.
Department of Cardiology, the Second Hospital of Jilin University, Changchun, Jilin, China.
J Affect Disord. 2025 Nov 1;388:119610. doi: 10.1016/j.jad.2025.119610. Epub 2025 Jun 6.
Depression is a significant public health concern, particularly among older adults. While variability in high-density lipoprotein cholesterol (HDL-C) has been associated with various health outcomes, its relationship with depression remains unclear. This study aimed to investigate the association between HDL-C variability and the risk of depression in a Chinese population, utilizing both observational data and Mendelian randomization (MR) analysis.
The study analyzed data from the China Health and Retirement Longitudinal Study (CHARLS), including 3014 participants. HDL-C variability was assessed using three metrics: variability independent of the mean (VIM), average real variability (ARV), and standard deviation (SD). Depressive symptoms were measured using the CESD-10 scale. Logistic regression models were used to evaluate the association between HDL-C variability and depression, adjusting for potential confounders. Additionally, MR analysis was conducted to explore the causal relationship between HDL-C change and depression risk, utilizing genetic instruments from large-scale genome-wide association studies (GWAS).
The observational study demonstrated that higher HDL-C variability, particularly as measured by ARV and SD, was significantly associated with an increased risk of depression. Participants in the highest quartiles of ARV and SD exhibited significantly higher depression scores compared to those in the lowest quartiles, with consistent results across multiple adjusted models. However, the MR analysis indicated that genetically predicted increases in HDL-C levels, rather than variability, were associated with a lower risk of depression. This discrepancy suggests that the relationship between HDL-C and depression may be influenced by different underlying mechanisms.
The study provides evidence that higher HDL-C variability is associated with an increased risk of depression in older Chinese adults based on observational data. However, MR analysis suggests a potentially protective effect of overall HDL-C changes against depression. These findings highlight the complex and multifaceted relationship between HDL-C and depression, underscoring the need for further research to disentangle the distinct impacts of HDL-C variability and overall changes on mental health.
抑郁症是一个重大的公共卫生问题，在老年人中尤为突出。虽然高密度脂蛋白胆固醇（HDL-C）的变异性与多种健康结果相关，但其与抑郁症的关系仍不明确。本研究旨在利用观察性数据和孟德尔随机化（MR）分析，探讨中国人群中HDL-C变异性与抑郁症风险之间的关联。
该研究分析了中国健康与养老追踪调查（CHARLS）的数据，包括3014名参与者。使用三个指标评估HDL-C变异性：独立于均值的变异性（VIM）、平均实际变异性（ARV）和标准差（SD）。使用CESD-10量表测量抑郁症状。采用逻辑回归模型评估HDL-C变异性与抑郁症之间的关联，并对潜在混杂因素进行调整。此外，利用大规模全基因组关联研究（GWAS）的基因工具进行MR分析，以探讨HDL-C变化与抑郁症风险之间的因果关系。
观察性研究表明，较高的HDL-C变异性，尤其是通过ARV和SD测量的变异性，与抑郁症风险增加显著相关。ARV和SD最高四分位数的参与者与最低四分位数的参与者相比，抑郁得分显著更高，多个调整模型的结果一致。然而，MR分析表明，基因预测的HDL-C水平升高而非变异性与较低的抑郁症风险相关。这种差异表明HDL-C与抑郁症之间的关系可能受不同潜在机制的影响。
该研究提供的证据表明，基于观察性数据，较高的HDL-C变异性与中国老年成年人抑郁症风险增加相关。然而，MR分析表明HDL-C总体变化对抑郁症具有潜在的保护作用。这些发现凸显了HDL-C与抑郁症之间复杂多面的关系，强调需要进一步研究以厘清HDL-C变异性和总体变化对心理健康的不同影响。
