Causal relationship and mediating role between depression and cognitive performance

作者：Xinyu Hao, Fuyang Cao, Ziyao Xu, Shaohua You, Tianyue Mi, Lei Wang, Yongxin Guo, Zhuoning Zhang, Jiangbei Cao, Jingsheng Lou, Yanhong Liu, Xianyang Chen, Zhikang Zhou, Weidong Mi, Tong Li · 发表于：The Journal of Prevention of Alzheimer s Disease · 年份：2025 · DOI：10.1016/j.tjpad.2025.100196 · 被引用次数：6 · 研究领域：Genetic Associations and Epidemiology、Functional Brain Connectivity Studies、Cognitive Abilities and Testing

Background Recent studies have increasingly emphasized the robust correlation between depression and cognitive function. However, it remains unclear whether this relationship is causal or merely coincidental. To address this uncertainty, we conducted two-sample bidirectional Mendelian randomization (MR) analyses to investigate the connection between depression and cognitive performance. Methods We sourced genome-wide association study (GWAS) data for depression (N SNPs =21,306,230) from the FinnGen (R10) and for cognitive performance (N SNPs =10,049,954) from the IEU GWAS database. Causal effects employed methodologies such as Inverse variance weighted (IVW), weighted median, MR Egger, simple mode and weighted mode. Two-step analysis determined the contribution of the mediator variable to the outcomes. To determine stability and reliability, sensitivity analyses were performed that included an assessment of heterogeneity, horizontal pleiotropy, and the leave-one-out techniques. Results This MR analysis identified 8 independent significant SNPs associated with depression and 81 SNPs linked to cognitive performance. Our findings revealed that depression increases the risk of developing deteriorating cognitive performance (IVW β , -0.11; 95 % confidence interval (CI), -0.18 – -0.05; P IVW value= 5.97E-04). Conversely, cognitive performance decline could also predispose individuals to depression [odds ratio (OR) IVW, 0.85; 95 % CI, 0.76 – 0.95; P IVW value=0.004]. Multivariate MR...