Chen Zheng, Sui Guanghong, Yang Caixia, Lv Zongshun, Wang Feng
Tianjin Haihe Hospital, Tianjin, China.
Department of Child and Adolescent Psychology, Tianjin Anding Hospital, Tianjin, China.
Clin Anat. 2025 May;38(4):464-470. doi: 10.1002/ca.24237. Epub 2024 Nov 2.
Understanding the impact of depression on brain aging benefits the prognosis of this disease and of the risk that other age-related brain disorders will develop in the same population. The aim of the present study was to explore the genetic effect of depression on longitudinal changes in brain structure throughout the lifespan using a Mendelian randomization approach. Summary data from a genome-wide association study of 195,321 to 377,277 participants in the FinnGen consortium were used to predict depression, anxiety disorders, mood disorders, and antidepressant use genetically. Data from 15,640 participants in the ENIGMA consortium were included to predict changes in 15 brain structures throughout the lifespan. The causal relationship between these depressive traits and the brain structure parameters was assessed by two-sample Mendelian randomization (including inverse-variance weighted). Sensitivity analyses were conducted for quality control. Depression slowed the decrease of cortical gray matter volume significantly throughout the lifespan (p = 0.001). Depression, anxiety, and mood disorders nominally decreased the rates of change of volume in the cerebellum gray matter, lateral ventricles, and cortical gray matter throughout the lifespan (p = 0.048, p = 0.021, p = 0.038, respectively). Antidepressants did not affect these rates of change significantly (p > 0.05). Sensitivity analyses confirmed the reliability of this study. Depression and its main symptoms have a slight effect on longitudinal changes in a few brain structures throughout the lifespan at the genetic level. These findings do not support the notion that depression affects macro-aging in the brain crucially.
了解抑郁症对大脑衰老的影响有助于改善该疾病的预后以及降低同一人群中发生其他与年龄相关的脑部疾病的风险。本研究的目的是使用孟德尔随机化方法探讨抑郁症对整个生命周期大脑结构纵向变化的遗传效应。利用芬兰基因联盟中195,321至377,277名参与者的全基因组关联研究的汇总数据，对抑郁症、焦虑症、情绪障碍和抗抑郁药物使用进行遗传预测。纳入了ENIGMA联盟中15,640名参与者的数据，以预测整个生命周期中15种脑结构的变化。通过两样本孟德尔随机化（包括逆方差加权）评估这些抑郁特征与脑结构参数之间的因果关系。进行敏感性分析以进行质量控制。抑郁症在整个生命周期中显著减缓了皮质灰质体积的减少（p = 0.001）。抑郁症、焦虑症和情绪障碍在名义上降低了整个生命周期中小脑灰质、侧脑室和皮质灰质体积的变化率（分别为p = 0.048、p = 0.021、p = 0.038）。抗抑郁药物对这些变化率没有显著影响（p > 0.05）。敏感性分析证实了本研究的可靠性。抑郁症及其主要症状在遗传水平上对整个生命周期中少数脑结构的纵向变化有轻微影响。这些发现不支持抑郁症对大脑宏观衰老有至关重要影响的观点。
