Dong Yiran, Zhang Pan, Zhong Jinghui, Wang Jinjing, Xu Yingjie, Huang Hongmei, Liu Xinfeng, Sun Wen
Department of Neurology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.
Department of Neurology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.
J Affect Disord. 2025 Mar 1;372:440-450. doi: 10.1016/j.jad.2024.12.038. Epub 2024 Dec 11.
Modifiable lifestyle factors are implicated as risk factors for neurological and psychiatric disorders, but whether these associations are causal remains uncertain. We aimed to evaluate associations and ascertain causal relationships between modifiable lifestyle factors, neurological and psychiatric disorder risk, and brain structural magnetic resonance imaging (MRI) markers.
We analyzed data from over 50,000 UK Biobank participants with self-reported lifestyle factors, including alcohol consumption, smoking, physical activity, diet, sleep, electronic device use, and sexual factors. Primary outcomes were stroke, all-cause dementia, Parkinson's disease (PD), Major depression disorder (MDD), Anxiety Disorders (ANX), and Bipolar Disorder (BIP), alongside MRI markers. Summary statistics were obtained from genome-wide association studies and Mendelian randomization (MR) analyses investigated bidirectional associations between lifestyle factors, neurological/psychiatric disorders, and MRI markers, with mediation assessed using multivariable Mendelian randomization (MVMR).
Cross-sectional analyses identified lifestyle factors were associated with neurological and psychiatric disorders and brain morphology. MR confirmed causal relationships, including lifetime smoking index on Stroke, PD, MDD, ANX and BIP; play computer games on BIP; leisure screen time on Stroke and MDD; automobile speeding propensity on MDD; sexual factors on MDD and BIP; sleep characteristics on BIP and MDD. Brain structure mediated several lifestyle-disorder associations, such as daytime dozing and dementia, lifetime smoking and PD and age first had sexual intercourse and PD.
Our results provide support for a causal effect of multiple lifestyle measures on the risk of neurological and psychiatric disorders, with brain structural morphology serving as a potential biological mediator in their associations.
可改变的生活方式因素被认为是神经和精神疾病的风险因素，但这些关联是否具有因果关系仍不确定。我们旨在评估可改变的生活方式因素、神经和精神疾病风险以及脑结构磁共振成像（MRI）标志物之间的关联，并确定因果关系。
我们分析了来自超过50000名英国生物银行参与者的数据，这些参与者自我报告了生活方式因素，包括饮酒、吸烟、身体活动、饮食、睡眠、电子设备使用和性因素。主要结局包括中风、全因痴呆、帕金森病（PD）、重度抑郁症（MDD）、焦虑症（ANX）和双相情感障碍（BIP），以及MRI标志物。汇总统计数据来自全基因组关联研究，孟德尔随机化（MR）分析调查了生活方式因素、神经/精神疾病和MRI标志物之间的双向关联，并使用多变量孟德尔随机化（MVMR）评估中介作用。
横断面分析发现生活方式因素与神经和精神疾病以及脑形态有关。MR证实了因果关系，包括中风、PD、MDD、ANX和BIP的终生吸烟指数；双相情感障碍的玩电脑游戏情况；中风和MDD的休闲屏幕时间；MDD的汽车超速倾向；MDD和双相情感障碍的性因素；双相情感障碍和MDD的睡眠特征。脑结构介导了几种生活方式与疾病的关联，如白天打瞌睡与痴呆、终生吸烟与PD以及首次性行为年龄与PD。
我们的结果为多种生活方式措施对神经和精神疾病风险的因果效应提供了支持，脑结构形态在它们的关联中作为潜在的生物学中介。
