表观遗传和结构脑老化及其与重度抑郁症的关系

IF 3.7 Q2 NEUROSCIENCES

Biological psychiatry global open science Pub Date : 2025-08-05 DOI:10.1016/j.bpsgos.2025.100577

Eileen Y. Xu , Claire Green , Daniel L. McCartney , Laura K.M. Han , Kathryn L. Evans , Rosie M. Walker , Danni A. Gadd , Douglas Steele , Gordon Waiter , Archie Campbell , Stephen M. Lawrie , James H. Cole , Andrew M. McIntosh , Xueyi Shen , Heather C. Whalley

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引用次数: 0

摘要

越来越多的证据表明，重度抑郁症（MDD）可能与过早的生物衰老有关。然而，迄今为止报道的大多数研究都是单独检查了基于大脑（BrainAge）和基于DNA甲基化（DNAm）的生物年龄（BioAge）测量（DNAmAge）。方法研究了两种生物年龄测量方法：BrainAge和DNAmAge（基于Horvath、Hannum、GrimAge和PhenoAge时钟的4种不同的DNAmAge测量方法）。我们使用来自GS:STRADL的横断面队列数据（苏格兰一代：纵向分层恢复力和抑郁）（BrainAge n = 833; DNAmAge n = 587；年龄范围26-76岁），并使用UK Biobank （UKB）数据来测试大脑年龄与MDD （BrainAge n = 12,018，年龄范围45-80岁）之间关联的复制。脑过早老化和dna老化作为预测年龄差异（PAD）进行操作，分析控制了年龄、性别、吸烟和饮酒。我们还使用逻辑回归测试了基于大脑和dnam的pad与终生/当前MDD的个体和附加关联。结果除Horvath年龄外，终生MDD患者的脑龄和DNAmAge均显著高于无MDD患者，在1.60 ~ 2.45岁之间。在英国没有发现大脑时代的差异。就PAD而言，终生MDD与GrimAge-PAD、PhenoAge-PAD和Brain-PAD显著相关，比值比(OR) = 1.21 - 1.30 （UKB中，Brain-PAD OR = 1.05）。DNAm-PAD和Brain-PAD显示了与终生MDD的共同和独特的关联，其中表型- pad加Brain-PAD解释了最大的方差（曲线下面积= 0.69,R2 = 9%）。未发现与当前MDD有显著关联。结论我们的研究结果强调了终身MDD患者脑过早和dna老化之间的共同和独特的关联。

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Epigenetic and Structural Brain Aging and Their Associations With Major Depressive Disorder

Background

A growing body of evidence suggests that major depressive disorder (MDD) may be associated with premature biological aging. However, most studies reported to date have examined brain-based (BrainAge) and DNA methylation (DNAm)–based measures (DNAmAge) of biological age (BioAge) in isolation.

Methods

We investigated 2 well-studied BioAge measures in lifetime and current MDD: BrainAge and DNAmAge (4 separate DNAmAge measures based on Horvath, Hannum, GrimAge, and PhenoAge clocks). We used cross-sectional cohort data from GS:STRADL (Generation Scotland: STratifying Resilience and Depression Longitudinally) (BrainAge n = 833; DNAmAge n = 587; age range 26–76 years) and used UK Biobank (UKB) data to test for replication of BrainAge associations with MDD (BrainAge n = 12,018, age range 45–80 years). Premature brain and DNAm aging were operationalized as predicted age difference (PAD), and analyses controlled for age, sex, smoking, and alcohol intake. We also tested individual and additive associations of brain- and DNAm-based PADs to lifetime/current MDD using logistic regression.

Results

Individuals with lifetime MDD showed significantly higher BrainAge and DNAmAge in GS, ranging from 1.60 to 2.45 years, than individuals without MDD for all measures except for Horvath age. No differences were found for BrainAge in the UKB. In terms of PAD, lifetime MDD was significantly associated with GrimAge-PAD, PhenoAge-PAD, and Brain-PAD, ranging from odds ratio (OR) = 1.21−1.30 (and in UKB, Brain-PAD OR = 1.05). DNAm-PAD and Brain-PAD demonstrated shared and distinctive associations with lifetime MDD, where PhenoAge-PAD plus Brain-PAD explained maximum variance (area under the curve = 0.69, R² = 9%). No significant associations were found for current MDD.