DNA methylation changes consistently throughout life and age-dependent alterations in DNA methylation can be used to estimate one’s epigenetic age. Post-mortem studies revealed higher epigenetic age in brains of patients with major depressive disorder, as compared with controls. Since MDD is highly correlated with anxiety, we hypothesized that symptoms of anxiety, as well as lower volume of grey matter (GM) in depression-related cortical regions, will be associated with faster epigenetic clock in a community-based sample of young adults. Participants included 88 young adults (53% men; 23-24 years of age) from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) who participated in its neuroimaging follow-up and provided saliva samples for epigenetic analysis. Epigenetic age was calculated according to Horvath (Horvath, 2013). Women had slower epigenetic clock than men (Cohen’s d=0.48). In women (but not men), slower epigenetic clock was associated with less symptoms of anxiety. In the brain, women (but not men) with slower epigenetic clock had greater GM volume in the cerebral cortex (brain size-corrected; R²=0.07). Lobe-specific analyses showed that in women (but not men), slower epigenetic clock was associated with greater GM volume in frontal lobe (R²=0.16), and that GM volume in frontal lobe mediated the relationship between the speed of epigenetic clock and anxiety trait (ab=0.15, SE=0.15, 95% CI [0.007; 0.369]). These findings were not replicated, however, in a community-based sample of adolescents (n=129; 49% men; 12 to 19 years of age), possibly due to the different method of tissue collection (blood vs. saliva) or additional sources of variability in the cohort of adolescents (puberty stages, socioeconomic status, prenatal exposure to maternal smoking during pregnancy).

DNA甲基化在整个生命中始终如一，并且DNA甲基化的年龄依赖性变化可用于估计一个人的表观遗传年龄。验尸研究显示，与对照组相比，重度抑郁症患者大脑的表观遗传年龄更高。由于MDD与焦虑高度相关，因此我们假设在以社区为基础的年轻人样本中，焦虑症状以及与抑郁症相关的皮质区域灰质（GM）含量降低将与更快的表观遗传钟相关。参加者包括来自欧洲妊娠与儿童纵向研究（ELSPAC）的88名年轻成年人（53％的男性； 23-24岁），他们参加了其神经影像学随访并提供了唾液样本用于表观遗传学分析。根据Horvath（Horvath，2013）计算了表观遗传年龄。女性的表观遗传时钟比男性慢（Cohen d = 0.48）。在女性（而非男性）中，较慢的表观遗传钟与较少的焦虑症状相关。在大脑中，表观遗传时钟较慢的女性（而非男性）在大脑皮层的GM体积更大（大脑尺寸校正； R² = 0.07）。特定于叶的分析表明，在女性（而非男性）中，表观遗传时钟变慢与额叶中的GM体积更大相关（R ² = 0.16），并且额叶中的GM体积介导了表观遗传时钟速度与表观遗传速度之间的关系。焦虑特质（ab = 0.15，SE = 0.15，95％CI [0.007; 0.369] ）。但是，这些发现并未在以社区为基础的青少年样本（n = 129； 49％的男性； 12至19岁）中得到重复，这可能是由于组织收集方法不同（血液还是唾液）或其他原因。青少年群体的变异性来源（青春期，社会经济状况，孕妇在产前暴露于孕妇吸烟中）。