From the Department of Psychiatry, VU University Medical Center, Amsterdam Neuroscience, GGZ inGeest, the Amsterdam Public Health Research Institute, Amsterdam; the Center for Biomarker Research and Precision Medicine, School of Pharmacy, Virginia Commonwealth University, Richmond; the Molecular Psychiatry Laboratory, Florey Department of Neuroscience and Mental Health, Melbourne, Australia; and the Centre for Mental Health, Faculty of Health, Arts, and Design, Swinburne University, Hawthorne, Australia.
Am J Psychiatry. 2018 Aug 1;175(8):774-782. doi: 10.1176/appi.ajp.2018.17060595. Epub 2018 Apr 16.
Major depressive disorder is associated with an increased risk of mortality and aging-related diseases. The authors examined whether major depression is associated with higher epigenetic aging in blood as measured by DNA methylation (DNAm) patterns, whether clinical characteristics of major depression have a further impact on these patterns, and whether the findings replicate in brain tissue.
DNAm age was estimated using all methylation sites in blood of 811 depressed patients and 319 control subjects with no lifetime psychiatric disorders and low depressive symptoms from the Netherlands Study of Depression and Anxiety. The residuals of the DNAm age estimates regressed on chronological age were calculated to indicate epigenetic aging. Major depression diagnosis and clinical characteristics were assessed with questionnaires and psychiatric interviews. Analyses were adjusted for sociodemographic characteristics, lifestyle, and health status. Postmortem brain samples of 74 depressed patients and 64 control subjects were used for replication. Pathway enrichment analysis was conducted using ConsensusPathDB to gain insight into the biological processes underlying epigenetic aging in blood and brain.
Significantly higher epigenetic aging was observed in patients with major depression compared with control subjects (Cohen's d=0.18), with a significant dose effect with increasing symptom severity in the overall sample. In the depression group, epigenetic aging was positively and significantly associated with childhood trauma score. The case-control difference was replicated in an independent data set of postmortem brain samples. The top significantly enriched Gene Ontology terms included neuronal processes.
As compared with control subjects, patients with major depression exhibited higher epigenetic aging in blood and brain tissue, suggesting that they are biologically older than their corresponding chronological age. This effect was even more profound in the presence of childhood trauma.
重度抑郁症与死亡率增加和与衰老相关的疾病有关。作者研究了重度抑郁症是否与血液中 DNA 甲基化（DNAm）模式所衡量的更高的表观遗传衰老有关，重度抑郁症的临床特征是否对这些模式有进一步的影响，以及这些发现是否可以在脑组织中复制。
使用来自荷兰抑郁和焦虑研究的 811 名抑郁患者和 319 名无终生精神障碍和低抑郁症状的对照受试者的血液中所有甲基化位点，估计 DNAm 年龄。计算 DNAm 年龄估计值从表型年龄减去的残差值，以表示表观遗传衰老。使用问卷和精神病访谈评估重度抑郁症的诊断和临床特征。分析调整了社会人口统计学特征、生活方式和健康状况。使用 74 名抑郁患者和 64 名对照受试者的死后脑组织样本进行复制。使用 ConsensusPathDB 进行途径富集分析，以深入了解血液和大脑中表观遗传衰老的生物学过程。
与对照组相比，重度抑郁症患者的表观遗传衰老明显更高（Cohen's d=0.18），在整个样本中，随着症状严重程度的增加，存在显著的剂量效应。在抑郁组中，表观遗传衰老与儿童创伤评分呈正相关且显著相关。病例对照差异在独立的死后脑组织样本数据集中得到了复制。最显著富集的基因本体论术语包括神经元过程。
与对照组相比，重度抑郁症患者的血液和脑组织表现出更高的表观遗传衰老，这表明他们的生物学年龄比相应的表型年龄大。在存在儿童创伤的情况下，这种影响更为明显。
