Epigenetic Aging in Major Depressive Disorder.
Epigenetic Aging in Major Depressive Disorder.
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DOI：
10.1176/appi.ajp.2018.17060595
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发表时间：
2018-08-01
期刊：
影响因子：
--
通讯作者：
Penninx BWJH
中科院分区：
文献类型：
--
作者：
Han LKM;Aghajani M;Clark SL;Chan RF;Hattab MW;Shabalin AA;Zhao M;Kumar G;Xie LY;Jansen R;Milaneschi Y;Dean B;Aberg KA;van den Oord EJCG;Penninx BWJH
重度抑郁症（MDD）与死亡和衰老相关疾病的风险增加有关。在这里，研究了MDD是否与通过DNA甲基化（DNAm）模式测量的血液中较高的表观遗传衰老（EA）相关，MDD的临床特征是否进一步影响这些模式，以及研究结果是否在脑组织中复制。DNAmAge使用荷兰抑郁症和焦虑症研究中811名抑郁症患者和319名对照者血液中的所有甲基化位点进行估计。计算根据实际年龄回归的DNAmAge估计值的残差，以指示表观遗传老化（EA）。通过问卷调查和精神病学访谈评估MDD诊断和临床特征。分析根据社会人口统计学、生活方式和健康状况进行调整。74例抑郁症患者和64例对照者的死后脑组织样本用于复制。使用ApplusPathDB进行途径富集分析，以深入了解血液和大脑中EA的生物学过程。与对照组相比，在MDD患者中观察到更高的EA（P=0.008; Cohen's d=0.18），总体样本中症状严重程度增加的剂量效应（P=0.001）。在MDD患者中，EA与儿童创伤评分呈正相关（P=0.02）。在一个独立的死后脑样本数据集中复制了病例对照差异（P=0.03）。最显著丰富的基因本体论术语包括神经元过程。与对照组相比，MDD患者在血液和脑组织中表现出更高的表观遗传衰老，表明他们在生物学上比他们相应的实际年龄更老。在童年创伤的情况下，这种影响甚至更为深远。
Major Depressive Disorder (MDD) is associated with increased risk of mortality and aging-related diseases. Here, it was examined whether MDD is associated with higher epigenetic aging (EA) in blood as measured by DNA methylation (DNAm) patterns, whether clinical characteristics of MDD further impact these patterns, and whether findings replicate in brain tissue. DNAmAge was estimated using all methylation sites in blood of 811 depressed patients and 319 controls from the Netherlands Study of Depression and Anxiety. The residuals of the DNAmAge estimates regressed on chronological age were calculated to indicate epigenetic aging (EA). MDD diagnosis and clinical characteristics were assessed with questionnaires and psychiatric interviews. Analyses were adjusted for sociodemographics, lifestyle, and health status. Post-mortem brain samples of 74 depressed patients and 64 controls were used for replication. Pathway enrichment analysis was conducted using ConsensusPathDB to gain insight into the biological processes underlying EA in blood and brain. Higher EA was observed in MDD patients compared to controls (P=0.008; Cohen’s d=0.18), with a dose-effect with increasing symptom severity in the overall sample (P=0.001). Within MDD patients, EA was positively associated with childhood trauma scores (P=0.02). The case-control difference was replicated in an independent dataset of post-mortem brain samples (P=0.03). Top significantly enriched Gene Ontology terms included neuronal processes. As compared to controls, MDD patients show 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.
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影响因子：
14.9
作者：
Kamburov A;Stelzl U;Lehrach H;Herwig R
通讯作者：
Herwig R
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
5.7
作者：
Breitling LP;Saum KU;Perna L;Schöttker B;Holleczek B;Brenner H
通讯作者：
Brenner H
影响因子：
3.4
作者：
Buigues, Cristina;Padilla-Sanchez, Celia;Cauli, Omar
通讯作者：
Cauli, Omar