Molecular signatures of major depression.
Molecular signatures of major depression.
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DOI：
10.1016/j.cub.2015.03.008
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发表时间：
2015-05-04
期刊：
影响因子：
9.2
通讯作者：
Flintl, Jonathan
中科院分区：
文献类型：
--
作者：
Cai, Na;Chang, Simon;Li, Yihan;Li, Qibin;Hu, Jingchu;Liang, Jieqin;Song, Li;Kretzschmar, Warren;Gan, Xiangchao;Nicod, Jerome;Rivera, Margarita;Deng, Hong;Du, Bo;Li, Keqing;Sang, Wenhu;Gao, Jingfang;Gao, Shugui;Ha, Baowei;Ho, Hung-Yao;Hu, Chunmei;Hu, Jian;Hu, Zhenfei;Huang, Guoping;Jiang, Guoqing;Jiang, Tao;Jin, Wei;Li, Gongying;Li, Kan;Li, Yi;Li, Yingrui;Li, Youhui;Lin, Yu-Ting;Liu, Lanfen;Liu, Tiebang;Liu, Ying;Liu, Yuan;Lu, Yao;Lv, Luxian;Meng, Huaqing;Qian, Puyi;Sang, Hong;Shen, Jianhua;Shi, Jianguo;Sun, Jing;Tao, Ming;Wang, Gang;Wang, Guangbiao;Wang, Jian;Wang, Linmao;Wang, Xueyi;Wang, Xumei;Yang, Huanming;Yang, Lijun;Yin, Ye;Zhang, Jinbei;Zhang, Kerang;Sun, Ning;Zhang, Wei;Zhang, Xiuqing;Zhang, Zhen;Zhong, Hui;Breen, Gerome;Wang, Jun;Marchini, Jonathan;Chen, Yiping;Xu, Qi;Xu, Xun;Mott, Richard;Huang, Guo-Jen;Kendler, Kenneth;Flintl, Jonathan
逆境，特别是在生命早期，可能会导致疾病。相关机制的线索可能在于压力分子特征的发现，其中一些包括个体体细胞基因组的改变。在这里，使用 11,670 名女性的基因组序列，我们观察到压力相关疾病、重度抑郁症与 mtDNA 量（p = 9.00 × 10−42，优势比 1.33 [95% 置信区间 [CI] = 1.29–1.37]）和端粒长度（p = 2.84 × 10−14，优势比）之间存在高度显着的关联。 0.85 [95% CI = 0.81–0.89]）。虽然端粒长度和线粒体 DNA 数量都与不良生活事件相关，但条件回归分析显示分子变化取决于抑郁状态。我们通过小鼠实验验证了这一假设，证明压力会引起两种分子变化，这些变化是部分可逆的，并且可以通过服用皮质酮来引发。总之，这些结果表明，线粒体 DNA 数量和端粒长度的变化是压力和进入抑郁状态的结果。这些发现将 mtDNA 含量的增加确定为 MD 的分子标记，对于理解压力如何导致这种疾病具有重要意义。在重性抑郁症中，线粒体 DNA 的量增加，端粒 DNA 缩短 这两种变化都可以由压力引起，但取决于抑郁状态 变化是组织特异性的，部分是由于糖皮质激素分泌 变化部分是可逆的，代表代谢策略的转变 Cai 等人。通过全基因组测序发现，在重度抑郁症病例中，线粒体 DNA 增加，端粒 DNA 减少。这两种变化都依赖于抑郁状态。暴露于慢性应激或糖皮质激素的小鼠表明，这些变化反映了代谢策略的转变，并且是组织特异性的且部分可逆的。
Adversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individual’s somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 × 10−42, odds ratio 1.33 [95% confidence interval [CI] = 1.29–1.37]) and telomere length (p = 2.84 × 10−14, odds ratio 0.85 [95% CI = 0.81–0.89]). While both telomere length and mtDNA amount were associated with adverse life events, conditional regression analyses showed the molecular changes were contingent on the depressed state. We tested this hypothesis with experiments in mice, demonstrating that stress causes both molecular changes, which are partly reversible and can be elicited by the administration of corticosterone. Together, these results demonstrate that changes in the amount of mtDNA and telomere length are consequences of stress and entering a depressed state. These findings identify increased amounts of mtDNA as a molecular marker of MD and have important implications for understanding how stress causes the disease. Amount of mtDNA is increased, and telomeric DNA is shortened in major depression Both changes can be induced with stress but are contingent on the depressed state Changes are tissue specific and in part due to glucocorticoid secretion Changes are in part reversible and represent switches in metabolic strategy Cai et al. found increases in mtDNA and a reduction in telomeric DNA in cases of major depression using whole-genome sequencing. Both changes are depression state dependent. Mice exposed to chronic stress or glucorticoids showed that these changes reflect switches in metabolic strategy and are tissue specific and partial reversible.
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影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
3.7
作者：
Chen J;Cai Y;Cong E;Liu Y;Gao J;Li Y;Tao M;Zhang K;Wang X;Gao C;Yang L;Li K;Shi J;Wang G;Liu L;Zhang J;Du B;Jiang G;Shen J;Zhang Z;Liang W;Sun J;Hu J;Liu T;Wang X;Miao G;Meng H;Li Y;Hu C;Li Y;Huang G;Li G;Ha B;Deng H;Mei Q;Zhong H;Gao S;Sang H;Zhang Y;Fang X;Yu F;Yang D;Liu T;Chen Y;Hong X;Wu W;Chen G;Cai M;Song Y;Pan J;Dong J;Pan R;Zhang W;Shen Z;Liu Z;Gu D;Wang X;Liu X;Zhang Q;Li Y;Chen Y;Kendler KS;Shi S;Flint J
通讯作者：
Flint J
DOI：
10.1073/pnas.1315458110
发表时间：
2013-10-15
影响因子：
11.1
作者：
Carroll, Judith E.;Gruenewald, Tara L.;Seeman, Teresa E.
通讯作者：
Seeman, Teresa E.
影响因子：
4.8
作者：
GIBBONS, JL;MCHUGH, PR
通讯作者：
MCHUGH, PR
影响因子：
15.1
作者：
Choi, Jenny;Fauce, Steven R.;Effros, Rita B.
通讯作者：
Effros, Rita B.