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Molecular Signatures of Major Depression
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 signif...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425463/ https://www.ncbi.nlm.nih.gov/pubmed/25913401 http://dx.doi.org/10.1016/j.cub.2015.03.008 |
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author | 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 Flint, Jonathan |
author_facet | 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 Flint, Jonathan |
author_sort | Cai, Na |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4425463 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44254632015-05-13 Molecular Signatures of Major Depression 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 Flint, Jonathan Curr Biol Article 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. Cell Press 2015-05-04 /pmc/articles/PMC4425463/ /pubmed/25913401 http://dx.doi.org/10.1016/j.cub.2015.03.008 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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 Flint, Jonathan Molecular Signatures of Major Depression |
title | Molecular Signatures of Major Depression |
title_full | Molecular Signatures of Major Depression |
title_fullStr | Molecular Signatures of Major Depression |
title_full_unstemmed | Molecular Signatures of Major Depression |
title_short | Molecular Signatures of Major Depression |
title_sort | molecular signatures of major depression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425463/ https://www.ncbi.nlm.nih.gov/pubmed/25913401 http://dx.doi.org/10.1016/j.cub.2015.03.008 |
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