Molecular Signatures of Major Depression

被引：199

作者：

Cai, Na ^{[1
]}

Chang, Simon ^{[2
]}

Li, Yihan ^{[1
]}

Li, Qibin ^{[3
]}

Hu, Jingchu ^{[3
]}

Liang, Jieqin ^{[3
]}

Song, Li ^{[3
]}

Kretzschmar, Warren ^{[1
]}

Gan, Xiangchao ^{[4
]}

Nicod, Jerome ^{[1
]}

Rivera, Margarita ^{[5
,6
,7
]}

Deng, Hong ^{[8
]}

Du, Bo ^{[9
]}

Li, Keqing ^{[9
]}

Sang, Wenhu ^{[9
]}

Gao, Jingfang ^{[10
]}

Gao, Shugui ^{[11
]}

Ha, Baowei ^{[12
]}

Ho, Hung-Yao ^{[13
]}

Hu, Chunmei ^{[14
]}

Hu, Jian ^{[15
]}

Hu, Zhenfei ^{[3
]}

Huang, Guoping ^{[16
]}

Jiang, Guoqing ^{[17
]}

Jiang, Tao ^{[3
]}

Jin, Wei ^{[3
]}

Li, Gongying ^{[18
]}

Li, Kan ^{[19
]}

Li, Yi ^{[20
]}

Li, Yingrui ^{[3
]}

Li, Youhui ^{[21
]}

Lin, Yu-Ting ^{[22
]}

Liu, Lanfen ^{[23
]}

Liu, Tiebang ^{[24
]}

Liu, Ying ^{[25
]}

Liu, Yuan ^{[3
]}

Lu, Yao ^{[3
]}

Lv, Luxian ^{[26
]}

Meng, Huaqing ^{[27
]}

Qian, Puyi ^{[3
]}

Sang, Hong ^{[28
]}

Shen, Jianhua ^{[29
]}

Shi, Jianguo ^{[30
]}

Sun, Jing ^{[31
]}

Tao, Ming ^{[32
]}

Wang, Gang ^{[33
]}

Wang, Guangbiao ^{[3
]}

Wang, Jian ^{[3
]}

Wang, Linmao ^{[3
]}

Wang, Xueyi ^{[34
]}

机构：

[1] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, Oxon, England

[2] Chang Gung Univ, Coll Med, Dept & Grad Inst Biomed Sci, Taoyuan 33302, Taiwan

[3] BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China

[4] Max Planck Inst Plant Breeding Res, Dept Comparat Dev Genet, D-50829 Cologne, Germany

[5] Univ Granada, CIBERSAM, Ctr Invest Med Red Salud Mental, Granada, Spain

[6] Kings Coll London, Inst Psychiat, MRC SGDP Ctr, London SE5 8AF, England

[7] Kings Coll London, Inst Psychiat, Biomed Res Ctr Mental Hlth, Natl Inst Hlth Res, London SE5 8AF, England

[8] Sichuan Univ, West China Hosp, Mental Hlth Ctr, Chengdu 610000, Sichuan, Peoples R China

[9] Hebei Mental Hlth Ctr, Baoding 71000, Hebei, Peoples R China

[10] Zhejiang Tradit Chinese Med Hosp, Hangzhou 310000, Zhejiang, Peoples R China

[11] Ningbo Kang Ning Hosp, Ningbo 315000, Zhejiang, Peoples R China

[12] Liaocheng 4 Hosp, Liaocheng 252000, Shandong, Peoples R China

[13] Chang Gung Univ, Coll Med, Dept Med Biotechnol & Lab Sci, Taoyuan 33302, Taiwan

[14] 3 Hosp Heilongjiang Prov, Beian 164000, Heilongjiang, Peoples R China

[15] Harbin Med Univ, Haerbin 150000, Heilongjiang, Peoples R China

[16] Sichuan Mental Hlth Ctr, Mianyang 621000, Sichuan, Peoples R China

[17] Chongqing Mental Hlth Ctr, Chongqing 404100, Peoples R China

[18] Jining Med Coll, Mental Hlth Inst, Jining 272000, Shandong, Peoples R China

[19] Mental Hosp Jiangxi Prov, Nanchang 330000, Jiangxi, Peoples R China

[20] Wuhan Mental Hlth Ctr, Wuhan 430000, Hubei, Peoples R China

[21] Zhengzhou Univ, Hosp 1, Zhengzhou 450000, Henan, Peoples R China

[22] Chang Gung Univ, Coll Med, Grad Inst Biomed Sci, Taoyuan 33302, Taiwan

[23] Shandong Mental Hlth Ctr, Jinan 250000, Shandong, Peoples R China

[24] Kangning Hosp, Shenzhen Key Lab Psychol Healthcare, Shenzhen 518000, Guangdong, Peoples R China

[25] China Med Univ, Hosp 1, Shenyang 110001, Liaoning, Peoples R China

[26] Psychiat Hosp Henan Prov, Xinxiang 453000, Henan, Peoples R China

[27] Chongqing Med Univ, Hosp 1, Chongqing 400016, Peoples R China

[28] Changchun Mental Hosp, Changchun 130000, Jilin, Peoples R China

[29] Tianjin Anding Hosp, Tianjin 300000, Peoples R China

[30] Xian Mental Hlth Ctr, Xian 710000, Shaanxi, Peoples R China

[31] Nanjing Med Univ, Brain Hosp, Nanjing 210000, Jiangsu, Peoples R China

[32] Zhejiang Chinese Med Univ, Affiliated Hosp 2, Hangzhou 310000, Zhejiang, Peoples R China

[33] Capital Univ Med Sci, Beijing Anding Hosp, Beijing 100000, Peoples R China

[34] Hebei Med Univ, Hosp 1, Shijiazhuang 50000, Hebei, Peoples R China

[35] China Med Univ, ShengJing Hosp, Shenyang 110001, Liaoning, Peoples R China

[36] Jilin Brain Hosp, Siping 136000, Jilin, Peoples R China

[37] Sun Yat Sen Univ, Hosp 3, Guangzhou 510000, Guangdong, Peoples R China

[38] Shanxi Med Univ, Hosp 1, Taiyuan 30000, Shanxi, Peoples R China

[39] Daqing 3 Hosp Heilongjiang Prov, Daqing 163000, Heilongjiang, Peoples R China

[40] Jiangsu Univ, Hosp 4, Zhenjiang 212000, Jiangsu, Peoples R China

[41] Anhui Mental Hlth Ctr, Hefei 230000, Anhui, Peoples R China

[42] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark

[43] Macau Univ Sci & Technol, Taipa 999078, Macau, Peoples R China

[44] King Abdulaziz Univ, Princess Al Jawhara Ctr Excellence Res Hereditary, Jeddah 21589, Saudi Arabia

[45] Univ Oxford, Dept Stat, Oxford OX1 3TG, Oxon, England

[46] Univ Oxford, CTSU, Oxford OX3 7LF, Oxon, England

[47] Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 10005, Peoples R China

[48] Chinese Acad Med Sci, Neurosci Ctr, Beijing 10005, Peoples R China

[49] Peking Union Med Coll, Beijing 10005, Peoples R China

[50] Virginia Commonwealth Univ, Dept Psychiat MCV, Richmond, VA 23298 USA

来源：

CURRENT BIOLOGY | 2015年 / 25卷 / 09期

基金：

英国惠康基金;

关键词：

CHILDHOOD SEXUAL-ABUSE; POSTTRAUMATIC-STRESS-DISORDER; DNA METHYLATION; CAUSAL RELATIONSHIP; TELOMERE LENGTH; T-LYMPHOCYTES; CHINESE WOMEN; LIFE EVENTS; DISEASE; ILLNESS;

D O I：

10.1016/j.cub.2015.03.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 x 10(-42), odds ratio 1.33 [95% confidence interval [CI] = 1.29-1.37]) and telomere length (p = 2.84 x 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.

引用

页码：1146 / 1156

页数：11

共 65 条

[1]

Quantitative reconstruction of leukocyte subsets using DNA methylation [J].

Accomando, William P. ;

Wiencke, John K. ;

Houseman, E. Andres ;

Nelson, Heather H. ;

Kelsey, Karl T. .

GENOME BIOLOGY, 2014, 15 (03)

[2]

Ahola, Kirsi ;

Siren, Ilari ;

Kivimaki, Mika ;

Ripatti, Samuli ;

Aromaa, Arpo ;

Lonnqvist, Jouko ;

Hovatta, Iiris .

PLOS ONE, 2012, 7 (07)

[3]

[Anonymous], 2004, LANG ENV STAT COMP

[4]

[Anonymous], 2010, BIOL PSYCHIAT

[5]

The role of corticotropin-releasing factor in depression and anxiety disorders [J].

Arborelius, L ;

Owens, MJ ;

Plotsky, PM ;

Nemeroff, CB .

JOURNAL OF ENDOCRINOLOGY, 1999, 160 (01) :1-12

[6]

ADRENAL CORTICAL ACTIVITY IN DEPRESSIVE ILLNESS [J].

CARPENTER, WT ;

BUNNEY, WE .

AMERICAN JOURNAL OF PSYCHIATRY, 1971, 128 (01) :31-+

[7]

Childhood abuse, parental warmth, and adult multisystem biological risk in the Coronary Artery Risk Development in Young Adults study [J].

Carroll, Judith E. ;

Gruenewald, Tara L. ;

Taylor, Shelley E. ;

Janicki-Deverts, Denise ;

Matthews, Karen A. ;

Seeman, Teresa E. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (42) :17149-17153

[8]

Childhood Sexual Abuse and the Development of Recurrent Major Depression in Chinese Women [J].

Chen, Jing ;

Cai, Yiyun ;

Cong, Enzhao ;

Liu, Ying ;

Gao, Jingfang ;

Li, Youhui ;

Tao, Ming ;

Zhang, Kerang ;

Wang, Xumei ;

Gao, Chengge ;

Yang, Lijun ;

Li, Kan ;

Shi, Jianguo ;

Wang, Gang ;

Liu, Lanfen ;

Zhang, Jinbei ;

Du, Bo ;

Jiang, Guoqing ;

Shen, Jianhua ;

Zhang, Zhen ;

Liang, Wei ;

Sun, Jing ;

Hu, Jian ;

Liu, Tiebang ;

Wang, Xueyi ;

Miao, Guodong ;

Meng, Huaqing ;

Li, Yi ;

Hu, Chunmei ;

Li, Yi ;

Huang, Guoping ;

Li, Gongying ;

Ha, Baowei ;

Deng, Hong ;

Mei, Qiyi ;

Zhong, Hui ;

Gao, Shugui ;

Sang, Hong ;

Zhang, Yutang ;

Fang, Xiang ;

Yu, Fengyu ;

Yang, Donglin ;

Liu, Tieqiao ;

Chen, Yunchun ;

Hong, Xiaohong ;

Wu, Wenyuan ;

Chen, Guibing ;

Cai, Min ;

Song, Yan ;

Pan, Jiyang .

PLOS ONE, 2014, 9 (01)

[9]

Reduced telomerase activity in human T lymphocytes exposed to cortisol [J].

Choi, Jenny ;

Fauce, Steven R. ;

Effros, Rita B. .

BRAIN BEHAVIOR AND IMMUNITY, 2008, 22 (04) :600-605

[10]

Aging and Environmental Exposures Alter Tissue-Specific DNA Methylation Dependent upon CpG Island Context [J].

Christensen, Brock C. ;

Houseman, E. Andres ;

Marsit, Carmen J. ;

Zheng, Shichun ;

Wrensch, Margaret R. ;

Wiemels, Joseph L. ;

Nelson, Heather H. ;

Karagas, Margaret R. ;

Padbury, James F. ;

Bueno, Raphael ;

Sugarbaker, David J. ;

Yeh, Ru-Fang ;

Wiencke, John K. ;

Kelsey, Karl T. .

PLOS GENETICS, 2009, 5 (08)

← 1 2 3 4 5 6 7 →