A common and functional mineralocorticoid receptor haplotype enhances optimism and protects against depression in females.
A common and functional mineralocorticoid receptor haplotype enhances optimism and protects against depression in females.
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DOI：
10.1038/tp.2011.59
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发表时间：
2011-12-13
影响因子：
6.8
通讯作者：
DeRijk RH
中科院分区：
文献类型：
--
作者：
Klok MD;Giltay EJ;Van der Does AJ;Geleijnse JM;Antypa N;Penninx BW;de Geus EJ;Willemsen G;Boomsma DI;van Leeuwen N;Zitman FG;de Kloet ER;DeRijk RH
盐皮质激素（MR）和糖皮质激素受体（GR）在边缘脑中大量表达，并介导皮质醇对应激反应和行为适应的影响。压力反应失调会损害适应能力，是抑郁症的一个风险因素，女性抑郁症的发病率是男性的两倍。由于MR对压力反应初始阶段评估过程的重要性，我们研究了特定MR单倍型是否与预测抑郁风险的人格特征相关。我们发现了一个共同的基因变异（单倍型2，频率0.38），导致增强MR活动。在研究1中，单倍型2与性格乐观有关，在研究2中与绝望和沉思有关。利用一项大型全基因组关联研究的数据，我们随后确定了单倍型2与抑郁症风险较低相关。有趣的是，所有的影响都仅限于女性。我们建议，共同的功能MR单倍型是个体间差异的重要决定因素，在妇女抑郁症的弹性通过差异介导皮质醇对压力系统的影响。
Mineralocorticoid (MR) and glucocorticoid receptors (GR) are abundantly expressed in the limbic brain and mediate cortisol effects on the stress-response and behavioral adaptation. Dysregulation of the stress response impairs adaptation and is a risk factor for depression, which is twice as abundant in women than in men. Because of the importance of MR for appraisal processes underlying the initial phase of the stress response we investigated whether specific MR haplotypes were associated with personality traits that predict the risk of depression. We discovered a common gene variant (haplotype 2, frequency ∼0.38) resulting in enhanced MR activity. Haplotype 2 was associated with heightened dispositional optimism in study 1 and with less hopelessness and rumination in study 2. Using data from a large genome-wide association study we then established that haplotype 2 was associated with a lower risk of depression. Interestingly, all effects were restricted to women. We propose that common functional MR haplotypes are important determinants of inter-individual variability in resilience to depression in women by differentially mediating cortisol effects on the stress system.
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影响因子：
11
作者：
通讯作者：
--
影响因子：
4.8
作者：
Klok, Melanie D.;Alt, Simone R.;DeRijk, Roel H.
通讯作者：
DeRijk, Roel H.
影响因子：
0.9
作者：
Boomsma, Dorret I.;de Geus, Eco J. C.;Willemsen, Gonneke
通讯作者：
Willemsen, Gonneke
影响因子：
12.8
作者：
Carver, Charles S.;Scheier, Michael F.;Segerstrom, Suzanne C.
通讯作者：
Segerstrom, Suzanne C.
影响因子：
6.6
作者：
Giltay, EJ;Zitman, FG;Kromhout, D
通讯作者：
Kromhout, D