期刊
TRANSLATIONAL PSYCHIATRY
卷 1, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/tp.2011.59
关键词
cortisol; depression; female prevalence; mineralocorticoid receptor; optimism; single-nucleotide polymorphisms
类别
资金
- Netherlands Brain Foundation [15F07(2).24, 10F02(2).37]
- Dutch Ministry of Health, Welfare and Sport, NWO [VICI 453-06-005, SPI 56-464-14192]
- International Research Training Group IRTG
- DFG [GRH 1389/1]
- NWO [DN95-420]
- psychiatric hospital Rivierduinen, ZonMW [904-61-090, 904-61-193, 480-04-004, 400-05-717]
- Center for Medical Systems Biology (NWO Genomics)
- Neuroscience Campus Amsterdam
- EMGO Institute for Health and Care Research
- Geestkracht program [10-000-1002]
- Genetic Association Information Network (GAIN) of the Foundation for the US NIH
- NIMH [MH081802]
- European Research Council [ERC-230374]
- ESF Eurostress
- Royal Netherlands Academy of Arts and Sciences
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 similar to 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. Translational Psychiatry (2011) 1, e62; doi:10.1038/tp.2011.59; published online 13 December 2011
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