Polymorphisms of the glucocorticoid receptor gene and major depression

被引:271
作者
van Rossum, EFC
Binder, EB
Majer, M
Koper, JW
Ising, M
Modell, S
Salyakina, D
Lamberts, SWJ
Holsboer, F
机构
[1] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands
[2] Max Planck Inst Psychiat, D-80804 Munich, Germany
关键词
depression; glucocorticoid receptor gene; polymorphism; glucocorticoid sensitivity; cognition; antidepressant treatment;
D O I
10.1016/j.biopsych.2006.02.007
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: The most consistent biological finding in patients with depression is a hyperactivity of the hypothalamic-pituitary-adrenal (HPA)-axis, which might be caused by impaired glucocorticoid signaling. Glucocorticoids act through the glucocorticoid receptor (GR) for which several polymorphisms have been described. The N363S and BclI polymorphisms have been associated with hypersensitivity to glucocorticoids, whereas the ER22/23EK polymorphism is related to glucocorticoid resistance. Methods: We studied whether the susceptibility to develop a depression is related to these polymorphisms by comparing depressive inpatients (h = 490) and healthy control subjects (n = 496). Among depressed patients, we also investigated the relation between GR variants and dysregulation of the HPA-axis, as measured by the combined dexamethasone suppression/corticotropin-releasing hormone (CRH)-stimulation test, clinical response to antidepressive treatment, and cognitive functioning. Results: Homozygous carriers of the BclI polymorphism and ER22/23EK-carriers had an increased risk of developing a major depressive episode. We found no genetic associations with functional HPA-axis measures in, depressed patients. The ER22/23EK-carriers, however, showed a significantly faster clinical response to antidepressant therapy as well as a trend toward better cognitive functioning during depression. Conclusions: The BclI and ER22/23EK polymorphisms were associated with susceptibility to develop major depression. In addition. the ER22/23EK polymorphism is associated with a faster clinical response to antidepressant treatment. These findings support the notion that variants of the GR gene might play a role in the pathophysiology of a major depression and can contribute to the variability of antidepressant response.
引用
收藏
页码:681 / 688
页数:8
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