PsyQ The Hague, Department of Mood Disorders, The Hague, The Netherlands.
Psychoneuroendocrinology. 2011 Nov;36(10):1460-9. doi: 10.1016/j.psyneuen.2011.03.020. Epub 2011 Apr 29.
The hypothalamus-pituitary-adrenal (HPA)-axis is often found to be dysregulated in bipolar disorder (BD) while stress and changes in day-night rhythms can trigger a new mood episode. Genetic variants of the glucocorticoid receptor (GR)- and mineralocorticoid receptor (MR)-gene influence both the reactivity of the stress-response and associate with changes in mood. In this study we tested the hypothesis that these polymorphisms associate with different clinical characteristics of BD.
We studied 326 outpatients with BD and performed GR genotyping of the TthIIII, ER22/23EK, N363S, BclI, and 9β polymorphisms, as well as MR genotyping of the 2G/C and I180V variants. All patients were interviewed for clinical characteristics.
Seasonal patterns of hypomania are related to the BclI haplotype and the TthIIII+9β haplotype of the GR gene (respectively, crude p=.007 and crude p=.005). Carriers of the ER22/23EK polymorphism had an almost 8 years earlier onset of their first (hypo)manic episode than non-carriers (crude p=.004, after adjustment p=.016). No evidence for a role of the MR in modifying clinical manifestations was found.
Polymorphisms of the GR-gene are factors which influence some clinical manifestations of BD, with respect to seasonal pattern of (hypo)mania and age of onset.
下丘脑-垂体-肾上腺（HPA）轴在双相情感障碍（BD）中经常被发现失调，而压力和昼夜节律的变化可能会引发新的情绪发作。糖皮质激素受体（GR）和盐皮质激素受体（MR）基因的遗传变异既影响应激反应的反应性，又与情绪变化相关。在这项研究中，我们检验了这些多态性与 BD 的不同临床特征相关的假设。
我们研究了 326 名 BD 门诊患者，并对 GR 的 TthIIII、ER22/23EK、N363S、BclI 和 9β 多态性以及 MR 的 2G/C 和 I180V 变体进行了基因分型。所有患者均接受了临床特征访谈。
轻躁狂的季节性模式与 BclI 单倍型和 GR 基因的 TthIIII+9β 单倍型有关（分别为粗 p=.007 和粗 p=.005）。与非携带者相比，携带 ER22/23EK 多态性的患者首次（轻躁狂）发作的年龄要早近 8 年（粗 p=.004，调整后 p=.016）。没有发现 MR 多态性在修饰临床表现方面的作用。
GR 基因的多态性是影响 BD 某些临床表现的因素，与（轻躁狂）的季节性模式和发病年龄有关。
