Claes Stephan
University Psychiatric Centre, Catholic University Leuven, Leuven, Belgium.
Ann N Y Acad Sci. 2009 Oct;1179:216-28. doi: 10.1111/j.1749-6632.2009.05012.x.
Major depressive disorder (MDD) often appears after exposure to acute or chronic stress, and dysfunction of stress response systems, such as the hypothalamic-pituitary-adrenal (HPA) axis, is thought to be a key element of MDD neurobiology. The glucocorticoid receptor (GR) is the most important regulator of the HPA axis negative feedback system, and GR sensitivity has been shown to be reduced in MDD in both in vitro and in vivo studies. Transgenic animals with partial impairment of GR function show behavioral changes consistent with MDD. This makes the GR gene a prime candidate for research into the genetic background of MDD. Several single nucleotide polymorphisms (SNPs) have been detected that have specific effects on GR function, metabolic parameters, and HPA axis function in response to stress. Genetic association studies have yielded preliminary evidence for a role of these genetic variations in the genetic vulnerability for MDD. Taken together, the evidence for a role of GR and the GR gene in the neurobiology of MDD is building rapidly.
重度抑郁症（MDD）常出现在遭受急性或慢性应激之后，应激反应系统功能失调，如下丘脑 - 垂体 - 肾上腺（HPA）轴，被认为是MDD神经生物学的关键要素。糖皮质激素受体（GR）是HPA轴负反馈系统最重要的调节因子，体外和体内研究均表明MDD患者的GR敏感性降低。GR功能部分受损的转基因动物表现出与MDD一致的行为变化。这使得GR基因成为研究MDD遗传背景的主要候选基因。已检测到几种单核苷酸多态性（SNP），它们对应激反应中的GR功能、代谢参数和HPA轴功能有特定影响。遗传关联研究已初步证明这些基因变异在MDD遗传易感性中起作用。综上所述，GR及其基因在MDD神经生物学中作用的证据正在迅速积累。
