Pariante Carmine M
Stress, Psychiatry and Immunology Laboratory, Section of Clinical Neuropharmacology, Division of Psychological Medicine, Institute of Psychiatry, King's College London, Denmark Hill, UK.
Stress. 2004 Dec;7(4):209-19. doi: 10.1080/10253890500069650.
Clinical studies have demonstrated an impairment of glucocorticoid receptor (GR)-mediated negative feedback on the hypothalamic--pituitary--adrenal (HPA) axis in patients with major depression (GR resistance), and its resolution by antidepressant treatment. Interestingly, a number of studies have also demonstrated that GR function is reduced in vitro, in peripheral tissues of depressed patients, as shown by a decreased sensitivity to the effects of glucocorticoids on immune and metabolic functions. This paper reviews the in vitro studies that have examined GR function in patients with major depression, and the possible molecular mechanisms involved in GR resistance. Since several studies have demonstrated similar regulation of GR in the brain and in peripheral tissues in humans, and given limited access to brain GR in clinical populations, this review claims that in vitro studies are of particular relevance to understand the molecular mechanisms underlying GR abnormalities in patients with major depression and its regulation by antidepressant treatment.
临床研究表明，重度抑郁症患者存在糖皮质激素受体（GR）介导的下丘脑 - 垂体 - 肾上腺（HPA）轴负反馈受损（GR抵抗），而抗抑郁治疗可使其恢复。有趣的是，多项研究还表明，抑郁症患者外周组织中GR功能在体外降低，表现为对糖皮质激素对免疫和代谢功能影响的敏感性降低。本文综述了检测重度抑郁症患者GR功能的体外研究，以及GR抵抗可能涉及的分子机制。由于多项研究已证明人类大脑和外周组织中GR的调节相似，且临床人群获取脑GR的机会有限，本综述认为体外研究对于理解重度抑郁症患者GR异常的分子机制及其受抗抑郁治疗调节的机制尤为重要。
