Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, United States.
Psychoneuroendocrinology. 2013 Jan;38(1):115-21. doi: 10.1016/j.psyneuen.2012.05.006. Epub 2012 Jun 21.
Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been linked with major depression, particularly psychotic major depression (PMD), with mineralocorticoid receptors (MRs) playing a role in HPA-axis regulation and the pathophysiology of depression. Herein we hypothesize that the MR agonist fludrocortisone differentially inhibits the HPA axis of psychotic major depression subjects (PMDs), non-psychotic major depression subjects (NPMDs), and healthy control subjects (HCs).
Fourteen PMDs, 16 NPMDs, and 19 HCs were admitted to the Stanford University Hospital General Clinical Research Center. Serum cortisol levels were sampled at baseline and every hour from 18:00 to 23:00h, when greatest MR activity is expected, on two consecutive nights. On the second afternoon at 16:00h all subjects were given 0.5mg fludrocortisone. Mean cortisol levels pre- and post-fludrocortisone and percent change in cortisol levels were computed.
There were no significant group differences for cortisol at baseline: F(2,47)=.19, p=.83. There were significant group differences for post-fludrocortisone cortisol: F(2,47)=5.13, p=.01, which were significantly higher in PMDs compared to HCs (p=.007), but not compared to NPMDs (p=.18). There were no differences between NPMD's and HC's (p=.61). Also, PMDs had a lower percent change from baseline in cortisol levels at 2200h than NPMDs (p=.01) or HCs (p=.009).
Individuals with psychotic major depression compared to healthy control subjects have diminished feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis in response to the mineralocorticoid receptor agonist fludrocortisone. To our knowledge, this is the first study to examine HPA axis response to MR stimulation in major depression (with and without psychosis), and only the third study to demonstrate that exogenously administered fludrocortisone can down-regulate the HPA axis in humans.
下丘脑-垂体-肾上腺（HPA）轴失调与重度抑郁症有关，尤其是精神病性重度抑郁症（PMD），其中，盐皮质激素受体（MRs）在 HPA 轴调节和抑郁症的病理生理学中发挥作用。在此，我们假设 MR 激动剂氟氢可的松可使精神病性重度抑郁症患者（PMD）、非精神病性重度抑郁症患者（NPMD）和健康对照组（HC）的 HPA 轴产生不同程度的抑制。
14 名 PMD、16 名 NPMD 和 19 名 HC 被收入斯坦福大学医院综合临床研究中心。在连续两个晚上的 18：00 至 23：00 时，即预计 MR 活性最大的时间，采集基线和每小时一次的血清皮质醇水平样本。在第二天下午 16：00 时，所有受试者均接受 0.5mg 氟氢可的松。计算皮质醇水平在氟氢可的松给药前后的平均值以及皮质醇水平的变化百分比。
在基线皮质醇方面，三组间无显著的组间差异：F（2，47）=0.19，p=0.83。氟氢可的松给药后皮质醇方面存在显著的组间差异：F（2，47）=5.13，p=0.01，PMD 组明显高于 HC 组（p=0.007），但与 NPMD 组相比则无差异（p=0.18）。NPMD 组与 HC 组之间无差异（p=0.61）。此外，PMD 组在 22：00 时的皮质醇水平从基线的变化百分比低于 NPMD 组（p=0.01）或 HC 组（p=0.009）。
与健康对照组相比，精神病性重度抑郁症患者对盐皮质激素受体激动剂氟氢可的松的下丘脑-垂体-肾上腺（HPA）轴反馈抑制作用减弱。据我们所知，这是首次研究重度抑郁症（伴或不伴精神病）患者的 HPA 轴对 MR 刺激的反应，也是仅有的第三次研究表明外源性给予氟氢可的松可下调人类的 HPA 轴。
