PATHOPHYSIOLOGY OF CORTICOSTEROID DYSREGULATION IN DEPRESSION

这项建议的总体目标是评估海马区和隔区的I型糖皮质激素受体(MR)在HPA轴调节中的作用，这些研究利用了合成的糖皮质激素地塞米松。本研究有四个目的：1)证实单剂量皮质酮抑制HPA轴的分泌是通过盐皮质激素受体(MR)起作用的，并评价皮质酮的血浆药代动力学。2)观察MR拮抗剂螺内酯对ACTH和皮质醇分泌的影响以及HPA轴昼夜节律的最高点和最低点。3)比较抑郁症患者和对照组HPA轴对皮质酮的反应和血浆药代动力学；4)检验DST结果与皮质酮反应、特定患者和疾病特征[年龄、性别、心境障碍家族史、抑郁累积史、抑郁严重程度和发作时间]之间的关系。

The overall objective of this proposal is to evaluate the role of Type I glucocorticoid receptors (MR) in the hippocampus and septum in the regulation of the HPA axis studies which have utilized the synthetic glucocorticoid, dexamethasone. The research proposed has 4 objectives: 1) Confirm that a single dose of corticosterone which suppresses HPA axis secretion is operating through mineralcorticoid receptors (MR) and evaluate the plasma pharmacokinetics of corticosterone. 2) Examine the effects of an MR antagonist (spironolactone) on ACTH and cortisol secretion and the zenith and nadir of the circadian rhythm of the HPA axis. 3) Compare the HPA axis responses to corticosterone and the plasma pharmacokinetics in depressed patients and controls, and 4) examine the relationship between the DST result and the response to corticosterone, and specific patient and illness characteristics [age, sex, family history of mood disorder, cumulative history of depression, severity of depression, and duration of episode].