PATHOPHYSIOLOGY OF CORTICOSTEROID DYSREGULATION IN DEPRESSION

本提案的总体目标是评价海马和隔中I型糖皮质激素受体（MR）在HPA轴调节研究中的作用，这些研究利用了合成糖皮质激素地塞米松。 本研究的目的有4个：1）证实单剂量皮质酮抑制HPA轴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)检查MR拮抗剂（螺内酯）对ACTH和皮质醇分泌以及HPA轴昼夜节律的最高点和最低点的影响。 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，以及4）检查DST结果与皮质酮反应之间的关系，以及特定患者和疾病特征[年龄，性别，心境障碍家族史，抑郁症累积史，抑郁症严重程度和发作持续时间]。

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].