PATHOPHYSIOLOGY OF CORTICOSTEROID DYSREGULATION IN DEPRESSION

压力会激活许多系统，尤其是下丘脑-垂体-肾上腺轴，导致皮质醇分泌。皮质醇通过作用于两种类型的受体MR和GR进行反馈以关闭其自身的分泌。MR和GR在许多情况下协同作用，尽管有时它们可以是拮抗的，因此MR和GR的适当平衡对于许多神经递质系统的调节是重要的。慢性压力会影响MR和GR的平衡，并通常会降低MR。患有抑郁症的人会增加皮质醇，不再适当地关闭皮质醇的分泌。因此，该项目旨在了解抑郁症患者是否有异常的MR功能。 我们通过给药螺内酯（一种MR拮抗剂）并测量ACTH和皮质醇分泌来实现这一点。

Stress activates a number of systems but particularly the hypothalamic-pituitary adrenal axis, resulting in cortisol secretion. Cortisol feeds back to turn off its own secretion by acting at two types of receptors, MR and GR. MR and GR function cooperatively in many instances, although at times they can be antagonistic, so the proper balance of MR and GR is important for regulation of a number of neurotransmitter systems. Chronic stress affects the balance of MR and GR and generally decreases MR. Individuals suffering from depression have increased cortisol and no longer turn off secretion of cortisol properly. Thus this project seeks to understand if individuals with depression have abnormal MR function. We accomplish this by administering spironolactone, an MR antagonist, and measuring ACTH and cortisol secretion.