DEPRESSION, PEPTIDES AND STERIODS IN CUSHING'S SYNDROME

很大一部分原发性抑郁症患者 紊乱表现为皮质醇分泌过多，昼夜节律变平 周期性，未能抑制血浆皮质醇与过夜 地塞米松试验、ACTH水平升高和/或异常 地塞米松抑制BLPH-β-内啡肽。 库欣氏 疾病是下丘脑-垂体-肾上腺的经典疾病 轴激活：患者显示皮质醇、ACTH和 BLPH-B内啡肽水平。 他们也有抑郁症， 情绪，植物人和认知症状， 患有这种疾病的患者。 我们建议研究ACTH和BLPH-BEndorphin分泌 特征以及情感和认知症状和体征 基线期间未接受治疗的库欣综合征（CS）患者 条件下和在甲吡酮和地塞米松激发期间。 我们的假设是抑郁程度的不同 CS患者中的证候与 这些肽的共分泌谱。 由于在 睡眠在CS患者中很常见，睡眠脑电图和褪黑激素 在基线和使用甲吡酮时的分泌特征， 还将进行地塞米松激发试验。 肾上腺皮质类固醇的代谢产物，如双烯醇酮和 脱氧皮质酮通过增强或抑制神经元兴奋性 体外GABA受体。 我们建议在以下患者中进行研究： CS与抑郁症患者的变异性的关系 15例患者尿排泄谱的综合征和异质性 肾上腺类固醇 拟议的临床研究将是第一个研究 同时，在基线条件下， 测试，抑郁症状与特定的 肾上腺类固醇和脑垂体肽 这些研究 应该会产生与ACTH，BEndorphin， 皮质醇和其他肾上腺皮质类固醇在发病机制中的作用 和原发性情感障碍的诊断学 为了研究这些概念在以下方面的潜在相关性， 原发性抑郁症，我们建议进行初步的 研究了15个未结合的 一组原发性抑郁症患者尿中类固醇激素的变化 disorder.

A significant proportion of patients with primary depressive disorder show cortisol hypersecretion, flattened circadian periodicity, failure to suppress plasma cortisol with the overnight dexamethasone test, increased ACTH levels, and/or abnormalities in suppression of BLPH-BEndorphin by dexamethasone. Cushing's disease is the classic disease of hypothalamic-pituitary-adrenal axis activation: patients show elevated cortisol, ACTH and BLPH-BEndorphin levels. They also have a depressive syndrome, with mood, vegetative and cognitive symptoms that vary among patients with this disorder. We propose to study ACTH and BLPH-BEndorphin secretory profiles together with affective and cognitive symptoms and signs in patients with untreated Cushing's syndrome (CS) during baseline conditions and during metyrapone and dexamethasone challenge. Our hypothesis is that differences in degree of the depressive syndrome among patients with CS are related to heterogneity in the co-secretion profiles of these peptides. Since alterations in sleep are common in patients with CS, sleep EEGs and melatonin secretory profiles at baseline and with metyrapone and dexamethasone challenge testing will also be obtained. Metabolites of adrenal cortical steroids such as pregnenolone and deoxycorticosterone enchance or inhibit neuronal excitability via the GABA receptor in vitro. We propose to study in patients with CS the relationship between variabiility in the depressive syndrome and heterogenity in the urinary excretion profiles of 15 adrenal steroids. The clinical studies proposed will be the first to study simutaneously, under baseline conditions and with provocative testing, the association of depressive symptoms with the specific profiles of adrenal steroids and pituitary peptides. These studies should yield data which bear on the role of ACTH, BEndorphin, cortisol and other adrenal cortical steroids in the pathogenesis and symptomatology of primary affective disorder. In order to study the potential relevance of these concepts in primary depressive disorder, we propose to conduct preliminary studies investigating variability in the profile of 15 uncojugated urinary steroids in a group of patients with primary depressive disorder.