DEPRESSION, PEPTIDES AND STEROIDS IN CUSHING'S SYNDROME

相当大比例的原发性抑郁症患者 紊乱表现为皮质醇分泌增多，昼夜节律变平 周期性，未能用隔夜抑制血浆皮质醇 地塞米松试验、ACTH水平升高和/或异常 地塞米松抑制BLPH-β内啡肽的作用。库欣‘s 疾病是下丘脑-垂体-肾上腺的经典疾病。 轴激活：患者皮质醇、ACTH和 BLPH-BEndformin水平。他们也有抑郁综合症， 情绪、植物人和认知症状各不相同 患有这种疾病的病人。 我们建议研究促肾上腺皮质激素和BLPH-去甲肾上腺素的分泌 与情感和认知症状和体征一起的概况 基线期间未经治疗的库欣综合征(CS)患者 条件和在甲替拉酮和地塞米松挑战期间。 我们的假设是抑郁程度的不同 CS患者的证候与异质性有关 这些多肽的共分泌图谱。由于更改了 睡眠在CS、睡眠脑电图和褪黑素患者中很常见 基线和甲替拉普酮的分泌情况 还将进行地塞米松挑战测试。 肾上腺皮质类固醇的代谢物，如孕烯醇酮和 脱氧皮质酮通过以下途径增强或抑制神经元兴奋性 体外的GABA受体。我们建议对患有癌症的患者进行研究。 抑郁症患者的变异性与CS的关系 15例患者尿液排泄谱中的综合征和异质性 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，并具有挑衅性 测试，抑郁症状与特定的 肾上腺类固醇和脑垂体肽的图谱。这些研究 应提供与ACTH、苯妥英、 皮质醇等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症状学。 为了研究这些概念在 原发性抑郁症，我们建议进行初步的 调查15个未结合的人的轮廓的变异性的研究 一组原发性抑郁症患者的尿类固醇激素 无序。

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.