DEPRESSION, PEPTIDES AND STEROIDS IN CUSHINGS SYNDROME

高水平的激素皮质醇被发现在老年患者与阿尔茨海默氏症和严重抑郁症。 从动物研究中积累的证据表明，认知和特定的大脑结构受到高水平皮质醇的负面影响。 我们提出的研究将推进关于皮质醇升高作为人类认知功能障碍机制的作用的知识。 患有库欣氏病（CD）的患者产生高度升高的皮质醇水平并发展为异常情绪、性欲和认知的综合征。 患者会在数月至数年内接触高水平的这种天然类固醇。 由于治疗后皮质醇水平恢复正常，也可以研究可逆性。动物研究表明，海马体的毒性可能是糖皮质激素升高导致认知功能障碍的机制。 我们将使用磁共振成像（MRI）的大脑与特定的神经心理学测试（NPT），以调查这样的机制，在CD患者。 我们将在治疗前检查CD患者的海马结构体积（HFV），并与匹配的正常对照组进行比较。我们将研究皮质醇升高的严重程度、NPT受损和HFV之间的关系。 其他大脑区域将被用作比较，以检查这种关联的特异性。 我们将在CD治疗后1年和2年重复NPT和MRI，以确定认知和HFV的变化是否至少部分可逆。 这些研究也与了解类固醇激素对需要长期服用类似类固醇的各种疾病患者大脑的影响有关。

Elevated levels of the hormone cortisol are found in the aged patients with Alzheimer's Disease and in Major Depressive Disorder. Evidence is accumulating from animal studies that cognition and specific brain structures are negatively affected by high levels of cortisol. The studies we propose will advance knowledge about the role of elevated cortisol as a mechanism contributing to cognitive dysfunction in humans. Patients with Cushing's Disease (CD) generate highly elevated cortisol levels and develop a syndrome of abnormal mood, libido and cognition. Patients are exposed to high levels of this natural steroid for months to years. Since cortisol levels normalize after treatment, reversibility can also be studied. Animal studies indicate toxicity to the hippocampus is a likely mechanism by which elevated glucocorticoids lead to cognitive dysfunction. We will use magnetic resonance imaging (MRI) of the brain together with specific neuropsychological tests (NPT) to investigate such a mechanism in patients with CD. We will examine, prior to treatment, hippocampal formation volume (HFV) in CD patients, and compare to matched normal controls. We will examine the association between severity of cortisol elevation, NPT impairment and HFV. Other brain regions will be used as comparisons to examine the specificity of the association. We will repeat NPT and MRI one and two years following treatment of CD to determine if changes in cognition and HFV are at least partially reversible. These studies also have relevance to understanding the impact of steroid hormones on the brain in patients with a wide variety of illnesses requiring long term administration of similar steroids.