DEPRESSION, PEPTIDES AND STEROIDS IN CUSHINGS SYNDROME

阿尔茨海默病和严重抑郁症患者体内的皮质醇激素水平升高。来自动物研究的越来越多的证据表明，高水平的皮质醇会对认知和特定的大脑结构产生负面影响。我们提出的研究将促进对皮质醇升高作为导致人类认知功能障碍的机制的作用的了解。库欣病(CD)患者的皮质醇水平高度升高，并出现情绪、性欲和认知异常的综合征。患者暴露在这种天然类固醇的高水平下几个月到几年。由于皮质醇水平在治疗后恢复正常，因此也可以研究可逆性。动物研究表明，对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一个机制。我们将使用脑部磁共振成像(MRI)结合特定的神经心理测试(NPT)来研究CD患者的这种机制。我们将在治疗前检测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损害和HFV之间的关系。其他大脑区域将被用作对比，以检验这种联系的特异性。我们将在CD治疗后一年和两年重复NPT和MRI，以确定认知和HFV的变化是否至少部分可逆。这些研究还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的大脑影响有关。

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.