STEROIDS, COGNITION AND IMAGING IN CUSHING'S SYNDROME

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 阿尔茨海默病和严重抑郁障碍的老年患者体内皮质醇水平升高。动物研究表明，高水平的皮质醇会影响海马体，海马体是大脑中涉及记忆和学习的部分。库欣综合征(CS)患者的皮质醇水平持续数月或数年的高度升高，并出现情绪、性冲动、学习和记忆异常等症状。我们提出的研究将促进对皮质醇升高对人类大脑影响的了解。动物研究还表明，皮质醇对海马体的毒性作用可能是类固醇升高导致这些症状的机制。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CS患者的这种机制。我们将在治疗前检查CS患者的海马体(HFV)体积，并将其与匹配的健康研究志愿者进行比较。然后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。由于皮质醇水平在治疗后恢复正常，我们将研究这些变化是否可逆。为此，我们将在治疗后12个月和24个月重复NPT和MRI。除了CS，这些研究还将有助于了解类固醇激素对各种疾病患者大脑的影响，这些疾病需要长期类固醇治疗，以及其他类固醇激素分泌异常的情况。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Elevated levels of the hormone cortisol are found in older patients with Alzheimer's Disease and in Major Depressive Disorder. Animal studies show that high levels of cortisol affect the hippocampus, the part of the brain involved in memory and learning. Patients with Cushing's Syndrome (CS) have highly elevated cortisol levels for months or years and develop symptoms such as abnormal mood, sex drive, learning and memory. The studies we propose will advance knowledge about the effect of elevated cortisol on the brain in humans. Animal studies also show that a toxic effect of cortisol on the hippocampus is the likely mechanism by which elevated steroids produce these symptoms. We will use magnetic resonance imaging (MRI) of the brain together with specific neuropsychological tests (NPT) to investigate such a mechanism on patients with CS. We will examine, prior to treatment, the volume of the hippocampus (HFV) in CS patients, and compare it to matched healthy research volunteers. We will then examine the association between the severity of cortisol elevation, NPT impairment and HFV. Other brain regions will be used as comparisons to examine the specificity of the association. Since cortisol levels normalize after treatment, we will study if these changes are reversible. For this purpose, we will repeat NPT and MRI 12 and 24 months following treatment. In addition to CS, these studies will help understand the impact of steroid hormones on the brain of patients with a wide variety of illnesses requiring long-term steroid treatment and other conditions in which steroid hormones are secreted abnormally.'