THE ROLE OF CORTISOL DYSREGULATION IN DEPRESSION AND HIPPOCAMPAL DYSFUNCTION

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。 在颞叶癫痫(TLE)患者中，抑郁、记忆功能障碍和海马区萎缩与癫痫发作控制不良有关。然而，人们对这些因素之间的相互关系及其潜在的作用机制知之甚少。研究表明，皮质醇与非癫痫抑郁症患者的记忆障碍和海马细胞丢失有关。然而，还没有发表的研究研究皮质醇在TLE患者的这些因素中可能起到的作用。这项初步研究的目的是研究皮质醇在40名内科难治性TLE患者的抑郁、记忆障碍和海马区萎缩中的作用，并评估一个多变量模型，以确定皮质醇是否在这些变量之间的关系中起中介作用。所有参与者都将完成神经心理检查(包括抑郁症和记忆力测试)和核磁共振研究，并测量他们的皮质醇水平。预计与皮质醇水平正常的患者相比，皮质醇水平升高的患者将有明显更多的抑郁症状、较低的记忆力评分和较低的海马体体积。进一步预计，建议的多变量模型将得到支持，表明皮质醇是一个重要的调节因子。这项研究的成功完成将提供关于皮质醇在TLE患者抑郁、记忆障碍和海马区萎缩中的作用的有价值的信息，并为更好地理解这些因素如何在TLE中协同作用提供一个模型。这些知识的获得对于了解这些因素的潜在神经内分泌基础至关重要，并可能为TLE患者的医疗和管理提供强有力的启示。

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. Depression, memory dysfunction, and hippocampal atrophy are associated with poorly controlled seizures in patients with temporal lobe epilepsy (TLE). However, little is known about the interrelationships among these factors and their potential mechanisms of action. Research has implicated cortisol in memory dysfunction and hippocampal cell loss in non-epileptic patients with depression. However, no published studies have examined the role cortisol may play in these factors in patients with TLE. The objective of this initial investigation is to examine the role of cortisol in depression, memory dysfunction, and hippocampal atrophy in 40 patients with medically intractable TLE and to evaluate a multivariate model to determine if cortisol mediates the relationships among these variables. All participants will complete neuropsychological examinations (including depression and memory measures) and MRI studies and have their cortisol levels measured. It is anticipated that patients with elevated cortisol levels will have significantly more depressive symptoms, lower memory scores, and lower hippocampal volumes than patients with normal range cortisol. It is further anticipated that the proposed multivariate model will be supported, demonstrating that cortisol is an important mediator. Successful completion of this research will provide valuable information about the role of cortisol in depression, memory dysfunction, and hippocampal atrophy in patients with TLE and provide a model for better understanding how these factors may work synergistically in TLE. The acquisition of such knowledge is critical to understanding the potential neuroendocrinological underpinnings of these factors and may provide strong implications for the medical treatment and management of TLE patients.