THE ROLE OF CORTISOL DYSREGULATION IN DEPRESSION AND HIPPOCAMPAL DYSFUNCTION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 抑郁、记忆功能障碍和海马萎缩与颞叶癫痫（TLE）患者控制不良的癫痫发作相关。 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功能障碍和海马细胞丢失有关。然而，没有发表的研究已经检查皮质醇可能在TLE患者的这些因素中发挥的作用。 本初步研究的目的是探讨皮质醇在40例难治性TLE患者抑郁症、记忆功能障碍和海马萎缩中的作用，并评估一个多变量模型，以确定皮质醇是否介导这些变量之间的关系。所有参与者将完成神经心理学检查（包括抑郁和记忆测量）和MRI研究，并测量他们的皮质醇水平。 预计皮质醇水平升高的患者与皮质醇水平正常的患者相比，抑郁症状明显增加，记忆力评分降低，海马体积减小。它进一步预计，所提出的多变量模型将得到支持，证明皮质醇是一个重要的调解人。这项研究的成功完成将提供有价值的信息皮质醇在抑郁症，记忆功能障碍和海马萎缩的TLE患者中的作用，并提供一个模型，更好地了解这些因素如何协同工作在TLE。 这些知识的获得对于理解这些因素的潜在神经内分泌基础至关重要，并可能为TLE患者的药物治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.