Why does cortisol enhance memory retrieval in patients with borderline personality disorder and posttraumatic stress disorder? Investigating the neuronal correlates of cortisol administration and the effects of stress exposure

我们最近的研究表明，氢化可的松增强而不是损害创伤后应激障碍（PTSD）和边缘性人格障碍（BPD）患者的记忆恢复。相比之下，在健康参与者中，与安慰剂相比，氢化可的松后记忆恢复受损。提出的研究旨在进一步调查这些发现并了解潜在的神经元相关性。在第一项研究中，将通过功能磁共振成像研究氢化可的松对BPD和PTSD患者记忆恢复增强的机制。第二项研究采用了更自然的设计，其中将应用社会心理压力源来调查当下丘脑中轴和交感神经系统都被激活时，记忆的改善是否也会出现。因此，我们提出了两个问题：1)在PTSD和BPD中，皮质醇诱导的记忆恢复增强与哪些神经元相关？2)皮质醇对记忆的积极影响是否也在心理社会应激后发现？在一项安慰剂对照研究中，将在PTSD和BPD患者中研究10mg氢化可的松对大脑活动（特别是海马体）的影响，并将其与健康对照参与者进行比较。在fMRI过程中，将进行陈述性记忆任务（检索以前学过的单词表）和自传式记忆测试。我们将分析氢化可的松对静息状态大脑活动和记忆提取相关神经元的影响。在第二项研究中，将对PTSD和BPD患者以及健康对照组进行心理社会压力测试和对照情境。应激暴露后，记忆恢复将被评估。此外，还将分析下丘脑轴和蓝斑去肾上腺素能系统的生理标志。这两项研究将有助于更好地理解应激调节系统（海马、HPA轴、LC-NA系统）的改变及其对BPD和PTSD患者记忆过程的影响。这些研究可能有助于改善治疗方案。

We have recently shown that hydrocortisone enhances rather than impairs memory retrieval in patients with posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD). In contrast, in healthy participants memory retrieval was impaired after hydrocortisone compared to placebo. The proposed studies aim to further investigate these findings and to understand the underlying neuronal correlates. In a first study, the mechanisms of enhanced memory retrieval after hydrocortisone in patients with BPD and PTSD will be investigated by fMRI. The second study consists of a more naturalistic design, in which a psychosocial stressor will be applied to investigate whether the memory improvement is also seen when both the HPA axis and the sympathetic nervous system are activated . Thus, two questions are addressed: 1) Which neuronal correlates underlie cortisol-induced enhancement of memory retrieval in PTSD and BPD?2) Are the positive effects of cortisol on memory also found after psychosocial stress?In a placebo-controlled study, the effects of 10mg hydrocortisone on brain activity, in particular the hippocampus, will be investigated in patients with PTSD and BPD and will be compared with those in healthy control participants. During the fMRI session, a declarative memory task (retrieval of a previous learned word list) and an autobiographical memory test will be performed. Effects of hydrocortisone on resting state brain activity and the neuronal correlates of memory retrieval will be analysed. In the second study, a psychosocial stress test and a control situation will be performed in PTSD and BPD patients as well as in healthy controls. After stress exposure, memory retrieval will be assessed. Furthermore, physiological markers of the HPA axis and the locus coeruleus noradrenergic system will be analysed. Both studies will contribute to a better understanding of altered stress regulation systems (hippocampus, HPA axis, LC-NA system) and their impact on memory processes in patients with BPD and PTSD. These studies may help to improve treatment options.