Dissociation: HPA Axis and Cognition

这项建议的总体目标是研究分离的四个组成部分及其相互关系：下丘脑-垂体-肾上腺轴、注意力和记忆系统、创伤和症状学。与创伤后应激障碍一样，分离性障碍是另一种主要的精神病因学，创伤在其发病机制中发挥着无可争辩的作用。然而，与创伤后应激障碍(PTSD)相比，对分离性障碍的研究明显更有限，而且大多局限于描述性方面。这项建议的重点是人格解体障碍(DPD)，这是四种主要的DSM-IV解离障碍之一。对解离的神经内分泌学的研究很少，但提示ETA轴可能失调，基础皮质醇水平正常到升高，皮质醇对小剂量地塞米松的反应是低抑制。另一方面，创伤后应激障碍与皮质醇水平低和地塞米松反应过度抑制有关。因此，创伤应激可能导致不同类型的HPA调节失调，并对不同类型的预防、早期干预和长期治疗产生重大影响。对分离的神经心理学研究开始描绘出一幅以注意力和外显记忆为中心的特定缺陷的图景，特别是在分心、信息过载和压力的情况下，而内隐记忆似乎在创伤刺激下保持甚至增强。将60名无创伤后应激障碍的DSM-IV去人格化障碍患者与60名无分离性障碍的DSM-IV创伤后应激障碍患者和60名正常对照组进行比较。HPA轴功能将通过24小时尿皮质醇排泄、每小时一小时血浆皮质醇分泌和小剂量地塞米松抑制试验来评估。基线认知将通过评估智商、持续的、选择性的和分散的注意力，以及工作、短期、长期和外显/内隐记忆的组合来评估。将进行心理社会压力测试，以检验急性应激对HPA轴响应性和认知的不同影响。在研究结束时，三组将从HPA轴功能、认知、童年/终身创伤、症状学及其相互关系方面进行比较。

The overall goal of this proposal is to investigate four components of dissociation and their interrelations: the hypothalamic- pituitary-adrenal axis, attention and memory systems, trauma, and symptomatology. Along with posttraumatic stress disorder, dissociative disorders comprise the other major psychiatric nosology in whose pathogenesis trauma plays an undisputed role. However, compared to posttraumatic stress disorder (PTSD), research in the dissociative disorders has been notably more limited and mostly confined to descriptive aspects. The particular focus of this proposal within dissociation is depersonalization disorder (DPD), one of the four major DSM-IV dissociative disorders. Studies of the neuroendocrinology of dissociation are sparse, yet suggest possible dysregulation of the ETA axis with normal to elevated baseline cortisol levels and hyposuppression of cortisol in response to low-dose dexamethasone administration. On the other hand, PTSD is associated with low cortisol levels and hypersuppression in response to dexamethasone. Therefore, different types of HPA dysregulation may result from traumatic stress with significant implications regarding different types of prevention, early intervention and long-term treatment. Neuropsychological studies of dissociation are beginning to draw a picture of specific deficits centering around attention and explicit memory, especially under conditions of distraction, information overload and stress, while implicit memory appears preserved or even enhanced for traumatic stimuli. Sixty subjects with DSM-IV depersonalization disorder without PTSD will be compared to 60 subjects with DSM-IV PTSD without dissociative disorder and 60 normal control subjects. HPA axis function will be evaluated by 24-hour urinary cortisol excretion, hourly diurnal plasma cortisol secretion, and a low-dose dexamethasone suppression test. Baseline cognition will be evaluated by a battery assessing IQ, sustained, selective and divided attention, as well as working, short-term, long-term and explicit/implicit memory. A psychosocial stress test will be performed to examine differential impact of acute stress on HPA axis responsivity and cognition. At the conclusion of the study, the three groups will be compared with respect to HPA axis function, cognition, childhood/lifetime trauma, symptomatology, and their interrelations.