Dissociation: HPA Axis and Cognition

该提案的总体目标是研究解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，分离性障碍构成了其他主要的精神疾病分类学，创伤在其发病机制中发挥着无可争议的作用。然而，与创伤后应激障碍（PTSD）相比，解离障碍的研究明显更加有限，并且大多局限于描述性方面。该提案在解离方面的特别关注点是人格解体障碍（DPD），它是 DSM-IV 四种主要解离障碍之一。对解离神经内分泌学的研究很少，但表明 ETA 轴可能失调，基线皮质醇水平正常至升高，并且低剂量地塞米松给药后皮质醇抑制不足。另一方面，PTSD 与低皮质醇水平和地塞米松反应过度抑制有关。因此，不同类型的 HPA 失调可能是由创伤应激引起的，对不同类型的预防、早期干预和长期治疗具有重大影响。对解离的神经心理学研究开始描绘出围绕注意力和外显记忆的特定缺陷的图景，特别是在分心、信息超载和压力的情况下，而内隐记忆似乎在创伤刺激下得以保留甚至增强。将 60 名患有 DSM-IV 人格解体障碍但不伴有 PTSD 的受试者与 60 名患有 DSM-IV PTSD 但不伴有解离障碍的受试者和 60 名正常对照受试者进行比较。 HPA轴功能将通过24小时尿皮质醇排泄、每小时昼间血浆皮质醇分泌和低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、选择性和分散注意力以及工作、短期、长期和外显/内隐记忆的电池来评估。将进行社会心理压力测试，以检查急性压力对 HPA 轴反应性和认知的不同影响。研究结束时，将对三组的 HPA 轴功能、认知、童年/一生创伤、症状及其相互关系进行比较。

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.