Dissociation: HPA Axis and Cognition

这个建议的总体目标是调查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，创伤和创伤学。沿着创伤后应激障碍，分离性障碍包括其他主要的精神疾病分类学，创伤在其发病机制中起着无可争议的作用。然而，与创伤后应激障碍（PTSD）相比，分离性障碍的研究明显更有限，大多局限于描述性方面。这一建议在解离中的特别焦点是人格解体障碍（DPD），这是DSM-IV四种主要解离性障碍之一。分离的神经内分泌学研究很少，但提示ETA轴可能失调，正常至基线皮质醇水平升高，低剂量地塞米松给药后皮质醇抑制不足。另一方面，创伤后应激障碍与低皮质醇水平和对地塞米松的过度抑制有关。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要意义。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、信息过载和压力的条件下，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但不伴有分离性障碍的受试者和60名正常对照受试者进行比较。将通过24小时尿皮质醇排泄、每小时昼夜血浆皮质醇分泌和低剂量地塞米松抑制试验评价HPA轴功能。基线认知将通过一组评估IQ、持续、选择性和分散注意力以及工作、短期、长期和外显/内隐记忆的组合进行评估。将进行心理社会应激测试，以检查急性应激对HPA轴反应性和认知的不同影响。在研究结束时，将比较三组的HPA轴功能、认知、童年/终身创伤、创伤学及其相互关系。

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.