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.
