Faculty Bibliography

BACKGROUND: This study examined the relationship of hypothalamic-pituitary-adrenal measures and hippocampal N-acetylaspartate (NAA) in posttraumatic stress disorder (PTSD) patients and control subjects. METHODS: Eleven patients with combat-related PTSD and 11 control subjects were evaluated with magnetic resonance spectroscopy as well as by morning salivary cortisol samples before and after administration of low-dose dexamethasone (.5 mg). RESULTS: Left hippocampal NAA was strongly associated with both pre-dexamethasone cortisol levels (n = 22, r =.53, p =.013) and post-dexamethasone cortisol levels (n = 22, r =.63, p =.002). After accounting for clinical symptom severity and hippocampal volume, cortisol levels accounted for 21.9% of the variance (F = 5.6, p =.004) in left hippocampal NAA and 12.6% of the variance (F = 3.2, p =.035) in right hippocampal NAA. CONCLUSIONS: This study shows a positive relationship between cortisol levels and hippocampal NAA in subjects without hypercortisolemia. Within the range of values seen in our subjects, cortisol may have a trophic effect on the hippocampus

BACKGROUND: This study investigated the efficacy of propranolol prescribed shortly after trauma exposure in the prevention of posttraumatic stress disorder (PTSD) symptoms and diagnosis. METHODS: Eleven patients received 40 mg of propranolol 3 times daily for 7 days, followed by a taper period of 8-12 days. They were compared with eight patients who refused propranolol but agreed to participate in the study. Though nonrandomized, the two groups did not differ on demographics, exposure characteristics, physical injury severity, or peritraumatic emotional responses. RESULTS: Posttraumatic stress disorder rates were higher in the group who refused propranolol (3/8) compared with those who received the medication (1/11), as were the levels of PTSD symptoms (U = 85, p =.037). CONCLUSIONS: Our results are consistent with earlier findings and suggest that propranolol may be useful for mitigating PTSD symptoms or perhaps even preventing the development of PTSD

We studied the effects of increasing threat conditions on self-reported emotion, eyeblink electromyogram, and skin conductance responses to startling sounds in 55 police officers who endorsed a range of PTSD (posttraumatic stress disorder) symptoms. We found that contextual threat affected both physiologic and self-reported emotional responses. Greater PTSD symptom severity was related to greater physiologic responses under the low and medium but not under the high threat condition. The relationship between PTSD symptoms and physiologic responses was neither explained by self-reported emotional responses nor preexisting reported exaggerated startle symptoms. Our results emphasize the importance of contextual threat and suggest that laboratory measures of startle improve upon self-reported exaggerated startle alone in indexing PTSD symptom severity in urban police officers

Metyrapone blocks cortisol synthesis, which results in the stimulation of hypothalamic cortiocotropin-releasing factor (CRF) and a reduction in delta sleep. We examined the effect of metyrapone administration on endocrine and sleep measures in male subjects with and without chronic PTSD. We hypothesized that metyrapone would result in a decrease in delta sleep and that the magnitude of this decrease would be correlated with the endocrine response. Finally, we utilized the delta sleep response to metyrapone as an indirect measure of hypothalamic CRF activity and hypothesized that PTSD subjects would have decreased delta sleep at baseline and a greater decrease in delta sleep induced by metyrapone. Three nights of polysomnography were obtained in 24 male subjects with combat-related PTSD and 18 male combat-exposed normal controls. On day 3, metyrapone was administered during normal waking hours until habitual sleep onset preceding night 3. Endocrine responses to metyrapone were measured in plasma obtained the morning following sleep recordings, the day before and after administration. Repeated measures ANOVAs were conducted to compare the endocrine and sleep response to metyrapone in PTSD and controls. PTSD subjects had significantly less delta sleep as indexed by stages 3 and 4, and total delta integrated amplitude prior to metyrapone administration. There were no differences in premetyrapone cortisol or ACTH levels in PTSD vs controls. PTSD subjects had a significantly decreased ACTH response to metyrapone compared to controls. Metyrapone caused an increase in awakenings and a marked decrease in quantitative measures of delta sleep that was significantly greater in controls compared to PTSD. The decline in delta sleep was significantly associated with the magnitude of increase in both 11-deoxycortisol and ACTH. The results suggest that the delta sleep response to metyrapone is a measure of the brain response to increases in hypothalamic CRF. These data also suggest that the ACTH and sleep EEG response to hypothalamic CRF is decreased in PTSD

OBJECTIVE: Posttraumatic stress symptoms have been associated with increased health problems across numerous studies. Sleep disruption, one of the principal symptoms resulting from traumatic stress, has also been shown to produce health problems. This study explored the hypothesis that the relationship between posttraumatic stress symptoms and health is mediated by sleep problems. METHOD: A sample of 741 police officers were administered measures of traumatic stress symptoms, sleep, health functioning, and somatic symptoms. RESULTS: Traumatic stress symptoms were significantly related to both somatic symptoms (R2 = 0.18, p <.001) and health functioning (R2 = 0.02, p <.01). The relationship between somatic symptoms and traumatic stress symptoms was partially mediated by sleep (p <.001). The relationship between traumatic stress symptoms and health functioning was fully mediated by sleep. CONCLUSIONS: Although design characteristics, such as cross-sectional sampling, limit the inferences that can be drawn, these findings suggest that sleep may serve as an important mediator between traumatic stress and somatic symptoms

BACKGROUND: This study assesses the efficacy of nefazodone treatment (target dose of 400-600 mg/day) on objective and subjective sleep quality in Vietnam combat veterans with chronic DSM-IV posttraumatic stress disorder (PTSD). METHOD: Medically healthy male Vietnam theater combat veterans with DSM-IV PTSD (N = 10) completed a 12-week open-label trial. Two nights of ambulatory polysomnography were obtained at baseline and at the end of the trial. PTSD and depressive symptoms and subjective sleep quality were assessed at baseline and after 12 weeks. Data were collected in 1999 and 2000. RESULTS: Nefazodone treatment led to a significant decrease in PTSD and depressive symptoms (p <.05), an improvement in global subjective sleep quality, and a reduction in nightmares. Nefazodone also resulted in a substantial improvement in objective measures of sleep quality, particularly increased total sleep time, sleep maintenance, and delta sleep as measured by period amplitude analysis. CONCLUSION: Nefazodone therapy results in an improvement of both subjective and objective sleep quality in subjects with combat-related PTSD

BACKGROUND: We examined P300 measures in patients with posttraumatic stress disorder (PTSD) and control subjects at two different time points to determine event-related potential (ERP) stability over time and the relationship of changes in ERPs to changes in symptom levels. METHODS: Auditory and visual P300 was recorded in a three-condition novelty oddball task in 25 male subjects with combat-related PTSD and 15 male combat-exposed normal control subjects at two time points separated by 6-12 months. Regression analyses were conducted to compare the temporal stability of ERP measures in PTSD and control subjects. Variability in ERP measures over time within PTSD subjects was examined for association with changes in symptom levels. RESULTS: There were no significant differences in P300 amplitude or latency in PTSD versus control subjects at either time point, regardless of stimulus type (target, novel) or modality (auditory, visual). Nine of 24 P300 measures were significantly less predictable over time in the PTSD group compared to control subjects. Variability of P300 measures over time was not associated with fluctuations in symptoms of depression or PTSD. CONCLUSIONS: P300 ERPs are more variable cross-sectionally and over time in PTSD subjects compared to trauma exposed control subjects. Measures of variability about the group mean appear to be more informative about the cognitive electrophysiology of PTSD than measures of central tendency

BACKGROUND: During future long-duration space missions, countermeasures need to be developed to deal with psychosocial issues that might impact negatively on crewmember performance and well-being. METHODS: In our recently completed NASA-funded study of 5 U.S. astronauts, 8 Russian cosmonauts, and 42 U.S. and 16 Russian mission control personnel who participated in the Shuttle/Mir program, we evaluated a number of important psychosocial issues such as group tension, cohesion, leadership role, and the displacement of negative emotions from crewmembers to people in mission control and from mission control personnel to management. RESULTS: Based on our findings, which are reviewed, a number of psychosocial countermeasures are suggested to help ameliorate the negative impact of potential psychosocial problems during future manned space missions. CONCLUSIONS: Crewmembers should be selected not only to rule out psychopathology but also to select-in for group compatibility and facility in a common language. Training should include briefings and team building related to a number of psychosocial issues and should involve both crewmembers and mission control personnel. During the mission, both experts on the ground and the crewmembers themselves should be alert to potential interpersonal problems, including the displacement of negative emotions from the crew to the ground. Supportive activities should consist of both individual and interpersonal strategies, including an awareness of changing leisure time needs. Finally, attention should be given to postmission readjustment and to supporting the families on Earth