Faculty Bibliography

OBJECTIVE: The purpose of this study was to assess the incidence, severity, and correlates of acute stress responses in women undergoing diagnostic mammographic surveillance and to explore the moderating impact of physician support on these symptoms. METHODS: Sixty-six female breast cancer outpatients (at least 12 months after diagnosis and primary treatment) and 69 healthy women undergoing mammographic surveillance completed measures of: acute stress response, somatization, trauma history, psychiatric history, social support, and physician satisfaction. RESULTS: Previous cancer, pre-mammography breast complaints, lower income, previous psychiatric medication use, greater instrumental support, greater somatization, greater perceived physician disengagement, and less perceived physician support were all associated with increased stress responses. Among women with a previous cancer diagnosis, those with greater distress reported higher levels of physician support. In contrast, among those without a previous cancer diagnosis, those with greater perceived physician support reported less distress. CONCLUSIONS: These findings suggest that cancer-related cues, such as follow-up surveillance, may trigger a sensitizing response in women with a previous cancer diagnosis. The association of distress with physician support may arise from the responsiveness of physicians to identified distress, from increased help-seeking behavior by those who are distressed, or both. The benefit of support provided by health care professionals to those at risk of developing stress response syndromes deserves further study

This study compared attention and declarative memory in a sample of combat veterans with posttraumatic stress disorder (PTSD, n = 24) previously reported to have reduced concentrations of the hippocampal neuronal marker N-acetyl aspartate (NAA), but similar hippocampal volume compared to veteran normal comparison participants (n = 23). Healthy, well-educated males with combat-related PTSD without current depression or recent alcohol/drug abuse did not perform differently on tests of attention, learning, and memory compared to normal comparison participants. Further, hippocampal volume, NAA, or NAA/Creatine ratios did not significantly correlate with any of the cognitive measures when adjustments for multiple comparisons were made. In this study, reduced hippocampal NAA did not appear to be associated with impaired declarative memory

OBJECTIVE: This article describes current approaches to the pharmacologic treatment of posttraumatic stress disorder (PTSD) and reviews the classes of pharmacologic agents used in the treatment of PTSD. Pharmacotherapy for PTSD that is comorbid with other psychiatric disorders is highlighted. METHODS: The primary-source literature was reviewed by using a MEDLINE search. Secondary-source review articles and chapters were also used. Results from studies of the psychophysiology of PTSD are outlined in the review to help inform treatment choices. The review gives more consideration to controlled studies than to open clinical trials. Recommendations for treatment are evidence based. RESULTS AND DISCUSSION: A growing body of evidence demonstrates the efficacy of pharmacologic treatment for PTSD. The effectiveness of the selective serotonin reuptake inhibitors sertraline and paroxetine in large-scale, well-designed, placebo-controlled trials resulted in their being the first medications to receive approval from the U.S. Food and Drug Administration for the treatment of PTSD. Observation of psychophysiologic alterations associated with PTSD has led to the study of adrenergic-inhibiting agents and mood stabilizers as therapeutic agents. Controlled clinical trials with these classes of medication are needed to determine their efficacy for treating PTSD. Finally, the choice of medication for treating PTSD is often determined by the prominence of specific PTSD symptoms and the pattern of comorbid psychiatric conditions

BACKGROUND: In patients with coronary heart disease (CHD), depression leads to worse cardiovascular outcomes. Depression has been associated with increased cortisol in medically healthy patients, suggesting that cortisol may act as a mediator in the pathway between depression and cardiovascular events. However, it is not known whether depression is associated with elevated cortisol levels in patients with CHD. METHODS: We examined the association between depression (assessed by the Computerized Diagnostic Interview Schedule) and 24-hour urinary cortisol in 693 medical outpatients with known CHD. RESULTS: Of 693 participants, 138 (20%) had current depression. Depressed participants had greater mean cortisol levels than those without depression (42 +/- 25 vs. 36 +/- 20 microg/day, p <.01). With each increasing quartile of cortisol concentration the frequency of depression increased (p <.01). Participants in the highest quartile of cortisol had a twofold increased odds of having depression, compared with those in the lowest quartile (odds ratio [OR] 2.1, 95% confidence interval [CR] 1.2-3.6, p =.01). This association remained strong after adjusting for potential confounding variables (OR 2.4, 95% CI 1.3-4.4, p <.01). In this cross-sectional analysis, elevated cortisol was not associated with worse cardiac function. CONCLUSIONS: In patients with CHD,depression is associated with elevated cortisol levels

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: 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

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

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

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