Faculty Bibliography

INTRODUCTION: Some studies have found that antidepressants increase serum brain-derived neurotrophic factor (BDNF) levels in patients with major depression and the expression of BDNF mRNA in limbic structures of rats. OBJECTIVES: This study addressed whether the SSRI escitalopram increases serum BDNF levels in subjects with PTSD and whether BDNF levels are associated with treatment response. METHODS: Medically healthy male subjects (N=16) with chronic PTSD completed a 12 week open-label trial of flexible dose (5-20 mg/day) escitalopram monotherapy. BDNF levels were obtained at baseline, and at weeks 4, 8 and 12. RESULTS: PTSD symptoms significantly declined over the course of the 12 week escitalopram treatment. Despite a substantial improvement in PTSD symptoms, there was virtually no change in BDNF levels over time. Nevertheless, mean BDNF levels across the trial were strongly correlated with the slope of PTSD symptoms over the 12 weeks (r=0.58, p=0.018). Lower mean BDNF was associated with a greater decrease in PTSD symptoms over the course of the trial. CONCLUSIONS: PTSD subjects with low BDNF levels demonstrated the largest treatment response from an agent with putative neurotrophic effects

Thousands of Sudanese refugees have fled to Cairo, Egypt in the wake of Sudanese civil conflicts. Sudanese refugees were evaluated with respect to symptoms of depression, post-traumatic stress disorder (PTSD) and social stress. Four respondents (22%) indicated that their interactions with the United Nations High Commissioner for Refugees (UNHCR) in Cairo, Egypt were the worst experiences since war-related atrocities. Fourteen participants (63.6%) felt 'extremely' betrayed by the UNHCR on a four point scale. Greater feelings of betrayal by the UNHCR were associated with greater avoidance and arousal symptoms of PTSD, symptoms of depression and trait anger. This is the first study of which we are aware that examines the relationship between sense of betrayal by the UNHCR and symptoms of PTSD, depression and anger among asylum seekers

Aviation, military, police, and health care personnel have been particularly interested in the operational impact of sleep restriction and work schedules given the potential severe consequences of making fatigue-related errors. Most studies examining the impact of sleep loss or circadian manipulations have been conducted in controlled laboratory settings using small sample sizes. This study examined whether the relationship between prior night sleep duration and performance on the psychomotor vigilance task could be reliably detected in a field study of healthy police academy recruits. Subjects (N = 189) were medically and psychiatrically healthy. Sleep-wake activity was assessed with wrist actigraphy for 7 days. Subjects performed the psychomotor vigilance task (PVT) for 5 min on a personal digital assistant (PDA) device before and after their police academy workday and on comparable times during their days off. Mixed-effects logistic regression was used to estimate the probability of having > or =1 lapse on the PVT as a function of the previous night sleep duration during the 7 days of field testing. Valid estimates of sleep duration were obtained for 1082 nights of sleep. The probability of a lapse decreased by 3.5%/h sleep the night prior to testing. The overall probability of having a lapse decreased by 0.9%/h since awakening, holding hours of sleep constant. Perceived stress was not associated with sleep duration or probability of performance lapse. These findings demonstrate the feasibility of detecting sleep and circadian effects on cognitive performance in large field studies. These findings have implications regarding the daytime functioning of police officers

OBJECTIVES: We examined gender differences in sociodemographic, military service, and mental health characteristics among Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans. We evaluated associations between these sociodemographic and service characteristics and depression and posttraumatic stress disorder (PTSD) diagnoses. METHODS: In a retrospective, cross-sectional study, we used univariate descriptive statistics and log binominal regression analyses of Department of Veterans Affairs (VA) administrative data on 329 049 OEF and OIF veterans seeking VA health care from April 1, 2002, through March 31, 2008. RESULTS: Female veterans were younger and more likely to be Black and to receive depression diagnoses than were male veterans, who were more frequently diagnosed with PTSD and alcohol use disorders. Older age was associated with a higher prevalence of PTSD and depression diagnoses among women but not among men. CONCLUSIONS: Consideration of gender differences among OEF and OIF veterans seeking health care at the VA will facilitate more targeted prevention and treatment services for these newly returning veterans

CONTEXT: Posttraumatic stress disorder (PTSD) is increasingly recognized as a cause of substantial disability. In addition to its tremendous mental health burden, PTSD has been associated with worse physical health status and an increased risk of cardiovascular disease. OBJECTIVE: To determine whether PTSD is associated with cardiovascular health status in patients with heart disease and whether this association is independent of cardiac function. DESIGN: Cross-sectional study. SETTING: The Heart and Soul Study, a prospective cohort study of psychological factors and health outcomes in adults with stable cardiovascular disease. PARTICIPANTS: One thousand twenty-two men and women with coronary heart disease. MAIN OUTCOME MEASURES: Posttraumatic stress disorder was assessed using the Computerized Diagnostic Interview Schedule for DSM-IV. Cardiac function was measured using left ventricular ejection fraction, treadmill exercise capacity, and inducible ischemia on stress echocardiography. Disease-specific health status was assessed using the symptom burden, physical limitation, and quality of life subscales of the Seattle Angina Questionnaire. We used ordinal logistic regression to evaluate the association of PTSD with health status, adjusted for objective measures of cardiac function. RESULTS: Of the 1022 participants, 95 (9%) had current PTSD. Participants with current PTSD were more likely to report at least mild symptom burden (57% vs 36%), mild physical limitation (59% vs 44%), and mildly diminished quality of life (62% vs 35%) (all P < or = .001). When adjusted for cardiovascular risk factors and objective measures of cardiac function, PTSD remained independently associated with greater symptom burden (odds ratio, 1.9; 95% confidence interval, 1.2-2.9; P = .004); greater physical limitation (odds ratio, 2.2; 95% confidence interval, 1.4-3.6; P = .001); and worse quality of life (odds ratio, 2.5; 95% confidence interval, 1.6-3.9; P < .001). Results were similar after excluding participants with depression. CONCLUSIONS: Among patients with heart disease, PTSD is more strongly associated with patient-reported cardiovascular health status than objective measures of cardiac function. Future studies should explore whether assessing and treating PTSD symptoms can improve function and quality of life in patients with heart disease

Replies to the comments made by Hadi M. Hussain (see record 2009-03021-027) on the authors' original article (see record 2007-19186-007). We certainly agree with Dr. Hussain that more research is needed regarding responsivity of patients with combat-related (compared to non-combat-related) posttraumatic stress disorder (PTSD) to selective serotonin reuptake inhibitors (SSRTs), other medications, and psychotherapy. We also agree that further research on predictors of response would be very useful.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been most consistently associated with exaggerated physiologic reactivity to startling sounds when such sounds occur in threatening contexts. There is conflicting evidence about whether startle hyperreactivity is a preexisting vulnerability factor for PTSD or an acquired result of posttrauma neural sensitization. Until now, there have been no prospective studies of physiologic reactivity to startling sounds in threatening contexts as predictors of PTSD symptoms. METHODS: One hundred and thirty-eight police academy cadets without current psychopathology were exposed to repeated 106-dB startling sounds under increasing (low, medium, or high) threat of mild electric shock while their eye-blink electromyogram, skin conductance, heart rate, and subjective fear responses were recorded. Measures of response habituation were also calculated. Following 1 year of exposure to police-related trauma, these participants were assessed for PTSD symptom severity. RESULTS: After accounting for other baseline variables that were predictive of PTSD symptom severity (age and general psychiatric distress), more severe PTSD symptoms were prospectively and independently predicted by the following startle measures: greater subjective fear under low threat, greater skin conductance under high threat, and slower skin conductance habituation. CONCLUSIONS: These results imply that hypersensitivity to contextual threat (indexed by greater fear under low threat), elevated sympathetic nervous system reactivity to explicit threat (indexed by larger responses under high threat), and failure to adapt to repeated aversive stimuli (evidenced by slower habituation) are all unique preexisting vulnerability factors for greater PTSD symptom severity following traumatic stress exposure. These measures may eventually prove useful for preventing PTSD

Hundreds of thousands of Darfur people affected by the Sudanese genocide have fled to Cairo, Egypt, in search of assistance. Collaborating with Africa and Middle East Refugee Assistance (AMERA), the authors conducted a mental health care needs assessment among Darfur refugees in Cairo. Information was collected using individual and focus group interviews to identify gaps in mental health care and develop understandings of emotional and relationship problems. The refugee mental health care system has a piecemeal structure with gaps in outpatient services. There is moderate to severe emotional distress among many Darfur refugees, including symptoms of depression and trauma, and interpersonal conflict, both domestic violence and broader community conflict, elevated relative to pregenocide levels. Given the established relationships between symptoms of depression/traumatic stress and interpersonal violence, improving mental health is important for both preventing mental health decompensation and stemming future cycles of intra- and intergroup conflict

The selective serotonin reuptake inhibitors (SSRIs) are considered the first-line pharmacological treatment for PTSD. However, even when treated with this class of drugs, response rates rarely exceed 60% and less than 20-30% of the patients achieve full remission. The aim of this study was to address this limitation by systematically reviewing the options left for the treatment of PTSD when patients do not respond satisfactorily to or tolerate SSRIs. A systematic review covering all original articles, letters and brief reports published in any language until October 2008 was conducted through searches in the ISI/Web of Science, PubMed and PILOTS databases. The search terms included the pharmacological class of each agent or its generic name plus 'PTSD' or 'stress disorder' in the title, in the abstract or as a keyword. Sixty-three articles were selected, covering the following categories: antipsychotics, anticonvulsants, adrenergic-inhibiting agents, opioid antagonists, benzodiazepines and other agents. None of the identified agents reached the level A of scientific evidence, 5 reached level B, 7 level C and 13 level D. The non-antidepressant agent with the strongest scientific evidence supporting its use in PTSD is risperidone, which can be envisaged as an effective add-on therapy when patients did not fully benefit from previous treatment with SSRIs. Prazosin, an adrenergic-inhibiting agent, is a promising alternative for cases of PTSD where nightmares and insomnia are prominent symptoms. So far, there is no consistent empirical support for using benzodiazepines in the prevention or in the treatment of PTSD, although these drugs could alleviate some associated non-specific symptoms, such as insomnia or anxiety. Further controlled clinical trials and meta-analysis are needed to guide clinicians in their search of effective pharmacological alternatives to antidepressants in PTSD