Faculty Bibliography

BACKGROUND: Alterations of hypothalamic-pituitary-adrenal (HPA) axis function and sympathetic-adrenal activity have been proposed as key factors in biological models of posttraumatic stress disorder (PTSD). METHODS: We examined neuroendocrine function in female survivors of intimate partner violence (IPV) with lifetime (current or remitted) PTSD (n=29) and in women who were exposed to IPV but never developed PTSD (n=20). Salivary cortisol was collected as a marker of HPA axis function at 1, 4, 9, and 11 h after awakening. Platelet epinephrine and norepinephrine were assayed as markers of sympathetic-adrenal activation. RESULTS: Women with lifetime PTSD had significantly higher cortisol levels across the day compared to abuse-exposed participants without PTSD, after controlling for age, depression, severity, and latency of abuse. There were no significant group differences in levels of platelet catecholamines. CONCLUSIONS: Elevated cortisol levels may be a biomarker of IPV-related lifetime PTSD, reflecting long-lasting changes associated with trauma-exposure or possibly a reflection of risk for PTSD in women

The relationship of type of critical incident (CI) stressor with peritraumatic responses and posttraumatic stress disorder symptoms was examined in police. Officers (N = 662) provided narratives of their most distressing CI experienced during police service and completed measures of related peritraumatic responses and posttraumatic stress disorder symptoms. Narratives were reliably rated (kappa = .80-1.0) on seven categories emerging from a series of factor analyses of a measure of critical incident stressors. Additional analysis revealed that the classification of primary narrative features required only five categories (personal life threat, duty-related violence, encountering physical or sexual assault victims, exposure to civilian death, other). When analyzed by further collapsing these five categories into high versus low personal threat, officers whose narratives contained high personal threat reported more peritraumatic dissociation, peritraumatic emotional distress, and current hyperarousal symptoms. Results suggest that greater personal threat during a CI may place an officer at greater risk for subsequent distress

We provide an overview of previous research conducted by our group on risk and resilience factors for PTSD symptoms in police and other first responders. Based on our work, the findings of other investigators on individual differences in risk for PTSD, and drawing on preclinical studies fear conditioning and extinction, we propose a conceptual model for the development of PTSD symptoms emphasizing the role of vulnerability and resilience to peritraumatic panic reactions. We tested this conceptual model in a cross-sectional sample of police officers (n = 715). Utilizing an hierarchical linear regression model we were able to explain 39.7% of the variance in PTSD symptoms. Five variables remained significant in the final model; greater peritraumatic distress (beta = 0.240, P < .001), greater peritraumatic dissociation (beta = 0.174, P < .001), greater problem-solving coping (beta = 0.103, P < .01), greater routine work environment stress (beta = 0.182, P < .001), and lower levels of social support (beta = -0.246, P < .001). These results were largely consistent with the proposed conceptual model. Next steps in this line of research will be to test this model prospectively in a sample of 400 police academy recruits assessed during training and currently being followed for the first 2 years of police service

Studies that have conducted quantitative analysis of the sleep electroencephalogram (EEG) have demonstrated decreased delta sleep in PTSD. Elevations in both hypothalamic (neurohormonal) and extrahypothalamic (neurotransmitter) corticotropin releasing factor (CRF) release is associated with decreased delta sleep activity. We present data from several studies examining the effect of metyrapone administration on the sleep EEG in PTSD and control subjects. Plasma ACTH, cortisol, and 11-deoxycorticol were obtained the morning following polysomnographic sleep recordings before and after metyrapone administration. Delta sleep was measured by period amplitude analysis. The results demonstrate: a) decreased delta sleep in male subjects with PTSD; b) metyrapone administration resulted in an activation of the sleep EEG and a robust decrease in quantitative delta sleep; c) the sleep and endocrine (increase in ACTH) responses to metyrapone were significantly decreased in PTSD in two different study samples; and d) the metyrapone-related disruption to sleep in both samples was predicted by the increase in ACTH measured the following morning. These findings strongly suggest that the delta sleep response to metyrapone is a measure of the brain response to a hypothalamic CRF challenge. The attenuated delta sleep and endocrine response to metyrapone challenge in PTSD is consistent with a model of enhanced negative feedback regulation or downregulation of CRF receptors in an environment of chronically increased CRF activity

Alexithymia has been associated with both posttraumatic stress disorder and neuroendocrine responses to stress. This study examined the relationship of alexithymia to salivary cortisol and 3-methoxy-4-hydroxy-phenylglycol (MHPG) in a sample of police academy recruits exposed to a video stress challenge. Alexithymia scores were negatively associated with catecholamine response to the video challenge but no association was found between alexithymia scores and cortisol reactivity

Intimate partner violence (IPV) is a chronic and recurrent traumatic stressor associated with PTSD; however, its biological correlates are not well understood. This study examined diurnal salivary cortisol and platelet catecholamines in women with lifetime IPV-related PTSD and in women exposed to IPV who did not develop PTSD. Cortisol was elevated in women with lifetime PTSD compared to controls. No differences were found for platelet catecholamines

The relationship of alexithymia to posttraumatic stress disorder (PTSD) symptomatology was examined cross-sectionally in 166 urban police officers surveyed between 1998 and 1999 and prospectively in 54 of these officers who participated in a follow-up survey after the September 11, 2001 (9/11) terrorist attacks. In cross-sectional analyses, alexithymia scores were positively associated with PTSD symptom levels and self-reported childhood emotional abuse--neglect, but not with cumulative level of critical incident exposure. Alexithymia scores accounted for 11.2% of the variance in PTSD symptoms prior to accounting for additional predictors, but did not retain significance in the final model. In prospective analyses, alexithymia scores significantly predicted 9/11-related PTSD symptom severity over and above pre-9/11 PTSD symptoms

Many important gains have been made in understanding PTSD and other responses to trauma as a result of neuroscience-based observations. Yet there are many gaps in our knowledge that currently impede our ability to predict those who will develop pathologic responses. Such knowledge is essential for developing appropriate strategies for mounting a mental health response in the aftermath of terrorism and for facilitating the recovery of individuals and society. This paper reviews clinical and biological studies that have led to an identification of pathologic responses following psychological trauma, including terrorism, and highlights areas of future-research. It is important to not only determine risk factors for the development of short- and long-term mental health responses to terrorism, but also apply these risk factors to the prediction of such responses on an individual level. It is also critical to consider the full spectrum of responses to terrorism, as well as the interplay between biological and psychological variables that contribute to these responses. Finally, it is essential to remove the barriers to collecting data in the aftermath of trauma by creating a culture of education in which the academic community can communicate to the public what is and is not known so that survivors of trauma and terrorism will understand the value of their participation in research to the generation of useful knowledge, and by maintaining the acquisition of knowledge as a priority for the government and those involved in the immediate delivery of services in the aftermath of large-scale disaster or trauma

Alterations of the hypothalamic-pituitary-adrenal (HPA) axis and sleep disturbances have been described separately in post-traumatic stress disorder (PTSD). It is not known if HPA alterations and sleep disturbances are associated in PTSD. This study examined sleep and HPA activity in 20 male medication-free subjects with PTSD and 16 matched healthy controls. Two nights of polysomnography were obtained and 24-h urinary cortisol was collected during day 2. Subjects self-administered a low-dose (0.5 mg) salivary dexamethasone test at home. Compared with controls, PTSD subjects had higher 24-h urinary microg cortisol/g creatinine (mean+/-SD 40+/-17 vs 28+/-12, p=0.03) but not significantly higher 24-h urinary cortisol (mean+/-SD 52+/-15 microg/day vs 43+/-23, p=0.19). PTSD subjects showed a trend towards less cortisol suppression after dexamethasone (73%+/-18 vs 83%+/-10, p=0.06). In the combined sample, delta sleep was significantly and negatively correlated with 24-h urinary cortisol (r=-0.36, p=0.04), and with 24-h urinary cortisol/g creatinine on a trend level (r=-0.34, p=0.06). Our results suggest that increased cortisol is negatively associated with delta sleep. This may contribute to sleep abnormalities in conditions associated with elevated cortisol, possibly including PTSD. Future studies should explore the temporal relationship between HPA activity, sleep disturbances, and psychopathology after a traumatic event

This study examines whether pre- or post-dexamethasone salivary cortisol is related to cumulative critical incident exposure, peritraumatic responses, or post-traumatic stress disorder (PTSD) symptom severity. Thirty active duty police officers completed the study protocol, which included measures of peritraumatic emotional distress, peritraumatic dissociation, duty-related trauma exposure, and PTSD symptoms. Salivary cortisol was consolidated into three outcome variables: (1) pre-dexamethasone free cortisol levels at 1, 30, 45, and 60 min after awakening, (2) post-dexamethasone cortisol levels at the identical wake times, and (3) percentage of cortisol suppression. Control variables included age, gender, average daily alcohol use, night shift work, routine work environment stressors, and salivary dexamethasone levels. Zero order correlations showed that greater levels of PTSD symptoms, peritraumatic distress, and peritraumatic dissociation were associated with lower levels of pre-dexamethasone cortisol levels on awakening, but were not associated with the other two cortisol variables. A trend was also noted for older subjects to have lower pre-dexamethasone cortisol on awakening. When these four predictors were entered simultaneously in a regression analysis, only age and PTSD symptom severity significantly predicted pre-dexamethasone awakening cortisol levels. These results replicate previous research indicating a relationship between greater PTSD symptoms and lower levels of basal cortisol on awakening, and extend this finding to a previously unstudied non-treatment seeking population, urban police