Faculty Bibliography

BACKGROUND: Enhanced glucocorticoid receptor (GR) sensitivity is present in people with posttraumatic stress disorder (PTSD), but the molecular mechanisms of GR sensitivity are not understood. Epigenetic factors have emerged as one potential mechanism that account for how trauma exposure leads to sustained PTSD symptoms given that PTSD develops in only a subset of trauma survivors. METHODS: Cytosine methylation of a relevant promoter of the GR gene (NR3C1-1F promoter) and three functional neuroendocrine markers of hypothalamic-pituitary-adrenal axis function were examined in a sample of 122 combat veterans. RESULTS: Lower NR3C1-1F promoter methylation in peripheral blood mononuclear cells (PBMCs) was observed in combat veterans with PTSD compared with combat-exposed veterans who did not develop PTSD. NR3C1-1F promoter methylation was also associated with three functional measures of glucocorticoid activity that have been associated with PTSD in combat veterans: PBMCs' lysozyme inhibition on the lysozyme suppression test, plasma cortisol decline on the low-dose (.50 mg) dexamethasone suppression test, and 24-hour urinary cortisol excretion. Finally, NR3C1-1F promoter methylation was inversely correlated with clinical markers and symptoms associated with PTSD. CONCLUSIONS: Alterations in NR3C1-1F promoter methylation may reflect enduring changes resulting from combat exposure that lead to functional neuroendocrine alterations. Because epigenetic measures are thought to reflect enduring effects of environmental exposures, they may be useful in distinguishing combat-exposed veterans who do or do not develop PTSD.

Abnormality in the "fear circuitry" has been known as a major neural characteristic of posttraumatic stress disorder (PTSD). Recent studies also revealed decreased functional connectivity in the default mode network in PTSD. The present study aims to investigate, in war-zone-related PTSD, the spontaneous activity and functional connectivity of the amygdala and the precuneus, which are two representative brain regions of the two networks, respectively. Two groups of 52 male US Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) veterans (PTSD vs. controls), well matched on age and ethnicity, were clinically assessed and then studied in a resting state functional magnetic resonance imaging (fMRI) procedure. Functional connectivity analysis was conducted on the resting state fMRI data with the amygdala and precuneus as seeds. Compared with controls, veterans with PTSD had lower functional connectivity in the default mode network, as well as lower amygdala-frontal functional connectivity. Both the PTSD and the control group had a significant positive precuneal-amygdala functional connectivity without a significant group difference. The magnitudes of spontaneous activity of the amygdala and the precuneus were negatively correlated in the PTSD group and showed significant quadratic relationships with the amount of emotional abuse in early life trauma. These findings may improve our understanding about the relationships between fear circuitry and the default mode network in the context of war-zone-related PTSD.

BACKGROUND: Chronic inflammation may be involved in combat-related Post-Traumatic Stress Disorder (PTSD) and may help explain comorbid physical diseases. However, the extent to which combat exposure per se, depression, or early life trauma, all of which are associated with combat PTSD, may confound the relationship between PTSD and inflammation is unclear. METHODS: We quantified interleukin (IL)-6, IL-1beta, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and C-reactive protein (CRP) in 51 combat-exposed males with PTSD and 51 combat-exposed males without PTSD, and assessed PTSD and depression severity as well as history of early life trauma. To decrease the possibility of Type I errors, we summed standardized scores of IL-1beta, IL-6, TNFalpha, IFNgamma and CRP into a total "pro-inflammatory score." PTSD symptom severity was assessed with the Clinician Administered PTSD Scale (CAPS) rating scale. RESULTS: Subjects with PTSD had significantly higher pro-inflammatory scores compared to combat-exposed subjects without PTSD (p=0.006), and even after controlling for early life trauma, depression diagnosis and severity, body mass index, ethnicity, education, asthma/allergies, time since combat and the use of possibly confounding medications (p=0.002). Within the PTSD group, the pro-inflammatory score was not significantly correlated with depressive symptom severity, CAPS total score, or with the number of early life traumas. CONCLUSIONS: Combat-related PTSD in males is associated with higher levels of pro-inflammatory cytokines, even after accounting for depression and early life trauma. These results, from one of the largest studies of inflammatory cytokines in PTSD to date, suggest that immune activation may be a core element of PTSD pathophysiology more so than a signature of combat exposure alone.

Heterogeneity in glucocorticoid response to experimental stress conditions has shown to differentiate individuals with healthy from maladaptive real-life stress responses in a number of distinct domains. However, it is not known if this heterogeneity influences the risk for developing stress related disorders or if it is a biological consequence of the stress response itself. Determining if glucocorticoid response to stress induction prospectively predicts psychological vulnerability to significant real life stressors can adjudicate this issue. To test this relationship, salivary cortisol as well as catecholamine responses to a laboratory stressor during academy training were examined as predictors of empirically identified distress trajectories through the subsequent 4 years of active duty among urban police officers routinely exposed to potentially traumatic events and routine life stressors (N = 234). During training, officers were exposed to a video vignette of police officers exposed to real-life trauma. Changes in salivary 3-methoxy-4-hydroxyphenylglycol (MHPG) and cortisol in response to this video challenge were examined as predictors of trajectory membership while controlling for age, gender, and baseline neuroendocrine levels. Officers who followed trajectories of resilience and recovery over 4 years mounted significant increases in cortisol in response to the experimental stressor, while those following a trajectory of chronic increasing distress had no significant cortisol change in response to the challenge. MHPG responses were not associated with distress trajectories. Cortisol response prospectively differentiated trajectories of distress response suggesting that a blunted cortisol response to a laboratory stressor is a risk factor for later vulnerability to distress following significant life stressors.

BACKGROUND: This article provides a description of the rationale, design, and methods of a multisite clinical trial which evaluates the potential benefits of an evidence-based psychosocial treatment, STAIR Narrative Therapy, among women with posttraumatic stress disorder (PTSD) related to interpersonal violence who are seeking services in public sector community mental health clinics. This is the first large multisite trial of an evidence-based treatment for PTSD provided in the context of community settings that are dedicated to the treatment of poverty-level patient populations. METHODS: The study is enrolling 352 participants in a minimum of community clinics. Participants are randomized into either STAIR Narrative Therapy or Treatment As Usual (TAU). Primary outcomes are PTSD, emotion management, and interpersonal problems. The study will allow a flexible application of the protocol determined by patient need and preferences. Secondary analyses will assess the relationship of outcomes to different patterns of treatment implementation for different levels of baseline symptom severity. DISCUSSION: The article discusses the rationale and study issues related to the use of a flexible delivery of a protocol treatment and of the selection of treatment as it is actually practiced in the community as the comparator.Trial registration: Clinicaltrials.gov identifier: NCT01488539.

The goal of the current study was to examine the relationship between early physical victimization and long-term mental health outcomes in a sample of first responder police and firefighter personnel involved in the relief efforts after Hurricane Katrina. Participants included 441 Biloxi and Gulfport Police and Firefighters. One fifth of participants reported having experienced physical victimization before age 18. After controlling for age, relationship status, and disaster exposure, early physical victimization was modestly associated with symptoms of PTSD, peritraumatic dissociation, depression, and sleep problems. The results suggest that early physical victimization might be a risk factor for mental health problems in police and fire personnel responding to mass disaster, pointing to the importance of developing interventions to mitigate risk related to a history of physical victimization in first-responders. C1 [Komarovskaya, Irina; Brown, Adam D.; Galatzer-Levy, Isaac R.; Madan, Anita; Henn-Haase, Clare; Marmar, Charles R.; Chemtob, Claude M.] NYU, Dept Psychiat, New York, NY 10016 USA. [Teater, Julie] Consulting Psychol Resources LLC, Biloxi, MS USA. [Clarke, Brandi H.] JW Hall LLC, Biloxi, MS USA

INTRODUCTION: It has been reported that posttraumatic stress disorder (PTSD) is associated with secondary spouse/partner (S/P) emotional distress and relationship violence. OBJECTIVE: To investigate the relationships between PTSD, S/P emotional distress and relationship violence among police recruits using a prospective design. METHODS: Two hypotheses were tested in 71 S/Ps: (1) Police officer reports of greater PTSD symptoms after 12 months of police service will be associated with greater secondary trauma symptoms among S/Ps; (2) Greater secondary trauma symptoms among S/Ps at 12 months will be associated with S/P reports of greater relationship violence. METHODS: 71 police recruits and their S/Ps were assessed at baseline and 12 months after the start of police officer duty. Using linear and logistic regression, we analyzed explanatory variables for 12 month S/P secondary traumatic stress symptoms and couple violence, including baseline S/P variables and couple violence, as well as exposure and PTSD reports from both S/P and officer. RESULTS: S/P perception of officer PTSD symptoms predicted S/P secondary traumatic stress. OS/P secondary trauma was significantly associated with both total couple violence (.34, p = .004) and S/P to officer violence (.35, p = .003). CONCLUSIONS: Although results from this relatively small study of young police officers and their S/Ps must be confirmed by larger studies in general populations, findings suggest that S/P perception of PTSD symptoms may play a key role in the spread of traumatic stress symptoms across intimate partner relationships and intimate partner violence in the context of PTSD.

Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder, especially in combat veterans. Existing functional neuroimaging studies have provided important insights into the neural mechanisms of PTSD using various experimental paradigms involving trauma recollection or other forms of emotion provocation. However it is not clear whether the abnormal brain activity is specific to the mental processes related to the experimental tasks or reflects general patterns across different brain states. Thus, studying intrinsic spontaneous brain activity without the influence of external tasks may provide valuable alternative perspectives to further understand the neural characteristics of PTSD. The present study evaluated the magnitudes of spontaneous brain activity of male US veterans with or without PTSD, with the two groups matched on age, gender, and ethnicity. Amplitudes of low frequency fluctuation (ALFF), a data driven analysis method, were calculated on each voxel of the resting state fMRI data to measure the magnitudes of spontaneous brain activity. Results revealed that PTSD subjects showed increased spontaneous activity in the amygdala, ventral anterior cingulate cortex, insula, and orbital frontal cortex, as well as decreased spontaneous activity in the precuneus, dorsal lateral prefrontal cortex and thalamus. Within the PTSD group, larger magnitudes of spontaneous activity in the thalamus, precuneus and dorsal lateral prefrontal cortex were associated with lower re-experiencing symptoms. Comparing our results with previous functional neuroimaging findings, increased activity of the amygdala and anterior insula and decreased activity of the thalamus are consistent patterns across emotion provocation states and the resting state.

Responses to both potentially traumatic events and other significant life stressors have been shown to conform to discrete patterns of response such as resilience, anticipatory stress, initial distress with gradual recovery, and chronic distress. The etiology of these trajectories is still unclear. Individual differences in levels of negative and positive emotion are believed to play a role in determining risk and resilience following traumatic exposure. In the current investigation, we followed police officers prospectively from academy training through 48 months of active duty, assessing levels of distress every 12 months. Using latent class growth analysis, we identified 4 trajectories closely conforming to prototypical patterns. Furthermore, we found that lower levels of self-reported negative emotion during academy training prospectively predicted membership in the resilient trajectory compared with the more symptomatic trajectories following the initiation of active duty, whereas higher levels of positive emotion during academy training differentiated resilience from a trajectory that was equivalently low on distress during academy training but consistently grew in distress through 4 years of active duty. These findings emerging from a prospective longitudinal design provide evidence that resilience is predicted by both lower levels of negative emotion and higher levels of positive emotion prior to active duty stressor exposure. (PsycINFO Database Record (c) 2013 APA, all rights reserved).