Prospects for the pharmacological prevention of post-traumatic stress in vulnerable individuals.

Biological studies of posttraumatic stress disorder (PTSD) have found alterations of physiological stress pathways [sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis] soon after trauma in individuals who have subsequently developed PTSD, leading researchers to hypothesize that pharmacological manipulation of stress hormone levels may aid in preventing the development of post-traumatic distress. The present paper first reviews the current understanding of the neurobiology of PTSD development and then provides the rationale and evidence for early pharmacological strategies to prevent/reduce post-traumatic distress in at-risk trauma victims. Emphasis is placed on those interventions targeting the SNS and the HPA axis. Furthermore, in light of recent calls to move away from categorical diagnostic outcomes, we discuss how examining post-traumatic distress from a transdiagnostic viewpoint may inform novel chemoprophylactic approaches (intervening pharmacologically after trauma to prevent post-traumatic distress). Current evidence is suggestive for medications, such as propranolol, hydrocortisone, morphine, and oxytocin, impacting early stress hormone levels and subsequent risk for post-traumatic distress; however, future research is needed prior to adapting recommendations for widespread use of any chemoprophylactic treatments.

Traumatic childhood experiences in the 21st century: broadening and building on the ACE studies with data from the National Child Traumatic Stress Network.

The study objectives were to (a) examine the association between total number of trauma types experienced and child/adolescent behavioral problems and (b) determine whether the number of trauma types experienced predicted youth behavioral problems above and beyond demographic characteristics, using a diverse set of 20 types of trauma. Data came from the National Child Traumatic Stress Network's (NCTSN) Core Data Set (CDS), which includes youth assessed and treated for trauma across the United States. Participants who experienced at least one type of trauma were included in the sample (N = 11,028; age = 1½-18 years; 52.3% girls). Random effects models were used to account for possible intraclass correlations given treatment services were provided at different NCTSN centers. Logistic regression analyses were used to investigate associations among demographic characteristics, trauma, and emotional and behavioral problems as measured by the Child Behavior Checklist (CBCL). Significant dose-response relations were found between total number of trauma types and behavior problems for all CBCL scales, except Sleep, one of the subscales only administered to 1½- to 5-year-olds. Thus, each additional trauma type endorsed significantly increased the odds for scoring above the clinical threshold. Results provide further evidence of strong associations between diverse traumatic childhood experiences and a diverse range of behavior problems, and underscore the need for a trauma-informed public health and social welfare approach to prevention, risk reduction, and early intervention for traumatized youth.

Do gender and age moderate the symptom structure of PTSD? Findings from a national clinical sample of children and adolescents.

A substantial body of evidence documents that the frequency and intensity of posttraumatic stress disorder (PTSD) symptoms are linked to such demographic variables as female sex (e.g., Kaplow et al., 2005) and age (e.g., Meiser-Stedman et al., 2008). Considerably less is known about relations between biological sex and age with PTSD's latent factor structure. This study systematically examined the roles that sex and age may play as candidate moderators of the full range of factor structure parameters of an empirically supported five-factor PTSD model (Elhai et al., 2011). The sample included 6591 trauma-exposed children and adolescents selected from the National Child Traumatic Stress Network's Core Data Set. Confirmatory factor analysis using invariance testing (Gregorich, 2006) and comparative fit index difference values (Cheung and Rensvold, 2002) reflected a mixed pattern of test item intercepts across age groups. The adolescent subsample produced lower residual error variances, reflecting less measurement error than the child subsample. Sex did not show a robust moderating effect. We conclude by discussing implications for clinical assessment, theory building, and future research.

The efficacy of initial hydrocortisone administration at preventing posttraumatic distress in adult trauma patients: a randomized trial.

UNLABELLED: OBJECTIVE/INTRODUCTION: Secondary pharmacological interventions have shown promise at reducing the development of posttraumatic stress disorder symptoms (PTSS) in preclinical studies. The present study examined the preliminary efficacy of a 10-day low-dose (20 mg bid) course of hydrocortisone at preventing PTSS in traumatic injury victims. METHODS: Sixty-four traumatic injury patients (34% female) were randomly assigned in a double-blind protocol to receive either a 10-day course of hydrocortisone or placebo initiated within 12 hours of the trauma. One-month and 3-months posttrauma participants completed an interview to assess PTSS and self-report measures of depression and health-related quality of life. RESULTS: Hydrocortisone recipients reported fewer PTSD and depression symptoms, and had greater improvements in health-related quality of life during the first 3 months posttrauma than did placebo recipients. Hydrocortisone recipients who had never received prior mental health treatment had the lowest PTSD scores. CONCLUSION: Low-dose hydrocortisone may be a promising approach to the prevention of PTSD in acutely injured trauma patients, and may be particularly efficacious in acutely injured trauma victims without a history of significant psychopathology.

Psychometric properties of the UCLA PTSD reaction index: part I.

This article presents psychometric characteristics of the UCLA PTSD Reaction Index for DSM IV (PTSD-RI) derived from a large sample of children and adolescents (N = 6,291) evaluated at National Child Traumatic Stress Network centers. Overall mean total PTSD-RI score for girls was significantly higher as compared with boys. Age-related differences were found in that overall mean total PTSD-RI scores and within sex groups were higher among those aged 7-9 years and 16-18 years. There were no significant differences in mean total PTSD-RI scores across racial/ethnic groups. The PTSD-RI total scale displayed good to excellent internal consistency reliability across age ranges, sex, and racial/ethnic groups (α = .88-.91). Correlations of PTSD-RI scores with PTS subscale scores on the TSCC-A for the entire sample and within sex, age, and ethnic/racial groups provided evidence of convergent validity, although not discriminant validity. In contradistinction to previously reported 4-factor models, an exploratory factor analysis revealed 3 factors that mostly reflected the underlying dimensions of PTSD in DSM IV. PTSD-RI scores were associated with increased odds ratios for functional/behavior problems (odds ratio [OR] = 1-1.80). These findings are striking in light of the wide range of trauma exposures, age, and race/ethnicity among subjects.

Psychometric properties of the UCLA PTSD reaction index. part II: investigating factor structure findings in a national clinic-referred youth sample.

We examined the underlying factor structure of the UCLA PTSD Reaction Index (PTSD-RI) using data from 6,591 children/adolescents exposed to trauma, presenting for treatment at any of 54 National Child Traumatic Stress Network (NCTSN) centers. Using confirmatory factor analysis, we tested the 3-factor DSM-IV PTSD model, 2 separate 4-factor models (Dysphoria vs. Emotional Numbing) and a recently conceptualized 5-factor Dysphoric Arousal model. We found a slight, but significant advantage for the Dysphoria model over the Emotional Numbing model on the PTSD-RI, with a difference in Bayesian information criterion (BIC) values of 81 points. As with several recent studies of adult trauma victims, we found a slight advantage for the Dysphoric Arousal model over the other models on the PTSD-RI, with BIC differences exceeding 300 points. Retaining the Dysphoric Arousal model, we tested the convergent validity of the PTSD-RI factors against subscales of the Trauma Symptom Checklist for Children. Supporting the convergent validity of the PTSD-RI, in the Dysphoric Arousal model, the dysphoric arousal factor related most strongly to anger, whereas the emotional numbing factor related most strongly to depression, and anxious arousal factor related most strongly to anxiety. Results support the use of the PTSD-RI for evaluating PTSD among youth.

Avoidant coping as a mediator between peritraumatic dissociation and posttraumatic stress disorder symptoms.

Peritraumatic dissociation consistently predicts posttraumatic stress disorder (PTSD). Avoidant coping may serve as a mechanism through which peritraumatic dissociation contributes to PTSD symptoms. Path analysis was used to examine whether avoidant coping assessed 6 weeks following a motor vehicle accident mediated the relationship between in-hospital peritraumatic dissociation and 6-month (n = 193) and 12-month (n = 167) chronic PTSD symptoms. Results revealed that, after controlling for age, gender, depression, and 6-week PTSD symptoms, avoidant coping remained a partial mediator between peritraumatic dissociation and chronic PTSD symptoms 6- and 12-months postaccident. Post-hoc multigroup analyses suggested that at 6-months posttrauma, the mediation was significant in women, but not in men. Gender-specific results were not significant at 12-months posttrauma. Interventions targeted at reducing avoidant coping in high dissociators may aid in reducing PTSD symptoms.

The impact of caregiver distress on the longitudinal development of child acute post-traumatic stress disorder symptoms in pediatric injury victims.

OBJECTIVE: The present study prospectively examined the development of child PTSD symptoms (PTSS) and the impact of caregiver PTSS on child PTSS following injury. METHODS: One hundred and eighteen ED patients and their caregivers were interviewed in-hospital and 2- and 6-weeks posttrauma. Structural equation modeling and hierarchical linear regressions examined the development of PTSS. RESULTS: A model combining child and caregiver 2-week PTSS into one latent family PTSS variable provided the best fit to the data. Child in-hospital avoidance symptoms predicted higher levels of 2-week family PTSS. Two-week family PTSS predicted child 6-week PTSS. Post hoc analyses revealed an interaction between in-hospital caregiver avoidance symptoms and child reexperiencing symptoms in predicting 6-week child PTSS. CONCLUSIONS: Results highlight the dynamic development of child PTSS. Different symptom clusters may be related to higher PTSS at differing times posttrauma and may inform the development of time-sensitive methods of assessment and intervention for injury victims.

DSM-V PTSD diagnostic criteria for children and adolescents: a developmental perspective and recommendations.

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) should ensure systematic attention to age-specific manifestations and selective modifications of the diagnostic criteria for posttraumatic stress disorder (PTSD) among children and adolescents. The authors propose developmental refinements to the conceptual framework for PTSD based on an appreciation of the different neurosignatures of danger and safety, and maturational processes that underlie symptom presentation. This includes preliminary evidence for the developmental salience of additional dimensions for PTSD (e.g., recklessness and thrill-seeking). The authors provide conservative recommendations for DSM-V diagnostic criteria that primarily highlight age-related developmental manifestations that, if included in the accompanying text, would bring a richer appreciation of developmentally linked symptom presentations.

Trauma history characteristics and subsequent PTSD symptoms in motor vehicle accident victims.

The present study examined the relationship between trauma history characteristics (number and type of traumas, age at first trauma, and subjective responses to prior traumas) and the development of posttraumatic stress disorder (PTSD) symptoms following a motor vehicle accident (MVA). One hundred eighty-eight adult MVA victims provided information about prior traumatization and were evaluated for PTSD symptoms 6 weeks and one year following the MVA. Results indicated that after controlling for demographics and depression, prior trauma history characteristics accounted for a small, but significant amount of the variance in PTSD symptoms. Distress from prior trauma and number of types of prior traumas were the most meaningful trauma history predictors. Results encourage further evaluation of trauma history as a multifaceted construct.

Acute child and mother psychophysiological responses and subsequent PTSD symptoms following a child's traumatic event.

This study examined the relationship between acute cortisol responses to trauma and subsequent PTSD symptoms (PTSS) in children and their biological mothers. Urinary cortisol levels were assessed in 54 children aged 8-18 upon admission to a level-1 trauma center. Six weeks posttrauma, 15-hour urine samples were collected from children and their mothers. Depression and PTSS were assessed at 6 weeks (N = 44) and 7 months (N = 38) posttrauma. Higher child in-hospital cortisol significantly predicted 6-week child PTSS. This was true only for boys at 7 months. In mothers, lower 6-week cortisol levels significantly predicted 7-month PTSS. Results extend findings of differing directions of acute hormonal predictors of PTSS in adults versus children to a sample of genetically related individuals.

Brief report: the impact of maternal posttraumatic stress disorder symptoms and child gender on risk for persistent posttraumatic stress disorder symptoms in child trauma victims.

OBJECTIVE: To longitudinally examine the impact of maternal posttraumatic stress disorder symptoms (PTSS) on child adjustment following a child's traumatic injury, focusing on child gender differences. METHODS: Forty-one child traumatic injury victims aged 8-18 years and their biological mothers were interviewed over two follow-ups (6 weeks and 7 months). Children were administered the Clinician-Administered Posttraumatic Stress Disorder (PTSD) Scale for Children and Adolescents (CAPS-CA), whereas mothers completed the CAPS. RESULTS: Six weeks post trauma, maternal PTSS were significantly related to PTSS in boys but not in girls. However, at 7 months, maternal PTSS were strongly related to child PTSS in both boys and girls. Significant 6-week maternal distress-child gender interactions suggested that maternal PTSS, especially avoidance, predicted greater 7-month PTSS but that this was primarily because of a significant relationship in females. CONCLUSIONS: Maternal distress was found to negatively impact subsequent child adjustment, particularly in females. These results underscore the importance of considering family-centered interventions for child PTSD, especially in girls.