Research Review: Changes in the prevalence and symptom severity of child posttraumatic stress disorder in the year following trauma – a meta-analytic study

Objective: Understanding the natural course of child and adolescent posttraumatic stress disorder (PTSD) has significant implications for the identification of, and intervention for, at-risk youth. We used a meta-analytic approach to examine longitudinal changes in youth PTSD prevalence and symptoms over the first 12 months posttrauma. Methods: We conducted a systematic review to identify longitudinal studies of PTSD in young people (5–18 years old), excluding treatment trials. The search yielded 27 peer-reviewed studies and one unpublished dataset for analysis of pooled prevalence estimates, relative prevalence reduction and standardised mean symptom change. Key moderators were also explored, including age, proportion of boys in the sample, initial prevalence of PTSD and PTSD measurement type. Results: Analyses demonstrated moderate declines in PTSD prevalence and symptom severity over the first 3–6 months posttrauma. From 1 to 6 months posttrauma, the prevalence of PTSD reduced by approximately 50%. Symptoms also showed moderate decline, particularly across the first 3 months posttrauma. There was little evidence of further change in prevalence or symptom severity after 6 months, suggesting that it is unlikely a child would lose a PTSD diagnosis without intervention beyond this point. Conclusions: The current findings provide key information about the likelihood of posttrauma recovery in the absence of intervention and have important implications for our understanding of child and adolescent PTSD. Results are discussed with reference to the timing of PTSD screening and the potential role of early interventions. Findings particularly highlight the importance of future research to develop our understanding of what factors prevent the action of normal recovery from the ‘acute’ posttrauma period

A core role for cognitive processes in the acute onset and maintenance of post-traumatic stress in children and adolescents

Background: Post-traumatic stress disorder (PTSD) is a common reaction to trauma in children and adolescents. While a significant minority of trauma-exposed youth go on to have persistent PTSD, many youth who initially have a severe traumatic stress response undergo natural recovery. The present study investigated the role of cognitive processes in shaping the early reactions of child and adolescents to traumatic stressors, and the transition to persistent clinically significant post-traumatic stress symptoms (PTSS). Methods: A prospective longitudinal study of youth aged 8-17 years who had attended a hospital emergency department following single trauma was undertaken, with assessments performed at two-to-four weeks (N=226) and two months (N=208) post-trauma. Acute stress disorder and PTSD were assessed using a structured interview, while PTSS, depression severity and peri-traumatic and post-traumatic cognitive processes were assessed using self-report questionnaires. On the basis of their PTSS scores at each assessment participants were categorised as being on a resilient, recovery or persistent trajectory. Results: PTSS decreased between the two assessments. Cognitive processes at the two-to-four week assessment accounted for the most variance in PTSS at both the initial and follow up assessment. The onset of post-traumatic stress was associated particularly with peritraumatic subjective threat, data-driven processing and pain. Its maintenance was associated with greater peri-traumatic dissociation and panic, and post-traumatic persistent dissociation, trauma memory quality, rumination and negative appraisals. Efforts to deliberately process the trauma were more common in youth who experienced the onset of clinically significant PTSS. Regression modelling indicated that the predictive effect of baseline negative appraisals remained when also accounting for baseline PTSS and depression. Conclusions: Cognitive processes play an important role in the onset and maintenance of PTSS in children and adolescents exposed to trauma. Trauma-related appraisals play a particular role when considering whether youth make the transition from clinically significant acute PTSS to persistent PTSS

Acute stress disorder and the transition to posttraumatic stress disorder in children and adolescents: Prevalence, course, prognosis, diagnostic suitability, and risk markers.

BACKGROUND: Early recovery from trauma exposure in youth is poorly understood. This prospective longitudinal study examined the early course of traumatic stress responses in recently trauma-exposed youth, evaluated the revised DSM-5 acute stress disorder (ASD) and PTSD diagnoses and alternative diagnoses, and identified risk factors for persistent traumatic stress. METHOD: Participants were 8- to 17-year-old emergency departments attendees exposed to single incident traumas. Structured clinical interviews were undertaken at 2 (n = 226) and 9 weeks (n = 208) posttrauma. RESULTS: Using the revised criteria in DSM-5, 14.2% met criteria for ASD at week 2 and 9.6% met criteria for PTSD at week 9. These prevalences were similar to the corresponding DSM-IV diagnoses (18.6% ASD at week 2; 8.7% PTSD at week 9). Using the same diagnostic criteria (DSM-IV or DSM-5) across assessments (i.e., "2-week PTSD") suggested that caseness declined in prevalence by approximately half. Overlap between DSM-IV and DSM-5 ASD and DSM-5 preschool child PTSD diagnoses was considerable. Two diagnoses were strongly predictive of corresponding week 9 diagnoses. Youth with ASD who subsequently had PTSD reported more negative alterations in cognition and mood at 2 weeks than those youth who did not develop PTSD. CONCLUSIONS: Youth exposed to single-event traumas experience considerable natural recovery in the first months posttrauma. Using DSM-5 criteria, ASD may not capture all clinically significant traumatic stress in the acute phase and is only moderately sensitive for later PTSD. Future research needs to address the role and etiology of negative alterations in cognition and mood symptoms

The Preliminary Development and Validation of a Trauma‐Related Safety‐Seeking Behavior Measure for Youth: The Child Safety Behavior Scale (CSBS)

Safety‐seeking behaviors (SSBs) may be employed after exposure to a traumatic event in an effort to prevent a feared outcome. Cognitive models of posttraumatic stress disorder propose SSBs contribute to maintaining this disorder by preventing disconfirmation of maladaptive beliefs and preserving a sense of current threat. Recent research has found that SSBs impact children's posttraumatic stress symptoms (PTSS) and recovery. In this paper, we sought to develop and validate a novel 22‐item Child Safety Behavior Scale (CSBS) in a school‐based sample of 391 pupils (age 12–15 years) who completed a battery of questionnaires as well as 68 youths (age 8–17 years) who were recently exposed to a trauma. Of the sample, 93.1% (N = 426) completed the new questionnaire. The sample was split (n = 213), and we utilized principal components analysis alongside parallel analysis, which revealed that 13 items loaded well onto a two‐factor structure. This structure was superior to a one‐factor model and overall demonstrated a moderately good model of fit across indices, based upon a confirmatory factory analysis with the other half of the sample. The CSBS showed excellent internal consistency, r = .90; good test–retest reliability, r = .64; and good discriminant validity and specificity. In a multiple linear regression, SSBs, negative appraisals, and number of trauma types each accounted for unique variance in a model of PTSS. This study provides initial support for the use of the CSBS in trauma‐exposed youth as a valuable tool for further research, clinical assessment, and targeted intervention

Translating the Cognitive Model of PTSD to the Treatment of Very Young Children: A Single Case Study of an 8-Year-Old Motor Vehicle Accident Survivor.

Posttraumatic stress disorder (PTSD) is a clinical condition that occurs after a discrete traumatic event, such as an accident or assault. Research into PTSD has primarily been adult-focused; however, there is a growing body of evidence evaluating the theory and treatment of PTSD in young children. Consequently, cognitive behavior therapy (CBT) interventions for PTSD in youth have been developed that focus on 3 core components of the cognitive model-a disorganized memory of the trauma, maladaptive appraisals of the trauma and its effects (meanings), and dysfunctional coping mechanisms (management). Here, we describe the extension of this treatment approach (termed CBT-3M) to very young children (3-8 years) through the case of Dylan, an 8-year-old motor vehicle accident survivor. This serves as an illustration of the underlying theory and its successful application. Further work is intended to provide evidence of the efficacy of this treatment via an ongoing treatment trial

Thermostabilization of adenovirus-vectored vaccines, removing the need for continual cold-chain storage

Challenges around affordable and reliable supply of vaccines that need to be transported and maintained in the cold-chain to remain effective are a hindrance to realizing their full potential. We will describe preparation for GMP manufacture and Phase I clinical trial of a new technology for vaccine thermostabilisation. We will also describe application of the same technology to a novel veterinary vaccine which is entering advanced development. The sugar-matrix thermostabilisation (SMT) technology involves application of vaccine in a simple disaccharide-based buffer to a non-woven matrix, similar to a pad of filter paper. This is followed by drying at ambient temperature and pressure (i.e. without a freezing step, enhancing suitability for freeze-sensitive products). The materials and process are simple and cheap. We have previously shown that SMT allows for the storage of viral vectored vaccines such as modified vaccinia virus Ankara (MVA) and adenovirus vectors at up to 45oC for several months with minimal losses1,2. More recently we have shown the technique can improve stability of various other vaccine types, ranging from virus-like particles through to enveloped RNA viruses. In many cases, the level of thermostability achieved would allow for “last mile” vaccine distribution via the ‘extended controlled temperature chain’ (ECTC), or even allow prolonged storage at uncontrolled ambient temperature. This would decrease distribution-associated costs/ losses and increase vaccination feasibility in hard-to-reach areas. We have now received funding for GMP manufacture and Phase I clinical trial of an SMT-formulated adenovirus-vectored rabies vaccine, ChAdOx2 RabG. We will describe the production of custom wet-laid non-woven matrices with optimized SMT performance, using processes and materials suitable for use as an input to a GMP process. We will further describe the development of simple apparatus suitable for executing the process for pilot GMP batches, the optimization of the drying process and excipient composition, and the application of frequency modulation spectroscopy for non-destructive analysis of residual moisture content. Finally, we will describe the application of the technology to a formulation of ChAdOx1 RVF, an adenovirus-vectored vaccine against Rift Valley Fever Virus which is being developed for both human and veterinary use. In this case, SMT is applied to an ultra-low-cost drug substance designed for veterinary use (cell lysate which has been clarified and ultrafiltered but not chromatographically purified), emphasizing the suitability of the approach for low-cost and One Health applications. 1. Alcock, R., et al., Long-Term Thermostabilization of Live Poxviral and Adenoviral Vaccine Vectors at Supraphysiological Temperatures in Carbohydrate Glass. Science Translational Medicine, 2010. 2(19):19ra12. 2. Dulal, P., et al., Potency of a thermostabilised chimpanzee adenovirus Rift Valley Fever vaccine in cattle. Vaccine, 2016. 34(20): p. 2296-8

Investigating the dissociative subtype of post-traumatic stress disorder in single- and multi-event trauma-exposed youth: Prevalence, course, prognosis, severity and functional impairment

OBJECTIVES: This study aimed, following both single- and multi-event trauma, to ascertain prevalence and course of the dissociative subtype of post-traumatic stress disorder (PTSD-DS) in youth; how well early PTSD-DS predicts later PTSD; and whether dissociation accounts for unique variance in post-traumatic stress symptoms (PTSS) and functional impairment over and above the effect of other post-trauma cognitive processing factors and PTSS respectively. DESIGN AND METHODS: This study is a secondary analysis of data from the Acute Stress Programme for Children and Teenagers study (n = 234) and the Coping in Care After Trauma study (n = 110) in which children had experienced single- and multi-event trauma respectively. RESULTS: PTSD-DS diagnosis was common in children with PTSD regardless of trauma experienced (>39.0%). PTSD-DS showed a similar trajectory of natural recovery to PTSD, and it was similarly predictive of later PTSD following single-event trauma. Finally, dissociation was a significant factor in PTSS and functional impairment. CONCLUSIONS: These results should be viewed in the context of several limitations including narrow sample of participants which reduces the generalizability of results, concerns around children's ability to conceptualize challenging concepts such as dissociation and the use of self-report measures to form diagnostic groups. The PTSD-DS diagnosis may offer clinical utility to the extant PTSD diagnosis in children and adolescents, as dissociation has been shown to be a contributory factor in the maintenance of both PTSS and functional impairment. Further research is required to inform further editions of the DSM and other diagnostic systems

The latent structure of Acute Stress Disorder symptoms in trauma-exposed children and adolescents.

BACKGROUND: The revision of Acute Stress Disorder (ASD) in the DSM-5 (DSM-5, 2013) proposes a cluster-free model of ASD symptoms in both adults and youth. Published evaluations of competing models of ASD clustering in youth have rarely been examined. METHODS: We used Confirmatory Factor Analysis (combined with multigroup invariance tests) to explore the latent structure of ASD symptoms in a trauma-exposed sample of children and young people (N = 594). The DSM-5 structure was compared with the previous DSM-IV conceptualization (4-factor), and two alternative models proposed in the literature (3-factor; 5-factor). Model fit was examined using goodness-of-fit indices. We also established DSM-5 ASD prevalence rates relative to DSM-IV ASD, and the ability of these models to classify children impaired by their symptoms. RESULTS: Based on both the Bayesian Information Criterion, the interfactor correlations and invariance testing, the 3-factor model best accounted for the profile of ASD symptoms. DSM-5 ASD led to slightly higher prevalence rates than DSM-IV ASD and performed similarly to DSM-IV with respect to categorising children impaired by their symptoms. Modifying the DSM-5 ASD algorithm to a 3+ or 4+ symptom requirement was the strongest predictor of impairment. CONCLUSIONS: These findings suggest that a uni-factorial general-distress model is not the optimal model of capturing the latent structure of ASD symptom profiles in youth and that modifying the current DSM-5 9+ symptom algorithm could potentially lead to a more developmentally sensitive conceptualization

Cognitive therapy as an early treatment for post-traumatic stress disorder in children and adolescents: a randomized controlled trial addressing preliminary efficacy and mechanisms of action.

BACKGROUND: Few efficacious early treatments for post-traumatic stress disorder (PTSD) in children and adolescents exist. Previous trials have intervened within the first month post-trauma and focused on secondary prevention of later post-traumatic stress; however, considerable natural recovery may still occur up to 6-months post-trauma. No trials have addressed the early treatment of established PTSD (i.e. 2- to 6-months post-trauma). METHODS: Twenty-nine youth (8-17 years) with PTSD (according to age-appropriate DSM-IV or ICD-10 diagnostic criteria) after a single-event trauma in the previous 2-6 months were randomly allocated to Cognitive Therapy for PTSD (CT-PTSD; n = 14) or waiting list (WL; n = 15) for 10 weeks. RESULTS: Significantly more participants were free of PTSD after CT-PTSD (71%) than WL (27%) at posttreatment (intent-to-treat, 95% CI for difference .04-.71). CT-PTSD yielded greater improvement on child-report questionnaire measures of PTSD, depression and anxiety; clinician-rated functioning; and parent-reported outcomes. Recovery after CT-PTSD was maintained at 6- and 12-month posttreatment. Beneficial effects of CT-PTSD were mediated through changes in appraisals and safety-seeking behaviours, as predicted by cognitive models of PTSD. CT-PTSD was considered acceptable on the basis of low dropout and high treatment credibility and therapist alliance ratings. CONCLUSIONS: This trial provides preliminary support for the efficacy and acceptability of CT-PTSD as an early treatment for PTSD in youth. Moreover, the trial did not support the extension of 'watchful waiting' into the 2- to 6-month post-trauma window, as significant improvements in the WL arm (particularly in terms of functioning and depression) were not observed. Replication in larger samples is needed, but attention to recruitment issues will be required

Long-term trial of protection provided by adenovirus-vectored vaccine expressing the PPRV H protein

A recombinant, replication-defective, adenovirus-vectored vaccine expressing the H surface glycoprotein of peste des petits ruminants virus (PPRV) has previously been shown to protect goats from challenge with wild-type PPRV at up to 4 months post vaccination. Here, we present the results of a longer-term trial of the protection provided by such a vaccine, challenging animals at 6, 9, 12 and 15 months post vaccination. Vaccinated animals developed high levels of anti-PPRV H protein antibodies, which were virus-neutralising, and the level of these antibodies was maintained for the duration of the trial. The vaccinated animals were largely protected against overt clinical disease from the challenge virus. Although viral genome was intermittently detected in blood samples, nasal and/or ocular swabs of vaccinated goats post challenge, viral RNA levels were significantly lower compared to unvaccinated control animals and vaccinated goats did not appear to excrete live virus. This protection, like the antibody response, was maintained at the same level for at least 15 months after vaccination. In addition, we showed that animals that have been vaccinated with the adenovirus-based vaccine can be revaccinated with the same vaccine after 12 months and showed an increased anti-PPRV antibody response after this boost vaccination. Such vaccines, which provide a DIVA capability, would therefore be suitable for use when the current live attenuated PPRV vaccines are withdrawn at the end of the ongoing global PPR eradication campaign