Long-Term Outcome of Early Interventions to Prevent Posttraumatic Stress Disorder

Shalev, Arieh Y.; Ankri, Yael; Gilad, Moran; Israeli-Shalev, Yossi; Adessky, Rhonda; Qian, Meng; Freedman, Sara

doi:10.4088/jcp.15m09932

Cited by 66 publications

(20 citation statements)

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“…A second possibility is that, immediately after the traumatic event, people are more preoccupied with immediate needs (such as pain, legal proceedings, post‐deployment activities, or dislocation) that distract their attention from their stress reactions – again, there is a paucity of evidence in favor of this explanation. The observation that many delayed PTSD cases experience significant acute stress responses that subsequently worsen has prompted the proposal that delayed PTSD may be caused by additional stressors in the post‐trauma phase, compounded with diminished resources to deal with these demands – indeed, there is evidence that delayed‐onset PTSD is predicted by the severity of post‐trauma stressors. One further possibility is that relief from the immediate threat of danger may provide people with a temporary sense of safety, that subsequently gives way to ongoing perceptions of threat, leading to PTSD – this interpretation may be especially applicable to military cohorts, who may be relieved by abandoning the combat zone, but may then have difficulties to readjust to ordinary life.…”

Section: Major Challenges For the Ptsd Fieldmentioning

confidence: 99%

Post‐traumatic stress disorder: a state‐of‐the‐art review of evidence and challenges

2019

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Post-traumatic stress disorder (PTSD) is arguably the most common psychiatric disorder to arise after exposure to a traumatic event. Since its formal introduction in the DSM-III in 1980, knowledge has grown significantly regarding its causes, maintaining mechanisms and treatments. Despite this increased understanding, however, the actual definition of the disorder remains controversial. The DSM-5 and ICD-11 define the disorder differently, reflecting disagreements in the field about whether the construct of PTSD should encompass a broad array of psychological manifestations that arise after trauma or should be focused more specifically on trauma memory phenomena. This controversy over clarifying the phenotype of PTSD has limited the capacity to identify biomarkers and specific mechanisms of traumatic stress. This review provides an up-to-date outline of the current definitions of PTSD, its known prevalence and risk factors, the main models to explain the disorder, and evidence-supported treatments. A major conclusion is that, although trauma-focused cognitive behavior therapy is the best-validated treatment for PTSD, it has stagnated over recent decades, and only two-thirds of PTSD patients respond adequately to this intervention. Moreover, most people with PTSD do not access evidence-based treatment, and this situation is much worse in low-and middle-income countries. Identifying processes that can overcome these major barriers to better management of people with PTSD remains an outstanding challenge.

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Section: Major Challenges For the Ptsd Fieldmentioning

confidence: 99%

Post‐traumatic stress disorder: a state‐of‐the‐art review of evidence and challenges

2019

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“…Little evidence is available regarding the long-term benefits of treatment for PTSD because most trials only assess outcomes in the short and medium term, but the few long term follow-ups that exist suggest initial treatment gains may not be maintained over time (Resick, Williams, Suvak, Monson, & Gradus, 2012;Shalev et al, 2016).…”

Section: Strategies To Increase Engagementmentioning

confidence: 99%

Treatment of military-related post-traumatic stress disorder: challenges, innovations, and the way forward

Forbes

Pedlar

Adler

et al. 2019

International Review of Psychiatry

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“…Further, many patients fail to respond to behavior-based treatments, such as exposure therapy (ET), or even experience an exacerbation of symptoms (6). Among those that do respond, the majority retain their PTSD diagnosis (7, 8). At the crux of this issue lies a lack of neurobiological understanding of the disorder.…”

Section: Introductionmentioning

confidence: 99%

Susceptibility and Resilience to Posttraumatic Stress Disorder–like Behaviors in Inbred Mice

Sillivan

Joseph

Jamieson

et al. 2017

Biological Psychiatry

100

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Background The limited neurobiological understanding of PTSD has been partially attributed to the need for improved animal models. Stress-enhanced fear learning (SEFL) in rodents recapitulates many PTSD-associated behaviors, including stress-susceptible (SS) and –resilient (SR) subgroups in outbred rats. Identification of subgroups requires additional behavioral phenotyping, a confound to mechanistic studies. Methods We employed a SEFL paradigm in inbred male and female C57BL/6 that combines acute stress with fear conditioning to precipitate “traumatic” memories. Extinction and long-term retention of extinction were examined after SEFL. Further characterization of SEFL effects on male mice was performed with additional behavioral tests, determination of regional activation by Fos immunofluorescence and RNA-sequencing of the basolateral amygdala (BLA). Results Stressed animals displayed persistently elevated freezing during extinction. While more uniform in females, SEFL produced male subgroups with differential susceptibility that were identified without post-training phenotyping. Additional phenotyping of males revealed PTSD-associated behaviors, including extinction-resistant fear memory, hyperarousal, generalization and dysregulated corticosterone in SS males. Altered Fos activation was also seen in the infralimbic cortex and BLA of SS males after remote memory retrieval. Key behavioral outcomes, including susceptibility, were replicated by two independent laboratories. RNA-sequencing of the BLA revealed transcriptional divergence between the male subgroups, including genes with reported polymorphic association to PTSD patients. Conclusions This SEFL model provides a tool for development of PTSD therapeutics that is compatible with the growing number of mouse-specific resources. Furthermore, use of an inbred strain allows for investigation into epigenetic mechanisms that are expected to critically regulate susceptibility and resilience.

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Long-Term Outcome of Early Interventions to Prevent Posttraumatic Stress Disorder

Abstract: ClinicalTrials.gov identifier: NCT00146900.

Cited by 66 publications

References 0 publications

Post‐traumatic stress disorder: a state‐of‐the‐art review of evidence and challenges

Post‐traumatic stress disorder: a state‐of‐the‐art review of evidence and challenges

Treatment of military-related post-traumatic stress disorder: challenges, innovations, and the way forward

Susceptibility and Resilience to Posttraumatic Stress Disorder–like Behaviors in Inbred Mice

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