The feasibility of prolonged exposure therapy for PTSD in low-and middle-income countries: a review

There is a need in the global south to evaluate and implement empirically supported psychological interventions to ameliorate symptoms of posttraumatic stress disorder (PTSD). Empirically supported treatments (ESTs) have increasingly been developed and implemented, yet the majority people in the global south do not have access to these treatments for mental disorders such as PTSD. Prolonged exposure therapy has accrued substantial empirical evidence to show it as an effective treatment for PTSD. Research on the effectiveness and acceptability of prolonged exposure in a low- and middle-income countries (LMICs) are sparse. This brief report presents a review of prolonged exposure (PE) therapy and its feasibility as a trauma therapy for PTSD in LMICs. First, we present a brief overview of PE as a first-line treatment for PTSD. Second, using South Africa as a case example, we present a brief overview of traumatic stress in South Africa and how mental healthcare has developed since the abolishment of apartheid in 1994. Lastly, we discuss the challenges pertaining to the dissemination and implementation of PE in LMICs and propose future perspectives regarding the implementation of ESTs such as PE in LMICs

Primum Non Nocere (First Do No Harm): Symptom Worsening And Improvement In Female Assault Victims After Prolonged Exposure For Ptsd

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106816/1/da22225.pd

Rape-related symptoms in adolescents: short- and long-term outcome after cognitive behavior group therapy

Background: Efficacy studies on treatment in adolescent victims of single rape are lacking, even though sexual victimization is most likely to occur during adolescence and despite the fact that adolescents are at risk to develop subsequent posttraumatic stress disorder. Aim: The aim of this prospective observational study was to evaluate the short- and long-term outcomes of a nine-session cognitive behavior group therapy (STEPS), including a parallel six-session parents’ group on rape-related symptomatology in female adolescents (13–18 years). STEPS includes psychoeducation, exposure in sensu as well as in vivo, cognitive restructuring, and relapse prevention. Methods: Fifty-five female adolescents with mental health problems due to single rape, but without prior sexual trauma, received STEPS while their parents participated in a support group. Subjects were assessed on posttraumatic stress (PTS) and comorbid symptoms using self-report questionnaires prior to and directly after treatment, and at 6 and 12 months follow-up. Results: Repeated measures analysis showed a significant and large decrease in symptoms of PTS, anxiety, depression, anger, dissociation, sexual concerns, and behavior problems directly after treatment, which maintained at 12 months follow-up. Time since trauma did not influence the results. Dropout during STEPS was 1.8%. Conclusions: The results potentially suggest that the positive treatment outcomes at short- and long-term may be caused by STEPS. The encouraging findings need confirmation in future controlled studies on the effectiveness of STEPS because it may be possible that the treatment works especially well for more chronic symptoms, while the less chronic part of the sample showed considerable improvement on its own

D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0

Ecto-5′-nucleotidase and intestinal ion secretion by enteropathogenic Escherichia coli

Enteropathogenic Escherichia coli (EPEC) triggers a large release of adenosine triphosphate (ATP) from host intestinal cells and the extracellular ATP is broken down to adenosine diphosphate (ADP), AMP, and adenosine. Adenosine is a potent secretagogue in the small and large intestine. We suspected that ecto-5′-nucleotidase (CD73, an intestinal enzyme) was a critical enzyme involved in the conversion of AMP to adenosine and in the pathogenesis of EPEC diarrhea. We developed a nonradioactive method for measuring ecto-5′-nucleotidase in cultured T84 cell monolayers based on the detection of phosphate release from 5′-AMP. EPEC infection triggered a release of ecto-5′-nucleotidase from the cell surface into the supernatant medium. EPEC-induced 5′-nucleotidase release was not correlated with host cell death but instead with activation of phosphatidylinositol-specific phospholipase C (PI-PLC). Ecto-5′-nucleotidase was susceptible to inhibition by zinc acetate and by α,β-methylene-adenosine diphosphate (α,β-methylene-ADP). In the Ussing chamber, these inhibitors could reverse the chloride secretory responses triggered by 5′-AMP. In addition, α,β-methylene-ADP and zinc blocked the ability of 5′-AMP to stimulate EPEC growth under nutrient-limited conditions in vitro. Ecto-5′-nucleotidase appears to be the major enzyme responsible for generation of adenosine from adenine nucleotides in the T84 cell line, and inhibitors of ecto-5′-nucleotidase, such as α,β-methylene-ADP and zinc, might be useful for treatment of the watery diarrhea produced by EPEC infection

Internet-based prevention of posttraumatic stress symptoms in injured trauma patients: design of a randomized controlled trial.

Background: Injured trauma victims are at risk of developing Posttraumatic Stress Disorder (PTSD) and other post-trauma psychopathology. So far, interventions using cognitive behavioral techniques (CBT) have proven most efficacious in treating early PTSD in highly symptomatic individuals. No early intervention for the prevention of PTSD for all victims has yet proven effective. In the acute psychosocial care for trauma victims, there is a clear need for easily applicable, accessible, cost-efficient early interventions. Objective: To describe the design of a randomized controlled trial (RCT) evaluating the effectiveness of a brief Internet-based early intervention that incorporates CBT techniques with the aim of reducing acute psychological distress and preventing long-term PTSD symptoms in injured trauma victims. Method: In a two armed RCT, 300 injured trauma victims from two Level-1 trauma centers in Amsterdam, the Netherlands, will be assigned to an intervention or a control group. Inclusion criteria are: being 18 years of age or older, having experienced a traumatic event according to the diagnostic criteria of the DSM-IV and understanding the Dutch language. The intervention group will be given access to the intervention's website (www.traumatips.nl), and are specifically requested to login within the first month postinjury. The primary clinical study outcome is PTSD symptom severity. Secondary outcomes include symptoms of depression and anxiety, quality of life, and social support. In addition, a cost-effectiveness analysis of the intervention will be performed. Data are collected at one week post-injury, prior to first login (baseline), and at 1, 3, 6 and 12 months. Analyses will be on an intention-to-treat basis. Discussion: The results will provide more insight into the effects of preventive interventions in general, and Internet-based early interventions specifically, on acute stress reactions and PTSD, in an injured population, during the acute phase after trauma. We will discuss possible strengths and limitations

Enhancing discovery of genetic variants for posttraumatic stress disorder through integration of quantitative phenotypes and trauma exposure information

Background Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). Methods A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. Results GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. Conclusions Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods