Effects of MDMA-assisted therapy for PTSD on self-experience.

INTRODUCTION: There is a resurgence of interest in the therapeutic potential of psychedelic substances such as 3,4-methylenedioxymethamphetamine (MDMA). Primary findings from our randomized, double-blind, placebo-controlled, multi-site Phase 3 clinical trial of participants with severe PTSD (NCT03537014) showed that MDMA-assisted therapy induced significant attenuation in the Clinician-Administered PTSD Scale for DSM-5 compared to Therapy with placebo. Deficits in emotional coping skills and altered self-capacities constitute major obstacles to successful completion of available treatments. The current analysis evaluated the differential effects of MDMA-assisted therapy and Therapy with placebo on 3 transdiagnostic outcome measures and explored the contribution of changes in self-experience to improvement in PTSD scores. METHODS: Participants were randomized to receive manualized therapy with either MDMA or placebo during 3 experimental sessions in combination with 3 preparation and 9 integration therapy visits. Symptoms were measured at baseline and 2 months after the last experimental session using the 20-item Toronto Alexithymia Scale (TAS-20), the 26-item Self Compassion Scale (SCS), and the 63-item Inventory of Altered Self-Capacities (IASC). RESULTS: 90 participants were randomized and dosed (MDMA-assisted therapy, n = 46; Therapy with placebo, n = 44); 84.4% (76/90) had histories of developmental trauma, and 87.8% (79/90) had suffered multiple traumas. MDMA-assisted therapy facilitated statistically significant greater improvement on the TAS-20, the SCS, and most IASC factors of interpersonal conflicts; idealization disillusionment; abandonment concerns; identity impairment; self-awareness; susceptibility to influence; affect dysregulation; affect instability; affect skill deficit; tension reduction activities; the only exception was identity diffusion. CONCLUSION: Compared with Therapy with placebo, MDMA-assisted therapy had significant positive effects on transdiagnostic mental processes of self-experience which are often associated with poor treatment outcome. This provides a possible window into understanding the psychological capacities facilitated by psychedelic agents that may result in significant improvements in PTSD symptomatology.

Correction: A Randomized Controlled Study of Neurofeedback for Chronic PTSD.

[This corrects the article DOI: 10.1371/journal.pone.0166752.].

A Randomized Controlled Study of Neurofeedback for Chronic PTSD.

INTRODUCTION: Brain/Computer Interaction (BCI) devices are designed to alter neural signals and, thereby, mental activity. This study was a randomized, waitlist (TAU) controlled trial of a BCI, EEG neurofeedback training (NF), in patients with chronic PTSD to explore the capacity of NF to reduce PTSD symptoms and increase affect regulation capacities. STUDY DESIGN: 52 individuals with chronic PTSD were randomized to either NF (n = 28) or waitlist (WL) (n = 24). They completed four evaluations, at baseline (T1), after week 6 (T2), at post-treatment (T3), and at one month follow up (T4). Assessment measures were:1. Traumatic Events Screening Inventory (T1); 2. the Clinician Administered PTSD Scale (CAPS; T1, T3, T4); 3. the Davidson Trauma Scale (DTS; T1-T4) and 4. the Inventory of Altered Self-Capacities (IASC; T1-T4). NF training occurred two times per week for 12 weeks and involved a sequential placement with T4 as the active site, P4 as the reference site. RESULTS: Participants had experienced an average of 9.29 (SD = 2.90) different traumatic events. Post-treatment a significantly smaller proportion of NF (6/22, 27.3%) met criteria for PTSD than the WL condition (15/22, 68.2%), χ2 (n = 44, df = 1) = 7.38, p = .007. There was a significant treatment condition x time interaction (b = -10.45, t = -5.10, p< .001). Measures of tension reduction activities, affect dysregulation, and affect instability exhibited a significant Time x Condition interaction. The effect sizes of NF (d = -2.33 within, d = - 1.71 between groups) are comparable to those reported for the most effective evidence based treatments for PTSD. DISCUSSION: Compared with the control group NF produced significant PTSD symptom improvement in individuals with chronic PTSD, as well as in affect regulation capacities. NF deserves further investigation for its potential to ameliorate PTSD and to improve affect regulation, and to clarify its mechanisms of action.

A Pilot Study of Neurofeedback for Chronic PTSD.

EEG Biofeedback (also known as neurofeedback) has been in use as a clinical intervention for well over 30 years; however, it has made very little impact on clinical care. One reason for this has been the difficulty in designing research to measure clinical change in the real world. While substantial evidence exists for its efficacy in treating attention deficit/hyperactivity disorder, relatively little evidence exists for its utility in other disorders including posttraumatic stress disorder (PTSD). The current study represents a "proof-of-concept" pilot for the use of neurofeedback with multiply-traumatized individuals with treatment-resistant PTSD. Participants completed 40 sessions of neurofeedback training two times per week with sensors randomly assigned (by the study coordinator, who was not blind to condition) to sensor placements of either T4-P4 or T3-T4. We found that neurofeedback significantly reduced PTSD symptoms (Davidson Trauma Scale scores averaged 69.14 at baseline to 49.26 at termination), and preceded gains in affect regulation (Inventory of Altered Self-Capacities-Affect Dysregulation scores averaged 23.63 at baseline to 17.20 at termination). We discuss a roadmap for future research.

Yoga as an adjunctive treatment for posttraumatic stress disorder: a randomized controlled trial.

BACKGROUND: More than a third of the approximately 10 million women with histories of interpersonal violence in the United States develop posttraumatic stress disorder (PTSD). Currently available treatments for this population have a high rate of incomplete response, in part because problems in affect and impulse regulation are major obstacles to resolving PTSD. This study explored the efficacy of yoga to increase affect tolerance and to decrease PTSD symptomatology. METHOD: Sixty-four women with chronic, treatment-resistant PTSD were randomly assigned to either trauma-informed yoga or supportive women's health education, each as a weekly 1-hour class for 10 weeks. Assessments were conducted at pretreatment, midtreatment, and posttreatment and included measures of DSM-IV PTSD, affect regulation, and depression. The study ran from 2008 through 2011. RESULTS: The primary outcome measure was the Clinician-Administered PTSD Scale (CAPS). At the end of the study, 16 of 31 participants (52%) in the yoga group no longer met criteria for PTSD compared to 6 of 29 (21%) in the control group (n = 60, χ²1 = 6.17, P = .013). Both groups exhibited significant decreases on the CAPS, with the decrease falling in the large effect size range for the yoga group (d = 1.07) and the medium to large effect size decrease for the control group (d = 0.66). Both the yoga (b = -9.21, t = -2.34, P = .02, d = -0.37) and control (b = -22.12, t = -3.39, P = .001, d = -0.54) groups exhibited significant decreases from pretreatment to the midtreatment assessment. However, a significant group × quadratic trend interaction (d = -0.34) showed that the pattern of change in Davidson Trauma Scale significantly differed across groups. The yoga group exhibited a significant medium effect size linear (d = -0.52) trend. In contrast, the control group exhibited only a significant medium effect size quadratic trend (d = 0.46) but did not exhibit a significant linear trend (d = -0.29). Thus, both groups exhibited significant decreases in PTSD symptoms during the first half of treatment, but these improvements were maintained in the yoga group, while the control group relapsed after its initial improvement. DISCUSSION: Yoga significantly reduced PTSD symptomatology, with effect sizes comparable to well-researched psychotherapeutic and psychopharmacologic approaches. Yoga may improve the functioning of traumatized individuals by helping them to tolerate physical and sensory experiences associated with fear and helplessness and to increase emotional awareness and affect tolerance. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00839813.

Understanding interpersonal trauma in children: why we need a developmentally appropriate trauma diagnosis.

Childhood exposure to victimization is prevalent and has been shown to contribute to significant immediate and long-term psychological distress and functional impairment. Children exposed to interpersonal victimization often meet criteria for psychiatric disorders other than posttraumatic stress disorder (PTSD). Therefore, this article summarizes research that suggests directions for broadening current diagnostic conceptualizations for victimized children, focusing on findings regarding victimization, the prevalence of a variety of psychiatric symptoms related to affect and behavior dysregulation, disturbances of consciousness and cognition, alterations in attribution and schema, and interpersonal impairment. A wide range of symptoms is common in victimized children. As a result, in the current psychiatric nosology, multiple comorbid diagnoses are necessary-but not necessarily accurate-to describe many victimized children, potentially leading to both undertreatment and overtreatment. Related findings regarding biological correlates of childhood victimization and the treatment outcome literature are also reviewed. Recommendations for future research aimed at enhancing diagnosis and treatment of victimized children are provided.

[Developmental trauma disorder: towards a rational diagnosis for chronically traumatized children]. / Entwicklungstrauma-Störung: Auf dem Weg zu einer sinnvollen Diagnostik für chronisch traumatisierte Kinder.

Less than eight years after the establishment of the National Child Traumatic Stress Network in 2001 it has become evident that the current diagnostic classification system is inadequate for tens of thousands of traumatized children. While the inclusion of PTSD in the psychiatric classification system in 1980 led to extensive scientific studies of that diagnosis, over the past 25 years there has been a parallel emergence of the field of Developmental Psychopathology, which has documented the effects of interpersonal trauma and disruption of caregiving systems on the development of affect regulation, attention, cognition, perception, and interpersonal relationships. Another significant development has been the increasing documentation of the effects of adverse early life experiences on brain development. The goal of introducing the diagnosis of Developmental Trauma Disorder is to capture the reality of the clinical presentations of children and adolescents exposed to chronic interpersonal trauma. Whether or not they exhibit some symptoms of PTSD, children who have developed in the context of ongoing danger, maltreatment, and inadequate caregiving systems are ill-served by the current diagnostic system, as it frequently leads to multiple unrelated diagnoses, an emphasis on behavioral control without recognition of interpersonal trauma and lack of safety in the etiology of symptoms, and a lack of attention to ameliorating the developmental disruptions that underlie the symptoms.

Neural correlates of reexperiencing, avoidance, and dissociation in PTSD: symptom dimensions and emotion dysregulation in responses to script-driven trauma imagery.

Research suggests that responses to script-driven trauma imagery in posttraumatic stress disorder (PTSD) include reexperiencing and dissociative symptom subtypes. This functional magnetic resonance imaging (fMRI) study employed a dimensional approach to characterizing script-driven imagery responses, using the Responses to Script-Driven Imagery Scale and correlational analyses of relationships between severity of state posttraumatic symptoms and neural activation. As predicted, state reexperiencing severity was associated positively with right anterior insula activity and negatively with right rostral anterior cingulate cortex (rACC). Avoidance correlated negatively with rACC and subcallosal anterior cingulate activity. In addition, as predicted, dissociation correlated positively with activity in the left medial prefrontal and right superior temporal cortices, and negatively with the left superior temporal cortex. Theoretical and clinical implications are discussed, particularly with respect to an emotion-dysregulation account of PTSD.

A randomized clinical trial of eye movement desensitization and reprocessing (EMDR), fluoxetine, and pill placebo in the treatment of posttraumatic stress disorder: treatment effects and long-term maintenance.

OBJECTIVE: The relative short-term efficacy and long-term benefits of pharmacologic versus psychotherapeutic interventions have not been studied for posttraumatic stress disorder (PTSD). This study compared the efficacy of a selective serotonin reup-take inhibitor (SSRI), fluoxetine, with a psychotherapeutic treatment, eye movement desensitization and reprocessing (EMDR), and pill placebo and measured maintenance of treatment gains at 6-month follow-up. METHOD: Eighty-eight PTSD subjects diagnosed according to DSM-IV criteria were randomly assigned to EMDR, fluoxetine, or pill placebo. They received 8 weeks of treatment and were assessed by blind raters posttreatment and at 6-month follow-up. The primary outcome measure was the Clinician-Administered PTSD Scale, DSM-IV version, and the secondary outcome measure was the Beck Depression Inventory-II. The study ran from July 2000 through July 2003. RESULTS: The psychotherapy intervention was more successful than pharmacotherapy in achieving sustained reductions in PTSD and depression symptoms, but this benefit accrued primarily for adult-onset trauma survivors. At 6-month follow-up, 75.0% of adult-onset versus 33.3% of child-onset trauma subjects receiving EMDR achieved asymptomatic end-state functioning compared with none in the fluoxetine group. For most childhood-onset trauma patients, neither treatment produced complete symptom remission. CONCLUSIONS: This study supports the efficacy of brief EMDR treatment to produce substantial and sustained reduction of PTSD and depression in most victims of adult-onset trauma. It suggests a role for SSRIs as a reliable first-line intervention to achieve moderate symptom relief for adult victims of childhood-onset trauma. Future research should assess the impact of lengthier intervention, combination treatments, and treatment sequencing on the resolution of PTSD in adults with childhood-onset trauma.

Resiliency factors in the relation between childhood sexual abuse and adulthood sexual assault in college-age women.

Research has suggested that childhood sexual abuse (CSA) may be a risk factor for adulthood sexual assault. This study examined associations between CSA experiences, cognitive resiliency variables, and revictimization. Participants were 73 college-age females who completed self-report questionnaires assessing CSA, adult assault, self-efficacy, locus of control (LOC), and coping styles. Sexual assault was categorized as forced or coerced assault based on the tactics used by the perpetrator. Results indicated that CSA alone was the strongest independent predictor of forced adult assault; however, LOC and positive coping were associated with resiliency to coercive sexual assault. The current findings have clinical implications in that LOC and coping styles are characteristics that can be enhanced through therapy.

Efficacy of sertraline in posttraumatic stress disorder secondary to interpersonal trauma or childhood abuse.

BACKGROUND: In posttraumatic stress disorder (PTSD), the nature of the trauma and the age of occurrence may have substantial effects on psychobiological sequelae and treatment response. Interpersonal trauma (physical/sexual assault) and childhood abuse are both prevalent and associated with later PTSD. This analysis was conducted to specifically assess the efficacy of sertraline in the treatment of PTSD secondary to interpersonal trauma or childhood abuse. METHODS: 395 adult patients with PTSD were randomized to 12-weeks double-blind treatment with flexible dose sertraline (50-200 mg/d) or placebo. Patients with different index traumas were compared in terms of baseline demographic and clinical characteristics, as well as treatment response. Primary efficacy variables included part 2 of the Clinician Administered PTSD Scale (CAPS-2). RESULTS: Interpersonal trauma and childhood abuse were both more common in females than males, and were associated with early age at time of index trauma and longer duration of PTSD, but not with PTSD symptom severity. Sertraline was significantly more effective than placebo on most primary efficacy variables, irrespective of whether patients had experienced interpersonal trauma or childhood abuse. CONCLUSIONS: These data demonstrate that sertraline is valuable for the treatment of PTSD, irrespective of whether the precipitating trauma involves interpersonal trauma in general, or childhood abuse in particular.

Clinical implications of neuroscience research in PTSD.

The research showing how exposure to extreme stress affects brain function is making important contributions to understanding the nature of traumatic stress. This includes the notion that traumatized individuals are vulnerable to react to sensory information with subcortically initiated responses that are irrelevant, and often harmful, in the present. Reminders of traumatic experiences activate brain regions that support intense emotions, and decrease activation in the central nervous system (CNS) regions involved in (a) the integration of sensory input with motor output, (b) the modulation of physiological arousal, and (c) the capacity to communicate experience in words. Failures of attention and memory in posttraumatic stress disorder (PTSD) interfere with the capacity to engage in the present: traumatized individuals "lose their way in the world." This article discusses the implications of this research by suggesting that effective treatment needs to involve (a) learning to tolerate feelings and sensations by increasing the capacity for interoception, (b) learning to modulate arousal, and (c) learning that after confrontation with physical helplessness it is essential to engage in taking effective action.

Dissociative symptomatology in posttraumatic stress disorder and disorders of extreme stress.

The present study was designed to assess differences in dissociative symptoms in adults with Posttraumatic Stress Disorder (PTSD) vs. PTSD plus Disorders of Extreme Stress Not Otherwise Specified (DESNOS). This study was done for two reasons: (1) to better understand the clinical profile of DESNOS clients in order to inform more effective treatment, and (2) to further empirical research on the validity of the DESNOS construct. To assess severity of dissociative symptoms, the authors administered the Dissociative Experiences Scale (DES) to 155 participants with PTSD. Using the Structured Interview for Disorders of Extreme Stress (SIDES), participants were divided into two groups: those who also met criteria for DESNOS and those who did not. DES means are provided for the two groups. Participants with PTSD plus DESNOS scored higher than participants with only PTSD on the measure of dissociative symptomatology, particularly on the DES scales that tap absorption/fantasy and depersonalization/derealization. The two groups did not differ on the amnesia subscale of the DES. Findings support the construct validity of the DESNOS concept and further delineate the clinical profiles of community-based PTSD with and without DESNOS, thus contributing to the knowledge base on the assessment of complex adaptations to trauma.

Preliminary evidence of parasympathetic influence on basal heart rate in posttraumatic stress disorder.

OBJECTIVE: Evidence of elevated basal heart rate (HR) in posttraumatic stress disorder (PTSD) has been interpreted in terms of elevated sympathetic cardiac activity, as have possible increased cardiovascular disease risks and outcomes associated with elevated HR. Yet it is well-established that the parasympathetic branch of the autonomic nervous system not only influences HR independently of the sympathetic branch, but makes a greater contribution to HR, including resting HR. Additionally, abnormally low tonic parasympathetic activity on the heart has been implicated in cardiovascular disease and hypertension. This study addressed a potential parasympathetic contribution to elevated basal HR in PTSD. METHODS: We used a descriptive and subgroup differences approach to investigate relationships between parasympathetic activity and basal HR in 59 adults (50 females) with PTSD, all of whom were participants in a treatment outcome study and assessed prior to exposure to trauma-related script-driven imagery. Consistent with the well-known relationship between parasympathetic activity and HR, we hypothesized that basal respiratory sinus arrhythmia (RSA), a measure of parasympathetic cardiac activity, would be negatively correlated with basal HR. More important, we predicted that pathologically elevated HRs previously associated with PTSD would only characterize a low-RSA subgroup. Potential confounds of age, respiration rate, and aerobic fitness were addressed. RESULTS: As predicted, mean HR was 80.5 bpm in the low-RSA tercile group, similar to mean HRs of PTSD groups in prior research and significantly higher than 69 and 65 bpm in the middle- and high-RSA groups, respectively, which are typical of non-PTSD controls. CONCLUSION: These findings suggest that a substantial proportion of those with PTSD may not have elevated basal HRs. Furthermore, among those who do exhibit elevated HR, there may be a parasympathetic contribution that is independent of any sympathetic one. Only measuring both branches at once, ideally with autonomic blockades, can definitively address these issues.

DESNOS in three postconflict settings: assessing cross-cultural construct equivalence.

This study examined the cross-cultural construct equivalence of the Structured Interview for Disorders of Extreme Stress (SIDES), an instrument designed to assess symptoms of Disorders of Extreme Stress Not Otherwise Specified (DESNOS). Participants completed the SIDES as a part of an epidemiological survey conducted between 1997 and 1999 among survivors of war or mass violence in Algeria (n = 652), Ethiopia (n = 1,200), and Gaza (n = 585). Findings indicated that the factor structure of the SIDES across samples was not stable; thus construct equivalence was not shown. A multistep interdisciplinary method is proposed to improve the cross-cultural construct validity of a psychiatric concept. This method accommodates universal chronic sequelae of extreme stress and accommodates culture-specific symptoms across a variety of cultures.

Disorders of extreme stress: The empirical foundation of a complex adaptation to trauma.

Children and adults exposed to chronic interpersonal trauma consistently demonstrate psychological disturbances that are not captured in the posttraumatic stress disorder (PTSD) diagnosis. The DSM-IV (American Psychiatric Association, 1994) Field Trial studied 400 treatment-seeking traumatized individuals and 128 community residents and found that victims of prolonged interpersonal trauma, particularly trauma early in the life cycle, had a high incidence of problems with (a) regulation of affect and impulses, (b) memory and attention, (c) self-perception, (d) interpersonal relations, (e) somatization, and (f) systems of meaning. This raises important issues about the categorical versus the dimensional nature of posttraumatic stress, as well as the issue of comorbidity in PTSD. These data invite further exploration of what constitutes effective treatment of the full spectrum of posttraumatic psychopathology.

Posttraumatic stress disorder treatment outcome research: The study of unrepresentative samples?

The authors review sample composition and enrollment data for 34 studies cited in the International Society for Traumatic Stress Studies (ISTSS) 2000 Practice Guidelines as meeting the Level A U.S. Agency for Health Care Policy and Research (AHCPR) classification for treatment of adult posttraumatic stress disorder (PTSD), and compare data from more recent research. Findings reveal that many published reports omitted vital data including exclusion criteria and rates, demographics, and trauma exposure history. Moreover, severe comorbid psychopathology, a common feature of treatment-seeking individuals with PTSD, emerged as the predominant reason for exclusion across studies. Subsequently published studies exhibited improved reporting of sample characteristics and demonstrated comparable outcomes despite inclusion of more diverse trauma exposure samples. Findings indicate the need for future efficacy research to adopt more comprehensive reporting requirements and to test the applicability of validated treatments to individuals suffering from as yet unstudied combinations of PTSD and prevalent comorbid disorders.

Memory fragmentation in dissociative identity disorder.

This study examined the quality of self-reported memories of traumatic experiences in participants with dissociative identity disorder (DID) and compared them with their memories of non-traumatic, but emotionally significant life experiences. Systematic interview data were gathered from 30 DID patients in The Netherlands. All participants reported a history of severe childhood abuse; 93.3% reported some period of amnesia for the index traumatic event, and 33.3% reported periods of amnesia for significant non-traumatic childhood experiences. All participants who had been amnestic for their trauma reported that their memories were initially retrieved in the form of somatosensory flashbacks. This suggests that, like PTSD patients, DID patients at least initially recall their trauma not as a narrative, but as somatosensory re-experiencing. Surprisingly, however, DID participants also recalled emotionally charged non-traumatic life events with significant somatosensory components, a phenomenon that has not been previously reported. This finding raises important issues regarding basic memory processing abnormalities in DID patients.