Repeated trauma exposure does not impair distress reduction during imaginal exposure for posttraumatic stress disorder.

BACKGROUND: Based on experimental research on threat extinction, individuals exposed to repeated traumatic events may have impaired outcome in exposure therapy compared to those who have experienced a single trauma (Lang & McTeague, ). This study examined whether repeated trauma exposure predicts smaller changes in self-reported distress during imaginal exposure and worse outcomes for patients with posttraumatic stress disorder (PTSD). METHODS: Adults (N = 116) with chronic PTSD received up to 10 sessions of prolonged exposure (PE) therapy. Trauma exposure was assessed via interview and number of traumatic events were summed for each participant. To examine reductions in distress during treatment, mean and peak values of distress during imaginal exposure were calculated for the first imaginal session (initial distress activation) and subsequent sessions (between-session change in distress). Change in PTSD symptoms from pre- to posttreatment and follow-up provided an additional index of outcome. RESULTS: In-session distress during imaginal exposure decreased over the course of treatment. PTSD symptoms also decreased over treatment, with gains being maintained through follow-up. Repeated trauma exposure was not significantly correlated with initial distress activation. Additionally, linear mixed-model analyses showed no significant association between repeated trauma exposure and between-session change in distress or PTSD symptoms. CONCLUSIONS: Contrary to recent speculation, repeated trauma exposure did not predict less change in self-reported distress during imaginal exposure or worse PTSD outcomes. The bench-to-bedside linkage of threat extinction to exposure therapy is discussed, noting strengths and weaknesses. Patients with repeated trauma exposure show reductions in distress with exposure treatment and benefit from PE as much as patients with single-exposure trauma histories.

Data management in clinical research: Synthesizing stakeholder perspectives.

OBJECTIVE: This study assesses data management needs in clinical research from the perspectives of researchers, software analysts and developers. MATERIALS AND METHODS: This is a mixed-methods study that employs sublanguage analysis in an innovative manner to link the assessments. We performed content analysis using sublanguage theory on transcribed interviews conducted with researchers at four universities. A business analyst independently extracted potential software features from the transcriptions, which were translated into the sublanguage. This common sublanguage was then used to create survey questions for researchers, analysts and developers about the desirability and difficulty of features. Results were synthesized using the common sublanguage to compare stakeholder perceptions with the original content analysis. RESULTS: Individual researchers exhibited significant diversity of perspectives that did not correlate by role or site. Researchers had mixed feelings about their technologies, and sought improvements in integration, interoperability and interaction as well as engaging with study participants. Researchers and analysts agreed that data integration has higher desirability and mobile technology has lower desirability but disagreed on the desirability of data validation rules. Developers agreed that data integration and validation are the most difficult to implement. DISCUSSION: Researchers perceive tasks related to study execution, analysis and quality control as highly strategic, in contrast with tactical tasks related to data manipulation. Researchers have only partial technologic support for analysis and quality control, and poor support for study execution. CONCLUSION: Software for data integration and validation appears critical to support clinical research, but may be expensive to implement. Features to support study workflow, collaboration and engagement have been underappreciated, but may prove to be easy successes. Software developers should consider the strategic goals of researchers with regard to the overall coordination of research projects and teams, workflow connecting data collection with analysis and processes for improving data quality.

Understanding heterogeneity in PTSD: fear, dysphoria, and distress.

Fear, dysphoria, and distress are prominent components in the conceptualization of posttraumatic stress disorder (PTSD). However, because our diagnostic categories are open concepts, relying on observed patterns of symptoms for classification, it is unclear whether these components represent core or auxiliary features of the disorder. Convergence across multiple indices is critical for this understanding. In this paper, we examine these components of PTSD across observed symptom patterns, broader theoretical conceptualizations, underlying information processing mechanisms of attention and memory, and underlying learning and neurobiological mechanisms. For each, evidence for similarity or distinctiveness of PTSD with other anxiety disorders and depression is examined. Throughout the review, key points of similarity to the anxiety disorders and divergence with depression argue for a distinction between core fear symptoms and auxiliary dysphoria and distress symptoms. Implications are discussed, noting that, as heterogeneity increases, core characteristics will become more diffused and ancillary constructs will gain an inflated degree of importance.

Effects of induced and naturalistic mood on the temporal allocation of attention to emotional information.

Building upon recent findings that affective states can influence the allocation of spatial attention, we investigate how state, trait and induced mood are related to the temporal allocation of attention to emotional information. In the present study, 125 unscreened undergraduates completed a modified rapid serial visual presentation task designed to assess the time course of attention to positive and negative information, comparing a neutral baseline mood induction to either a positive or negative mood induction. Induced negative mood facilitated attentional engagement to positive information while decreasing attentional engagement to negative information. Greater naturally occurring negative state mood was associated with faster or more efficient disengagement of attention from negative information in the presence of manipulated negative mood, relative to baseline. The engagement findings were inconsistent with our mood-congruence hypotheses and may be better explained by mood repair or affective counter-regulation theories. In contrast, the disengagement findings for state mood were somewhat consistent with our mood-congruence hypotheses. The relationship between mood and attention to emotional information may differ depending on the combination of attentional mechanism (engagement versus disengagement), aspect of mood (state, trait or induced), stimulus valence (positive versus negative) and timescale (early versus late) under investigation.

The impact of pretrauma analogue GAD and posttraumatic emotional reactivity following exposure to the September 11 terrorist attacks: a longitudinal study.

The relation between analogue generalized anxiety disorder (GAD) assessed the day before the events of September 11, 2001 (9/11) and long-term outcome was examined in 44 young adults who were directly exposed the following day to the terrorist attacks in New York City. After controlling for high exposure to the attacks, preattack analogue GAD was associated with greater social and work disability, loss of psychosocial resources, anxiety and mood symptoms, and worry, but not symptoms of posttraumatic stress, assessed 12 months after 9/11. Fear and avoidance of emotions assessed 4 months after 9/11 statistically mediated the relation between preattack analogue GAD and social and work disability, loss of psychosocial support, mood and anxiety symptoms, and worry at 12-month follow-up. Avoidance of emotions 4 months after 9/11 also mediated the relation between preattack analogue GAD and posttraumatic stress symptoms 12 months after 9/11.

The contributory role of worry in emotion generation and dysregulation in generalized anxiety disorder.

The role of worry in generalized anxiety disorder (GAD) has been posited to serve as an avoidance of emotional experience, and emotion regulation deficits in GAD have been found in several previous studies. It remains unclear whether those with GAD experience more dysregulated emotions during periods of euthymia and positive affect or whether these deficits occur only during periods of worry. Individuals with GAD (with and without co-occurring dysphoria) and non-anxious controls were randomly assigned to receive a worry, neutral, or relaxation induction. Following the induction, all participants viewed a film clip documented to elicit sadness. Intensity of emotions and emotion regulation were examined following the induction period and film clip. The results revealed that, regardless of co-occurring dysphoria, individuals with GAD in the worry condition experienced more intense depressed affect than GAD participants in the other conditions and controls participants. In contrast, presence of worry appeared to have less impact on indices of emotion dysregulation, which were greater in participants with GAD compared to controls, but largely insensitive to contextual effects of worry or of relaxation. Following film viewing, both GAD participants with and without dysphoria displayed poorer understanding, acceptance, and management of emotions than did controls. However, acceptance and management deficits were most pronounced in individuals with both GAD and co-occurring dysphoria. Implications for the role of emotions in conceptualization and treatment of GAD are discussed.

Enhancing Extinction Learning in Posttraumatic Stress Disorder With Brief Daily Imaginal Exposure and Methylene Blue: A Randomized Controlled Trial.

OBJECTIVE: The memory-enhancing drug methylene blue (MB) administered after extinction training improves fear extinction retention in rats and humans with claustrophobia. Robust findings from animal research, in combination with established safety and data showing MB-enhanced extinction in humans, provide a foundation to extend this work to extinction-based therapies for posttraumatic stress disorder (PTSD) such as prolonged exposure (PE). METHODS: Patients with chronic PTSD (DSM-IV-TR; N = 42) were randomly assigned to imaginal exposure plus MB (IE + MB), imaginal exposure plus placebo (IE + PBO), or waitlist (WL/standard PE) from September 2011 to April 2013. Following 5 daily, 50-minute imaginal exposure sessions, 260 mg of MB or PBO was administered. Waitlist controls received PE following 1-month follow-up. Patients were assessed using the independent evaluator-rated PTSD Symptom Scale-Interview version (primary outcome), patient-rated PTSD, trauma-related psychopathology, and functioning through 3-month follow-up. RESULTS: Both IE + MB and IE + PBO showed strong clinical gains that did not differ from standard PE at 3-month follow-up. MB-augmented exposure specifically enhanced independent evaluator-rated treatment response (number needed to treat = 7.5) and quality of life compared to placebo (effect size d = 0.58). Rate of change for IE + MB showed a delayed initial response followed by accelerated recovery, which differed from the linear pattern seen in IE + PBO. MB effects were facilitated by better working memory but not by changes in beliefs. CONCLUSIONS: The findings provide preliminary efficacy for a brief IE treatment for PTSD and point to the potential utility of MB for enhancing outcome. Brief interventions and better tailoring of MB augmentation strategies, adjusting for observed patterns, may have the potential to reduce dropout, accelerate change, and improve outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01188694.

Pharmacological treatment of anxiety disorders: current treatments and future directions.

Modern pharmacological treatments for anxiety disorders are safer and more tolerable than they were 30 years ago. Unfortunately, treatment efficacy and duration have not improved in most cases despite a greater understanding of the pathophysiology of anxiety. Moreover, innovative treatments have not reached the market despite billions of research dollars invested in drug development. In reviewing the literature on current treatments, we argue that evidence-based practice would benefit from better research on the causes of incomplete treatment response as well as the comparative efficacy of drug combinations and sequencing. We also survey two broad approaches to the development of innovative anxiety treatments:the continued development of drugs based on specific neuroreceptors and the pharmacological manipulation of fear-related memory. We highlight directions for future research, as neither of these approaches is ready for routine clinical use.

Efficacy of CBT for benzodiazepine discontinuation in patients with panic disorder: Further evaluation.

Despite its acute efficacy for the treatment of panic disorder, benzodiazepines (BZs) are associated with a withdrawal syndrome that closely mimics anxiety sensations, leading to difficulty with treatment discontinuation and often disorder relapse. An exposure-based cognitive-behavioral treatment for BZ discontinuation, Panic Control Treatment for BZ Discontinuation (CBT) targets the fear of these sensations and has demonstrated efficacy in preventing disorder relapse and facilitating successful BZ discontinuation among patients with panic disorder. In this randomized controlled trial, CBT was compared to taper alone and a taper plus a relaxation condition to control for the effect of therapist contact and support among 47 patients with panic disorder seeking taper from BZs. Based on the primary outcome of successful discontinuation of BZ use, results indicate that adjunctive CBT provided additive benefits above both taper alone and taper plus relaxation, with consistently medium and large effect sizes over time that reached significance at the six month follow-up evaluation. The efficacy of CBT relative to either of the other taper conditions reflected very large and significant effect sizes at that time. These findings suggest that CBT provides specific efficacy for the successful discontinuation from BZs, even when controlling for therapist contact and relaxation training.

Bupropion sustained release for panic disorder.

Despite anecdotal reports suggesting that bupropion may be effective for panic disorder, both clinical lore and the results of one small controlled study suggest otherwise. There remains a paucity of systematic prospective data addressing this issue. Twenty outpatients meeting criteria for panic disorder with or without agoraphobia were entered in an 8 week, two center open-label flexible dose trial of bupropion SR. Treatment with bupropion SR resulted in a clinically and statistically significant mean reduction of 1 to 2 points in the primary outcome measure, the CGI Severity score, in both the intent to treat (ITT; t=4.36, df=19, p<0.001) and completer samples (t=3.89, df=13, p<0.002). Significant improvement was also noted in both completer and ITT samples for all other panic symptom measures, which included the Panic Disorder Severity Scale (PDSS), number of panic attacks in the past two weeks, and the proportion of time anticipatory anxiety was present. Although results may be influenced by the open nature of this trial, our findings suggest that bupropion SR may be effective for the treatment of panic disorder. Further controlled study of its efficacy for this condition are warranted.