Impaired action-safety learning and excessive relief during avoidance in patients with anxiety disorders.

Anxiety-related disorders are characterized by high levels of avoidance, but experimental research into avoidance learning in patients is scarce. To fill this gap, we compared healthy controls (HC, n = 47) with patients with obsessive-compulsive disorder (OCD, n = 33), panic disorder with agoraphobia (PDA, n = 40), and post-traumatic stress disorder (PTSD, n = 66) in a computer-based avoidance learning task, in order to examine (1) differences in rates of avoidance responses, (2) differences in action-safety learning during avoidance, and (3) differences in subjective relief following successful avoidance. The task comprised aversive negative pictures (unconditional stimulus, US) that followed pictures of two colored lamps (conditional stimuli, CS+), but not a third colored lamp (safety stimulus, CS-), and could be avoided by pressing a button during one CS+ (CS+ avoidable) but not the other (CS+ unavoidable). Participants rated their US-expectancy and level of relief on a trial-by-trial basis. Compared to the HC group, patient groups displayed higher levels of avoidance to the safety stimulus, and higher levels of US-expectancy and relief following the safety and avoidable danger stimulus. We propose that patients with anxiety disorders have low confidence in the safety consequences of avoidance actions, which induces increased relief during US omissions that reinforce the avoidance action.

Impact of dissociation on the effectiveness of psychotherapy for post-traumatic stress disorder: meta-analysis.

BACKGROUND: Many patients with post-traumatic stress disorder (PTSD) experience dissociative symptoms. The question of whether these dissociative symptoms negatively influence the effectiveness of psychotherapy for PTSD is unresolved. AIMS: To determine the influence of dissociative symptoms on psychotherapy outcome in PTSD. METHOD: We conducted a systematic search in Cochrane, Embase, PILOTS, PsycINFO, PubMed and Web of Science for relevant clinical trials. A random-effects meta-analysis examined the impact of dissociation on psychotherapy outcome in PTSD (pre-registered at Prospero CRD42018086575). RESULTS: Twenty-one trials (of which nine were randomised controlled trials) with 1714 patients were included. Pre-treatment dissociation was not related to treatment effectiveness in patients with PTSD (Pearson's correlation coefficient 0.04, 95% CI -0.04 to 0.13). Between-study heterogeneity was high but was not explained by moderators such as trauma focus of the psychotherapy or risk of bias score. There was no indication for publication bias. CONCLUSIONS: We found no evidence that dissociation moderates the effectiveness of psychotherapy for PTSD. The quality of some of the included studies was relatively low, emphasising the need for high-quality clinical trials in patients with PTSD. The results suggest that pre-treatment dissociation does not determine psychotherapy outcome in PTSD.

Endogenous testosterone levels are predictive of symptom reduction with exposure therapy in social anxiety disorder.

The Hypothalamus-Pituitary-Gonadal (HPG)-axis, and testosterone in particular, play an important role in social motivational behavior. Socially avoidant behavior, characteristic of social anxiety disorder (SAD), has been linked to low endogenous testosterone levels, and can be alleviated by testosterone administration in SAD. Although these beneficial effects of testosterone may translate to exposure therapy, it remains unknown whether testosterone increases prior to exposure improve therapy outcomes. In this proof-of-principle study, we tested whether pre-exposure (reactive and baseline) endogenous testosterone levels were predictive of exposure outcome in SAD. Seventy-three participants (52 females) with a principal SAD diagnosis performed four speech exposures: three during one standardized exposure therapy session and one at post-assessment one week later. Subjective fear levels were assessed before and after each speech exposure and social anxiety symptoms were assessed at pre- and post-treatment. Pre-treatment testosterone levels were assessed before (baseline) and in response to a pre-exposure instruction session (reactive). Pre-treatment testosterone levels were not related to fear levels during exposure therapy, but predicted pre- to post-treatment reductions in social anxiety symptom severity. Specifically, low baseline and high reactive pre-treatment testosterone levels were associated with larger reductions in social anxiety symptom severity. These findings support the role of HPG-axis in social fear reduction. Specifically, our finding that high reactive testosterone as well as low baseline testosterone predicted exposure outcome in SAD, suggests that good reactivity of the HPG-axis is a promising marker for the symptom-reducing effects of exposure therapy.

Improving treatment for patients with childhood abuse related posttraumatic stress disorder (IMPACT study): protocol for a multicenter randomized trial comparing prolonged exposure with intensified prolonged exposure and phase-based treatment.

BACKGROUND: Childhood abuse related posttraumatic stress disorder (CA-PTSD) is associated with a high burden of disease and with treatment response rates that leave room for improvement. One of the treatments for PTSD, prolonged exposure (PE), is effective but has high drop-out rates and remission rates are relatively low. An intensified form of PE (iPE) was associated with good response and low drop-out rates in PTSD and has not yet been tested in a controlled trial in CA-PTSD. Phase-based treatment (PBT), in which PE is preceded by skills training may improve overall outcomes in this population. We will assess the effectiveness and cost-effectiveness of standard PE, iPE and PBT in patients with CA-PTSD. METHODS/DESIGN: Multi-center randomized controlled trial. Treatment conditions are: prolonged exposure (PE; maximum of 16 sessions in 16 weeks); intensified PE (iPE; maximum of 12 sessions in four weeks and two booster sessions); phase-based treatment (PBT; maximum of eight sessions skills training followed by eight sessions PE in 16 weeks). PRIMARY OUTCOME: Clinician-rated PTSD symptom severity. SECONDARY OUTCOMES: loss of PTSD diagnosis, self-reported PTSD symptom severity, comorbid symptom severity and quality of life. Moreover, we will examine cost-effectiveness and moderators and mediators of treatment outcome. TARGET POPULATION: adults with CA-PTSD (N = 150). Assessments in weeks 0, 4, 8, 16, 26 and 52. DISCUSSION: Given that no consensus yet exists about the treatment guidelines for patients with CA-PTSD, the present study may have important implications for the treatment of CA-PTSD. TRAIL REGISTRATION: Registered at C.C.M.O. on Sept 7, 2016 (NL57984.058.16); retrospectively registered at June 21, 2017 at clinicaltrials.gov identifier: NCT03194113 .