Reduction of PTSD Symptoms With Pre-Reactivation Propranolol Therapy: A Randomized Controlled Trial

Mappe: Authors/Alain Brunet/2018 a

Alain Brunet, Ph.D., Daniel Saumier, Ph.D., Aihua Liu, Ph.D., David L. Streiner, Ph.D., Jacques Tremblay, M.D., Roger K. Pitman, M.D.

Objective: The authors assessed the efficacy of trauma memory reactivation performed under the influence of propranolol, a noradrenergic beta-receptor blocker, as a putative reconsolidation blocker, in reducing symptoms of posttraumatic stress disorder (PTSD).

Method:Thiswasa6-week,double-blind,placebo-controlled, randomized clinical trial in 60 adults diagnosed with longstanding PTSD. Propranolol or placebo was administered 90 minutes before a brief memory reactivation session, once a week for 6 consecutive weeks. The hypothesis predicted a significant treatment effect of trauma reactivation with propranolol compared with trauma reactivation with placebo in reducing PTSD symptoms on both the ClinicianAdministered PTSD Scale (CAPS) and the patient-rated PTSD Checklist–Specific (PCL-S) in an intention-to-treat analysis.

Results: The estimated group difference in posttreatment CAPS score, adjusted for pretreatment values (analysis of covariance), was a statistically significant 11.50. The within-group pre- to posttreatment effect sizes (Cohen’s d) were 1.76 for propranolol and 1.25 for placebo. For the PCL-S, the mixed linear model’s estimated time-by-group interaction yielded an average decrease of 2.43 points per week, for a total significant difference of 14.58pointsabovethatofplacebo.Thepre-toposttreatmenteffect sizes were 2.74 for propranolol and 0.55 for placebo. Per protocol analyses for both outcomes yielded similar significant results.

Conclusions: Pre-reactivation propranolol, a treatment protocol suggested by reconsolidation theory, appears to beanovel and efficacious treatment for PTSD. Replication studies using a long-termfollow up in various trauma populations are required.

Reconsolidation and Extinction Are Dissociable and Mutually Exclusive Processes: Behavioral and Molecular Evidence

Mappe: Boudaries

Emiliano Merlo, Amy L. Milton, Zara Y. Gooze´e, David E. Theobald, and Barry J. Everitt


Memory persistence is critically influenced by retrieval. In rats, a single presentation of a conditioned fear stimulus induces memory reconsolidation and fear memory persistence, while repeated fear cue presentations result in loss of fear through extinction. These two opposite behavioral outcomes are operationally linked by the number of cue presentations at memory retrieval. However, the behavioral properties and mechanistic determinants of the transition have not yet been explored; in particular, whether reconsolidation and extinction processes coexist or are mutually exclusive, depending on the exposure to non-reinforced retrieval events. We characterized both behaviorally and molecularly the transition from reconsolidation to extinction of conditioned fear and showed that an increase in calcineurin (CaN) in the basolateral amygdala (BLA) supports the shift from fear maintenance to fear inhibition. Gradually increasing the extent of retrieval induces a gradual decrease in freezing responses to the conditioned stimulus and a gradual increase in amygdala CaN level. This newly synthesized CaN is required for the extinction, but not the reconsolidation, of conditioned fear. During the transition from reconsolidation to extinction, we have revealed an insensitive state of the fear memory where NMDA-type glutamate receptor agonist and antagonist drugs are unable either to modulate CaN levels in the BLA or alter the reconsolidation or extinction processes. Together, our data indicate both that reconsolidation and extinction are mutually exclusive processes and also reveal the presence of a transitional, or “limbo,” state of the original memory between these two alternative outcomes of fear memory retrieval, when neither process is engaged.

Memory Reconsolidation Interference as an Emerging Treatment for Emotional Disorders: Strengths, Limitations, Challenges, and Opportunities

Tom Beckers 1 and Merel Kindt 2

Experimental research on emotional memory reconsolidation interference, or the induction of amnesia for previously established emotional memory, has a long tradition, but the potential of that research for the development of novel interventions to treat psychological disorders has been recognized only recently. Here we provide an overview of basic research and clinical studies

on emotional memory reconsolidation interference. We point out specific advantages of interventions based on memory reconsolidation interference over traditional treatment for emotional disorders. We also explain how findings from basic research suggest limitations and challenges to clinical translation that may help to understand why clinical trials have met with mixed success so far and how their success can be increased. In closing, we preview new intervention approaches beyond the induction of amnesia that the phenomenon of memory reconsolidation may afford for alleviating the burden imposed by emotional memories and comment on theoretical controversies regarding the nature of memory reconsolidation.

Reminder duration determines threat memory modification in humans

Mappe:  Authors/ D.Schiller

Daniela Schiller.  Jun 2018

Memory reminders can return a memory into an unstable state such that it will decay unless actively restabilized into long-term memory through reconsolidation. Exposure to a memory reminder, however, does not always lead to destabilization. The ‘trace dominance’ principle posits that the extent of exposure to memory reminders governs memory susceptibility to disruption. Here, we provide a first systematic investigation of reminder duration effects on threat memory modification in humans. Reminder duration was parametrically varied across 155 participants in a three-day protocol. We found that short reminders (1 s and 4 s) made the memory prone to interference from post-retrieval extinction, suggesting that the memory had been updated. In contrast, no reminder or long reminders (30 s and 3 min) made the memory resistant to such interference, and robustly return. Reminder duration therefore influences memory stability and may be a critical determinant of therapeutic efficacy.

PTSD: Extinction, Reconsolidation, and the Visual-Kinesthetic Dissociation Protocol

Mappe: teorier-protokolor/NLP/2012 a

Richard M. Gray 1 and Richard F. Liotta 1

Traumatology 18(2) 3–16 2012

Abstract Every year thousands of returning military, state, and local police officers and civilians of every description suffer from the intrusive symptoms of posttraumatic stress disorder (PTSD). Current treatments rooted largely in extinction protocols require extensive commitments of time and money and are often ineffective. This study reviews several theories of PTSD and two important mechanisms that explain when treatment does and doesn’t work: extinction and reconsolidation. It then reviews the research about and suggests an explanatory mechanism for the visual-kinesthetic dissociation protocol (V/ KD), also known as the rewind technique. The technique is notable for its lack of discomfort to the client, the possibility of being executed as a content-free intervention, its speed of operation, and its long-term, if largely anecdotal, efficacy. A case study, specific diagnostics for extinction, and reconsolidative mechanisms and suggestions for future research are pro