Fear-based disorders, such as anxiety and traumatic stress disorders are associated with lost productivity, increased health care utilization, and mortality. Fear memories are thought to underlie these disorders and are central to their treatment. Current evidence-based treatments for these disorders attempt to offset existing fear memories with new memories of safety. Although this is relatively effective, the original fear memories are maintained and fear can return for various reasons. Targeting the original fear memories themselves would theoretically lead to a permanent, or at least more powerful, change in fear. It has long been assumed that once fear memories are consolidated, they are not susceptible to change. Recent research, however, has revealed that when memories are reactivated, they go through a process called reconsolidation when they are once again malleable and susceptible to modification. Fear conditioning studies in animals and humans support that the reconsolidation of conditioned fear memories can be interrupted and the return of fear can be prevented using a non-pharmacological paradigm of memory reactivation coupled with exposure called post-retrieval extinction (PRE). It remains to be studied, however, whether PRE would be effective for clinical fear memories, which are stronger and more complex. Researchers have begun to explore whether memory strength impacts the efficacy of PRE in animals;some have named this a """"""""boundary condition"""""""" to PRE, while others suggest that stronger memories may be more resistant, but not immune to disruption via PRE. Furthermore, no studies have applied PRE to an anxious population, a step that is necessary to bridge the gap between this compelling research and ultimate application of these findings to clinical intervention with anxiety and traumatic stress disorder populations. Through a series of fear conditioning studies with anxious individuals, this application aims to: 1) replicate the efficacy f PRE for 1x conditioned fear memories, 2) explore the efficacy of PRE for stronger (3x conditioned) fear memories, and 3) investigate a method to enhance the administration of PRE for stronger fear memories. As research suggests that the hippocampus may be involved in modulating the efficacy of PRE, we will also explore this hypothesis in the context of our research. Lastly, we will explore whether PRE appears to have differential effects among individuals of various dimensions of anxiety symptoms. This project will examine a potential method to intervene on fear, a construct within the negative valence domain of the NIMH Research Domain Criteria, which underlies many psychological disorders. In addition, the proposed project will allow the applicant to gain hands-on training with fear conditioning and psychophysiological data collection methods and develop her knowledge of translational research, memory reconsolidation, and the treatment of anxiety and traumatic stress disorders. In combination with relevant coursework and mentorship, this training grant will aid in the applicant's long-term goal of applying translational research to develop novel and effective interventions for fear-related disorders.
Fear-based disorders, such as anxiety and traumatic stress disorders, encompass the most common class of mental health disorders affecting the adult population and result in significant individual and societal costs. Current exposure-based psychosocial treatments offer clear benefits to patients with anxiety and traumatic stress disorders, but additional strategies are needed to improve treatment outcome and resistance to relapse. This study draws from animal research and aims to examine the efficacy and boundaries of a novel intervention strategy, called post-retrieval extinction, to diminish fear memories and reduce the return of fear in individuals with anxiety and traumatic stress disorders.
|Kredlow, M Alexandra; Unger, Leslie D; Otto, Michael W (2016) Harnessing reconsolidation to weaken fear and appetitive memories: A meta-analysis of post-retrieval extinction effects. Psychol Bull 142:314-36|
|Otto, Michael W; Kredlow, M Alexandra; Smits, Jasper A J et al. (2016) Enhancement of Psychosocial Treatment With D-Cycloserine: Models, Moderators, and Future Directions. Biol Psychiatry 80:274-83|