Abstract

Extinction learning is the most important underlying mechanism of exposure therapy, a cognitive-behavioral psychotherapy commonly used for the treatment of posttraumatic stress disorder and anxiety disorders. Extinction creates a new inhibitory memory, which presumably does not affect the original (e.g., fear) memory; therefore, relapse (e.g., return of fear) might occur after treatment. In recent years, various research groups aimed to augment extinction learning by the use of pharmacological adjuvants, e.g., the glucocorticoid (GC) stress hormone cortisol. However, the role of timing of treatment on relapse has remained unclear until lately. Based on recent works from our lab and additional groups, in this talk I will introduce the StaR (Stress Timing affects Relapse) model, a theoretical model of the time-dependent effects of stress/GCs on extinction memory and relapse. In particular, our findings show that (1) pre-extinction stress/GCs promote memory consolidation in a context-independent manner, making extinction memory more resistant to relapse following context change. (2) Post-extinction stress also enhances the consolidation of extinction, but in a context-bound manner. These differences may result from the timing dependent effects of cortisol on emotional memory contextualization. At the neural level, the facilitation of extinction is reflected in alterations in the amygdala-hippocampal-prefrontal cortex network. (3) Stress/GCs exposure before retrieval impairs extinction recall and promotes relapse. This may result from the stress-induced strengthening of amygdala activation, or disruption of the prefrontal cortex inhibitory functioning and its communication with additional brain regions that are crucial for extinction recall. I then discuss how the STaR model can contribute to the understanding and prevention of relapse processes.