Impact of Stress and Exercise on Fear Extinction.

This chapter reviews the literature on the impact of stress and exercise on fear extinction. Given that key brain regions of the fear circuitry (e.g., hippocampus, amygdala and frontal cortex) can be modulated by stress hormones, it is important to investigate how stress influences this process. Laboratory-based studies performed in healthy adults have yielded mixed results, which are most likely attributable to various methodological factors. Among these factors, inter-individual differences modulating the stress response and timing of stressor administration with respect to the task may contribute to this heterogeneity. Given that fear is a core manifestation of various psychopathologies and that exposure-based therapy relies on fear extinction principles, several studies have attempted to assess the role of stress hormones on exposure-based therapy in patients suffering from post-traumatic stress disorder or anxiety disorders. These studies tend to suggest a beneficial impact of stress hormones (through either natural endogenous variations or synthetic administration) on exposure-based therapy as assessed mostly by subjective fear measures. Similar to stress, exercise can have an impact on many physiological and biological systems in humans. Of note, exercise modulates biomarkers such as brain-derived neurotrophic factor (BDNF) and anandamide (EAE) that act on brain regions implicated in the fear circuitry, supporting the importance of studying the impact of exercise on fear extinction. Overall, the results converge and indicate that fear extinction (tested in the laboratory or via exposure-based therapy in clinical populations) can be enhanced with exercise. Further research is needed to understand the mechanisms by which stress and exercise modulate fear learning and extinction processes, as well as to maximize the applicability to clinical contexts.