Exercise-induced increases in Anandamide and BDNF during extinction consolidation contribute to reduced threat following reinstatement: Preliminary evidence from a randomized controlled trial. Psychoneuroendocrinology 2021 Oct;132:105355
Date
07/20/2021Pubmed ID
34280820Pubmed Central ID
PMC8487992DOI
10.1016/j.psyneuen.2021.105355Scopus ID
2-s2.0-85110337155 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
INTRODUCTION: We recently demonstrated that moderate-intensity aerobic exercise delivered during the consolidation of fear extinction learning reduced threat expectancy during a test of extinction recall among women with posttraumatic stress disorder (PTSD). These findings suggest that exercise may be a potential candidate for improving the efficacy of exposure-based therapies, which are hypothesized to work via the mechanisms of fear extinction learning. The purpose of this secondary analysis was to examine whether exercise-induced increases in circulating concentrations of candidate biomarkers: endocannabinoids (anandamide [AEA]; 2-arachidonoylglycerol [2-AG], brain-derived neurotrophic factor (BDNF), and homovanillic acid (HVA), mediate the effects of exercise on extinction recall.
METHODS: Participants (N = 35) completed a 3-day fear acquisition (day 1), extinction (day 2), and extinction recall (day 3) protocol, in which participants were randomly assigned to complete either moderate-intensity aerobic exercise (EX) or a light-intensity control (CON) condition following extinction training (day 2). Blood was obtained prior to and following EX or CON. Threat expectancy ratings during tests of extinction recall (i.e., initial fear recall and fear recall following reinstatement) were obtained 24 h following EX or CON. Mediation was tested using linear-mixed effects models and bootstrapping of the indirect effect.
RESULTS: Circulating concentrations of AEA and BDNF (but not 2-AG and HVA) were found to mediate the relationship between moderate-intensity aerobic exercise and reduced threat expectancy ratings following reinstatement (AEA 95% CI: -0.623 to -0.005; BDNF 95% CI: -0.941 to -0.005).
CONCLUSIONS: Exercise-induced increases in peripheral AEA and BDNF appear to play a role in enhancing consolidation of fear extinction learning, thereby leading to reduced threat expectancies following reinstatement among women with PTSD. Future mechanistic research examining these and other biomarkers (e.g., brain-based biomarkers) is warranted.
Author List
Crombie KM, Sartin-Tarm A, Sellnow K, Ahrenholtz R, Lee S, Matalamaki M, Almassi NE, Hillard CJ, Koltyn KF, Adams TG, Cisler JMAuthor
Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Arachidonic AcidsBrain-Derived Neurotrophic Factor
Endocannabinoids
Extinction, Psychological
Fear
Female
Humans
Polyunsaturated Alkamides
