我们最近证明,在合并恐惧灭绝学习期间进行的中等强度有氧运动减少了患有创伤后应激障碍(PTSD)的女性的灭绝回忆测试中的威胁预期。这些发现表明,运动可能是提高基于暴露疗法疗效的潜在候选者。它们被假设通过恐惧灭绝学习的机制起作用。此二次分析的目的是检查运动是否引起候选生物标志物循环浓度的增加:内源性大麻素(anandamide[AEA];2-花生四酰基甘油[2-AG],脑源性神经营养因子(BDNF),高香草酸(HVA),调解运动对灭绝召回的影响。
参与者(N=35)完成了为期3天的恐惧获取(第1天),灭绝(第2天),和灭绝召回(第3天)协议,其中参与者被随机分配到灭绝训练后(第2天)完成中等强度有氧运动(EX)或光强度控制(CON)条件.在EX或CON之前和之后获得血液。灭绝召回测试期间的威胁预期评级(即,最初的恐惧回忆和恢复后的恐惧回忆)在EX或CON后24小时获得。使用线性混合效应模型和间接效应的引导来测试中介。
发现循环浓度的AEA和BDNF(但不是2-AG和HVA)介导中等强度有氧运动与恢复后威胁预期等级降低之间的关系(AEA95%CI:-0.623至-0.005;BDNF95%CI:-0.941至-0.005)。
运动引起的外周AEA和BDNF的增加似乎在增强恐惧灭绝学习的巩固中发挥作用,从而导致创伤后应激障碍妇女复职后威胁预期减少。未来的机械研究检查这些和其他生物标志物(例如,基于大脑的生物标志物)是有必要的。
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.
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.
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).
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.