University of California, San Francisco, San Francisco, CA, USA.
San Francisco VA Health Care System, San Francisco, CA, USA.
Neuropsychopharmacology. 2022 Oct;47(11):1945-1952. doi: 10.1038/s41386-021-01222-z. Epub 2021 Nov 19.
Fear extinction underlies prolonged exposure, one of the most well-studied treatments for posttraumatic stress disorder (PTSD). There has been increased interest in exploring pharmacological agents to enhance fear extinction learning in humans and their potential as adjuncts to PE. The objective of such adjuncts is to augment the clinical impact of PE on the durability and magnitude of symptom reduction. In this study, we examined whether hydrocortisone (HC), a corticosteroid, and D-Cycloserine (DCS), an N-methyl-D-aspartate receptor partial agonist, enhance fear extinction learning and consolidation in individuals with PTSD. In a double-blind placebo-controlled 3-group experimental design, 90 individuals with full or subsyndromal PTSD underwent fear conditioning with stimuli that were paired (CS+) or unpaired (CS-) with shock. Extinction learning occurred 72 h later and extinction retention was tested one week after extinction. HC 25 mg, DCS 50 mg or placebo was administered one hour prior to extinction learning. During extinction learning, the DCS and HC groups showed a reduced differential CS+/CS- skin conductance response (SCR) compared to placebo (b = -0.19, CI = -0.01 to -37, p = 0.042 and b = -0.25, CI = -08 to -0.43, p = 0.005, respectively). A nonsignificant trend for a lower differential CS+/CS- SCR in the DCS group, compared to placebo, (b = -0.25, CI = 0.04 to -0.55, p = 0.089) was observed at retention testing, one week later. A single dose of HC and DCS facilitated fear extinction learning in participants with PTSD symptoms. While clinical implications have yet to be determined, our findings suggest that glucocorticoids and NMDA agonists hold promise for facilitating extinction learning in PTSD.
恐惧消退是暴露疗法的基础，暴露疗法是创伤后应激障碍（PTSD）最常用的治疗方法之一。人们越来越感兴趣的是探索药理学药物来增强人类的恐惧消退学习，以及它们作为暴露疗法的辅助手段的潜力。这些辅助手段的目的是增强暴露疗法对症状减轻的持久性和幅度的临床影响。在这项研究中，我们研究了皮质酮（HC），一种皮质类固醇，和 D-环丝氨酸（DCS），一种 N-甲基-D-天冬氨酸受体部分激动剂，是否能增强 PTSD 个体的恐惧消退学习和巩固。在一项双盲安慰剂对照的 3 组实验设计中，90 名有完全或亚综合征 PTSD 的个体接受了带有与电击配对（CS+）或不配对（CS-）的刺激的恐惧条件反射。72 小时后进行消退学习，一周后进行消退保持测试。HC 25mg、DCS 50mg 或安慰剂在消退学习前一小时给予。在消退学习期间，DCS 和 HC 组与安慰剂组相比，皮肤电反应（SCR）的 CS+/CS-差异减小（b=-0.19，CI=-0.01 至-37，p=0.042 和 b=-0.25，CI=-0.08 至-0.43，p=0.005）。在一周后的保持测试中，DCS 组与安慰剂组相比，CS+/CS- SCR 的差异也呈现出下降的趋势（b=-0.25，CI=0.04 至-0.55，p=0.089）。单次给予 HC 和 DCS 可促进 PTSD 症状参与者的恐惧消退学习。虽然临床意义尚未确定，但我们的发现表明，糖皮质激素和 NMDA 激动剂有望促进 PTSD 中的消退学习。
