Randomized controlled experimental study of hydrocortisone and D-cycloserine effects on fear extinction in PTSD.
Randomized controlled experimental study of hydrocortisone and D-cycloserine effects on fear extinction in PTSD.
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氢化可的松和D-环丝氨酸对PTSD恐惧灭绝的影响的随机对照实验研究。
DOI：
10.1038/s41386-021-01222-z
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发表时间：
2022-10
影响因子：
7.6
通讯作者：
Neylan, Thomas C.
中科院分区：
文献类型：
--
作者：
Inslicht, Sabra S.;Niles, Andrea N.;Metzler, Thomas J.;Lipshitz, Sa'ar L.;Otte, Christian;Milad, Mohammed R.;Orr, Scott P.;Marmar, Charles R.;Neylan, Thomas C.
恐惧消退是长期暴露的基础，这是对创伤后应激障碍(PTSD)研究最充分的治疗方法之一。人们对探索药理制剂以增强人类的恐惧消退学习及其作为体育辅助手段的潜力越来越感兴趣。这些辅助物的目的是增加PE在耐久性和症状减轻程度上的临床影响。在这项研究中，我们研究了皮质类固醇氢化可的松(HC)和N-甲基-D-天冬氨酸受体部分激动剂D-环丝氨酸(DC)是否能促进PTSD患者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名患有完全或亚综合征创伤后应激障碍的个体接受了恐惧条件作用，刺激是配对的(CS+)或未配对的(CS−)伴休克。72 h后开始消退学习，消退1周后进行消退保持试验。Hc25 mg、DCS50 mg或安慰剂在消退学习前1小时给予。在消退学习过程中，与安慰剂相比，DC组和HC组的CS+/CS−皮肤电导反应(SCr)显著降低(分别为b = −0.19，CI = −0.01to−37，p = 0.042和b = −0.25，CI = −08至−0.43，p = 0.005)。在一周后的保持试验中，与安慰剂组相比，dcs组的CS+/CS−血肌率差值较低(b = −为0.25，CI = 为0.04至−为0.55，p = 为0.089)，没有明显的趋势。单一剂量的HC和DC促进了有创伤后应激障碍症状的参与者的恐惧消退学习。虽然临床意义尚未确定，但我们的研究结果表明，糖皮质激素和NMDA激动剂有望促进创伤后应激障碍患者的消退学习。
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.
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Hofmann, SG;Meuret, AE;Otto, MW
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