期刊
NEUROPSYCHOPHARMACOLOGY
卷 47, 期 11, 页码 1945-1952出版社
SPRINGERNATURE
DOI: 10.1038/s41386-021-01222-z
关键词
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资金
- Department of Veteran Affairs CSRD [CDA-2-037-07F]
- Mental Illness Research and Education Clinical Center (MIRECC) of the US Veterans Health Administration
- Office of the Director, National Institutes of Health, through a UCSF-CTSI Grant [KL2 RR024130]
- German Research Foundation [OT 209/7-3, 14-1, EXC 2049]
- European Commission [IMI2 859366]
- German Federal Ministry of Education and Research [KS2017-067]
- Berlin Institute of Health [B3010350]
- Steven and Alexandra Cohen Foundation
- Cohen Veterans Bioscience
- Cohen Veterans Network
- Home Depot Foundation
- McCormick Foundation
- Robin Hood Foundation
This study found that a single dose of hydrocortisone and D-Cycloserine can facilitate fear extinction learning in individuals with PTSD symptoms, with reduced skin conductance response during extinction learning, especially in the DCS and HC groups compared to placebo. These findings suggest that glucocorticoids and NMDA agonists hold promise for enhancing extinction learning in PTSD.
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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