Randomized controlled experimental study of hydrocortisone and D-cycloserine effects on fear extinction in PTSD - PubMed (original) (raw)
Randomized Controlled Trial
. 2022 Oct;47(11):1945-1952.
doi: 10.1038/s41386-021-01222-z. Epub 2021 Nov 19.
Affiliations
- PMID: 34799682
- PMCID: PMC9485259
- DOI: 10.1038/s41386-021-01222-z
Randomized Controlled Trial
Randomized controlled experimental study of hydrocortisone and D-cycloserine effects on fear extinction in PTSD
Sabra S Inslicht et al. Neuropsychopharmacology. 2022 Oct.
Abstract
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.
© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
Conflict of interest statement
The authors declare no competing interests.
Figures
Fig. 1. Timeline of study procedures.
Psychophysiological testing occurred over 3 sessions. These included: Session 1: Habituation and fear conditioning. Session 2: Drug administration and fear extinction learning. Session 2 was scheduled 72 h following fear conditioning. A single dose of HC 25 mg, DCS 50 mg or placebo was administered 1 hr prior to extinction learning. Session 3: Extinction retention was tested 1 week after extinction learning.
Fig. 2. All study trials by group.
Group mean skin conductance response scores for the conditioned stimulus (CS) intervals of CS+ and CS− trials during habituation, fear conditioning, extinction learning, and extinction retention. Data was converted to z scores to correct for variability in each participant’s range of responses.
Fig. 3. CS+/CS− difference for extinction learning and retention by group.
CS+/CS− difference for early and late extinction (first 5 CS+ and 5 CS− trials and second 5 CS+ and 5 CS− trials) and retention (first 4 CS+ and 4 CS− trials) by group: Differential scores (CS+ minus CS−) for the conditioned stimulus (CS) intervals during the extinction learning and retention phases for each drug condition. Plotted values are marginal effects from the mixed models.