Psychophysiological treatment outcomes: Corticotropin-releasing factor type 1 receptor antagonist increases inhibition of fear-potentiated startle in PTSD patients.
Adult
Azabicyclo Compounds
/ administration & dosage
Conditioning, Classical
/ drug effects
Double-Blind Method
Fear
/ drug effects
Female
Humans
Inhibition, Psychological
Middle Aged
Oxadiazoles
/ administration & dosage
Receptors, Corticotropin-Releasing Hormone
/ antagonists & inhibitors
Reflex, Startle
/ drug effects
Stress Disorders, Post-Traumatic
/ drug therapy
Treatment Outcome
conditioning
fear conditioning
psychiatric
psychopathology
startle blink
stress
Journal
Psychophysiology
ISSN: 1540-5958
Titre abrégé: Psychophysiology
Pays: United States
ID NLM: 0142657
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
22
05
2018
revised:
21
01
2019
accepted:
05
02
2019
pubmed:
27
2
2019
medline:
7
1
2021
entrez:
27
2
2019
Statut:
ppublish
Résumé
After exposure to a traumatic event, a subset of people develop post-traumatic stress disorder (PTSD). One of the key deficits in PTSD is regulation of fear, and impaired inhibition of fear-potentiated startle (FPS) has been identified as a potential physiological biomarker specific to PTSD. As part of a larger clinical trial, this study investigated the effects of a CRF receptor 1 antagonist, GSK561679, on inhibition of fear-potentiated startle during a conditional discrimination fear-conditioning paradigm, termed AX+/BX-. Prior research using this paradigm has demonstrated deficits in inhibition of conditioned fear in several PTSD populations. The randomized, double-blind, placebo-controlled clinical trial compared fear inhibition between female PTSD participants taking 350 mg/day GSK561679 (n = 47 pre- and 29 post-treatment) and patients taking a placebo pill (n = 52 pre- and 30 post-treatment) daily for 6 weeks. There was no significant difference between the two groups in their acquisition of fear or discrimination between threat and safety cues, and no pre-post-treatment effect on these measures. However, there was a significant effect of treatment on inhibition of FPS during the AB trials in the AX+/BX- transfer test (p < 0.05). While all PTSD participants showed typical impairments in fear inhibition prior to treatment, GSK561679 enhanced fear inhibition post-treatment, independent of clinical effects. The current study suggests that CRF receptor 1 antagonism may have specific effects within neural circuitry mediating fear inhibition responses, but not overall symptom presentation, in PTSD.
Identifiants
pubmed: 30807663
doi: 10.1111/psyp.13356
pmc: PMC6710166
mid: NIHMS1011907
doi:
Substances chimiques
Azabicyclo Compounds
0
NBI 77860
0
Oxadiazoles
0
Receptors, Corticotropin-Releasing Hormone
0
CRF receptor type 1
5CLY6W2H1M
Banques de données
ClinicalTrials.gov
['NCT01018992']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13356Subventions
Organisme : NIMH NIH HHS
ID : F32 MH070129
Pays : United States
Organisme : NIMH NIH HHS
ID : K23 MH086690
Pays : United States
Organisme : NIMH NIH HHS
ID : U19 MH069056
Pays : United States
Organisme : NIH HHS
ID : U19 MH069056
Pays : United States
Informations de copyright
© 2019 Society for Psychophysiological Research.
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