Psychophysiological treatment outcomes: Corticotropin-releasing factor type 1 receptor antagonist increases inhibition of fear-potentiated startle in PTSD patients

Psychophysiology. 2020 Jan;57(1):e13356. doi: 10.1111/psyp.13356. Epub 2019 Feb 26.


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.

Trial registration: NCT01018992.

Keywords: conditioning; fear conditioning; psychiatric; psychopathology; startle blink; stress.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Azabicyclo Compounds / administration & dosage
  • Azabicyclo Compounds / pharmacology*
  • Conditioning, Classical / drug effects*
  • Double-Blind Method
  • Fear / drug effects*
  • Female
  • Humans
  • Inhibition, Psychological*
  • Middle Aged
  • Oxadiazoles / administration & dosage
  • Oxadiazoles / pharmacology*
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Reflex, Startle / drug effects*
  • Stress Disorders, Post-Traumatic / drug therapy*
  • Stress Disorders, Post-Traumatic / physiopathology*
  • Treatment Outcome


  • Azabicyclo Compounds
  • NBI 77860
  • Oxadiazoles
  • Receptors, Corticotropin-Releasing Hormone
  • CRF receptor type 1

Associated data