Cortisol administration after extinction in a fear-conditioning paradigm with traumatic film clips prevents return of fear

Alexandra H Brueckner, Johanna Lass-Hennemann, Frank H Wilhelm, Diana S Ferreira de Sá, Tanja Michael, Alexandra H Brueckner, Johanna Lass-Hennemann, Frank H Wilhelm, Diana S Ferreira de Sá, Tanja Michael

Abstract

Cortisol is a stress hormone and potent modulator of learning and memory processes. If administered after learning, cortisol can enhance memory consolidation. Yet it is unknown whether cortisol administration after fear extinction learning strengthens extinction memory. Extinction is a crucial mechanism underlying psychotherapy of posttraumatic stress disorder (PTSD). The present study examined whether extinction can be enhanced by administering cortisol after extinction training. In a registered, randomized, double-blind and placebo controlled trial, 50 healthy participants were exposed to a differential fear-conditioning paradigm with neutral faces as conditioned stimuli (CS) and traumatic film clips as unconditioned stimuli (US). They received either cortisol (n = 25) or placebo (n = 25) immediately after extinction. The cortisol group showed less fear during a return of fear manipulation (reinstatement) evidenced by attenuated fear potentiated startle responses and US-expectancy ratings than the placebo group. Results indicate that cortisol administration after fear extinction strengthens extinction memory and suggest that it might be advantageous to administer cortisol subsequent to successful exposure treatment sessions.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1. Experimental design.
Fig. 1. Experimental design.
The experiment included three appointments on three consecutive days: acquisition (day 1), extinction (day 2), and return of fear (ROF) manipulation and ROF test (day 3). Cortisol (30 mg) or placebo was administered directly after extinction training
Fig. 2. Reinforced conditioning trials.
Fig. 2. Reinforced conditioning trials.
CS duration was 8 s. Startle probe was presented 7 s after CS onset. At CS offset either a traumatic film clip (US) or a neutral film clip as control condition (CC) was presented for 16 s
Fig. 3. Behavioral outcome measures.
Fig. 3. Behavioral outcome measures.
a US-Expectancy ratings for CS+ and CS− during ROF test for cortisol and placebo group b valence ratings for CS+ and CS− during ROF test for cortisol and placebo group (means +/− standard errors)
Fig. 4. Physiological outcome measures.
Fig. 4. Physiological outcome measures.
a Startle Response to CS+ and CS− at the end of extinction and during reinstatement test for cortisol and placebo groups b skin conductance response to CS+ and CS− at the end of extinction and during reinstatement test for cortisol and placebo groups

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