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Cortisol and DHEA-S are associated with startle potentiation during aversive conditioning in humans

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Abstract

Rationale

Fear conditioning reliably increases the startle reflex and stress hormones, yet very little is known about the effect of stress hormones on fear-potentiated startle. Cortisol and the sulfate ester of dehydroepiandrosterone (DHEA-S) are involved in stress and anxiety. Evidence suggests that low cortisol/DHEA-S ratio has a buffering effect on stress and anxiety in preclinical and clinical studies, suggesting that there may be a relationship between fear-potentiated startle and cortisol and DHEA-S activity.

Objective

The aim of the study was to examine whether there is a relationship between cortisol/DHEA-S ratio and fear-potentiated startle.

Methods

Thirty healthy subjects participated in a differential aversive conditioning experiment during which one of two stimuli (CS+) was paired with a shock, and the other was not (CS−). Conditioned responses were assessed with the startle reflex, defined as startle potentiation during CS+ compared to CS−. DHEA-S and cortisol levels were assayed from blood samples collected in both a baseline and an aversive conditioning session. Subjective state anxiety, arousal, and valence were assessed at various times during testing.

Results

Fear-potentiated startle was larger in individuals with high compared to low cortisol/DHEA-S ratio. Multiple regression analyses revealed that fear-potentiated startle was positively associated with cortisol and negatively associated with DHEA-S. There was no significant correlation between DHEA-S and cortisol levels.

Conclusion

These data suggest that cortisol and DHEA-S are involved in fear conditioning.

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Acknowledgements

This research was supported by the Intramural Research Program of the National Institute of Mental Health.

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Authors and Affiliations

  1. NIMH/NIH/DHHS, Mood and Anxiety Disorder Program, 15K North Drive, MSC 2670, Bethesda, MD, 20892-2670, USA

    Christian Grillon, Daniel S. Pine, Megan Lawley & Valerie Ellis

  2. Department of Psychonomics, Utrecht University, P.O. Box 80.140, 3508 TC, Utrecht, The Netherlands

    Johanna M. P. Baas

  3. Mount Sinai Hospital, New York, NY, USA

    Dennis S. Charney

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  1. Christian Grillon
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  2. Daniel S. Pine
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Correspondence to Christian Grillon.

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Grillon, C., Pine, D.S., Baas, J.M.P. et al. Cortisol and DHEA-S are associated with startle potentiation during aversive conditioning in humans. Psychopharmacology 186, 434–441 (2006). https://doi.org/10.1007/s00213-005-0124-2

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