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Author Notes:

Correspondence: Tanja Jovanovic, PhD, Associate in Psychiatry, Emory University, Department of Psychiatry and Behavioral Sciences, 49 Jesse Hill Jr Dr, Atlanta, GA 30303; Phone: (404)778-1485; Email: tjovano@emory.edu

Acknowledgments: We thank Allen Graham, BA, Joshua Castleberry, BS, Daniel Crain, BS, Abby Powers, BS, Rachel Herschenberg, BS as well as the nurses and staff of the Grady GCRC for their assistance with data collection and support.

Disclosures: Ms. Blanding, Ms. Phifer and Dr. Weiss have no financial disclosures or conflicts of interest.

Dr. Duncan reported consultations for Bristol-Myers Squibb; and honoraria from Janssen Pharmaceutica.

Dr. Davis reported consultations for AstraZeneca and Tikvah Therapeutics; honoraria from AstraZeneca; and a patent pending with Tikvah Therapeutics.

Dr. Ressler reported a consulting agreement with Tikvah Therapeutics.


Research Funding:

Funding for this study was provided by NIMH grants (MH071537 and MH47840), NIH National Centers for Research Resources (M01 RR00039), and the Burroughs Wellcome Fund

Dr. Jovanovic has research support from NIMH (F32 MH070129).

Dr. Norrholm has research support from the National Alliance for Research on Schizophrenia and Depression (NARSAD), the Department of Defense (DOD)/Congressionally Directed Medical Research Program (CDMRP), and the Emory University Research Committee.

Dr. Duncan reported research support from VA Merit Review Program; NIDA (R01 DA018294); NIMH (R01 MH078775, R01 MH070880, R01 MH07 1537, P50 MH 058922); Janssen Pharmaceutica; Eli Lilly; Abbott Laboratories; Bristol-Myers Squibb

Dr. Bradley reported research support from American Foundation for Suicide Prevention.

Dr. Davis reported research support from AstraZeneca; NIMH (R37 MH47840, U19 MH06905602, P50 MH058922, R01 MH070880, P50 MH52384, R01 DA018294, R21 MH076869)

Dr. Ressler reported research support from NIMH (MH071537); NIH National Centers for Research Resources (M01 RR00039); NIDA; NARSAD; Burroughs Wellcome Foundation; Lundbeck


  • PTSD
  • Trauma
  • Physiology
  • Startle Response
  • HPA
  • Cortisol

Fear Potentiation is Associated With Hypothalamic-Pituitary-Adrenal Axis Function in PTSD


Journal Title:



Volume 35, Number 6


, Pages 846-857

Type of Work:

Article | Post-print: After Peer Review


Summary A central problem in posttraumatic stress disorder (PTSD) is the inability to suppress fear under safe conditions. We have previously shown that PTSD patients cannot inhibit conditioned fear. Another relevant finding in PTSD is the hypersensitivity of the hypothalamic-pituitary adrenal (HPA) axis feedback. Given their common neurobiological pathways, alterations in HPA function in PTSD may be associated with impaired fear inhibition. The present study examined the relationship between HPA axis function and fear-potentiated startle and inhibition of conditioned fear in trauma-exposed individuals. We used a conditional discrimination procedure (AX+/BX−), in which one set of shapes (AX+) was paired with aversive airblasts to the throat (danger signal), and the same X shape with a different shape (BX−) were presented without airblasts (safety signal). The paradigm also included a transfer of fear inhibition test (AB). In addition to fear-potentiated startle, blood was drawn for neuroendocrine analysis and the dexamethasone suppression test (DEX) was performed; cortisol and ACTH were assessed at baseline and post-DEX. Ninety highly traumatized individuals recruited from Grady Hospital in Atlanta, GA participated in the study. The sample was divided into those who met DSM-IV criteria for PTSD (n=29) and Non-PTSD controls (n=61) using the PTSD symptom scale (PSS). Both groups showed significant reduction in cortisol and ACTH levels after DEX. Subjects with PTSD had higher fear-potentiated startle to the safety signal, BX− (F(1,88)=4.44, p<0.05) and fear inhibition trials, AB (F(1,88)=5.20, p<0.05), both indicative of less fear inhibition in the presence of B, compared to control subjects. In addition, fear-potentiated startle to AX+, BX−, and AB was positively correlated with baseline and post-DEX ACTH in PTSD subjects. These results suggest that impaired fear inhibition and associated alterations in HPA feedback may reflect amygdala hyperactivity in subjects with PTSD.

Copyright information:

© 2009 Elsevier Ltd. Published by Elsevier Ltd. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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