Cortisol awakening response in PTSD treatment: Predictor or mechanism of change

doi:10.1016/j.psyneuen.2020.104714

Psychoneuroendocrinology

Volume 118, August 2020, 104714

https://doi.org/10.1016/j.psyneuen.2020.104714 Get rights and content

Highlights

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Male combat veterans with PTSD showed lower cortisol awakening response than combat controls at baseline.
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Higher PTSD severity was also related to lower cortisol awakening response.
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When controlling for PTSD severity, higher baseline cortisol awakening response was related to attenuated reduction in PTSD over treatment.

Abstract

PTSD is associated with abnormalities in hypothalamic-pituitary-adrenal (HPA) axis activity. This includes enhanced HPA axis negative feedback, attenuated cortisol awakening response, and attenuated cortisol response to personal trauma script. Whether HPA axis function predicts treatment response or treatment related symptom reduction in PTSD remains unclear. In addition, the relative effects of different treatment modalities (i.e., medication and psychotherapy) on HPA axis is unclear. To address this gap in knowledge, the PROGrESS study examined cortisol awakening response across treatment in Veterans with chronic PTSD randomized to receive Prolonged Exposure + Placebo (PE + PLB), Sertraline + PE (SERT + PE) or Sertraline + Enhanced Medication Management (SERT + EMM). Salivary cortisol awakening response (CAR) was assessed at baseline, mid-treatment (week 6 and 12), post-treatment (week 24) and follow-up (week 36 and 52). Among males at baseline, combat veterans with PTSD showed lower CAR Area Under the Curve Increase (AUCi; M = 3.15, SD = 9.57) than Combat controls (M = 7.63, SD = 9.07; p = .02), demonstrating combat veterans with PTSD have a less responsive system than combat controls. Higher PTSD severity was also related to lower CAR AUCi (r = -0.52, p = .03). When controlling for PTSD severity, higher baseline CAR AUCi was related to attenuated reduction in PTSD and lower likelihood of high treatment response over treatment (z = -2.06, p = .04).

Section snippets

Method

The PROlonGed ExpoSure and Sertraline Trial (PROGrESS) is a randomized controlled trial (RCT) approved by site IRBs and DOD Human Research Protection Office (HRPO) and registered at ClinicalTrials.gov (NCT01524133). The current study presents planned mechanistic analyses examining CAR. PE occurred in the first 13 weeks with pills administered for 24 weeks. Follow-up occurred at 36 and 52 weeks. Readers are referred to the previously published in depth methods paper (Rauch et al., 2018) and the

Results

CAR AUCi and PTSD Severity Within Timepoints. In a mean comparison of combat Veterans with and without PTSD at baseline, we found significantly lower CAR AUCi in combat Veterans with PTSD (N = 144; M (SD) = 3.1(±9.6) than controls (N = 28; M (SD) = 7.6 (±9.1), p = 0.02). In a regression, we found that lower AUCi was related to higher CAPS (coefficient = -0.52, p = 0.03).

During follow-up, no symptom assessments were made in combat control veterans. At each follow-up, we no longer found a

Discussion

In the current study we replicated previous findings of lower CAR at baseline in PTSD patients, as well as baseline CAR relationships with PTSD symptom severity. This is important as it shows that previous studies with non-veteran samples are consistent with veterans in a relatively large sample, and validates the procedures and the potential generalizability of this finding. Specifically, finding that combat veterans with PTSD have lower cortisol than combat veterans without PTSD is an

Disclosures

Dr. Rauch receives support from Wounded Warrior Project (WWP), Department of Veterans Affairs (VA), National Institute of Health (NIH), Woodruff Foundation, and Department of Defense (DOD). Dr. Rauch receives royalties from Oxford University Press. Dr. King has nothing to disclose. Dr Kim has nothing to disclose. Dr. Powell has nothing to disclose. Ms. Rajaram has nothing to disclose. Margaret R. Venners has nothing to disclose. Dr Simon has no competing interests in relation to the manuscript

Acknowledgements

Funding: This work was supported by the U.S. Department of Defense through the U.S. Army Medical Research and Materiel Command (MRMC; Randomized Controlled Trial of Sertraline, Prolonged Exposure Therapy, and Their Combination in OEF/OIF Combat Veterans with PTSD; Award #W81XWH-11-1-0073; PI: Rauch); the National Center for Advancing Translational Sciences of the National Institutes of Health (Award #UL1TR000433). This material is the result of work supported with resources and the use of

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Published by Elsevier Ltd.

Cortisol awakening response in PTSD treatment: Predictor or mechanism of change

Highlights

Abstract

Section snippets

Method

Results

Discussion

Disclosures

Acknowledgements

J. Anxiety Disordders

Neuropsychopharmacology

J. Anxiety Disord.

Psychoneuroendocrinology

Behav. Res. Ther.

Psychoneuroendocrinology

Psychoneuroendocrinology

Contemp. Clin. Trials

Biol. Psychiatry

Psychoneuroendocrinology

Psychoneuroendocrinology

Psychoneuroendocrinology

Psychoneuroendocrinology

Higher cortisol levels following exposure to traumatic reminders in abuse-related PTSD

Neuropsychopharmacology

Prolonged Exposure Therapy for PTSD: Therapist Guide