Time of trauma prospectively affects PTSD symptom severity: The impact of circadian rhythms and cortisol

• Type of Material: Article
• Authors: Evelina Sterina, Emory University; Vasiliki Michopoulos, Emory University; Sarah D Linnstaedt, Department of Anesthesiology, Institute of Trauma Recovery, UNC School of Medicine, Chapel Hill, NC, USA.; Thomas C Neylan, University of California San Francisco; Gari Clifford, Emory University; Kelly Ethun, Emory University; Adriana Lori, Emory University; Aliza Wingo, Emory University; Barbara Rothbaum, Emory University; Kerry J Ressler, Department of Psychiatry, McLean Hospital, Boston, MA, USA.; Jennifer Stevens, Emory University
• Language: English
• Date: 2022-04-09
• Publisher: PERGAMON-ELSEVIER SCIENCE LTD
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.psyneuen.2022.105729
• Title of Journal or Parent Work: PSYCHONEUROENDOCRINOLOGY
• Volume: 141
• Start Page: 105729
• End Page: 105729
• Grant/Funding Information: This work was supported in part by the National Center for Advancing Translational Sciences UL1TR002378 (ES) and TL1TR002382 (ES); National Institute of Mental Health R01MH096764 (KJR).
• Keywords: MEMORY; PERIOD; Psychiatry; Life Sciences & Biomedicine; POSTTRAUMATIC-STRESS-DISORDER; Neurosciences; Endocrinology & Metabolism; Neurosciences & Neurology; RESPONSES; Science & Technology; GLUCOCORTICOIDS; PERIPHERAL-TISSUES; EXPRESSION
• Research Categories: Health Sciences, Medicine and Surgery; Engineering, Biomedical; Health Sciences, Pathology

Abstract

A key feature of posttraumatic stress disorder (PTSD) is a disruption of hypothalamic-pituitary-adrenal (HPA) axis feedback sensitivity and cortisol levels. Despite known diurnal rhythmicity of cortisol, there has been little exploration of the circadian timing of the index trauma and consequent cortisol release. Stress-related glucocorticoid pulses have been shown to shift clocks in peripheral organs but not the suprachiasmatic nucleus, uncoupling the central and peripheral clocks. A sample of 425 participants was recruited in the Emergency Department following a DSM-IV-TR Criterion A trauma. The Zeitgeber time of the trauma was indexed in minutes since sunrise, which was hypothesized to covary with circadian blood cortisol levels (high around sunrise and decreasing over the day). Blood samples were collected M(SD)= 4.0(4.0) hours post-trauma. PTSD symptoms six months post-trauma were found to be negatively correlated with trauma time since sunrise (r(233) = −0.15, p = 0.02). The effect remained when adjusting for sex, age, race, clinician-rated severity, education, pre-trauma PTSD symptoms, and time of the blood draw (β = -0.21, p = 0.00057). Cortisol levels did not correlate with blood draw time, consistent with a masking effect of the acute stress response obscuring the underlying circadian rhythm. Interactions between trauma time and expression of NPAS2 (punadjusted=0.042) and TIMELESS (punadjusted=0.029) predicted six-month PTSD symptoms. The interaction of trauma time and cortisol concentration was significantly correlated with the expression of PER1 (padjusted=0.029). The differential effect of time of day on future symptom severity suggests a role of circadian effects in PTSD development, potentially through peripheral clock disruption.