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

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, BMI, race, clinician-rated severity, education, pre-trauma PTSD symptoms, and trauma type (b=-0.21, p=0.00061). 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 ARNTL (punadj=0.043) and TIMELESS(punadj=0.010) predicted six-month PTSD symptoms. The interaction of trauma time and cortisol concentration was significantly correlated with the expression of PER1 (punadj = 1.4x10^-3).  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

Table of Contents

Table of Contents

INTRODUCTION

METHODS

Participants

Assessment

Blood collection and assay of cortisol and mRNA

Data Analysis

Time of Trauma

Cortisol

Gene Expression

RESULTS

Sample characteristics

Association between time of trauma and 6-month PTSD symptom severity

Association between gene expression and time of trauma, cortisol, and 6-month PTSD symptom severity

Interaction between trauma timing and cortisol in predicting expression of circadian genes

Interaction of trauma timing and expression of circadian genes in predicting PTSD severity

DISCUSSION

AUTHOR CONTRIBUTIONS

REFERENCES

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About this Master's Thesis

Rights statement

• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Laney Graduate School
Department	Clinical Research
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Biology, Neuroscience Psychology, Physiological Psychology, Psychobiology
Palabra Clave	ptsd circadian
Committee Chair / Thesis Advisor	Jennifer Stevens, Emory University
Committee Members	Amita Manatunga, Emory University Jennifer Felger, Emory University

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