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Sex Differences in Peritraumatic Inflammatory Cytokines and Steroid Hormones Contribute to Prospective Risk for Nonremitting Posttraumatic Stress Disorder

Women are at higher risk for developing posttraumatic stress disorder (PTSD) compared to men, yet little is known about the biological contributors to this sex difference. One possible mechanism is differential immunological and neuroendocrine responses to traumatic stress exposure. In the current p...

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Autores principales: Lalonde, Chloe S., Mekawi, Yara, Ethun, Kelly F., Beurel, Eleonore, Gould, Felicia, Dhabhar, Firdaus S., Schultebraucks, Katharina, Galatzer-Levy, Isaac, Maples-Keller, Jessica L., Rothbaum, Barbara O., Ressler, Kerry J., Nemeroff, Charles B., Stevens, Jennifer S., Michopoulos, Vasiliki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477354/
https://www.ncbi.nlm.nih.gov/pubmed/34595364
http://dx.doi.org/10.1177/24705470211032208
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author Lalonde, Chloe S.
Mekawi, Yara
Ethun, Kelly F.
Beurel, Eleonore
Gould, Felicia
Dhabhar, Firdaus S.
Schultebraucks, Katharina
Galatzer-Levy, Isaac
Maples-Keller, Jessica L.
Rothbaum, Barbara O.
Ressler, Kerry J.
Nemeroff, Charles B.
Stevens, Jennifer S.
Michopoulos, Vasiliki
author_facet Lalonde, Chloe S.
Mekawi, Yara
Ethun, Kelly F.
Beurel, Eleonore
Gould, Felicia
Dhabhar, Firdaus S.
Schultebraucks, Katharina
Galatzer-Levy, Isaac
Maples-Keller, Jessica L.
Rothbaum, Barbara O.
Ressler, Kerry J.
Nemeroff, Charles B.
Stevens, Jennifer S.
Michopoulos, Vasiliki
author_sort Lalonde, Chloe S.
collection PubMed
description Women are at higher risk for developing posttraumatic stress disorder (PTSD) compared to men, yet little is known about the biological contributors to this sex difference. One possible mechanism is differential immunological and neuroendocrine responses to traumatic stress exposure. In the current prospective study, we aimed to identify whether sex is indirectly associated with the probability of developing nonremitting PTSD through pro-inflammatory markers and whether steroid hormone concentrations influence this effect. Female (n = 179) and male (n = 197) trauma survivors were recruited from an emergency department and completed clinical assessment within 24 h and blood samples within ∼three hours of trauma exposure. Pro-inflammatory cytokines (IL-6, IL-1 [Formula: see text] , TNF, IFNγ), and steroid hormone (estradiol, testosterone, progesterone, cortisol) concentrations were quantified in plasma. Compared to men, women had a higher probability of developing nonremitting PTSD after trauma (p = 0.04), had lower pro-inflammatory cytokines and testosterone (p’s<0.001), and had higher cortisol and progesterone (p’s<0.001) concentrations. Estradiol concentrations were not different between the sexes (p = 0.24). Pro-inflammatory cytokines were a significant mediator in the relationship between sex and probability of developing nonremitting PTSD (p < 0.05), such that men had higher concentrations of pro-inflammatory cytokines which were associated with lower risk of nonremitting PTSD development. This effect was significantly moderated by estradiol (p < 0.05), as higher estradiol levels in men were associated with higher pro-inflammatory cytokine concentrations and lower risk for developing nonremitting PTSD. The current results suggest that sex differences in the pro-inflammatory cytokine response to trauma exposure partially mediate the probability of developing nonremitting PTSD, and that the protective ability to mount an pro-inflammatory cytokine response in men may depend on higher estradiol levels in the aftermath of trauma exposure.
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spelling pubmed-84773542021-09-29 Sex Differences in Peritraumatic Inflammatory Cytokines and Steroid Hormones Contribute to Prospective Risk for Nonremitting Posttraumatic Stress Disorder Lalonde, Chloe S. Mekawi, Yara Ethun, Kelly F. Beurel, Eleonore Gould, Felicia Dhabhar, Firdaus S. Schultebraucks, Katharina Galatzer-Levy, Isaac Maples-Keller, Jessica L. Rothbaum, Barbara O. Ressler, Kerry J. Nemeroff, Charles B. Stevens, Jennifer S. Michopoulos, Vasiliki Chronic Stress (Thousand Oaks) Original Article Women are at higher risk for developing posttraumatic stress disorder (PTSD) compared to men, yet little is known about the biological contributors to this sex difference. One possible mechanism is differential immunological and neuroendocrine responses to traumatic stress exposure. In the current prospective study, we aimed to identify whether sex is indirectly associated with the probability of developing nonremitting PTSD through pro-inflammatory markers and whether steroid hormone concentrations influence this effect. Female (n = 179) and male (n = 197) trauma survivors were recruited from an emergency department and completed clinical assessment within 24 h and blood samples within ∼three hours of trauma exposure. Pro-inflammatory cytokines (IL-6, IL-1 [Formula: see text] , TNF, IFNγ), and steroid hormone (estradiol, testosterone, progesterone, cortisol) concentrations were quantified in plasma. Compared to men, women had a higher probability of developing nonremitting PTSD after trauma (p = 0.04), had lower pro-inflammatory cytokines and testosterone (p’s<0.001), and had higher cortisol and progesterone (p’s<0.001) concentrations. Estradiol concentrations were not different between the sexes (p = 0.24). Pro-inflammatory cytokines were a significant mediator in the relationship between sex and probability of developing nonremitting PTSD (p < 0.05), such that men had higher concentrations of pro-inflammatory cytokines which were associated with lower risk of nonremitting PTSD development. This effect was significantly moderated by estradiol (p < 0.05), as higher estradiol levels in men were associated with higher pro-inflammatory cytokine concentrations and lower risk for developing nonremitting PTSD. The current results suggest that sex differences in the pro-inflammatory cytokine response to trauma exposure partially mediate the probability of developing nonremitting PTSD, and that the protective ability to mount an pro-inflammatory cytokine response in men may depend on higher estradiol levels in the aftermath of trauma exposure. SAGE Publications 2021-09-23 /pmc/articles/PMC8477354/ /pubmed/34595364 http://dx.doi.org/10.1177/24705470211032208 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Article
Lalonde, Chloe S.
Mekawi, Yara
Ethun, Kelly F.
Beurel, Eleonore
Gould, Felicia
Dhabhar, Firdaus S.
Schultebraucks, Katharina
Galatzer-Levy, Isaac
Maples-Keller, Jessica L.
Rothbaum, Barbara O.
Ressler, Kerry J.
Nemeroff, Charles B.
Stevens, Jennifer S.
Michopoulos, Vasiliki
Sex Differences in Peritraumatic Inflammatory Cytokines and Steroid Hormones Contribute to Prospective Risk for Nonremitting Posttraumatic Stress Disorder
title Sex Differences in Peritraumatic Inflammatory Cytokines and Steroid Hormones Contribute to Prospective Risk for Nonremitting Posttraumatic Stress Disorder
title_full Sex Differences in Peritraumatic Inflammatory Cytokines and Steroid Hormones Contribute to Prospective Risk for Nonremitting Posttraumatic Stress Disorder
title_fullStr Sex Differences in Peritraumatic Inflammatory Cytokines and Steroid Hormones Contribute to Prospective Risk for Nonremitting Posttraumatic Stress Disorder
title_full_unstemmed Sex Differences in Peritraumatic Inflammatory Cytokines and Steroid Hormones Contribute to Prospective Risk for Nonremitting Posttraumatic Stress Disorder
title_short Sex Differences in Peritraumatic Inflammatory Cytokines and Steroid Hormones Contribute to Prospective Risk for Nonremitting Posttraumatic Stress Disorder
title_sort sex differences in peritraumatic inflammatory cytokines and steroid hormones contribute to prospective risk for nonremitting posttraumatic stress disorder
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477354/
https://www.ncbi.nlm.nih.gov/pubmed/34595364
http://dx.doi.org/10.1177/24705470211032208
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