Trauma-induced human glucocorticoid receptor expression increases predict subsequent HPA-axis blunting in a prospective longitudinal design

Lycia D de Voogd; Rosalie Anne Kampen; Reinoud Kaldewaij; Wei Zhang; Mahur Melina Hashemi; Saskia B J Koch; Floris Klumpers; Jeffrey C Glennon; Karin Roelofs

doi:10.1016/j.psyneuen.2022.105909

Trauma-induced human glucocorticoid receptor expression increases predict subsequent HPA-axis blunting in a prospective longitudinal design

Psychoneuroendocrinology. 2022 Dec:146:105909. doi: 10.1016/j.psyneuen.2022.105909. Epub 2022 Aug 30.

Authors

Lycia D de Voogd¹, Rosalie Anne Kampen², Reinoud Kaldewaij³, Wei Zhang³, Mahur Melina Hashemi³, Saskia B J Koch³, Floris Klumpers⁴, Jeffrey C Glennon⁵, Karin Roelofs⁴

Affiliations

¹ Donders Institute, Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, the Netherlands; Behavioural Science Institute, Radboud University, Nijmegen, the Netherlands. Electronic address: l.devoogd@donders.ru.nl.
² Donders Institute, Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, the Netherlands; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
³ Donders Institute, Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, the Netherlands.
⁴ Donders Institute, Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, the Netherlands; Behavioural Science Institute, Radboud University, Nijmegen, the Netherlands.
⁵ Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands; Conway Institute for Biomolecular and Biomedical Research, School of Medicine, University College Dublin, Ireland.

PMID: 36162182
DOI: 10.1016/j.psyneuen.2022.105909

Abstract

One of the hallmarks of post-traumatic stress disorder (PTSD) is abnormalities in the HPA-axis. This includes alterations in its negative feedback regulation. Although altered glucocorticoid receptor (GR) mRNA expression is thought to play a crucial role herein, direct longitudinal evidence in humans is lacking to support this assumption. The current prospective longitudinal study assessed the consequence of repeated trauma exposure on GR mRNA expression from saliva samples in early-career police recruits (n = 112) by assessing them before and after trauma exposure. We did not observe a relationship between change in GR mRNA expression and development of PTSD symptom severity. However, the more traumatic events were experienced during police training the stronger GR mRNA expression was increased. Moreover, increases in GR mRNA expression were associated with blunted HPA-axis stress-reactivity at follow-up compared to baseline. This study provides the first longitudinal evidence of a dose-response relationship between trauma and human GR mRNA expression (extracted from saliva) changes; therefore, replication is warranted. Our finding might contribute a possible explanatory framework for blunted HPA-axis function associated with PTSD.

Keywords: Cortisol; Glucocorticoid receptor; HPA; PTSD; Trauma; mRNA.