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

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. •The current prospective longitudinal study assessed the consequence of prolonged trauma exposure on GR mRNA expression in early-career police recruits (n = 112).•The more traumatic events were experienced during police training the stronger GR mRNA expression was increased.•Increases in GR mRNA expression were associated with blunted HPA-axis stress-reactivity at follow-up compared to baseline.•First longitudinal evidence of a dose-response relationship between trauma and human GR mRNA expression changes.