Posttraumatic stress disorder (
PTSD) is an
anxiety disorder that may develop in response to a traumatic event. Approximately 10% of
trauma-exposed individuals subsequently develop
PTSD. It is hypothesized that the development of
PTSD is associated with biological vulnerability factors, which are already present prior to the onset of symptoms. In this review we present an overview of currently identified vulnerability factors in the
glucocorticoid (GC) signaling pathway for the development of
PTSD. In addition, the implications of the identified vulnerability factors for potential preventive intervention strategies, including
glucocorticoid receptor (GR) agonists and
oxytocin, are discussed. Summarized, the findings of these studies indicate that individuals vulnerable for development of
PTSD have dysregulations on various levels of the GC-signaling cascade: i.e. low levels of circulating levels of
cortisol shortly after
trauma, high GR number in peripheral blood mononuclear cells (PBMCs), high GILZ
mRNA expression and low FKBP5 expression in PBMCs prior to
trauma, and high sensitivity of T-cells for regulation by GCs prior to
trauma. Furthermore, single nucleotide polymorphisms in the GR and FKBP5 genes have been found to be associated with increased risk for
PTSD. Collectively, the identified vulnerability factors tentatively suggest that the development of
PTSD may be preceded by a high sensitivity of various cells for regulation by GCs. The identification of these vulnerability factors may ultimately aid selective targeting of preventive interventions towards individuals at risk for
PTSD. In addition, the identification of these vulnerability factors may eventually result in new preventive pharmacological strategies for
PTSD.