Oktober 2012

Review over mulige prædisponerende faktorer til PTSD i glukokortikoid signalering og betydningen heraf på fremtidig præventiv farmakologisk indsats

Ætiologi, patofysiologi og risikofaktorer til PTSD er endnu ikke afdækket. Oktober måneds artikel giver mulighed for at få et overblik over litteraturen med fokus på HPA akse aktivitet og glucocorticoid receptor funktion og de farmakologiske muligheder, der i øjeblikket arbejdes på med hensyn til at forebygge PTSD hos personer udsat for potentielt tramatiserende oplevelser.

Abstract:
Posttraumatic stress disorder (PTSD) is an anxiety disorder that may develop in response to a traumaticevent. 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.

Predicting PTSD: Pre-existing vulnerabilities in glucocorticoid-signaling and implications for preventive interventions.
van Zuiden M, Kavelaars A, Geuze E, Olff M, Heijnen CJ.
Brain Behav Immun. 2012 Sep 5. pii: S0889-1591(12)00423-0. doi: 10.1016/j.bbi.2012.08.015. [Epub ahead of print]

Mia Greisen Søndergaard
DPS’ forskningsudvalg