Gene × environment vulnerability factors for PTSD: the HPA-axis

Post-traumatic stress disorder (PTSD) is a severely debilitating psychiatric condition. Although a lifetime trauma incidence of 40-90% has been reported in the general population, the overall lifetime prevalence for PTSD ranges between 7-12%, suggesting individual-specific differences towards the susceptibility to PTSD. While studies investigating main genetic effects associated with PTSD have yielded inconsistent findings, there is growing evidence supporting the role of gene-environment (G × E) interactions in PTSD. The hypothalamus pituitary adrenal (HPA) axis is one of the main systems activated after exposure to a trauma and perturbations in this system are one of the more consistent neurobiological abnormalities observed in PTSD. Genes regulating the HPA-axis are therefore interesting candidates for G × E studies in PTSD. This article will review the concept and initial results of G × E interactions with polymorphisms in these genes for PTSD. In addition, the use of alternate phenotypes and more complex interaction models such as G × G × E or G × E × E will be explored. Finally, putative molecular mechanisms for these interactions will be presented. The research presented in this article indicates that a combined analysis of environmental, genetic, endophenotype and epigenetic data will be necessary to better understand pathomechanisms in PTSD. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.