Gene x 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 x 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 x E studies in PTSD. This article will review the concept and initial results of G x E interactions with polymorphisms in these genes for PTSD. In addition, the use of alternate phenotypes and more complex interaction models such as G x G x E or G x E x 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'. (C) 2011 Elsevier Ltd. All rights reserved.