 Study Design: We have generated some preliminary data supporting our hypothesis by examining 5-HTTLPR and the 3-UTR-VNTR of SLC6A3 genotypes in 109 combat veterans with and without PTSD. In this proposal, we will expand on these findings by recruiting 300 veterans exposed to sufficient combat stress defined by Combat Exposure ScaleCES score of 10 and who qualify for DSM-IV category A PTSD diagnostic criteria, including approximately 150 veterans with PTSD veterans with PTSD defined using DSM-IV diagnostic criteria, Clinician Administered PTSD Scale CAPS score 45 and 150 healthy combat-exposed veterans as defined by a CAPS score 15. We will first apply a newly developed extreme discordant phenotype EDP method to examine how 5-HTTLPR and 3-UTR-VNTR genotypes affect trauma related psychopathology in combat veterans only with the highest 45and lowest 15 CAPS scores. Secondly, single nucleotide polymorphisms SNPswill be examined across both genes and assessed for relatedness to PTSD susceptibility or resistance. Further analyses of relationship of these polymorphisms with comorbidities will also be performed. Thirdly, a pharmacogenetic trail using sertraline as a therapeutic agent will be applied to assess how gene variants influence PTSD treatment outcome. To Safeguard against population stratification, a genome control method will be applied in all the genetic analyses. 