Abstract: Methods regarding DNA methylation signature of post-traumatic stress disorder (PTSD) in brains of susceptible, resilient animals methylated in response to trauma, and S-adensoyl methionine (SAM) treated animals for deriving targets for PTSD therapeutics. Method regarding pathway analysis of the DNA methylation landscape to derive novel targets for therapeutic interventions such as retinoic acid pathway or estrogen receptor pathways. A method of treatment of PTSD comprised of Epigenetic modulators using general DNA methylation modulators such as SAM. A method of treatment of PTSD comprised of retinoic acid or vitamin A and its natural and synthetic analogs such as all-trans-retinoic acid (Tretinoin), 9-cis-retinoic acid (Alitretinoin), and 13-cis-retinoic acid (Isotretinoin) to treat PTSD. A method of treatment of PTSD comprised of a combination of Sadenosylmethionine and retinoic acid or vitamin A and its synthetic and natural analogs such as Tretinoin, Alitretinoin, and Isotretinoin.