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Rationale : Life-threatening experiences, including the observations of severe trauma and/or violence, coupled with feelings of extreme fear and helplessness can result in posttraumatic stress disorder (PTSD). Unpredictability, uncontrollability, and novelty are considered key factors in eliciting and influencing the intensities of the stress responses. Personal coping strategies may affect resilience and susceptibility to stressors and, in PTSD patients, may also affect responses to stressors such as cortisol secretion. Recent interest in PTSD models focuses on the drivers of susceptibility versus resilience factors and the identification of potential targets for prevention and/or treatment of PTSD. Following a traumatic event, most individuals experience at least some symptoms of PTSD. However, many trauma survivors who develop PTSD recover over the course of months. Methods : Systems and integrative biology approaches were applied to characterize the development of PTSD using an animal model of repeated social trauma/stress. Behavioral, physiological, and histopathological consequences of repeated social stress were evaluated using a modified "6 hour box-in-box resident-intruder" model. At the end of the stress episodes, mouse blood samples and organs were collected and brains were dissected into 17 different regions. Transciptomic, metabolomic, proteomic, and epigenomic changes were analyzed using microarrays. Results : Pan-omic analyses of this mouse model that simulate aspects of PTSD revealed that genes involved in axonal guidance signaling, apoptosis, inflammation, corticotropin releasing hormone signaling, synaptic long-term depression, dendritic branching, and cardiac hypertrophy were upregulated in stressed mice compared to the control. Suppressed transcripts were involved in synaptic long-term potentiation, lymphocyte activation, gap junction signaling, and glucocorticoid receptor pathway. Conclusions : We characterized the regulation patterns of genes, metabolites, protein, DNA methylation, and their associated networks in a mouse model of PTSD. These patterns can be used as part of a diagnostic panel for the development of PTSD and for the validation of therapeutic interventions.