The worker response to the World Trade Center (WTC) attacks was unprecedented in scope, involving tens of thousands of traditional and nontraditional responders in rescue, recovery, and cleanup efforts. Posttraumatic stress disorder (PTSD) arising in response to equally unprecedented traumatic exposures, and characterized by disabling intrusive memories of the disaster, repeated nightmares, avoidance of disaster reminders, increased fear of another attack, disrupted sleep and other symptoms, is both highly prevalent and persistent in WTC responders, even over a decade after 9/11. Since 2012, in our ongoing study funded by CDC/NIOSH grant U01 OH010407, Biomarkers of Psychological Risk and Resilience in World Trade Center Responders, we are conducting an indepth characterization of a projected sample of 500 WTC rescue and recovery workers, whose trajectories of PTSD symptom severity following the 9/11 terrorist attacks span the range from resistant/resilient to severe, chronic PTSD. To date, we have enrolled n = 203 participants in our funded study. Of the 181 eligible responders, 178 (98%) have given permission for us to collect blood samples and store them for additional biomarker studies. By the end of our NIOSHfunded study in 2016, we plan to have collected blood samples from a total of n = 500 WTC responders spanning the range of PTSD symptom severity. The proposed study capitalizes on the existence of this rich and wellcharacterized sample of WTC responders, recruited from a cohort of over 10,000 WTC responders with diverging longitudinal PTSD symptom trajectories followed at the WTC Health Program. This study adds an important dimension to our integrative, theoretical model aiming to evaluate functional differences in key neurobiological systems implicated in the onset and development of PTSD, by measuring a set of additional, key biomarkers in blood samples from 500 WTC responders selected from 4 subgroups (125 responders in each group) with distinct longitudinal PTSD symptom trajectories since the 9/11 terrorist attacks: severe chronic PTSD, delayedonset PTSD, recovering, and resistant trajectories. Testing will include: (1) whole blood genome-wide gene expression profiling to detect differences in gene expression in key biological systems linked to the cause of PTSD? (2) Combining results from genomewide gene expression and genetic testing, the latter conducted during our ongoing NIOSHfunded study, to further understand how PTSD develops? and (3) measuring, in blood, components of the endocannabinoid system, a group of neuromodulatory lipids and their receptors that play a key role in the organism's adaptation to stress, working in concert with stress hormones in regulating responses to stress and trauma. The goal of the study is to further the field's understanding of PTSD risk and protective factors i disaster responders with varying degrees of preparedness and training in disaster response. Findings on risk factors can be used to improve future prevention and treatment strategies, while findings on protective factors can be applied to bolster resilience in rescue and recovery workers prior to disaster exposure.