Comparing the molecular correlates of PTSD in first responders and the broader molecular PTSD literature: a hybrid review.
Frontiers in psychology · 2026-01-01 · Systematic review
Abstract
First responders are trained civilian professionals, including firefighters, law enforcement, emergency medical services, and frontline medical workers, who have a vocational duty and are expected to respond in person to emergency situations. The chronic exposure to adverse traumatic events while working with public health and safety can lead to the clinical presentation of post-traumatic stress disorder (PTSD), which also occurs in other trauma-exposed populations such as military personnel, veterans, refugees, and individuals who experience interpersonal violence. Examining epigenetic and transcriptomic profiles through DNA methylation (DNAm) and RNA transcripts allows researchers to observe how genetic predispositions interact with environmental exposures, shaping biological processes that underlie PTSD across time frames. This review synthesized published analyses on first responders to assess if the observed epigenetic and transcriptomic signatures of PTSD were shared with or distinct from the potential convergence in evidence within the broader molecular PTSD literature as derived from reviews and meta-analyses. In comparing molecular profiles of PTSD across populations, this review assessed the value of integrating epigenetic and transcriptomic markers alongside clinical assessments to understand molecular adaptations, protective and risk factors, and resilience. With the exception of consistently privileged candidate genes, such as NR3C1 and FKBP5, individual studies identified unique DNA methylation sites and transcripts, likely reflecting differences in statistical significance and replication. This highlights the need for standardized methodologies across trauma-exposed populations. Future research should address chronic occupational trauma in first responders to better characterize PTSD manifestation in this unique population and utilize molecular profiling to identify distinct epigenetic and transcriptomic signatures associated with symptom development, treatment trajectories, and risk of reemergence. The field has the potential to inform our understanding of the long-term health consequences and treatment of PTSD for first responders and all those exposed to trauma.