Literature review and methodological considerations for understanding circulating risk biomarkers following trauma exposure

Abstract

Exposure to traumatic events is common. While many individuals recover following trauma exposure, a substantial subset develop adverse posttraumatic neuropsychiatric sequelae (APNS) such as posttraumatic stress, major depression, and regional or widespread chronic musculoskeletal pain. APNS cause substantial burden to the individual and to society, causing functional impairment and physical disability, risk for suicide, lost workdays, and increased health care costs. Contemporary treatment is limited by an inability to identify individuals at high risk of APNS in the immediate aftermath of trauma, and an inability to identify optimal treatments for individual patients. Our purpose is to provide a comprehensive review describing candidate blood-based biomarkers that may help to identify those at high risk of APNS and/or guide individual intervention decision-making. Such blood-based biomarkers include circulating biological factors such as hormones, proteins, immune molecules, neuropeptides, neurotransmitters, mRNA and noncoding RNA expression signatures, while we do not review genetic and epigenetic biomarkers due to other recent reviews of this topic. The current state of the literature on circulating risk biomarkers of APNS is summarized, and key considerations and challenges for their discovery and translation are discussed. We also describe the AURORA study, a specific example of current scientific efforts to identify such circulating risk biomarkers and the largest study to date focused on identifying risk and prognostic factors in the aftermath of trauma exposure.

Peritraumatic 17β-estradiol levels influence chronic posttraumatic pain outcomes

“…To date, few peritraumatic risk biomarkers and early posttraumatic mediators of CPTP have been identified. 28 Here, longitudinal cohort data from individuals experiencing 3 types of trauma exposure indicate that in women E2 is a resiliency biomarker and potential mediator of CPTP. Women with E2 levels in the highest tertile reported 28% less musculoskeletal pain during the year after trauma than women in the lowest tertile, and this association was not accounted for by differences in age, ethnicity, education level, and acute pain.…”

“…20,41 Few peritraumatic biomarkers of chronic posttraumatic pain (CPTP) vulnerability have been identified. 28 Furthermore, the molecular changes occurring in the early aftermath of trauma exposure that influence an individual's recovery after trauma are poorly understood. The identification of novel risk biomarkers and molecular mechanisms of CPTP development could contribute to clinical prediction tools that identify high-risk individuals, yield new understanding of biologic mechanisms, and/or lead to novel preventative therapeutics.…”

microRNA let-7i-5p mediates the relationship between muscle fat infiltration and neck pain disability following motor vehicle collision: a preliminary study

“…The longitudinal study design in which we measured both microRNA expression levels and fatty infiltrates of muscle in the early peritraumatic period enabled the preliminary identification of biological predictors of a persistent posttraumatic outcome. Such type of discovery is currently in its infancy but holds promise for identifying susceptibility/risk biomarkers of at-risk individuals 10 . This study design also enables the discovery of promising candidates for preventative therapeutics.…”

The Roadmap for Resilience: The California Surgeon General's Report on Adverse Childhood Experiences, Toxic Stress, and Health

“…[299][300][301] A diverse set of factors attached to DNA, called epigenetic markers, can alter the While there currently exist no widely agreed-upon clinical diagnostic criteria for toxic stress, a number of biomarkers associated with neuro-endocrine-immune-metabolic disruption are under investigation. [332][333][334] Although the definition continues to be refined, in broad terms, a biomarker is "a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or biological responses to an exposure or intervention, including therapeutic interventions. Molecular, histologic, radiographic, or physiologic characteristics are types of biomarkers."…”