Potential peripheral biomarkers associated with the emergence and presence of posttraumatic stress disorder symptomatology: A systematic review

Background: Evidence suggests posttraumatic stress disorder (PTSD) involves an interplay between psychological manifestations and biological systems. Biological markers of PTSD could assist in identifying individuals with underlying dysregulation and increased risk; however, accurate and reliable biomarkers are yet to be identified.

Methods: A systematic review following the PRISMA guidelines was conducted. Databases included EMBASE, MEDLINE, and Cochrane Central. Studies from a comprehensive 2015 review (Schmidt et al., 2015) and English language papers published subsequently (between 2014 and May 2022) were included. Forty-eight studies were eligible.

Results: Alterations in neuroendocrine and immune markers were most commonly associated with PTSD symptoms. Evidence indicates PTSD symptoms are associated with hypothalamic-pituitary-adrenal axis dysfunction as represented by low basal cortisol, a dysregulated immune system, characterized by an elevated pro-inflammatory state, and metabolic dysfunction. However, a considerable number of studies neglected to measure sex or prior trauma, which have the potential to affect the biological outcomes of posttraumatic stress symptoms. Mixed findings are indicative of the complexity and heterogeneity of PTSD and suggest the relationship between allostatic load, biological markers, and PTSD remain largely undefined.

Conclusions: In addition to prospective research design and long-term follow up, it is imperative future research includes covariates sex, prior trauma, and adverse childhood experiences. Future research should include exploration of biological correlates specific to PTSD symptom domains to determine whether underlying processes differ with symptom expression, in addition to subclinical presentation of posttraumatic stress symptoms, which would allow for greater understanding of biomarkers associated with disorder risk and assist in untangling directionality.