Prospective biomarkers of posttraumatic stress disorder in children and adolescents: a systematic review and meta-analysis

Trauma exposure in children and young people (CYP) can lead to the development of posttraumatic stress disorder (PTSD). Identification of biomarkers prospectively associated with PTSD can provide critical insight into the mechanisms underpinning this disorder and potentially aid in identifying CYP vulnerable to persistent symptoms. A systematic search of databases was conducted up until February 2024 to identify studies testing associations of prospective biomarkers with PTSD outcomes in CYP. A narrative synthesis of study characteristics, quality, and findings was conducted. Meta-analysis using a random-effects model was performed when two or more comparable studies were identified. Searches yielded 2039 articles, with 283 identified as relevant after title/abstract screening. Twenty-one studies met eligibility criteria in the following biological domains: hormonal, immunological, cardiovascular, and multisystem. The majority of studies focussed on naturalistic recovery of CYP exposed to acute trauma. Significant heterogeneity was observed, including in trauma type, selection, and biomarker measurement. Across biomarkers, relatively consistent evidence was observed for a prospective association between elevated heart rate post-trauma and increased risk of PTSD persistence only, with limited evidence in other domains. Our review highlights a limited evidence base for prospective biomarkers of the development of PTSD in CYP, with methodological issues limiting inferences that can be drawn. A notable lack of evidence from low-and-middle income countries, despite chronic and severe trauma being endemic in these settings, was identified. Further research using standardised protocols from large, representative samples will be critical in the identification of biomarkers of PTSD risk and resilience.