Biological Markers of Burnout Severity: A Systematic Review

Burnout syndrome (BOS) represents an enduring challenge for preventive medicine. While biomarkers of chronic stress have been explored within the allostatic load framework, BOS lacks a consistent physiological signature, hindering early and comprehensive identification of individuals at risk. This systematic review synthesises current evidence on BOS-related biomarkers, aiming to identify potential physiological correlates. We conducted a comprehensive search of PubMed and EMBASE, yielding 111 studies evaluating 36 biomarkers in adult populations. Our analysis revealed inconsistent associations across most physiological systems, including the hypothalamic-pituitary-adrenal axis (e.g., cortisol, DHEA), the immune system, and cardiovascular parameters. While some biomarkers such as HbA1c and blood glucose showed relatively more consistent associations with BOS, the overall findings remain largely inconclusive. Overall, the current biological evidence is insufficient to identify a BOS biosignature that could support routine clinical diagnosis. Future research should prioritise a more unified and comprehensive definition of BOS and investigate physiological patterns within more standardized research frameworks to advance objective identification and prevention strategies.