Biomarkers of stress across biological systems: conceptual and measurement perspectives

Stress and the ability to regulate stress substantially influence an individual's psychological health and wellbeing. There is growing evidence that the biological component of stress makes a unique contribution to understanding stress, yielding insights that are distinct from those specific to stress-related feelings and thoughts. The purpose of this paper is to provide an overview of selected biomarkers of stress as well as key issues regarding their use. Biomarkers associated with the hypothalamic–pituitary–adrenal axis (cortisol, dehydroepiandrosterone), the autonomic nervous system (heart rate variability, alpha-amylase), the immune system (cytokines and C-reactive protein), genetics (telomeres, DNA methylation), and multi-omics are discussed. Each biomarker is defined, along with the empirical and/or conceptual rationale for its use as a stress measure and examples of its research application. Collection, storage, and processing considerations for biospecimens or sensor-derived, physiologic data are addressed. For each biomarker, its utility in measurement of acute vs. chronic stress is differentiated, and established relationships to resilience are noted. In addition, key advantages and limitations of each marker are summarized. Lastly, significant areas for future research are highlighted that can move the field forward. Biomarkers represent a critical asset in the overall scope of research on stress and stress regulation, advancing knowledge of their health-related impact in fundamental and unique ways.