Parsing inter- and intra-individual variability in key nervous system mechanisms of stress responsivity and across functional domains.

Abstract Exposure to stressful events is omnipresent in modern human life, yet people show considerable heterogeneity in the impact of stress exposure(s) on their functionality and overall health. Encounter with stressor(s) is counteracted by an intricate repertoire of nervous-system responses. This narrative review starts with a brief summary of the vast evidence that supports heart rate variability, cortisol secretion, and large-scale cortical network interactions as kay physiological, endocrinological, and neural mechanisms of stress responsivity, respectively. The second section highlights potential sources for inter-individual variability in these mechanisms, by focusing on biological, environmental, social, habitual, and psychological factors that may influence stress responsivity patterns and thus contribute to heterogeneity in the impact of stress exposure on functionality and health. The third section introduces intra-individually variability in stress responsivity across functional domains as a novel putative source for heterogeneity in the impact of stress exposure. Challenges and future directions are further discussed. Parsing inter- and intra-individual variability in nervous-system mechanisms of stress responsivity and across functional domains is critical towards potential clinical translation.