Early life stressors display a high universal prevalence and constitute a major public health problem with two thirds of youth being exposed to potentially traumatic experiences by the age of 17. Traumatic stress exposure during critical periods of development may have essential and long-lasting effects on the physical and mental health of individuals and represents a developmental risk factor mediating risk for disease. Early-life stress (ELS) and childhood trauma (CT) can both have an impact on sensitive neuronal brain networks involved in stress reactions, and could exert a programming effect on glucocorticoid signaling leading to chronic hyper- or hypo-activation of the stress system. In addition, alterations in emotional and autonomic reactivity, circadian rhythm disruption, functional and structural changes in the brain, as well as immune and metabolic dysregulation have been lately identified as important risk factors for a chronically impaired homeostatic balance after ELS/CT. Furthermore, human genetic background and epigenetic modifications through stress-related gene expression could interact with these alterations and explain inter-individual variation in vulnerability or resilience to stress. This narrative review presents relevant evidence from mainly human research on the most acknowledged neurobiological allostatic pathways exerting enduring adverse effects of ELS/CT even decades later. Future studies should prospectively investigate potential confounders, their temporal sequence and combined effects at the biological level, while considering the potentially delayed time-frame for the expression of their effects. Finally, screening strategies for ELS/CT and trauma need to be improved. Information about ELS/CT history and the number of adverse experiences could help to better identify the individual risk for disease development, predict individual treatment response and design prevention strategies to reduce the negative effects of ELS/CT.
Keywords: Early life stress; autonomic nervous system; childhood trauma; glucocorticoids; hypothalamus-pituitary-adrenal-axis (HPA axis).