Abstract
Early life stressors display a high universal prevalence and constitute a major public health problem. Prolonged psychoneurobiological alterations as sequelae of early life stress (ELS) could represent a developmental risk factor and mediate risk for disease, leading to higher physical and mental morbidity rates in later life. ELS could exert a programming effect on sensitive neuronal brain networks related to the stress response during critical periods of development and thus lead to enduring hyper- or hypo-activation of the stress system and altered glucocorticoid signaling. 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. 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 ten most acknowledged neurobiological allostatic pathways exerting enduring adverse effects of ELS even decades later (hypothalamic-pituitary-adrenal axis, autonomic nervous system, immune system and inflammation, oxidative stress, cardiovascular system, gut microbiome, sleep and circadian system, genetics, epigenetics, structural, and functional brain correlates). Although most findings back a causal relation between ELS and psychobiological maladjustment in later life, the precise developmental trajectories and their temporal coincidence has not been elucidated as yet. Future studies should prospectively investigate putative mediators and their temporal sequence, while considering the potentially delayed time-frame for their phenotypical expression. Better screening strategies for ELS are needed for a better individual prevention and treatment.
Highlights
Stress is defined as the state of threatened homeodynamic balance of the organism [1, 2]
Early Life Stress (ELS)/Childhood Trauma (CT) constitute a major public health issue, as they occur at ominously high rates, with over 30–40% of the general adult population having experienced some form of disrupting early life adversities [13,14,15,16]
As the microbiome plays an important role in the programming of the HPA axis and stress reactivity [244], ELS/CT may affect the signaling of the MGB axis in a major fashion and alter immune, and central nervous system (CNS) and stress system functioning with lifelong emotional and behavioral consequences [223, 239, 241, 245, 246]
Summary
Stress is defined as the state of threatened homeodynamic balance of the organism [1, 2]. Despite the resilience of many abused individuals in their early years, ELS/CT significantly increases the risk for impaired physical and psychological well-being and adaptive functioning in adulthood All these findings suggest that ELS/CT may trigger a healthrelated risk cascade and be conceptualized as a common developmental risk factor and cumulative health risk mediator, associated with an increased physical and mental morbidity and all-cause mortality in later life [13, 15, 36, 52,53,54,55,56,57,58,59]. Many other related, but distinct biological systems may play a role and have lately emerged as important pathophysiological pathways This current review discusses further potential pathophysiological mechanisms exerting the enduring adverse effects of ELS/CT and mediating the cumulative long-term risk for disease vulnerability in later life, a topic that cannot yet be approached via systematic reviews. The ten most important neurobiological concepts, as backed from current evidence, were synthesized under the headings reported in this narrative review
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