PNA Medical Corner: Early Life Stress and Its Long-Term Neurobiological Effects

Chrousos George approved 768x960This month the PNA Medical Corner showcases an article co-authored by longtime PNA member Dr. George Chrousos. The study looks at the ways early life stress manifests itself in brain changes and poor health in many other manifestations, even decades later.

Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation.
Agorastos A1, Pervanidou P2, Chrousos GP2, Baker DG3,4.

1  II. Department of Psychiatry, Division of Neurosciences, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
2  Unit of Developmental and Behavioral Pediatrics, First Department of Pediatrics, School of Medicine, Aghia Sophia Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.
3  Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States.
4  VA Center of Excellence for Stress and Mental Health, San Diego, La Jolla, CA, United States.


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.


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