Early life stress and trauma: developmental neuroendocrine aspects of prolonged stress system dysregulation

Hormones (Athens). 2018 Dec;17(4):507-520. doi: 10.1007/s42000-018-0065-x. Epub 2018 Oct 2.


Experience of early life stress (ELS) and trauma is highly prevalent in the general population and has a high public health impact, as it can trigger a health-related risk cascade and lead to impaired homeostatic balance and elevated cacostatic load even decades later. The prolonged neuropsychobiological impact of ELS can, thus, be conceptualized as a common developmental risk factor for disease associated with increased physical and mental morbidity in later life. ELS during critical periods of brain development with elevated neuroplasticity could exert a programming effect on particular neuronal networks related to the stress response and lead to enduring neuroendocrine alterations, i.e., hyper- or hypoactivation of the stress system, associated with adult hypothalamic-pituitary-adrenal axis and glucocorticoid signaling dysregulation. This paper reviews the pathophysiology of the human stress response and provides evidence from human research on the most acknowledged stress axis-related neuroendocrine pathways exerting the enduring adverse effects of ELS and mediating the cumulative long-term risk of disease vulnerability in adulthood.

Keywords: Autonomic nervous system; Childhood adversity; Childhood trauma; Cortisol; Early life stress; Endocrine system; Glucocorticoids; HPA axis.

Publication types

  • Review

MeSH terms

  • Autonomic Nervous System Diseases / etiology
  • Autonomic Nervous System Diseases / metabolism*
  • Endocrine System Diseases / etiology
  • Endocrine System Diseases / metabolism*
  • Humans
  • Hypothalamo-Hypophyseal System / metabolism*
  • Pituitary-Adrenal System / metabolism*
  • Psychological Trauma / complications
  • Psychological Trauma / metabolism*
  • Stress, Psychological / complications
  • Stress, Psychological / metabolism*