Developmental Neuroendocrinology of Early-Life Stress: Impact on Child Development and Behavior.

Our internal balance, or homeostasis, is threatened or perceived as threatened by stressful stimuli, the stressors. The stress system is a highly conserved system that adjusts homeostasis to the resting state. Through the concurrent activation of the hypothalamic-pituitary-adrenal axis and the locus coeruleus/norepinephrine-autonomic nervous systems, the stress system provides the appropriate physical and behavioral responses, collectively termed as "stress response", to restore homeostasis. If the stress response is prolonged, excessive or even inadequate, several acute or chronic stress-related pathologic conditions may develop in childhood, adolescence and adult life. On the other hand, earlylife exposure to stressors has been recognized as a major contributing factor underlying the pathogenesis of non-communicable disorders, including neurodevelopmental disorders. Accumulating evidence suggests that early-life stress has been associated with an increased risk for attention deficit hyperactivity disorder and autism spectrum disorder in the offspring, although findings are still controversial. Nevertheless, at the molecular level, early-life stressors alter the chemical structure of cytosines located in the regulatory regions of genes, mostly through the addition of methyl groups. These epigenetic modifications result in the suppression of gene expression without changing the DNA sequence. In addition to DNA methylation, several lines of evidence support the role of non-coding RNAs in the evolving field of epigenetics. In this review article, we present the anatomical and functional components of the stress system, discuss the proper, in terms of quality and quantity, stress response, and provide an update on the impact of early-life stress on child development and behavior.