Epigenetic programming of the neuroendocrine stress response by adult life stress

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis is critically involved in the neuroendocrine regulation of stress adaptation, and the restoration of homeostasis following stress exposure. Dysregulation of this axis is associated with stress-related pathologies like major depressive disorder, post-traumatic stress disorder, panic disorder and chronic anxiety. It has long been understood that stress during early life can have a significant lasting influence on the development of the neuroendocrine system and its neural regulators, partially by modifying epigenetic regulation of gene expression, with implications for health and well-being in later life. Evidence is accumulating that epigenetic plasticity also extends to adulthood, proposing it as a mechanism by which psychological trauma later in life can long-lastingly affect HPA axis function, brain plasticity, neuronal function and behavioural adaptation to neuropsychological stress. Further corroborating this claim is the phenomenon that these epigenetic changes correlate with the behavioural consequences of trauma exposure. Thereby, epigenetic modifications provide a putative molecular mechanism by which the behavioural phenotype and transcriptional/translational potential of genes involved in HPA axis regulation can change drastically in response to environmental challenges, and appear an important target for treatment of stress-related disorders. However, improved insight is required to increase their therapeutic (drug) potential. Here, we provide an overview of the growing body of literature describing the epigenetic modulation of the (primarily neuroendocrine) stress response as a consequence of adult life stress and interpret the implications for, and the challenges involved in applying this knowledge to, the identification and treatment of stress-related psychiatric disorders.

Gestational chronodisruption leads to persistent changes in the rat fetal and adult adrenal clock and function

“…In fact, the adrenal gland has been shown to play a crucial role in the stress‐response capacity of several other models used to study fetal programming (Dirven et al . ).…”

MicroRNAs in Psychological Stress Reactions and Their Use as Stress-Associated Biomarkers, Especially in Human Saliva

“…Aside from miRNAs, other epigenetic mechanisms such as DNA methylation and histone modification were found to regulate the neuroendocrine stress response, mainly by regulating glucocorticoid or mineralocorticoid receptors. Dirven et al [55] provided a detailed analysis of this epigenetic regulation of HPA axis activation in their review. …”

Maternal childhood and lifetime traumatic life events and infant bronchiolitis

“…Maternal stress‐induced activation of the hypothalamic‐pituitary‐adrenal (HPA) axis can result in increased cortisol during pregnancy, altering immune and oxidative balance . Similar effects can occur following stress that precedes pregnancy: trauma can increase maternal cortisol levels during pregnancy independent of response symptoms during pregnancy, suggesting such events may result in altered long‐term HPA functioning, potentially due to epigenetic modification . Infants exposed prenatally to elevated cortisol or maternal traumatic stress have been shown to exhibit impaired stress responses themselves, including elevated pre‐stress cortisol and decreased stress‐response cortisol, and impaired cardiorespiratory recovery following stress exposure .…”

“…36,37 Similar effects can occur following stress that precedes pregnancy: trauma can increase maternal cortisol levels during pregnancy independent of response symptoms during pregnancy, suggesting such events may result in altered long-term HPA functioning, 17 potentially due to epigenetic modification. 38,39 Infants exposed prenatally to elevated cortisol or maternal traumatic stress have been shown to exhibit impaired stress responses themselves, including elevated pre-stress cortisol and decreased stress-response cortisol, 40 and impaired cardiorespiratory recovery following stress exposure. 41 Elevated cortisol has also been observed in infants of women with exposure to child abuse and comorbid post-traumatic stress.…”