Early-Life Stress, HPA Axis Adaptation, and Mechanisms Contributing to Later Health Outcomes

Abstract

Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early-life stress can impact on later health but less is known about how early-life stress impairs HPA axis activity, contributing to maladaptation of the stress–response system. Early-life stress exposure (either prenatally or in the early postnatal period) can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical, and experimental studies have demonstrated that early-life stress produces long term hyper-responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviors. Recently, evidence has emerged on early-life stress-induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early-life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1). We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early-life stress-induced maladaptation of the HPA axis, and its subsequent effects on energy utilization and expenditure. The effects of positive later environments as a means of ameliorating early-life stress-induced health deficits, and proposed mechanisms underpinning the interaction between early-life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early-life stress and later health outcomes will also be addressed.

Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders

“…Experiments in rats have shown that rats exposed to early life stress show elevated GCs as adults [21]. Similar observations have been made in human subjects who show chronically elevated GCs and altered stress response long after a traumatic event [17]. The effects of stress can therefore be persistent, lasting long after termination of the stressor.…”

“…However, after chronic stress and long term elevations of GCs, the effects of GCs are detrimental with neurotoxic, immunosuppressive, and metabolic consequences [17][18][19]. Accordingly, many neuropsychiatric disorders are associated with abnormalities in the HPA axis, with chronically elevated cortisol and reduced sensitivity to GC [20], suggesting stress may contribute to their development.…”

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks

“…The consequences of early-life (prenatal as well as postnatal) stress on emotional and social behaviors have been a subject of several recent reviews (eg, Sandi and Haller, 2015;Nishi et al, 2014). Here, we summarize in Table form the consequences of chronic early-life adversity provoked by abnormal maternal care in the limited bedding-nesting environment (Gilles et al, 1996;Molet et al, 2014), a model recently adopted and adapted by over 50 laboratories around the world (eg, Raineki et al, 2010;Wang et al, 2011;Bolton et al, 2013;Machado et al, 2013;Maniam et al, 2014;Kohl et al, 2015;Naninck et al, 2015; Table 1). …”

Anxiety, Family Functioning and Neuroendocrine Biomarkers in Obese Children

“…[12][13][14] Moreover, it also seems sound and acceptable to consider that obesity be mediated through effects on appetite, sleep, and activity. [12][13][14] The (re)activity of the hypothalamic-pituitary-adrenal (HPA)-system plays a role in the course of disorders of anxiety and depression. In the few studies that have investigated the association between anxiety disorders and cortisol levels in children and adolescents, findings have been as inconclusive as in adults.…”