Early-life adversity programs emotional functions and the neuroendocrine stress system: the contribution of nutrition, metabolic hormones and epigenetic mechanisms

Abstract

Clinical and pre-clinical studies have shown that early-life adversities, such as abuse or neglect, can increase the vulnerability to develop psychopathologies and cognitive decline later in life. Remarkably, the lasting consequences of stress during this sensitive period on the hypothalamic-pituitary-adrenal axis and emotional function closely resemble the long-term effects of early malnutrition and suggest a possible common pathway mediating these effects. During early-life, brain development is affected by both exogenous factors, like nutrition and maternal care as well as by endogenous modulators including stress hormones. These elements, while mostly considered for their independent actions, clearly do not act alone but rather in a synergistic manner. In order to better understand how the programming by early-life stress takes place, it is important to gain further insight into the exact interplay of these key elements, the possible common pathways as well as the underlying molecular mechanisms that mediate their effects. We here review evidence that exposure to both early-life stress and early-life under-/malnutrition similarly lead to life-long alterations on the neuroendocrine stress system and modify emotional functions. We further discuss how the different key elements of the early-life environment interact and affect one another and next suggest a possible role for the early-life adversity induced alterations in metabolic hormones and nutrient availability in shaping later stress responses and emotional function throughout life, possibly via epigenetic mechanisms. Such knowledge will help to develop intervention strategies, which gives the advantage of viewing the synergistic action of a more complete set of changes induced by early-life adversity.

Prenatal and postnatal stress and asthma in children: Temporal- and sex-specific associations

“…Exposure to psychological stress in critical developmental windows, including pregnancy and early childhood, may result in permanently altered changes in stress response systems (e.g., immune, autonomic, neuroendocrine, oxidation)(10–12) thought to play a role in the programming of respiratory disorders including asthma(13–16). The fetus is particularly vulnerable to stress due to immature immune, neuroendocrine and antioxidant defenses(17, 18).…”

Food for thought: how nutrition impacts cognition and emotion

“…Whether these metabolic alterations contribute to the ESinduced cognitive deficits warrants further investigation. 39 In addition to peripheral metabolism, ES-induced alterations in the nutritional composition of the dam's milk, and/or nutrient intake/absorption by the pup 25,28,40 could have lasting consequences for brain structure and function. Indeed, the essential micronutrient, methionine, a critical component of the one-carbon (1-C) metabolism that is required for methylation, and for synthesis of proteins, phospholipids and neurotransmitters, is reduced after ES exposure in plasma and hippocampus of postnatal day 9 offspring.…”

Hormonal and nutritional regulation of postnatal hypothalamic development

“…This latter effect is predictive 325 of heightened anxiety (Laurent et al, 2015). In rats, chronic early life stress also leads to 326 exacerbated HPA axis responses to stress (Yam et al, 2015;Yoshihara and Yawaka, 2008). 327 As with rodents, in non-human primates, the hypothalamic content of kisspeptin and its 368 receptor increase in the prepubertal period (Keen et al, 2008;Shahab et al, 2005).…”