Interactions between early life stress and metabolic stress in programming of mental and metabolic health

The long-term consequences of psychosocial and socioeconomic challenges are hardly distinguishable from those of inappropriate nutrition, suggesting the existence of common physiological pathways funnelling the effects of early adversity. Obesity and mood disorders are highly prevalent and co-morbid in adult subjects. In order to unravel such co-morbidity, and to gain a more complete understanding of how the programming by early-life stress takes place, it is necessary to describe the common pathways, as well as the underlying molecular mechanisms. There is now robust evidence to indicate that the body reacts to stress through changes in the hypothalamic-pituitary-adrenal (HPA) axis, setting up adult responsiveness to environmental stressors and leading to individual vulnerability/resilience to stress and disease. Glucocorticoids (GCs) and neurotrophins, such as brain-derived neurotrophic factor (BDNF), play a critical role in the integration of behavioural and metabolic responses to external challenges, including nutrients availability, and have important effects on brain plasticity. In addition, very recent data indicate the existence of the gut-brain axis as another important target and mediator of the effects of early life stress and nutrition. A complete understanding of these complex regulations needs to take into account multiple intervening variables, such as sex and genetic/epigenetic landscapes, and consider the developmental/life stage in a life-long perspective. Integrative and multidisciplinary approaches will be needed in the future to advance the field and to devise early intervention strategies for a life-long mental and behavioural health.