Early life stress and iron metabolism in developmental psychoneuroimmunology

An estimated 250 million children face adverse health outcomes from early life exposure to severe or chronic social, economic, and nutritional adversity, highlighting/emphasizing the pressing concern about the link between ELS and long-term implications on mental and physical health. There is significant overlap between populations experiencing high levels of chronic stress and those experiencing iron deficiency, spotlighting the potential role of iron as a key mediator in this association. Iron, an essential micronutrient for brain development and immune function, is often depleted in stress conditions. Iron deficiency among the most common nutrient deficiencies in the world. Fetal and infant iron status may thus serve as a crucial intermediary between early chronic psychological stress and subsequent immune system changes to impact neurodevelopment. The review presents a hypothesized pathway between early life stress (ELS), iron deficiency, and neurodevelopment through the hypothalamic-pituitary-adrenocortical (HPA) axis and the IL-6-hepcidin axis. This hypothesis is derived from (1) evidence that stress impacts iron status (2) long-term neurodevelopmental outcomes that are shared by ELS and iron deficiency exposure, and (3) possible mechanisms for how iron may mediate the relation between ELS and iron deficiency through alterations in the developing immune system. The article concludes by proposing future research directions, emphasizing the need for rigorous studies to elucidate how stress and iron metabolism interact to modify the developing immune system. Understanding these mechanisms could open new avenues for improving human health and neurodevelopment for women and children globally, making it a timely and vital area of study in psychoneuroimmunology research.