Reid Brie M
Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, USA.
Center for Behavioral and Preventive Medicine, The Miriam Hospital, USA.
Brain Behav Immun Health. 2024 Jul 16;40:100824. doi: 10.1016/j.bbih.2024.100824. eCollection 2024 Oct.
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.
据估计，2.5亿儿童因早年暴露于严重或慢性社会、经济和营养逆境而面临不良健康后果，这凸显了对早期生活应激（ELS）与身心健康长期影响之间联系的紧迫担忧。经历高水平慢性应激的人群与缺铁人群之间存在显著重叠，这突出了铁作为这种关联中关键调节因子的潜在作用。铁是大脑发育和免疫功能所必需的微量营养素，在应激状态下往往会耗尽。缺铁是世界上最常见的营养缺乏症之一。因此，胎儿和婴儿的铁状态可能是早期慢性心理应激与随后免疫系统变化之间的关键中介，从而影响神经发育。该综述提出了一条通过下丘脑-垂体-肾上腺皮质（HPA）轴和白细胞介素-6-铁调素轴，连接早期生活应激（ELS）、缺铁与神经发育的假设途径。这一假设源于：（1）应激影响铁状态的证据；（2）ELS和缺铁暴露所共有的长期神经发育结果；（3）铁可能通过发育中的免疫系统改变来介导ELS与缺铁之间关系的可能机制。文章最后提出了未来的研究方向，强调需要进行严谨的研究，以阐明应激和铁代谢如何相互作用来改变发育中的免疫系统。了解这些机制可能为改善全球妇女和儿童的人类健康和神经发育开辟新途径，使其成为心理神经免疫学研究中一个及时且至关重要的研究领域。
