Department of Health Sciences, Faculty of Applied Health Sciences, Brock University, Canada; Brock-Niagara Centre for Health and Well-Being, Brock University, Canada.
Department of Health Sciences, Faculty of Applied Health Sciences, Brock University, Canada; Brock-Niagara Centre for Health and Well-Being, Brock University, Canada.
Brain Behav Immun. 2021 Mar;93:254-263. doi: 10.1016/j.bbi.2020.12.018. Epub 2020 Dec 21.
Adverse childhood experiences (ACEs), such as maltreatment and severe household dysfunction, represent a significant threat to public health as ACEs are associated with increased prevalence of several chronic diseases. Biological embedding, believed to be rooted in dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, is the prevailing theory by which chronic diseases become imprinted in individuals following childhood adversity. A shift towards HPA axis hypoactivity occurs in response to ACEs exposure and is proposed to contribute towards altered cortisol secretion, chronic low-grade inflammation, and dysregulated hemodynamic and autonomic function. This shift in HPA axis activity may be a long-term effect of glucocorticoid receptor methylation with downstream effects on hemodynamic and autonomic function. Emerging evidence suggests syncopal tendencies are increased among those with ACEs and coincides with altered neuroimmune function. Similarly, chronic low-grade inflammation may contribute towards arterial baroreceptor desensitization through increased arterial stiffness, negatively impacting autonomic regulation following posture change and increasing rates of syncope in later life, as has been previously highlighted in the literature. Although speculative, baroreceptor desensitization may be secondary to increased arterial stiffness and changes in expression of glucocorticoid receptors and arginine vasopressin, which are chronically altered by ACEs. Several research gaps and opportunities exist in this field and represent prospective areas for future investigation. Here, we synthesize current findings in the areas of acute psychosocial stress reactivity pertaining to HPA axis function, inflammation, and hemodynamic function while suggesting ideas for future research emphasizing systemic interactions and postural stress assessments among those with ACEs. This review aims to identify specific pathways which may contribute towards orthostatic intolerance in populations with history of childhood adversity.
不良的童年经历（ACEs），如虐待和严重的家庭功能障碍，对公共健康构成了重大威胁，因为 ACEs 与几种慢性疾病的患病率增加有关。生物嵌入，据信源于下丘脑-垂体-肾上腺（HPA）轴的功能障碍，是一种流行的理论，即慢性疾病在个体经历童年逆境后会被印记。HPA 轴活性的这种转变是对 ACEs 暴露的反应，据推测有助于改变皮质醇分泌、慢性低度炎症以及血液动力学和自主功能失调。HPA 轴活性的这种转变可能是糖皮质激素受体甲基化的长期影响，对血液动力学和自主功能有下游影响。新出现的证据表明，经历 ACEs 的人晕厥倾向增加，同时伴有神经免疫功能改变。同样，慢性低度炎症可能通过增加动脉僵硬导致动脉压力感受器脱敏，从而对体位变化后的自主调节产生负面影响，并增加晚年晕厥的发生率，这在以前的文献中已有强调。虽然推测性的，但压力感受器脱敏可能继发于动脉僵硬增加和糖皮质激素受体和精氨酸加压素表达的改变，这些改变是由 ACEs 慢性改变引起的。该领域存在几个研究空白和机会，代表了未来研究的前瞻性领域。在这里，我们综合了当前关于 HPA 轴功能、炎症和血液动力学功能的急性心理社会应激反应领域的研究结果，并提出了未来研究的思路，强调了 ACEs 患者的系统相互作用和体位应激评估。本综述旨在确定可能导致有童年逆境史的人群出现直立不耐受的特定途径。
