Stress History is Recorded in Tooth Enamel

描述（由申请人提供）：长期目标是开发一种客观、快速、非侵入性的体内方法来测量个人压力史。我们建议证明和验证使用牙釉质作为儿童期应激源暴露的指数，永久记录在牙釉质生物矿化过程中，通过“牙釉质化”的增量生长线，每日横纹以及较长范围的标记，Retzius纹，大致类似于树木年轮中捕获的干旱和火灾的记录。我们最近表明，釉质生物标志物对应于身体大小和板层骨密度测定，确认它作为身体调节的其他重要模式的替代品。我们假设：第三磨牙中的釉质分析是一个人从大约8岁到11岁的压力历史的生物标志物测量。越来越多的证据表明，生命早期的压力暴露和经历，包括社会经济地位和恶劣/混乱和/或非养育性的童年环境，与成年健康轨迹有关，包括心血管和其他生物风险状况升高，免疫功能受损，多种慢性病风险增加，以及整体寿命缩短，这与McEwan的“非稳态负荷”概念一致，其描述了在个体的一生中长期暴露于神经、神经内分泌和神经内分泌免疫调节系统的应激反应的累积生理代价。客观记录儿童期的压力源，包含线性和累积数据，而不是主观的历史，将是极端的临床价值。它将减少对主观的、可能不准确或不情愿的、关于遥远事件和条件的报告以及昂贵的“快照”实验室测试的依赖。这种记录对于查明可能面临更大风险的易受伤害的个人是至关重要的，这些人可能面临各种不利的健康结果;及早查明这些人将为采取可能更有效的干预措施提供机会，以避免出现明显的疾病病理。与其他生物标志物不同，牙釉质是惰性的，在形成后或成年期不能愈合，修改或收集更多的应力损伤。牙齿捕获重叠的釉质记录，从早在子宫内4个月到晚至出生后11年。长期以来，人类学家一直使用组织学釉质记录来衡量各种外部压力源的影响，包括饮食，情绪压力和疾病，在现代，历史和化石人群中。这些数据明确地建立了儿童压力源的牙釉质记录。我们将把这个模型扩展到：（1）测量长期和累积压力记录，以及线性短期急性压力源;（2）非侵入性表面和次表面成像;（3）当代定义的人群。我们整合了必要的行为，牙科，组织学，表面和亚表面成像，数学和分析领域的专业知识和新兴技术，以证明记录在牙釉质中的早期压力与已知与非法寻求药物相关的压力相关风险因素有关。我们将定义未来的无创临床筛查工具。 公共卫生相关性：我们建议证明和验证使用牙釉质作为儿童期应激暴露的不可变指标，永久记录在牙釉质生物矿化过程中。我们试图将记录在牙釉质中的早期压力与不良的儿童环境压力源、生活事件和已知与寻求非法药物导致成瘾有关的创伤联系起来。这种客观的记录对于确定可能面临更大风险的易受伤害的个人至关重要，这些人可能面临各种不利的健康结果;及早确定这些人将为采取可能更有效的干预措施提供机会，以避免出现明显的疾病病理。我们将定义未来的无创临床筛查仪器。

DESCRIPTION (provided by applicant): Long-term goal is to develop an objective rapid non-invasive, in vivo means of measuring personal stress history. We propose to demonstrate and validate the use of tooth enamel as an index of childhood stressor exposures, permanently recorded during enamel biomineralization via "fossilized" incremental growth lines, daily cross-striations as well as longer-range markings, striae of Retzius, broadly analogous to the record of droughts and fires captured in the growth rings of a tree. We have recently shown that an enamel biomarker corresponds to body size and to lamellar bone densitometry, confirming it as a surrogate for other important patterns of body regulation. We hypothesize that: Analysis of enamel in third molar teeth is a biomarker measure of a person's stress history from approximately 8 to 11 years of age. Growing evidence links early life stress exposure and experience, including socio-economic status and harsh/chaotic and/or non-nurturant childhood environments, to adult health trajectories including elevated cardiovascular and other biological risk profiles, impaired immune function, increased risks for multiple chronic conditions, as well as decreased overall longevity, consistent with McEwan's concept of "allostatic load" describing the cumulative physiologic cost of chronic exposure to the neural, neuroendocrine and neuroendocrine-immune regulatory systems' stress responses over the course of an individual's lifetime. An objective record of childhood stressors, containing both linear and cumulative data, rather than a subjective history, would be of extreme clinical value. It would reduce reliance on subjective, and possibly inaccurate or reluctant, reports on distant events and conditions, and on expensive "snapshot" lab tests. Such a record would be crucial in identifying vulnerable individuals who may be at increased risk to a wide range of adverse health outcomes; earlier identification of such individuals would offer opportunities for potentially more effective interventions to avert onset of frank disease pathology. Unlike other biomarkers, tooth enamel is inert and cannot be healed, modified, or collect more stress damage after formation, or during adulthood. Teeth capture overlapping enamel records from as early as 4 months in-utero to as late as 11 years after birth. Anthropologists have long used histological enamel records to measure the influence of a variety of external stressors, including diet, emotional stressors, and disease, in modern, historic, and fossil populations. These data have unequivocally established the tooth enamel record of childhood stressors. We will extend this model to: (1) measure long-term and cumulative stress records, as well as linear short-term acute stressors; (2) non-invasive surface and subsurface imaging; (3) contemporary defined populations. We integrate expertise and emergent technology in the necessary behavioral, dental, histological, surface and subsurface imaging, mathematical, and analytical domains so as to demonstrate that early stress, recorded in tooth enamel, is related to stress-related risk factors known to be associated with illicit drug-seeking leading to addiction. We will define a future non-invasive clinical screening instrument. PUBLIC HEALTH RELEVANCE: We propose to demonstrate and validate the use of tooth enamel as an immutable index of childhood stressor exposures, permanently recorded during enamel biomineralization. We seek to relate early stress, recorded in tooth enamel, to adverse childhood environmental stressors, life events, and traumas known to be associated with illicit drug-seeking leading to addiction. Such an objective record would be crucial in identifying vulnerable individuals who may be at increased risk to a wide range of adverse health outcomes; earlier identification of such individuals would offer opportunities for potentially more effective interventions to avert onset of frank disease pathology. We will define a future non-invasive clinical screening instrument.