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、无创的体内测量个人应激史的方法。我们建议证明并验证牙釉质作为儿童应激源暴露的指标的使用，在牙釉质生物矿化过程中通过“化石”增量生长线，日常交叉条纹以及更长距离的标记，Retzius条纹永久记录，大致类似于树木生长年轮中捕获的干旱和火灾记录。我们最近的研究表明，牙釉质生物标志物与身体大小和板层骨密度测量相对应，证实了它作为身体调节其他重要模式的替代品。我们假设：第三磨牙牙釉质的分析是一个人从大约8到11岁的压力史的生物标志物。越来越多的证据表明，早期生活压力暴露和经历，包括社会经济地位和恶劣/混乱和/或无教养的童年环境，与成人健康轨迹（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总体寿命缩短）有关。与麦克尤恩的“适应负荷”概念一致，该概念描述了个体一生中慢性暴露于神经、神经内分泌和神经内分泌-免疫调节系统应激反应的累积生理成本。童年压力源的客观记录，包括线性和累积数据，而不是主观的历史，将具有极大的临床价值。它将减少对遥远事件和情况的主观、可能不准确或不情愿的报告，以及对昂贵的“快照”实验室测试的依赖。这种记录对于识别可能面临更大范围不良健康后果风险的弱势个人至关重要；早期识别这些个体将为潜在的更有效的干预提供机会，以避免坦率的疾病病理的发生。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、修饰或收集更多的压力损伤。牙齿从子宫内4个月到出生后11年都有重叠的牙釉质记录。长期以来，人类学家一直使用组织釉质记录来衡量各种外部压力源的影响，包括饮食、情绪压力源和疾病，在现代、历史和化石人群中。这些数据明确地建立了童年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)无创地表和地下成像；(3)当代限定人群。我们整合了行为学、牙科、组织学、表面和地下成像、数学和分析等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的与非法寻求药物导致成瘾相关的压力相关风险因素有关。我们将定义一种未来的非侵入性临床筛查仪器。

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.