Stress History is Recorded in Tooth Enamel

描述(申请人提供)：长期目标是开发一种客观、快速、非侵入性、活体测量个人应激史的方法。我们建议演示和验证牙釉质作为童年应激源暴露的指数的使用，在釉质生物矿化过程中，通过“石化”的增量生长线、每日交叉条纹以及更远距离的标记、Retzius条纹，永久地记录下来，这大致类似于在树的生长轮中捕捉到的干旱和火灾的记录。我们最近已经证明，釉质生物标志物与身体大小和板层骨密度测定相对应，证实了它是其他重要的身体调节模式的替代品。我们假设：对第三磨牙牙釉质的分析是一个生物标记物，可以测量一个人从大约8岁到11岁的压力史。越来越多的证据将早期生活压力暴露和经历，包括社会经济状况和恶劣/混乱和/或非养育的童年环境，与成人健康轨迹联系起来，包括心血管和其他生物风险特征升高，免疫功能受损，多种慢性病风险增加，以及总体寿命下降，这与麦克尤恩的“平衡负荷”概念一致，该概念描述了在个人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成本。对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，将具有极端的临床价值。它将减少对关于遥远事件和情况的主观、可能不准确或不情愿的报告的依赖，以及对昂贵的“快照”实验室测试的依赖。这样的记录对于确定可能面临各种不利健康后果的风险增加的脆弱个人至关重要；及早确定这类个人将为采取可能更有效的干预措施以避免出现坦率的疾病病理提供机会。与其他生物标志物不同，牙釉质是惰性的，不能在形成后或成年期修复、修饰或收集更多的应力损伤。牙齿捕捉到重叠的牙釉质记录，从宫内4个月到出生后11年。人类学家长期以来一直使用组织学牙釉质记录来衡量各种外部应激源在现代、历史和化石种群中的影响，包括饮食、情绪应激源和疾病。这些数据明确地建立了儿童应激源的牙釉质记录。我们将把这个模型扩展到：(1)测量长期和累积的应激记录，以及线性短期急性应激源；(2)非侵入性表面和亚表面成像；(3)当代定义的人群。我们整合了必要的行为学、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紧急技术，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导致成瘾有关的压力相关风险因素有关。我们将定义一种未来的无创临床筛查仪器。 公共卫生相关性：我们建议证明和验证牙釉质作为儿童应激源暴露的不变指标的使用，在牙釉质生物矿化期间永久记录。我们试图将牙釉质中记录的早期压力与不良的童年环境应激源、生活事件和创伤联系起来，这些都与非法寻求药物导致成瘾有关。这种客观记录对于确定可能面临各种不利健康后果风险增加的脆弱个人至关重要；及早确定这类个人将为采取可能更有效的干预措施以避免出现坦率的疾病病理提供机会。我们将定义一种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.