Childhood Adversity, Biopsychosocial Pathways, and Telomere Length in Adolescence

总结 不良童年经历（ACE）和较短的端粒长度（TL）都与慢性粒细胞白血病相关。 然而，很少有研究人员在生命过程的早期研究ACE对TL的影响， 在发育的敏感时期，限制了早期和/或发育定时干预的机会。 此外，研究集中在假设的生物和心理机制，通过这些机制，ACE 对端粒缩短的贡献有限。此外，环境暴露之外的影响， 青少年的邻里对TL还没有被检查。在我们之前的研究中，我们发现青少年 他们35%的清醒时间都在居住的人口普查区域之外，因此， 包括青少年的社区和其他常规地点（例如学校、同龄人、活动等），已知 作为他们的“活动空间”，对TL的研究还没有被研究。我们的研究将增加证据， 通过检查在特定发育时期（出生， 幼儿期、中期和青春期）以及累积。我们还将研究生物学 (HPA轴;头发皮质醇）和心理（抑郁和焦虑症状）的压力途径， ACE可能影响TL。此外，我们还将使用新的活动空间数据来研究 青少年暴露于当代个人和社会空间逆境和TL。我们的具体目标是 检查：儿童期和青春期（出生、0-5岁、6-10岁和11 - 15岁）发生的ACE模式 17岁）及其对青少年生物应激、心理困扰和TL的影响; 生物压力和TL和心理困扰和TL;生物压力和TL的程度 心理困扰在儿童/青少年ACE模式与青少年TL之间起中介作用; 当代青少年个体和活动空间ACE模式及其对青少年的影响 生物应激、心理困扰和TL，占11岁之前ACE的比例;以及 生物压力和心理困扰调解当代模式之间的关系， 个人和活动空间ACE和青少年TL，占11岁之前的ACE。在分析中 对于每一个目标，我们将探讨性作为假设关系的调节剂。这项研究是一项次要的 分析从两项NIH资助的研究中收集的1,018名青少年的数据。将构建研究变量 根据现有数据并使用描述性统计分析数据分布，识别离群值， 转换（如果需要）以实现正态性，并总结受试者特征。我们将使用潜在类 分析和多重线性回归模型进行假设检验。我们的方法将确定 儿童期和青春期的ACE增加了青少年较短TL的风险， 哪些生理和心理压力途径解释了这些关系。调查结果将告知 制定针对特定暴露模式和压力对TL的影响的干预措施。

Summary Both adverse childhood experiences (ACEs) and shorter telomere length (TL) have been associated with chronic disease in adulthood, however, few researchers have examined effects of ACEs on TL early in the life course or at sensitive periods in development, limiting opportunities for earlier and/or developmentally timed intervention. Additionally, studies focused on hypothesized biological and psychological mechanisms through which ACEs contribute to shortening of telomeres are limited. Moreover, the effect of contextual exposures outside of adolescents' neighborhood on TL has not been examined. In our previous research, we found that adolescents spend 35% of their waking time outside of their residential census tract, thus the effect of contextual exposures encompassing adolescents' neighborhood and other routine locations (e.g. school, peers, activities, etc.), known as their “activity space,” on TL has not been examined. Our study will add to the evidence on the relationship between ACEs and TL in adolescence by examining ACEs occurring at specific developmental periods (birth, early childhood, middle childhood, and adolescence) as well as cumulatively. We will also investigate biological (HPA axis; hair cortisol) and psychological (depressive and anxious symptoms) stress pathways through which ACEs may affect TL. Moreover, we will also use novel activity space data to examine relationships between adolescents' exposure to contemporary individual and sociospatial adversity and TL. Our specific aims are to examine: patterns of ACEs occurring across childhood and adolescence (birth, 0-5 years, 6-10 years, and 11 to 17 years) and their effect on adolescent biological stress, psychological distress, and TL; relationships between biological stress and TL and psychological distress and TL; the extent to which biological stress and psychological distress mediate the relationship between patterns of child/adolescent ACEs and adolescent TL; patterns of contemporary individual and activity space ACEs during adolescence and their effect on adolescent biological stress, psychological distress, and TL, accounting for ACEs prior to age 11 years; and the extent to which biological stress and psychological distress mediate the relationship between patterns of contemporary individual and activity space ACEs and adolescent TL, accounting for ACEs prior to age 11 years. In the analysis of each aim we will explore sex as a moderator of the hypothesized relationships. The study is a secondary analysis of data collected from two NIH funded studies of 1,018 adolescents. Study variables will be constructed from existing data and analyzed using descriptive statistics for data distribution, identify outliers, conduct data transformation if needed to achieve normality, and summarize subject characteristics. We will use latent class analysis and multiple linear regressions models for hypothesis testing. Our approach will identify sub-groups of ACEs across childhood and adolescence that increase adolescents' risk for shorter TL as well as the extent to which biological and psychological stress pathways explain these relationships. The findings will inform the development of interventions targeted to specific exposure patterns and the effects of stress on TL.