Telomere Length as a Mediator Between Early Life Stress and Child Health Outcomes

 描述(由申请人提供)：早期生活压力(ELS)，包括虐待、忽视和丧失，与发展心理和身体健康问题的终身风险的急剧增加有关。然而，ELS为这些负面结果带来风险的机制尚不清楚。紧张的生活经历激活了压力反应系统，而高水平的压力与端粒缩短有关，端粒缩短是衰老的表观遗传标志。因此，较短的端粒长度可能是ELS在以后的生活中导致负面健康后果的机制之一。在这项拟议的研究中，我们将研究ELS与细胞老化的测量以及儿童时期心理和身体健康的测量之间的关联。更具体地说，我们将在青春期前的男孩和女孩中研究ELS和端粒长度之间的联系，以及青春期期间端粒磨损率作为早期压力经验的函数。我们会 还要检查ELS和易怒之间的联系，易怒是几种精神障碍的共同特征，与更严重和慢性形式的精神健康问题有关。此外，我们还将研究ELS与身体健康之间的联系，因为儿童时期的全球健康衡量标准可能早于成年后特定衰老疾病的发病。最后，我们将研究端粒长度的变化在多大程度上解释易怒和身体健康问题的个体 ELS的历史，以测试早期不良经历导致不适应结果的潜在机制。这项研究的结果不仅将增加我们对ELS、端粒长度和健康结果之间的关系的理解，而且还将为深入了解ELS后精神健康问题的发病风险增加的青春期重要发育期的细胞纵向衰老的标志物提供洞察。因此，我们预计，目前的研究将有助于我们理解ELS后精神病理学的发病模式，以及ELS增加负面健康后果风险的机制。这项拟议研究的结果将增加我们对压力的生物反应的知识，并将为早期逆境后疾病的发生和发展提供洞察。

 DESCRIPTION (provided by applicant): Early life stress (ELS), including abuse, neglect, and loss, is associated with dramatic increases in lifelong risk for the development of mental and physical health difficulties. The mechanisms through which ELS confers risk for these negative outcomes, however, are not well understood. Stressful life experiences activate the stress response systems, and high levels of stress have been linked to telomere shortening, an epigenetic marker of aging. Thus, shorter telomere length may be one mechanism through which ELS leads to negative health outcomes later in life. In the proposed study we will examine the association of ELS with a measure of cellular aging, as well as with measures of mental and physical health during childhood. More specifically, we will examine in a large sample of pre-pubertal boys and girls the association between ELS and telomere length, as well as rate of telomere attrition across the pubertal period as a function of early experiences of stress. We will also examine the link between ELS and irritability, a common characteristic of several psychiatric disorders, that has been associated with more severe and chronic forms of mental health difficulties. In addition, we also will examine the association between ELS and physical health, given that global measures of health in childhood are likely to precede the onset of specific diseases of aging in adulthood. Finally, we will examine the degree to which variability in telomere length explains increased irritability and physical health problems in individuals with a history of ELS, in order to test a potential mechanism by which early adverse experiences result in maladaptive outcomes. The results of this study will not only increase our understanding of the relations among ELS, telomere length, and health outcomes, but will also provide insight into a markers of cellular aging longitudinally during the important developmental period of adolescence, a stage of increased risk for the onset of mental health difficulties following ELS. Thus, we anticipate that the current study will contribute to our understanding both of models of the onset of psychopathology following ELS and of mechanisms by which ELS confers heightened risk for negative health outcomes. Findings from the proposed study will increase our knowledge of biological responses to stress and will provide insight into the onset and progression of disease following early adversity.