Linking DNA methylation with child maltreatment and mental health across adolescence

将 DNA 甲基化与儿童虐待和整个青春期的心理健康联系起来

• 批准号: 10558621
• 负责人: Sonya L Negriff
• 金额: $ 60.71万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10558621
• 关键词: Acceleration; Address; Adolescence; Adolescent; Affect; Age; Aging; Animals; Archives; Biological; Biological Aging; Child; Child Abuse and Neglect; Chronology; DNA Methylation; Data; Dependence; Development; Epigenetic Process; Exhibits; Gene Expression; Genes; Heterogeneity; Human; Investigation; Knowledge; Length; Life Experience; Life Stress; Link; Longitudinal Studies; Measures; Mediating; Mediation; Mediator; Mental Health; Modeling; Neighborhoods; Outcome; Outcome Assessment; Outcome Measure; Pattern; Prevention approach; Process; Research; Resolution; Risk Assessment; Sampling; Site; Socioeconomic Factors; Statistical Models; Symptoms; Testing; Time; Trauma; Youth; childhood adversity; clinical development; comparison group; depressive symptoms; early life adversity; early life stress; experience; genome-wide; genomic data; indexing; innovation; longitudinal design; maltreatment; methylation pattern; population health; psychosocial; puberty transition; risk prediction; saliva sample; sample archive; symptomatology; telomere; trauma symptom

Abstract Child maltreatment is among the most devastating of childhood adversities and increases vulnerability for deleterious outcomes across a number of domains of functioning. However, not all who experience child maltreatment develop problems and those with similar maltreatment experiences may show very different outcomes. Differential biological embedding of maltreatment likely explains this heterogeneity in outcomes. Epigenetics, or the processes that influence gene expression, are crucial to our understanding of how child maltreatment influences later development. DNA methylation (DNAm) is the most well-studied epigenetic mechanism and has been proposed to link early life experiences to alterations in gene expression and mental health symptoms. Only a few studies have used a genome-wide approach to examine these associations and importantly have shown different DNAm patterns for maltreated youth within genes linked with mental health, but did not actually assess outcomes. No longitudinal investigations have tested genome-wide differences in DNAm that emerge after maltreatment and predict the emergence of, or change in, mental health symptoms. A relatively new measure of biological vulnerability, DNAm age, has emerged as an indicator of biological aging that is associated with life stress and has initial support for predicting risk for poor mental health functioning. Although maltreatment is linked with advanced biological aging using other indices (e.g., telomere length), there have been no longitudinal studies testing the effect of maltreatment on DNAm age, nor testing DNAm age as a mediator between maltreatment and later mental health symptoms. To address these gaps, we will use an existing longitudinal sample of maltreated and comparison children (n=454) followed for 10 years with 4 waves of archived samples and a myriad of psychosocial data. This data is optimal to assess the timing of maltreatment effects on genome-wide DNAm, DNAm patterns associated with subsequent mental health, and the potential resolution of problematic DNAm patterns across adolescence (ages 9-23). This is an unprecedented opportunity to capitalize on existing data from a well-designed longitudinal study of maltreated youth with a matched comparison group, which allows us to separate maltreatment effects from other aspects of early life stress and adversity, including neighborhood and socioeconomic factors. This study will contribute important new evidence crucial to our understanding of how maltreatment affects genome-wide epigenetic patterns of vulnerability that result in mental health problems. This will further the development of clinical risk assessment and prevention approaches for maltreated youth which will be of substantial benefit to population health.

摘要 虐待儿童是最具破坏性的童年逆境之一， 在许多功能领域产生有害的结果。然而，并不是所有经历过孩子的人 虐待会产生问题，而那些有类似虐待经历的人可能会表现出非常不同的问题。 结果。虐待的不同生物学嵌入可能解释了结果的异质性。 表观遗传学，或者说影响基因表达的过程，对于我们理解儿童是如何 虐待影响后来的发展。DNA甲基化（DNAm）是研究最充分的表观遗传学 机制，并已提出将早期生活经历与基因表达和精神状态的改变联系起来。 健康症状。只有少数研究使用全基因组方法来检查这些关联， 重要的是，在与精神健康相关的基因中， 但实际上并没有评估结果。没有纵向研究测试了基因组范围内的差异， 虐待后出现的DNA m，并预测心理健康症状的出现或变化。一 DNA年龄是一种相对较新的生物脆弱性指标，已成为生物老化的指标 这与生活压力有关，并初步支持预测心理健康功能不良的风险。 虽然虐待与使用其他指标的高级生物老化有关（例如，端粒长度）， 没有纵向研究测试虐待对DNAm年龄的影响，也没有测试DNAm 年龄是虐待和后来的心理健康症状之间的中介。为了弥补这些差距，我们将 使用现有的受虐待儿童和对照儿童（n=454）的纵向样本，随访10年， 大量的存档样本和无数的社会心理数据。该数据对于评估 虐待对全基因组DNAm的影响，与随后的心理健康相关的DNAm模式，以及 在青春期（9-23岁）有问题的DNA模式的潜在解决方案。这是一 一个前所未有的机会，利用现有的数据，从一个精心设计的纵向研究虐待 青少年与匹配的对照组，这使我们能够从其他方面分开虐待的影响 早期生活压力和逆境，包括邻里和社会经济因素。这项研究将有助于 重要的新证据对我们理解虐待如何影响全基因组表观遗传至关重要 导致心理健康问题的脆弱性模式。这将进一步发展临床风险 对受虐待青年的评估和预防办法， 健康