Childhood adversity, DNA methylation, and psychopathology symptoms: A longitudinal study of sensitive periods and chrono-epigenetics
童年逆境、DNA 甲基化和精神病理学症状:敏感期和时间表观遗传学的纵向研究
基本信息
- 批准号:10444309
- 负责人:
- 金额:$ 67.03万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-07-18 至 2027-02-28
- 项目状态:未结题
- 来源:
- 关键词:AdultAffectAgeAwardBiologicalBiological MarkersBirthBloodBlood BanksBlood specimenBrainCandidate Disease GeneCell Culture TechniquesChildChild HealthChild Mental HealthChildhood Acute Lymphocytic LeukemiaChronicCoinCross-Sectional StudiesDNA MethylationDataData AnalysesData StoreDevelopmentDiseaseEnsureEnvironmentEnvironmental Risk FactorEpidemiologyEpigenetic ProcessEuropeanExposure toFamilyFunctional disorderGene ExpressionGenesGeneticGenetic DeterminismGenetic VariationGenomeGenotypeHealth ResourcesHouseholdHumanIndividual DifferencesInterventionInvestmentsLeadLifeLife Cycle StagesLinkLongevityLongitudinal StudiesMeasuresMediatingMediationMediator of activation proteinMendelian randomizationMental DepressionMental HealthMental disordersModelingModificationMolecularOutcomePatternPerinatalPopulation HeterogeneityPsychopathologyPublic HealthRecordsRegulationResearchRiskRisk FactorsRoleSamplingScientistShapesSouth AfricaStructureSumSymptomsTestingTimeUmbilical Cord BloodWorkYouthbasechildhood adversitycohortearly childhoodearly life adversityepigenomeethnic diversityexperienceexperimental studygenome-widehigh dimensionalityhigh riskin silicoin vivoinsightlifetime riskmethylation patternneuropsychiatric disorderpopulation basedpostnatalpreventprospectiveracial and ethnicsocialsocial determinantssocial factorssociodemographic factorstoolviolence exposure
项目摘要
Project Summary. Childhood adversity is a potent risk factor for depression, increasing lifetime risk of
this common and burdensome disorder by at least two-fold. While the association between adversity and
depression is well documented, the mechanisms explaining this relationship are poorly understood. In a
BRAINS R01 award, we made several new discoveries about how childhood adversity could become
biologically embedded to shape depression risk through DNA methylation (DNAm), a major type of
epigenetic modification. We showed that DNAm associations with adversity may not merely be molecular
records of adversity exposure, but rather, possibly function as a biological mediator linking childhood
adversity to depression risk. We also identified potential sensitive periods after birth and in the first five
years of postnatal life when adversity exposure imparted more enduring effects on the epigenome and in
shaping depression risk. However, these analyses were limited to mostly European-ancestry samples of
children with low/moderate adversity exposure and only 2 time points of blood DNAm. In this renewal, we
build on our prior work by exploring these relationships in a population-based longitudinal sample of
children in South Africa, who are part of the Drakenstein Child Health Study (DCHS). Relative to our prior
work and the field of epigenetics at large, the DCHS birth cohort provides an unprecedented opportunity
to study these associations within an established group of more racially/ethnically diverse children, many
of whom have experienced considerable early adversity directly or indirectly through their families own
exposure. We will capitalize on existing, repeated adversity markers collected by the DCHS during early
childhood and derive epigenetic data from stored blood samples collected at ages 1, 3, and 5. With these
rich longitudinal data, we will identify the genetic and social drivers and outcomes of chrono-epigenetics,
a newly coined term to describe the temporal dynamics of epigenetic processes, across the early life
course. In Aim 1, we will characterize the effects of genotype on DNAm levels at specific ages and
DNAm trajectories across time. In Aim 2, we will investigate the role of repeated adversity exposure
measures before age 5 on DNAm patterns using a two-stage structured life-course modeling approach
that our interdisciplinary team developed for high-dimensional epigenetic analyses. In Aim 3, we will use
statistical mediation and causal inference approaches (e.g., Mendelian Randomization) to evaluate the
extent to which these DNAm patterns explain the relationship between adversity timing and children’s
internalizing symptoms at age 8, one of the earliest signs of depression risk. In sum, this renewal project
will identify specific genetic and social factors shaping DNAm patterns, determine the ages when
adversity is most likely to affect this biomarker, and generate biological insights that may lead to new
intervention strategies to prevent depression, ensuring these findings apply to diverse samples of youth.
项目摘要。童年的逆境是抑郁症的一个潜在的危险因素,会增加一生患抑郁症的风险。
这一常见和繁重的疾病至少有两个方面。而逆境和灾难之间的联系
抑郁症是有充分证据的,但解释这种关系的机制却知之甚少。在一个
Brains R01奖,我们有了几个关于童年逆境如何变成
通过DNA甲基化(DNaM)生物嵌入形成抑郁风险,dNaM是一种主要的
表观遗传修饰。我们表明,dNaM与逆境的联系可能不仅仅是分子上的。
逆境暴露的记录,但相反,可能作为联系童年的生物中介发挥作用
逆境到抑郁的风险。我们还确定了出生后和出生后前五年的潜在敏感期。
出生后多年的生活,当逆境暴露对表观基因组和
形成抑郁的风险。然而,这些分析主要限于欧洲血统的样本。
低/中度逆境暴露且只有2个时间点的血dNaM的儿童。在这次更新中,我们
在我们先前工作的基础上,通过基于人群的纵向样本来探索这些关系
南非儿童,他们是Drakenstein儿童健康研究(DCHS)的一部分。相对于我们之前的
在整个表观遗传学领域,DCHS的出生队列提供了一个前所未有的机会
为了研究更多种族/民族多样性儿童的既定群体中的这些联系,许多
他们中的许多人通过他们的家庭直接或间接地经历了相当大的早期逆境
曝光。我们将利用疗养院在早期收集的现有的、重复的逆境标记。
并从1岁、3岁和5岁时收集的存储血液样本中获得表观遗传学数据。
丰富的纵向数据,我们将确定遗传和社会驱动因素和结果的时间表观遗传学,
一个新创造的术语,用来描述跨越早期生命的表观遗传过程的时间动力学
当然了。在目标1中,我们将表征基因对特定年龄和特定年龄的dNaM水平的影响
DNaM跨越时间的轨迹。在目标2中,我们将调查反复逆境暴露的作用
使用两阶段结构化生命过程建模方法测量5岁之前的dNaM模式
我们的跨学科团队为高维表观遗传学分析而开发的。在目标3中,我们将使用
统计调解和因果推断方法(例如,孟德尔随机化)以评估
这些dNaM模式在多大程度上解释了逆境时机和儿童的
在8岁时内化症状,这是抑郁症风险的最早迹象之一。总而言之,这个重建项目
将确定塑造dNaM模式的特定遗传和社会因素,确定何时年龄
逆境最有可能影响这个生物标记物,并产生可能导致新的
预防抑郁症的干预策略,确保这些发现适用于不同的青年样本。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Erin Cathleen Dunn其他文献
Erin Cathleen Dunn的其他文献
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{{ truncateString('Erin Cathleen Dunn', 18)}}的其他基金
Sensitive periods for prenatal alcohol exposure: a longitudinal study of DNA methylation and subsequent mental health
产前酒精暴露的敏感期:DNA 甲基化和随后心理健康的纵向研究
- 批准号:
10573715 - 财政年份:2023
- 资助金额:
$ 67.03万 - 项目类别:
Genomic and bioinformatic approaches for understanding the effects of childhood adversity on primary tooth formation and caries development in young children
基因组和生物信息学方法用于了解童年逆境对幼儿乳牙形成和龋齿发展的影响
- 批准号:
10739519 - 财政年份:2023
- 资助金额:
$ 67.03万 - 项目类别:
Epigenetic predictors of time-varying exposures to childhood adversity and depression
童年逆境和抑郁随时间变化的表观遗传预测因子
- 批准号:
10645726 - 财政年份:2023
- 资助金额:
$ 67.03万 - 项目类别:
Childhood adversity, DNA methylation, and risk for depression: A longitudinal study of protective factors and sensitive periods in development
童年逆境、DNA 甲基化和抑郁风险:保护因素和发育敏感期的纵向研究
- 批准号:
10658070 - 财政年份:2023
- 资助金额:
$ 67.03万 - 项目类别:
Evaluating teeth as fossil records of children's prenatal/perinatal trauma exposure and future mental health risk
评估牙齿作为儿童产前/围产期创伤暴露和未来心理健康风险的化石记录
- 批准号:
10580772 - 财政年份:2022
- 资助金额:
$ 67.03万 - 项目类别:
Evaluating teeth as fossil records of children's prenatal/perinatal trauma exposure and future mental health risk
评估牙齿作为儿童产前/围产期创伤暴露和未来心理健康风险的化石记录
- 批准号:
10354569 - 财政年份:2022
- 资助金额:
$ 67.03万 - 项目类别:
Childhood adversity, DNA methylation, and risk for depression: A longitudinal study of sensitive periods in development
童年逆境、DNA 甲基化和抑郁风险:发育敏感期的纵向研究
- 批准号:
9377336 - 财政年份:2017
- 资助金额:
$ 67.03万 - 项目类别:
Childhood adversity, DNA methylation, and psychopathology symptoms: A longitudinal study of sensitive periods and chrono-epigenetics
童年逆境、DNA 甲基化和精神病理学症状:敏感期和时间表观遗传学的纵向研究
- 批准号:
10602521 - 财政年份:2017
- 资助金额:
$ 67.03万 - 项目类别:
Childhood adversity, DNA methylation, and risk for depression: A longitudinal study of sensitive periods in development
童年逆境、DNA 甲基化和抑郁风险:发育敏感期的纵向研究
- 批准号:
9893016 - 财政年份:2017
- 资助金额:
$ 67.03万 - 项目类别:
Genes, early adversity, and sensitive periods in social-emotional development
基因、早期逆境和社会情感发展的敏感期
- 批准号:
8765685 - 财政年份:2014
- 资助金额:
$ 67.03万 - 项目类别:
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