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:10602521
- 负责人:
- 金额:$ 65.37万
- 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 HealthChildhoodChronicCoinCross-Sectional StudiesDNA MethylationDataDevelopmentDiseaseEnsureEnvironmentEnvironmental Risk FactorEpidemiologyEpigenetic ProcessEuropean ancestryExposure toFamilyFunctional disorderGene ExpressionGenesGeneticGenetic DeterminismGenetic VariationGenomeGenotypeHealth ResourcesHouseholdHumanIndividual DifferencesInterventionInvestmentsLifeLife Cycle StagesLinkLongevityLongitudinal StudiesMeasuresMediatingMediationMediatorMendelian randomizationMental DepressionMental HealthMental disordersModelingModificationMolecularOutcomePatternPerinatalPopulation HeterogeneityPsychopathologyPublic HealthRecordsRegulationResearchRiskRisk FactorsRisk ReductionRoleSamplingScientistShapesSouth AfricaStructureSymptomsTestingTimeUmbilical Cord BloodWorkYouthchildhood adversitycohortearly childhoodearly life adversityepigenomeethnic diversityexperienceexperimental studygenome-widehigh dimensionalityhigh riskin silicoin vivoinsightlifetime riskmethylation patternneuropsychiatric disorderpopulation basedpostnatalpreventprospectiveracial diversitysocialsocial 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.
项目总结。童年的逆境是抑郁症的一个潜在危险因素,增加了一生中患抑郁症的风险
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
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:
$ 65.37万 - 项目类别:
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:
$ 65.37万 - 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:
$ 65.37万 - 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:
$ 65.37万 - 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:
$ 65.37万 - 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:
$ 65.37万 - 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:
$ 65.37万 - 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:
10444309 - 财政年份:2017
- 资助金额:
$ 65.37万 - 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:
$ 65.37万 - 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:
$ 65.37万 - 项目类别:
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