Childhood adversity correlates with stable changes in DNA methylation trajectories in children and converges with epigenetic signatures of prenatal stress DOI Creative Commons
Jade Martins, Darina Czamara,

Susann Sauer

et al.

Neurobiology of Stress, Journal Year: 2021, Volume and Issue: 15, P. 100336 - 100336

Published: May 13, 2021

Childhood maltreatment (CM) is an established major risk factor for a number of negative health outcomes later in life. While epigenetic mechanisms, such as DNA methylation (DNAm), have been proposed means embedding this environmental factor, little known about its timing and trajectory, especially very young children. It also not clear whether additional adversities, often experienced by these children, converge on similar DNAm changes. Here, we calculated cumulative adversity score, which additionally to CM includes socioeconomic status (SES), other life events, parental psychopathology biomarkers prenatal smoking alcohol consumption. We investigated the effects alone well score longitudinal trajectories Berlin Longitudinal Child Study. This cohort 173 children aged 3-5 years at baseline whom 86 were exposed CM. These followed-up 2 with extensive psychometric biological assessments saliva collection 5 time points providing genome-wide levels. Overall, only few patterns stable over timeframe, but less than 10 regions showed significant At baseline, neither nor associated However, 6 differentially methylated (DMRs), significantly moderated time. A DMRs previously adverse exposures. In our study, presented signatures indicative increased exposure tobacco alcohol, compared non-CM strongly correlate score. Finally, weighted correlation network analysis revealed module CpGs exclusively study identifies loci specifically CM, within long non-coding RNAs, majority associations found convergent association indicators highlights importance mapping epigenome exposome extending observational timeframe before birth.

Language: Английский

Gene–environment correlations and causal effects of childhood maltreatment on physical and mental health: a genetically informed approach DOI Creative Commons
Varun Warrier, Alex S. F. Kwong, Mannan Luo

et al.

The Lancet Psychiatry, Journal Year: 2021, Volume and Issue: 8(5), P. 373 - 386

Published: March 18, 2021

BackgroundChildhood maltreatment is associated with poor mental and physical health. However, the mechanisms of gene–environment correlations potential causal effects childhood on health are unknown. Using genetics, we aimed to delineate sources correlation for relationship between health.MethodsWe did a genome-wide association study meta-analysis using data from UK Biobank (n=143 473), Psychiatric Genomics Consortium (n=26 290), Avon Longitudinal Study Parents Children (n=8346), Adolescent Brain Cognitive Development (n=5400), Generation R (n=1905). We included individuals who had phenotypic genetic available. investigated single nucleotide polymorphism heritability among different subtypes, operationalisations, reports maltreatment. Family-based population-based polygenic score analyses were done elucidate mechanisms. used Mendelian randomisation identify shared genetics test relationships conditions.FindingsOur studies (N=185 414) identified 14 independent loci (13 novel). high overlap (genetic 0·24–1·00) reporting methods. Within-family provided some support active reactive but not show absence passive correlation. Robust suggested role in depression (unidirectional), as well both schizophrenia ADHD (bidirectional), conditions (coronary artery disease, type 2 diabetes) or inflammation (C-reactive protein concentration).InterpretationChildhood has heritable component, substantial retrospective prospective point correlation, equivocal supports (primarily bidirectional) health, conditions. Our identifies research avenues inform prevention its long-term effects.FundingWellcome Trust, Medical Research Council, Horizon 2020, National Institute Mental Health, Health Biomedical Centre.

Language: Английский

Citations

162
A systematic review of childhood maltreatment and DNA methylation: candidate gene and epigenome-wide approaches DOI Creative Commons
Stephanie H. Parade, Lindsay Huffhines, Teresa E. Daniels

et al.

Translational Psychiatry, Journal Year: 2021, Volume and Issue: 11(1)

Published: Feb. 19, 2021

Childhood maltreatment is a major risk factor for chronic and severe mental physical health problems across the lifespan. Increasing evidence supports hypothesis that associated with epigenetic changes may subsequently serve as mechanisms of disease. The current review uses systematic approach to identify summarize literature related childhood alterations in DNA methylation humans. A total 100 empirical articles were identified our research published prior or during March 2020, including studies focused on candidate genes leveraged epigenome-wide data both children adults. Themes arising from literature, consistent inconsistent patterns results, are presented. Several directions future research, important methodological considerations study design, discussed. Taken together, underscores complexity transactions between environment biology development.

Language: Английский

Citations

124
Socioeconomic Disadvantage and the Pace of Biological Aging in Children DOI
Laurel Raffington, Daniel W. Belsky, Meeraj Kothari

et al.

PEDIATRICS, Journal Year: 2021, Volume and Issue: 147(6)

Published: May 17, 2021

Children who grow up in socioeconomic disadvantage face increased burden of disease and disability throughout their lives. One hypothesized mechanism for this is that early-life accelerates biological processes aging, increasing vulnerability to subsequent disease. To evaluate hypothesis the potential impact preventive interventions, measures are needed can quantify early acceleration aging childhood.

Language: Английский

Citations

100
Epistemic trust and personality functioning mediate the association between adverse childhood experiences and posttraumatic stress disorder and complex posttraumatic stress disorder in adulthood DOI Creative Commons
Hanna Kampling,

Johannes Kruse,

Astrid Lampe

et al.

Frontiers in Psychiatry, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 10, 2022

Background Adverse childhood experiences (ACEs) are associated with posttraumatic and complex stress disorder symptoms in adulthood (PTSD/cPTSD), as well reduced epistemic trust (trust the authenticity personal relevance of interpersonally transmitted information) impaired personality functioning. The present work aims to investigate predictive value trust—the capacity for social learning—on mediating effect functioning association ACEs PTSD/cPTSD. Methods We conducted structural equation modeling (SEM) based on representative data German population ( N = 2,004). Personality (OPD-SQS) was applied a mediator between PTSD/cPTSD (ITQ), while (ETMCQ) added predictor OPD-SQS. TLI, CFI, RMSEA (95%-CI) determined models’ fit. Results 477 (23.8%) participants reported at least one ACE n 218 (10.9%) ≥4 ACEs. Fit indices were good both PTSD (TLI 0.96; CFI 0.99; 0.06; 95%CI: 0.041–0.078) cPTSD 0.043–0.081). significantly (β 0.44, p < 0.001) 0.29, 0.001), explaining 20 8% its variance. Adding increased explained variance 47 19% direct cPTSD/PTSD decreased 0.21/β 0.17), thus, indicating partial mediation. Including substantially (41%) compared single (16%). Conclusion add previous research emphasizing symptoms. Offering insights underlying mechanisms, we show that relevant mediators. Since modifiable by psychotherapy, knowledge about role these constructs can inform psychotherapeutic interventions prevention.

Language: Английский

Citations

51
The mediating role of attachment and mentalising in the relationship between childhood maltreatment, self-harm and suicidality DOI Creative Commons
Maria Stagaki, Tobias Nolte,

Janet Feigenbaum

et al.

Child Abuse & Neglect, Journal Year: 2022, Volume and Issue: 128, P. 105576 - 105576

Published: March 18, 2022

Although the relationship between childhood maltreatment, self-harm and suicidality is well-established, less known about mediating mechanisms explaining it. Based on a developmental mentalisation-based theoretical framework, adversity compromises mentalising ability attachment security, which in turn increase vulnerability to later stressors adulthood.

Language: Английский

Citations

43
DNA methylation signatures of early-life adversity are exposure-dependent in wild baboons DOI Creative Commons
Jordan A. Anderson, Dana Lin, Amanda J. Lea

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(11)

Published: March 5, 2024

The early-life environment can profoundly shape the trajectory of an animal's life, even years or decades later. One mechanism proposed to contribute these effects is DNA methylation. However, frequency and functional importance methylation in shaping on adult outcomes poorly understood, especially natural populations. Here, we integrate prospectively collected data fitness-associated variation early with estimates at 477,270 CpG sites 256 wild baboons. We find highly heterogeneous relationships between adulthood: aspects linked resource limitation (e.g., low-quality habitat, drought) are associated many more than other types environmental stressors low maternal social status). Sites enriched gene bodies putative enhancers, suggesting they functionally relevant. Indeed, by deploying a baboon-specific, massively parallel reporter assay, show that subset windows containing capable regulatory activity, that, for 88% drought-associated windows, enhancer activity methylation-dependent. Together, our results support idea patterns contain persistent signature environment. also indicate not all exposures leave equivalent mark suggest socioenvironmental time sampling likely be important. Thus, multiple mechanisms must converge explain fitness-related traits.

Language: Английский

Citations

10
Epigenetics and ADHD: Reflections on Current Knowledge, Research Priorities and Translational Potential DOI Creative Commons
Charlotte A. M. Cecil, Joel T. Nigg

Molecular Diagnosis & Therapy, Journal Year: 2022, Volume and Issue: 26(6), P. 581 - 606

Published: Aug. 6, 2022

Attention-deficit/hyperactivity disorder (ADHD) is a common and debilitating neurodevelopmental influenced by both genetic environmental factors, typically identified in the school-age years but hypothesized to have developmental origins beginning utero. To improve current strategies for prediction, prevention treatment, central challenge delineate how, at molecular level, influences jointly shape ADHD risk, phenotypic presentation, course. Epigenetic processes that regulate gene expression, such as DNA methylation, emerged promising system search biomarkers mechanisms address this challenge. In Current Opinion, we discuss relevance of epigenetics (specifically methylation) research clinical practice, starting with state knowledge, what challenges yet overcome, future may hold terms methylation-based applications personalized medicine ADHD. We conclude field still its infancy, potential transformative translational remains distant goal. Nevertheless, rapid methodological advances, together rise collaborative science increased availability high-quality, longitudinal data make thriving area contribute development new tools improved management, treatment

Language: Английский

Citations

35
An insight into sex-specific neurotoxicity and molecular mechanisms of DEHP: A critical review DOI
Yiyun Liu, Zhiling Guo,

Ruihong Zhu

et al.

Environmental Pollution, Journal Year: 2022, Volume and Issue: 316, P. 120673 - 120673

Published: Nov. 16, 2022

Language: Английский

Citations

32
Childhood maltreatment and DNA methylation: A systematic review DOI
Mackenzie Rubens, Dagmar Bruenig, Jessica Ann May Adams

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 147, P. 105079 - 105079

Published: Feb. 9, 2023

Language: Английский

Citations

21
Foster Care: How We Can, and Should, Do More for Maltreated Children DOI Open Access
Sarah A. Font, Elizabeth T. Gershoff

Social policy report, Journal Year: 2020, Volume and Issue: 33(3), P. 1 - 40

Published: Nov. 1, 2020

Abstract Foster care provides round‐the‐clock substitute for nearly 700,000 U.S. children who are temporarily or permanently separated from their family of origin each year. Each state manages its own foster system according to federal regulations. Despite numerous large‐scale policy reforms over the past several decades, substantial concerns remain about experiences and outcomes in system. The most recent effort reform care, Family First Prevention Services Act 2018, attempts both reduce use increase quality care. In this report, we review how has shaped where succeeded, it falls short achieving goals. We then identify opportunities better support safety, health, well‐being

Language: Английский

Citations

45