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

Eating Disorders, Heredity and Environmental Activation: Getting Epigenetic Concepts into Practice DOI Open Access
Howard Steiger, Linda Booij

Journal of Clinical Medicine, Journal Year: 2020, Volume and Issue: 9(5), P. 1332 - 1332

Published: May 3, 2020

Epigenetic mechanisms are believed to link environmental exposures alterations in gene expression, and so doing, provide a physical substrate for the activation of hereditary potentials by life experiences. In keeping with this idea, accumulating data suggest that epigenetic processes implicated eating-disorder (ED) etiology. This paper reviews literature on putative links between factors EDs, examines ways which programming expression could account gene-environment interactions acting EDs. The also presents evidence suggesting malnutrition stresses (gestational, perinatal, childhood, adult) risk ED development. Drawing from empirical clinical experience, we propose an epigenetically informed understanding etiology can benefit patients, caregivers, clinicians alike, sense perspective reduce judgmental or blameful attitudes part increase self-acceptance optimism about recovery those affected.

Language: Английский

Citations

43
Childhood trauma, the stress response and metabolic syndrome: A focus on DNA methylation DOI
Jacqueline S. Womersley, Jani Nöthling, Sylvanus Toikumo

et al.

European Journal of Neuroscience, Journal Year: 2021, Volume and Issue: 55(9-10), P. 2253 - 2296

Published: June 25, 2021

Childhood trauma (CT) is well established as a potent risk factor for the development of mental disorders. However, potential adverse early experiences to exert chronic and profound effects on physical health, including aberrant metabolic phenotypes, has only been more recently explored. Among these consequences syndrome (MetS), which characterised by at least three five related cardiometabolic traits: hypertension, insulin resistance/hyperglycaemia, raised triglycerides, low high-density lipoprotein central obesity. The deleterious CT health outcomes may be partially attributable dysregulation hypothalamic-pituitary-adrenal (HPA) axis, coordinates response stress, consequent fostering pro-inflammatory environment. Epigenetic tags, such DNA methylation, are sensitive environmental influences provide means whereby can biologically embedded persist into adulthood affect well-being. methylome regulates transcription genes involved in stress response, metabolism inflammation. This narrative review examines evidence methylation MetS order identify shared neuroendocrine immune correlates that mediate increased following exposure. Our specifically highlights differential FKBP5, gene encodes FK506-binding protein 51 pleiotropic responding, inflammation energy metabolism, candidate understand molecular aetiology underlying CT-associated risk.

Language: Английский

Citations

37
Combined effects of genotype and childhood adversity shape variability of DNA methylation across age DOI Creative Commons
Darina Czamara, Elleke Tissink,

Johanna Tuhkanen

et al.

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

Published: Feb. 1, 2021

Lasting effects of adversity, such as exposure to childhood adversity (CA) on disease risk, may be embedded via epigenetic mechanisms but findings from human studies investigating the main measures, including DNA methylation (DNAm), are inconsistent. Studies in perinatal tissues indicate that variability DNAm at birth is best explained by joint genotype and prenatal environment. Here, we extend these analyses postnatal stressors. We investigated contribution CA, cis (G), their additive (G + CA) interactive × blood or saliva five independent cohorts with a total sample size 1074 ranging age late adulthood. Of these, 541 were exposed which was assessed retrospectively using self-reports verified through social services registries. For majority sites (over 50%) adult cohorts, G CA almost never alone. Across ages tissues, 1672 showed consistency model all interactions explaining most variance. The consistent mapped genes enriched brain-specific transcripts Gene Ontology terms related development synaptic function. Interaction genotypes strongest variability, stable across functionally relevant genes. This underscores importance impact environmental factors marks.

Language: Английский

Citations

35
Exposure to the plasticizer, Di-(2-ethylhexyl) phthalate during juvenile period exacerbates autism-like behavior in adult BTBR T + tf/J mice due to DNA hypomethylation and enhanced inflammation in brain and systemic immune cells DOI
Ahmed Nadeem,

Naif O. Al‐Harbi,

Sheikh F. Ahmad

et al.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2021, Volume and Issue: 109, P. 110249 - 110249

Published: Jan. 23, 2021

Language: Английский

Citations

34
Transmission of the adverse consequences of childhood maltreatment across generations: Focus on gestational biology DOI Creative Commons
Nora K. Moog, Christine Heim, Sonja Entringer

et al.

Pharmacology Biochemistry and Behavior, Journal Year: 2022, Volume and Issue: 215, P. 173372 - 173372

Published: March 5, 2022

Childhood maltreatment (CM) has well-established consequences for the mental and physical health of exposed individual. Accumulating evidence now suggests that detrimental sequelae CM may be transmitted from one generation to next, thereby extending long-term ramifications early adverse experiences constituting intergenerational continuity in poor outcomes. In this review, current state knowledge on effects maternal exposure is summarized transmission pathways are discussed, specifically direct as well indirect involving variation gestational biology. The review begins with a definition an overview clinical neurobiological offspring generation. intrauterine period biology identified potential time window mechanism transmission, respectively. Furthermore, summary available supporting both biological development included. Finally, gaps challenges investigation role mechanisms addressed considerations future study designs along our studies provided.

Language: Английский

Citations

27
Childhood constipation: Current status, challenges, and future perspectives DOI Open Access
Shaman Rajindrajith, Niranga Manjuri Devanarayana, Marc A. Benninga

et al.

World Journal of Clinical Pediatrics, Journal Year: 2022, Volume and Issue: 11(5), P. 385 - 404

Published: Sept. 6, 2022

Constipation in children is a major health issue around the world, with global prevalence of 9.5%. They present to clinicians myriad clinical signs. The Rome IV symptom-based criteria are used diagnose functional constipation. Functional constipation also huge financial burden for healthcare system and has detrimental impact on health-related quality life children. There various risk factors identified globally, including centrally connected such as child abuse, emotional behavioral issues, psychological stress. precipitated by low-fiber diet, physical inactivity, an altered intestinal microbiome. main pathophysiological mechanism stool withholding, while rectal function, anal sphincter, pelvic floor, colonic dysfunction play important roles. Clinical evaluation critical making diagnosis, most investigations only required refractory patients. In treatment childhood constipation, both nonpharmacological (education de-mystification, dietary changes, toilet training, interventions, biofeedback, floor physiotherapy), pharmacological (osmotic stimulant laxatives novel drugs like prucalopride lubiprostone) interventions used. For transanal irrigation, botulinum toxin, neuromodulation, surgical treatments reserved. While frequent use probiotics still experimental stage, healthy habits, living lifestyle limiting exposure stressful events, all beneficial preventive measures.

Language: Английский

Citations

27
The body keeps the score: The neurobiological profile of traumatized adolescents DOI Creative Commons
Daniela Laricchiuta,

Anna Panuccio,

Eleonora Picerni

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 145, P. 105033 - 105033

Published: Jan. 4, 2023

Trauma-related disorders are debilitating psychiatric conditions that affect people who have directly or indirectly witnessed adversities. Experiencing multiple types of traumas appears to be common during childhood, and even more so adolescence. Dramatic brain/body transformations occurring adolescence may provide a highly responsive substrate external stimuli lead trauma-related vulnerability conditions, such as internalizing (anxiety, depression, anhedonia, withdrawal) externalizing (aggression, delinquency, conduct disorders) problems. Analyzing relations among neuronal, endocrine, immune, biochemical signatures trauma behaviors, including the role personality traits in shaping these conducts, this review highlights marked effects traumatic experience on involve changes at nearly every level analysis, from brain structure, function connectivity endocrine immune systems, gene expression (including gut) development personality.

Language: Английский

Citations

16
Examining the biological mechanisms of human mental disorders resulting from gene-environment interdependence using novel functional genomic approaches DOI Creative Commons
Patrícia Pelufo Silveira, Michael J. Meaney

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 178, P. 106008 - 106008

Published: Jan. 20, 2023

We explore how functional genomics approaches that integrate datasets from human and non-human model systems can improve our understanding of the effect gene-environment interplay on risk for mental disorders. start by briefly defining G-E paradigm its challenges then discuss different levels regulation gene expression corresponding data existing in humans (genome wide genotyping, transcriptomics, DNA methylation, chromatin modifications, chromosome conformational changes, non-coding RNAs, proteomics metabolomics), discussing novel to application these study origins health. Finally, we multilevel integration diverse types data. Advance use context a perspective improves detection vulnerabilities, informing development preventive therapeutic interventions.

Language: Английский

Citations

14
Childhood Maltreatment and Longitudinal Epigenetic Aging DOI Creative Commons
Olivia D. Chang, Helen C.S. Meier, Kathryn Maguire‐Jack

et al.

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(7), P. e2421877 - e2421877

Published: July 29, 2024

Importance Child physical and emotional abuse neglect may affect epigenetic signatures of accelerated aging several years after the exposure. Objective To examine longitudinal outcomes early-childhood midchildhood exposures to maltreatment on later childhood adolescent profiles aging. Design, Setting, Participants This cohort study used data from Future Families Wellbeing Study (enrolled 1998-2000), a US birth with available DNA methylation (DNAm) at ages 9 15 (assayed between 2017 2020) phenotypic (wave 1), 3 3), 5 4), 5), 6) years. Data were analyzed June 18 December 10, 2023. Exposures Emotional aggression, assault, neglect, via Parent-Child Conflict Tactics Scale Main Outcomes Measures Epigenetic (DNAmAA) was measured using machine learning–derived surrogates (GrimAge, PhenoAge, DunedinPACE) 2 age (Horvath PedBE), residualized for in months. Results A total 1971 children (992 [50.3%] male) representative births large cities 1998 2000 included. Physical assault positively associated DNAmAA PhenoAge (β = 0.073; 95% CI, 0.019-0.127), aggression negatively −0.107; −0.162 −0.052). 0.051; 0.006-0.097). Cumulative exposure 0.063; 0.003-0.123); −0.104; −0.165 −0.043). The association these measures almost fully mediated by DNAm acceleration. Similar patterns found GrimAge, DunedinPACE, but only those remained adjustments multiple comparisons. Conclusions Relevance In this study, altered sensitive type timing child appeared be more proximate biological embedding stress.

Language: Английский

Citations

6
A Systematic Review of the Biological Correlates and Consequences of Childhood Maltreatment and Adverse Childhood Experiences DOI
Eric M. Cooke, Eric J. Connolly,

Danielle Boisvert

et al.

Trauma Violence & Abuse, Journal Year: 2021, Volume and Issue: 24(1), P. 156 - 173

Published: June 9, 2021

Childhood maltreatment (CM) and adverse childhood experiences (ACEs) are two primary forms of interpersonal victimization that have been associated with a host deleterious health outcomes. Studies over the past decade begun to use range biologically informed methods better understand role biology plays in relationship between CM, ACEs, later life This line research has shown both occur at sensitive periods development, which can increase likelihood “getting under skin” influence behavior across course. review examines current state knowledge on this hypothesis. One hundred ninety-nine studies included systematic based criteria they be written English, method, conducted samples humans. Results reveal latent additive genetic influences, biological system functioning captured by biomarkers, polygenic risk scores, neurobiological factors commonly exposure response CM ACEs. The implication these findings for existing body early recommendations future policy discussed.

Language: Английский

Citations

29