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Adverse childhood experiences, DNA methylation age acceleration, and cortisol in UK children: a prospective population-based cohort study.

ABSTRACT: BACKGROUND:Epigenetic mechanisms may partly explain the persistent effects of adverse childhood experiences (ACEs) on health outcomes in later life. DNA methylation can predict chronological age, and advanced methylation-predicted age beyond chronological age (DNA methylation age acceleration) is associated with ACEs, adverse mental and physical health, and elevated diurnal and baseline salivary cortisol. Childhood adversity is also associated with dysregulation of the hypothalamic-pituitary-adrenal axis, which produces the neuroendocrine hormone cortisol. It remains unknown whether these associations are specific to certain types of adversity. Herein, we investigate the associations of ACEs with DNA methylation age acceleration and plasma cortisol in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. METHODS:In this study of the children in ALSPAC, we used multiple linear regression to examine associations of cumulative exposure to ACE, as well as exposure to ten individual types of ACEs, with Horvath-estimated DNA methylation age acceleration and with baseline plasma cortisol. The ten ACEs were those included in the World Health Organization's ACE International Questionnaire. Data on ACEs were prospectively collected from age 0-14?years. DNA methylation age acceleration and plasma cortisol were measured at mean 17.1?years and 15.5?years, respectively. RESULTS:We included 974 UK children in the present study. Exposure to four or more ACEs compared to zero was associated with DNA methylation age acceleration in girls (?, 95% CI = 1.65, 0.25 to 3.04?years) but not in boys (?, 95% CI = - 0.11, - 1.48 to 1.26?years). Also, in girls, emotional abuse and physical abuse were each associated with DNA methylation age acceleration (?, 95% CI = 1.20, 0.15 to 2.26?years and ?, 95% CI = 1.22, 0.06 to 2.38?years, respectively). No other ACEs were associated with accelerated DNA methylation age in either sex. Associations were also null between ACE and cortisol, and cortisol and DNA methylation age acceleration. CONCLUSIONS:In this prospective population-based study of UK children, cumulative ACE exposure, emotional abuse, and physical abuse between age 0 and 14?years were each associated with Horvath-estimated DNA methylation age acceleration at age 17?years in girls but not in boys.

SUBMITTER: Tang R

PROVIDER: S-EPMC7137290 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Adverse childhood experiences, DNA methylation age acceleration, and cortisol in UK children: a prospective population-based cohort study.

Tang Rosalind R Howe Laura D LD Suderman Matthew M Relton Caroline L CL Crawford Andrew A AA Houtepen Lotte C LC

Clinical epigenetics 20200407 1

<h4>Background</h4>Epigenetic mechanisms may partly explain the persistent effects of adverse childhood experiences (ACEs) on health outcomes in later life. DNA methylation can predict chronological age, and advanced methylation-predicted age beyond chronological age (DNA methylation age acceleration) is associated with ACEs, adverse mental and physical health, and elevated diurnal and baseline salivary cortisol. Childhood adversity is also associated with dysregulation of the hypothalamic-pitui ...[more]

PMID: 32264940

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Project description:BackgroundAdverse childhood experiences (ACEs) increase the risk of poor health outcomes later in life. Psychosocial stressors may also have intergenerational health effects by which parental ACEs are associated with mental and physical health of children. Epigenetic programming may be one mechanism linking parental ACEs to child health. This study aimed to investigate epigenome-wide associations of maternal preconception ACEs with DNA methylation patterns of children. In the Center for the Health Assessment of Mothers and Children of Salinas study, cord blood DNA methylation was measured using the Illumina HumanMethylation450 BeadChip. Preconception ACEs, which occurred during the mothers' childhoods, were collected using a standard ACE questionnaire including 10 ACE indicators. Maternal ACE exposures were defined in this study as (1) the total number of ACEs; (2) the total number of ACEs categorized as 0, 1-3, and > 4; and (3) individual ACEs. Associations of ACE exposures with differential methylated positions, regions, and CpG modules determined using weighted gene co-expression network analysis were evaluated adjusting for covariates.ResultsData on maternal ACEs and cord blood DNA methylation were available for 196 mother/newborn pairs. One differential methylated position was associated with maternal experience of emotional abuse (cg05486260/FAM135B gene; q value < 0.05). Five differential methylated regions were significantly associated with the total number of ACEs, and 36 unique differential methylated regions were associated with individual ACEs (Šidák p value < 0.05). Fifteen CpG modules were significantly correlated with the total number of ACEs or individual ACEs, of which 8 remained significant in fully adjusted models (p value < 0.05). Significant modules were enriched for pathways related to neurological and immune development and function.ConclusionsMaternal ACEs prior to conception were associated with cord blood DNA methylation of offspring at birth. Although there was limited overlap between differential methylated regions and CpGs in modules associated with ACE exposures, statistically significant regions and networks were related to genes involved in neurological and immune function. Findings may provide insights to pathways linking psychosocial stressors to health. Further research is needed to understand the relationship between changes in DNA methylation and child health.

Project description:Adverse childhood experiences (ACEs) are linked to adverse health outcomes for adults and children in the United States. The prevalence of critically ill children who are exposed to ACEs is not known. Our objective was to compare the frequency of ACEs of critically ill children with that of the general pediatric population of Georgia and the United States using publicly available National Survey of Children's Health (NSCH) data. The impact of ACEs on patient-reported outcome measures of emotional, social, and physical health in critically ill children is not known. We sought to determine whether a higher total number of ACEs was associated with poorer patient-reported measures of emotional, social, and physical health. We conducted a prospective cross-sectional study of children < 18 years of age who were admitted to a 36-bed free-standing, quaternary academic pediatric intensive care unit in Atlanta, Georgia from June 2020-December 2021. Parents of patients who were admitted to the pediatric intensive care unit completed a survey regarding their child's ACEs, health care use patterns, and patient-reported outcome measures (PROMIS) of emotional, social, and physical health. Prevalence estimates of ACEs were compared with national and state data from the NSCH using Rao-Scott Chi-square tests. PROMIS measures reported within the PICU cohort were compared with population normed T-scores. The association of cumulative ACEs within the PICU cohort with patient-reported outcomes of emotional, social, and physical health were evaluated with a t-test. Among the 84 participants, 54% had ≥ 1 ACE, 29% had ≥ 2 ACEs, and 10% had ≥ 3 ACEs. Children with ≥ 2 ACEs had poorer anxiety and family relationship T-scores compared to those with ≤ 1 ACE. Given the high burden of ACEs in critically ill children, screening for ACEs may identify vulnerable children that would benefit from interventions and support to mitigate the negative effects of ACEs and toxic stress on emotional, social, and physical health.

Dataset Information

Adverse childhood experiences, DNA methylation age acceleration, and cortisol in UK children: a prospective population-based cohort study.

Publications

Adverse childhood experiences, DNA methylation age acceleration, and cortisol in UK children: a prospective population-based cohort study.

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