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The effect of maltreatment developmental timing on ANKK1 methylation. Significant contrast: early onset–not recent . nonmaltreated. p , .05.
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In the present investigation, differential methylation analyses of the whole genome were conducted among a sample of 548 school-aged low-income children (47.8% female, 67.7% Black, M age = 9.40 years), 54.4% of whom had a history of child maltreatment. In the context of a summer research camp, DNA samples via saliva were obtained. Using GenomeStudi...
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Epigenetics processes may play a vital role in the biological embedding of early environmental adversity and the development of psychopathology. Accumulating evidence suggests that maltreatment is linked to methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), which is a key regulator of the hypot...
Citations
... We observed that methylation in NR3C1 was largely not associated with our measures of interest. In summary, although NR3C1 is commonly found to be hypermethylated with increasing incidence of adversity (for review, see Parade et al. (2021)), some studies have reported that NR3C1 methylation is not linked with adversity or maternal sensitivity (Berretta et al., 2021;Cicchetti et al., 2016;Daskalakis & Yehuda, 2014;Hecker et al., 2016), and our results presented here align with these latter findings. ...
... Overall, this study was one of the largest intervention trials to date that longitudinally tracked child and adult DNA methylation in saliva and in relationship to adversity and the home social environment and to an intervention exposure. Our results somewhat agree with other clinical trials that demonstrate an epigenetic response to psychological interventions in infants (Euclydes et al., 2022;Hoye et al., 2020) and children (Bleker et al., 2019;Brody et al., 2016;Cicchetti et al., 2016) at risk of experiencing adversity, but many of our measures were not associated with DNA methylation. We assayed results in saliva, which is readily accessible, but cannot necessarily be used to infer DNA methylation in the central nervous system or other biologically relevant tissues. ...
Introduction
Early childhood development is a strong predictor of long‐term health outcomes, potentially mediated via epigenetics (DNA methylation). The aim of the current study was to examine how childhood experiences, punitive parenting, and an intergenerational psychotherapeutic intervention may impact DNA methylation in young children and their mothers.
Methods
Mothers and their infants/toddlers between 0 and 24 months were recruited at baseline (n = 146, 73 pairs) to participate in a randomized control trial evaluating the effectiveness of The Michigan Model of Infant Mental Health Home Visiting (IMH‐HV) parent–infant psychotherapy compared to treatment as usual. Baseline and 12‐month post‐enrollment data were collected in the family's home and included self‐report questionnaires, biological saliva samples, home environment observation, video‐taped parent–child interaction, and audio‐recorded interviews. Saliva DNA methylation was measured at the genes, nuclear receptor subfamily 3 group C member 1 (NR3C1), solute carrier family 6 member 4 (SLC6A4), brain‐derived neurotrophic factor (BDNF), and the genetic element, long interspersed nuclear element‐1 (LINE1).
Results
For mothers, baseline methylation of BDNF, SLC6A4, NR3C1, or LINE1 was largely not associated with baseline measures of their childhood adversity, adverse life experiences, demographic characteristics related to structurally driven inequities, or to IMH‐HV treatment effect. In infants, there were suggestions that methylation in SLC6A4 and LINE1 was associated with parenting attitudes. Infant BDNF methylation suggested an overall decrease in response to IMH‐HV psychotherapy over 12 months.
Conclusions
Overall, our findings suggest that the epigenome in infants and young children may be sensitive to both early life experiences and parent–infant psychotherapy.
... There may also be a genetic component to this intergenerational link. For example, several studies have reported changes in their DNA (in the form of higher levels of methylation) across several sites in people subjected to CM versus those who were not (Cicchetti et al., 2016;Pezzoli et al., 2019), and therefore genetic explanations need to be considered in these groups. ...
... That is, in individuals who have been maltreated in childhood, although decades ago, lower NR3C1 gene expression in the brain suggests vulnerability in the negative feedback system of the HPA axis. Many other studies have reported the association of DNA methylation of the NR3C1 with childhood maltreatment, not in brain tissue, but in peripheral tissues such as blood and saliva [40][41][42][43] . Thus, epigenetic changes in the NR3C1 gene resulting from chronic extreme stress in CM may cause a vulnerable HPA axis. ...
Childhood maltreatment is reportedly associated with atypical gray matter structures in the primary visual cortex (V1). This study explores the hypothesis that retinal structures, the sensory organs of vision, are associated with brain atypicality and child maltreatment and examines their interrelation. General ophthalmologic examinations, visual cognitive tasks, retinal imaging, and structural magnetic resonance imaging (MRI) were conducted in children and adolescents aged 9–18 years with maltreatment experiences (CM) and typically developing (TD) children. The retinal nerve fiber layer (RNFL), the most superficial of the ten distinct retinal layers, was found to be significantly thinner in both eyes in CM. While whole-brain analysis using Voxel-based morphometry revealed a significantly larger gray matter volume (GMV) in the thalamus in CM, no significant correlation with RNFL thickness was observed. However, based on region-of-interest analysis, a thinner RNFL was associated with a larger GMV in the right V1. Although it cannot be ruled out that this outcome resulted from maltreatment alone, CM demonstrated subclinical structural atypicality in the retina, which may also correlate with the immaturity of V1 development. Examination of retinal thickness offers a novel clinical approach to capturing characteristics associated with childhood maltreatment.
... Department of Health & Human Services, 2020). For many decades, the research literature has indicated that children who suffer from maltreatment are more likely to develop problems in multiple domains of functioning (Cicchetti et al., 2016;Turner et al., 2010: Widom, 2014. ...
Child maltreatment is a global health concern that affects approximately one in four children worldwide and significantly affects the well-being over the life course of those involved (World Health Organization, 2016). Interest has increasingly focused on the role of neighborhood and community context in understanding child maltreatment. Our study objective was to examine what neighbors, who were themselves child caregivers, would recommend to other neighborhood families in need of assistance, paying particular attention to the degree to which informal support was recommended compared to other options. The stratified random sample of 400 residents of 20 urban neighborhoods who cared for at least one child under 18 years of age was presented with five scenarios, each involving a specific need: baby care, child care, parenting issues, basic needs, and medical care. Qualitative analyses of open-ended responses revealed four primary findings: (1) formal support is a consistent and stable resource for any need; (2) informal support is a complicated and nuanced form of assistance to recommend; (3) the church is a dominant resource for basic needs; and (4) most participants recommended something. Findings suggest that although most neighbors offer suggestions, these may be nuanced and conditional, depending on family needs, particularly for informal support. Findings suggest that development of community-based programs building on informal support mechanisms must account for the perspective of neighborhood residents, who are in the position to recommend resources and offer support.
... Violence in childhood can have long-term consequences through direct and indirect pathways, by the risk of immediate physical injury, psychological disorders, and chronic stress, and then the adoption of coping strategies such as smoking and drug use which add further risk to future health (Lawrence et al., 2023;Nelson et al., 2020). There is now growing evidence to suggest violence in childhood can impact brain development and produce epigenetic changes, which when combined with mediators such as psychological distress and health risk behaviours, can result in lower educational attainment, poor health outcomes and therefore impact economic and disease burden (Cicchetti et al., 2016;Nelson et al., 2020). ...
... Less than ten EWAS attempts with children close to the time of their maltreatment have been conducted. 5,6,7,8,9,10,11 Conducted in highly di cult environments, their results have limitations. The aforementioned studies have provided genome-wide analysis results but have not yet been su cient, such as have only presented a list of thousands of relevant methylations 6 , have been limited to results for candidate genes 5 , have only shown qualitative differences in methylation patterns 8 , or have had rare subjects and small sample sizes 7 . ...
... 5,6,7,8,9,10,11 Conducted in highly di cult environments, their results have limitations. The aforementioned studies have provided genome-wide analysis results but have not yet been su cient, such as have only presented a list of thousands of relevant methylations 6 , have been limited to results for candidate genes 5 , have only shown qualitative differences in methylation patterns 8 , or have had rare subjects and small sample sizes 7 . Recently, a large prospective cohort study examined the association between blood DNA methylation at age 15 and childhood adversity experienced from ages 0-11 years old. ...
... PA: physical abuse, EA: emotional abuse, SA: sexual abuse, NG: neglect, SDQ; Strength and Di culties Questionnaire, DSRS-C; Depression Self-Rating Scale for Children, a : Missing data for CM (3), and TD (7), b : Missing data for CM(5), -values were computed using t-test (for continuous variables) and c2 test (for categorical variables) for comparison of CM and TD groups. PA: physical abuse, EA: emotional abuse, SA: sexual abuse, NG: neglect, SDQ; Strength and Di culties Questionnaire, DSRS-C; Depression Self-Rating Scale for Children, a : Missing data for CM(3), and TD (7), b : Missing data for CM (5), c : Missing data for CM(5) Judicial Autopsy Cases Twenty-six children authenticated by a forensic pathologist (M.N.) during 2000-2021 were included. Of these, 15 (CM) cases had cause of death due to child abuse and the other 11 (TD) cases were due to fatal accidents or illness (Supplementary ...
Child maltreatment (CM) leads to adverse outcomes in later life. We describe the epigenome-wide analyses and meta-analysis results of three original cohorts consisting of judicially or socially certified CM cases and controls to gain further insight into the epigenetic signatures engraved in maltreated children. We also show associations with biological indicators (endophenotypes) in each cohort that represent CM features with maltreatment history, thus providing further confidence in the identified methylations. Four methylations in ATE1 , CHST11 , SERPINB9P1 , and FOXP1 associate with CM in the meta-analysis, in addition to several genome-wide level significant methylations in each cohort. FOXP1 , a gene related to neurodevelopmental disorders, is of particular interest, as its methylation level correlates with atypical brain structures representing in maltreated children and contributes to the accuracy of a methylation risk score to predict CM. These results suggest that severe CM experiences may contribute to neurodevelopmental-like and traumatic symptoms via epigenetic alterations.
... That is, in individuals who have been maltreated in childhood, although decades ago, NR3C1 gene expression in the brain could be lower, suggesting that the negative feedback system of the HPA axis is vulnerable. Many other studies have reported that DNA methylation of the NR3C1 gene is associated with child maltreatment, not in brain tissue, but peripheral tissues, such as blood and saliva [40][41][42][43]. Therefore, epigenetic changes in the NR3C1 gene resulting from chronic extreme stress in CM may cause a vulnerable HPA axis. ...
Individuals who experienced childhood maltreatment reportedly have atypical gray matter structures in their primary visual cortex (V1). Thus, we hypothesized that the sensory structures of vision may also be affected by these influences and are related to each other. General ophthalmologic examinations, visual cognitive tasks, retinal imaging, and brain structural magnetic resonance imaging (MRI) were performed to compare the differences between children and adolescents aged 9–18 years with maltreatment experiences (CM) and typically developing (TD) children. The retinal nerve fiber layer (RNFL) and the segment (GCL++) summed with the RNFL and ganglion cell layer with the inner plexiform layer of the macular were significantly thinner in both eyes in CM. Although whole-brain analysis of Voxel-Based Morphometry revealed a significantly larger gray matter volume (GMV) in the thalamus compared to TD, there was no significant correlation with RNFL and GCL + + thickness. Based on the region-of-interest analysis, the thinner RNFL and GCL + + were associated with a larger GMV in the right V1. Owing to abusive experiences, CM showed subclinical structural atypicality in the retina, which may account for the immature V1 development since brain regions remain larger. Examination of retinal thickness could be a new clinical approach to capture CM characteristics.
... In addition to changes in immunological function, changes in DNA methylation occur after exposure to ACEs and in the setting of low socioeconomic status [42,45]. In a study [46] of 548 children participating in day camps for low-income families, there were significant differences in DNA methylation patterns in saliva samples between children who were maltreated compared to those who were not. The saliva samples were taken during the time of maltreatment, as the researchers worked with a population of low income children who were exposed during the time of the study. ...
... The saliva samples were taken during the time of maltreatment, as the researchers worked with a population of low income children who were exposed during the time of the study. These alterations included genomic regions of both hyper-and hypo-methylation in the maltreated children when they were compared to the healthy controls [46]. These findings have been corroborated in other studies [45,47], one of which was longitudinal [45] while the other was not [47]. ...
Objective:
To review the literature regarding systemic lupus erythematosus (SLE) in American Indian/Alaska Native (AI/AN) people and relate prevalence and/or disease severity to our emerging understanding of the biology of trauma and toxic stress.
Methods:
We conducted a search and review of the literature using search terms "lupus and American Indians" "ACEs and disease outcome" "Biology of Adversity" "lupus and ACE scores," " lupus and childhood abuse." These search criteria were entered into Google Scholar and articles retrieved from PubMed, NBCI. This approach yielded a small numbers of papers used throughout this review. We excluded articles that were not published in a peer reviewed journals, as well as editorial commentaries.
Results:
In the AI/AN population, SLE shows high prevalence rates and severe disease manifestations, comparable to the African American population. AI/AN populations also have high rates of childhood trauma. Toxic stress and trauma such as those catalogued in the Adverse Childhood Experiences (ACE) study have broad-reaching immunologic and epigenetic effects that are likely to be relevant to our understanding of SLE in AI/AN people.
Conclusions:
AI/AN people have high rates of SLE. These high rates are likely to be driven by many complex factors, not all of which are genetic. Future research is needed to establish (or refute) a causal connection between the biology of adversity and SLE in socially marginalized and historically traumatized populations.
... In recent years, increased research interest in the topic of child maltreatment has allowed for a better understanding and recognition of its devastating short-term and lifelong consequences on children, including physical health problems (Afifi et al., 2016;Monnat & Chandler, 2015), psychological and mental health difficulties (Bick & Nelson, 2016;Cicchetti et al., 2016), behaviour difficulties and risk-taking behaviour (LeTendre & Reed, 2017;Thompson et al., 2017), and enduring neurobiological effects (Teicher & Samson, 2016). Child maltreatment encompasses all types of child abuse and neglect that occur in the context of a relationship based on trust, power or responsibility and have actual or potential consequences of harm to a child (World Health Organisation [WHO], 2022). ...
Child neglect has devastating enduring consequences for children and its identification and assessment remains challenging for practitioners. In England, assessment tools and standardised measures have been incorporated in welfare and safeguarding practice to help practitioners' critical observation and analysis and improve their assessments of risk. However, the picture regarding child neglect assessment practice trends on the ground remains unknown. This mapping exercise aimed to, firstly, provide an overview of the approaches to neglect practice and neglect assessment tools promoted by Local Safeguarding Children Partnerships (LSCPs) across England, and secondly, provide a brief examination of the types of tools advocated. An email survey was sent to the safeguarding leads or chairs of LSCPs in England ( n = 121). Forty‐two valid responses were received (34.7%). Almost all participating LSCPs had a Neglect Strategy in place and recommended the use of tools and chronologies when working with neglect. Eighteen individual neglect tools were reported with only two of these having undergone psychometric testing. The findings affirm that the use of tools or instruments with low or no testing for psychometric properties continues to be widespread in children's social care and welfare practice in England. Implications and recommendations for practice, policy and future research are discussed.
... Over the first 18 years of life, it is estimated that 1 in 8 U.S. children will be substantiated victims of child maltreatment (Wildeman et al., 2014). Child maltreatment has deleterious consequences for children and families, with victims of maltreatment being more likely to have academic, social, and behavioral challenges (Pei, Yoon, Maguire-Jack, & Lee, 2022), physical and mental health issues (Cicchetti, Hetzel, Rogosch, Handley, & Toth, 2016), and longer-term consequences with higher rates of involvement in other systems such as juvenile justice and adult corrections (Widom, 2017). In addition to neighborhood context, there are a number of factors associated with child abuse, including the parent-child relationship, parent perception of the child as a problem, parent anger/hyper-reactivity, child social competence, parent age, and high family conflict and low family cohesion (Stith et al., 2009). ...
Introduction:
Using data from the nationally representative longitudinal Future of Families and Child Wellbeing Study, the current study sought to examine associations between neighborhood disorder and physical characteristics of the neighborhood at child age three with the likelihood of experiencing physical and psychological abuse and neglect at age five.
Methods:
Negative binomial regression and zero inflated negative binomial regression models were used to estimate the associations.
Results:
Resident perceptions of neighborhood disorder and outside observation of neighborhood physical characteristics were both found to be independently related to the likelihood of physical assault. Resident perceptions were related to psychological aggression. A more positive perception of the neighborhood environment for children (lack of neighborhood disorder) and physical characteristics of the neighborhood were protective against maltreatment. These relationships were not significant for neglect.
Discussion:
Neighborhood environment is a crucial contributor to maltreatment risk. Findings from the present study showed that multiple perceptions of neighborhood quality were associated with lower risk for child physical assault and psychological aggression. Mothers' perceptions of a more positive neighborhood environment were associated with significantly lower physical assault and psychological aggression scores.
