Multi-epigenome-wide analyses and meta-analysis of child maltreatment in judicial autopsies and intervened children and adolescents
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE239522 | GEO | 2025/09/16
REPOSITORIES: GEO
Similar Datasets
Project description:Child maltreatment (CM) is associated with adverse physical, psychological, and neurodevelopmental outcomes later in life. Epigenetic modifications, particularly DNA methylation, have been proposed as potential mechanisms underlying these long-term effects. To identify robust CM-associated methylation signatures, we conducted epigenome-wide analyses across three independent cohorts: judicial autopsy cases (CM:11, Controls:7), toddlers shortly after social intervention (CM:36, Controls:49), and adolescents who underwent brain MRI (CM:61, Controls:62). Each cohort was analyzed separately, followed by a meta-analysis to identify common methylation sites associated with CM exposure. The meta-analysis identified four significant CpG sites located within the ATE1, SERPINB9P1, CHST11, and FOXP1 genes. Among these, methylation of FOXP1 was consistently associated with structural brain alterations, including increased gray matter volume (GMV) in the orbitofrontal cortex (OFrC) and middle/posterior cingulate gyrus (MPCG), and decreased GMV in the occipital fusiform gyrus (OFuG). These brain regions are implicated in emotional regulation, memory retrieval, and social cognition, suggesting a potential neurobiological mechanism linking CM to later psychopathology. Furthermore, methylation risk scores (MRS) derived from these four CpGs successfully discriminated individuals who experienced early-life adversity in an independent validation dataset, achieving an area under the receiver operating characteristic curve (AUC) of 0.672, highlighting their potential utility as biomarkers. Gene ontology and pathway analyses revealed enrichment of cholinergic and glutamatergic synaptic transmission pathways, supporting their involvement in traumatic memory formation. Our findings provide novel insights into the epigenetic mechanisms underlying CM and identify potential biomarkers for early detection, prevention, and therapeutic intervention, ultimately contributing to breaking the intergenerational cycle of maltreatment.
2025-09-16 | GSE239521 | GEO
Project description:Child maltreatment (CM) is associated with adverse physical, psychological, and neurodevelopmental outcomes later in life. Epigenetic modifications, particularly DNA methylation, have been proposed as potential mechanisms underlying these long-term effects. To identify robust CM-associated methylation signatures, we conducted epigenome-wide analyses across three independent cohorts: judicial autopsy cases (CM:11, Controls:7), toddlers shortly after social intervention (CM:36, Controls:49), and adolescents who underwent brain MRI (CM:61, Controls:62). Each cohort was analyzed separately, followed by a meta-analysis to identify common methylation sites associated with CM exposure. The meta-analysis identified four significant CpG sites located within the ATE1, SERPINB9P1, CHST11, and FOXP1 genes. Among these, methylation of FOXP1 was consistently associated with structural brain alterations, including increased gray matter volume (GMV) in the orbitofrontal cortex (OFrC) and middle/posterior cingulate gyrus (MPCG), and decreased GMV in the occipital fusiform gyrus (OFuG). These brain regions are implicated in emotional regulation, memory retrieval, and social cognition, suggesting a potential neurobiological mechanism linking CM to later psychopathology. Furthermore, methylation risk scores (MRS) derived from these four CpGs successfully discriminated individuals who experienced early-life adversity in an independent validation dataset, achieving an area under the receiver operating characteristic curve (AUC) of 0.672, highlighting their potential utility as biomarkers. Gene ontology and pathway analyses revealed enrichment of cholinergic and glutamatergic synaptic transmission pathways, supporting their involvement in traumatic memory formation. Our findings provide novel insights into the epigenetic mechanisms underlying CM and identify potential biomarkers for early detection, prevention, and therapeutic intervention, ultimately contributing to breaking the intergenerational cycle of maltreatment.
2025-09-16 | GSE239517 | GEO
Project description:Child maltreatment (CM) is associated with adverse physical, psychological, and neurodevelopmental outcomes later in life. Epigenetic modifications, particularly DNA methylation, have been proposed as potential mechanisms underlying these long-term effects. To identify robust CM-associated methylation signatures, we conducted epigenome-wide analyses across three independent cohorts: judicial autopsy cases (CM:11, Controls:7), toddlers shortly after social intervention (CM:36, Controls:49), and adolescents who underwent brain MRI (CM:61, Controls:62). Each cohort was analyzed separately, followed by a meta-analysis to identify common methylation sites associated with CM exposure. The meta-analysis identified four significant CpG sites located within the ATE1, SERPINB9P1, CHST11, and FOXP1 genes. Among these, methylation of FOXP1 was consistently associated with structural brain alterations, including increased gray matter volume (GMV) in the orbitofrontal cortex (OFrC) and middle/posterior cingulate gyrus (MPCG), and decreased GMV in the occipital fusiform gyrus (OFuG). These brain regions are implicated in emotional regulation, memory retrieval, and social cognition, suggesting a potential neurobiological mechanism linking CM to later psychopathology. Furthermore, methylation risk scores (MRS) derived from these four CpGs successfully discriminated individuals who experienced early-life adversity in an independent validation dataset, achieving an area under the receiver operating characteristic curve (AUC) of 0.672, highlighting their potential utility as biomarkers. Gene ontology and pathway analyses revealed enrichment of cholinergic and glutamatergic synaptic transmission pathways, supporting their involvement in traumatic memory formation. Our findings provide novel insights into the epigenetic mechanisms underlying CM and identify potential biomarkers for early detection, prevention, and therapeutic intervention, ultimately contributing to breaking the intergenerational cycle of maltreatment.
2025-09-16 | GSE239520 | GEO
Project description:Child maltreatment (CM) is associated with adverse physical, psychological, and neurodevelopmental outcomes later in life. Epigenetic modifications, particularly DNA methylation, have been proposed as potential mechanisms underlying these long-term effects. To identify robust CM-associated methylation signatures, we conducted epigenome-wide analyses across three independent cohorts: judicial autopsy cases (CM:11, Controls:7), toddlers shortly after social intervention (CM:36, Controls:49), and adolescents who underwent brain MRI (CM:61, Controls:62). Each cohort was analyzed separately, followed by a meta-analysis to identify common methylation sites associated with CM exposure. The meta-analysis identified four significant CpG sites located within the ATE1, SERPINB9P1, CHST11, and FOXP1 genes. Among these, methylation of FOXP1 was consistently associated with structural brain alterations, including increased gray matter volume (GMV) in the orbitofrontal cortex (OFrC) and middle/posterior cingulate gyrus (MPCG), and decreased GMV in the occipital fusiform gyrus (OFuG). These brain regions are implicated in emotional regulation, memory retrieval, and social cognition, suggesting a potential neurobiological mechanism linking CM to later psychopathology. Furthermore, methylation risk scores (MRS) derived from these four CpGs successfully discriminated individuals who experienced early-life adversity in an independent validation dataset, achieving an area under the receiver operating characteristic curve (AUC) of 0.672, highlighting their potential utility as biomarkers. Gene ontology and pathway analyses revealed enrichment of cholinergic and glutamatergic synaptic transmission pathways, supporting their involvement in traumatic memory formation. Our findings provide novel insights into the epigenetic mechanisms underlying CM and identify potential biomarkers for early detection, prevention, and therapeutic intervention, ultimately contributing to breaking the intergenerational cycle of maltreatment.
2025-09-16 | GSE239518 | GEO
Project description:In the current study a three-generational design was used to investigate intergenerational transmission of child maltreatment (ITCM) using multiple sources of information on child maltreatment: mothers, fathers and children. A total of 395 individuals from 63 families reported on maltreatment. Principal Component Analysis (PCA) was used to combine data from mother, father and child about maltreatment that the child had experienced. This established components reflecting the convergent as well as the unique reports of father, mother and child on the occurrence of maltreatment. Next, we tested ITCM using the multi-informant approach and compared the results to those of two more common approaches: ITCM based on one reporter and ITCM based on different reporters from each generation. Results of our multi-informant approach showed that a component reflecting convergence between mother, father, and child reports explained most of the variance in experienced maltreatment. For abuse, intergenerational transmission was consistently found across approaches. In contrast, intergenerational transmission of neglect was only found using the perspective of a single reporter, indicating that transmission of neglect might be driven by reporter effects. In conclusion, the present results suggest that including multiple informants may be necessary to obtain more valid estimates of ITCM.
| S-EPMC7067458 | biostudies-literature
Project description:BackgroundChild maltreatment poses high risks to the mental health and cognitive functioning of children not only in childhood but also in later life. However, it remains unclear whether child maltreatment is directly associated with impaired cognitive functioning or whether this link is mediated by mental health problems. Our study aimed at examining this research question among children and adolescents in Uganda.MethodsA sample of 232 school-going children and adolescents with a mean age of 14.03 (SD = 3.25) was assessed on multiple forms of maltreatment using the Maltreatment and Abuse Chronology Exposure-Pediatric Version (pediMACE). Executive functions were assessed by the Tower of London task and working memory by the Corsi Block Tapping task, while mental health problems were assessed using the Child PTSD Symptom Scale for PTSD and the Center for Epidemiological Studies Depression Scale for Children (CES-DC).ResultsIn total, 232 (100%) of the participant reported to have experienced at least one type of maltreatment in their lifetime including emotional, physical, and sexual violence as well as neglect. We found a negative association between child maltreatment and executive functions (β = - 0.487, p < 0.001) and working memory (β = - 0.242, p = 0.001). Mental health problems did not mediate this relationship.ConclusionsChild maltreatment seems to be related to lower working memory and executive functioning of affected children and adolescents even after controlling for potential cofounders. Our study indicates that child maltreatment the affects children's cognitive functionality beyond health and well-being.
| S-EPMC8091686 | biostudies-literature
Project description:Injuries constitute a large share of childhood morbidity and mortality. This study examines whether adolescents with self-reported experiences of different types of child maltreatment more frequently reported unintentional injury events requiring health- or dental care during the last year and/or hospitalization at any time during childhood. Cross-sectional data from a Swedish national representative school survey (2016) including 4741 adolescents were used (78.5% response rate). Data were analyzed with univariate tests and multiple logistic regression. Statistically significant associations between reported experiences of physical, psychological and sexual abuse, neglect, and witnessing partner violence during childhood and reported unintentional injuries requiring health- or dental care during the last year were found (aOR:s between 1.39-1.77). The corresponding association for poly-victimization was aOR 1.91 (95% CI 1.39-2.62). Furthermore, a linear-by-linear association was seen for degree of victimization and number of episodes of unintentional injuries that required care in the last year (p = 0.000), as well as lifetime hospitalizations (p = 0.000). This study shows significant associations between child maltreatment and unintentional injuries requiring health- and/or dental care and hospitalization. To improve both injury and child maltreatment prevention, healthcare professionals need to pay particular attention to children and adolescents who repeatedly seek healthcare services due to injurious events.
| S-EPMC10093922 | biostudies-literature
Project description:ObjectivesTo determine the prevalence in Australia of multi-type child maltreatment, defined as two or more maltreatment types (physical abuse, sexual abuse, emotional abuse, neglect, or exposure to domestic violence) and to examine its nature, family risk factors, and gender and age cohort differences.DesignRetrospective cross-sectional survey using a validated questionnaire.Setting and participantsMobile phone random digit-dial sample of the Australian population aged 16 years and older.Main outcome measuresNational estimates of multi-type child maltreatment up to age 18 years using the Juvenile Victimisation Questionnaire-R2: Adapted Version (Australian Child Maltreatment Study).ResultsOf 8503 participants, 62.2% (95% CI, 60.9-63.6%) experienced one or more types of child maltreatment. Prevalence of single-type maltreatment was 22.8% (95% CI, 21.7-24.0%), whereas 39.4% (95% CI, 38.1-40.7%) of participants reported multi-type maltreatment and 3.5% (95% CI, 3.0-4.0%) reported all five types. Multi-type maltreatment was more common for gender diverse participants (66.1% [95% CI, 53.7-78.7%]) and women (43.2% [95% CI, 41.3-45.1%]) than for men (34.9% [95% CI, 33.0-36.7%]). Multi-type maltreatment prevalence was highest for those aged 25-44 years. Family-related adverse childhood experiences - especially mental illness and alcohol or substance misuse - increased risk. Exposure to domestic violence was the maltreatment type most often present in multi-type maltreatment patterns.ConclusionsMulti-type child maltreatment is prevalent in Australia and more common in women and gender diverse individuals. Child protection services, health practitioners, and prevention and intervention services must assess and manage multi-type maltreatment in children and address its health consequences across the lifespan. Public health policy should consider prevention services or strategies that target multi-type child maltreatment.
| S-EPMC10952595 | biostudies-literature
Project description:We present data on maltreatment profiles and psychopathology of 358 children and adolescents (4-17 years). Data on maltreatment profiles has been categorized into six major maltreatment types: physical abuse, emotional abuse, sexual abuse, sexual abuse with penetration, exposure to intimate partner violence and neglect. The data on history of maltreatment is based on the interview version of the Juvenile Victimization Questionnaire (JVQ). Additionally data on psychopathology in general as well as specific disorders according to DSM-IV based on K-SADS-PL is presented. The data was used to examine patterns of co-occurrences of maltreatment and associated clinical outcome variables using latent class analysis (LCA), "Experience by children and adolescents of more than one type of maltreatment: association of different classes of maltreatment profiles with clinical outcome variables" (Witt et al.,) [1].
| S-EPMC4993853 | biostudies-literature
Project description:Objective:There is a well-documented link between child maltreatment and poor health across the lifespan. This provides a strong case for ongoing research with youth involved in the child welfare system to reduce negative outcomes and support resilience while being inclusive of youth voices. However, detailed inquiries about maltreatment history and health consequences may cause re-experiencing of events and psychological distress for study participants. Data that accounts for different contexts, such as severity of maltreatment history and current trauma symptomatology, have been limited in considering the question of potential harms to youth who participate in research-especially longitudinal studies. Methods:This study compared self-reported impact of research participation against maltreatment history and current post-traumatic stress symptomatology among a randomly selected group of adolescents (<?18 years old) in the child protection service (CPS) system. Results:Adolescents who report more serious child maltreatment and current trauma symptom severity reported higher scores on distress questions from pre- to post-assessment participation. Critically, participants who were more negatively impacted by study involvement also reported greater benefit from study involvement. Conclusion:The increase in both negative and positive impact does not shift the risk/reward ratio for participation, as risks alone do not increase for this vulnerable group of CPS involved youth. These results are consistent with previous findings from studies involving non-CPS populations and underlies the importance of empirical data to address the question of change in the risk/reward ratio and what factors might play a role in any change. This information can inform inclusion/exclusion criteria for future research with these vulnerable populations, thereby reducing the risk of distress among study participants.
| S-EPMC6410491 | biostudies-literature