Childhood maltreatment and DNA methylation: A systematic review

Rubens, Mackenzie; Bruenig, Dagmar; Adams, Jessica A M; Suresh, Shruthi M; Sathyanarayanan, Anita; Haslam, Divna; Shenk, Chad E.; Mathews, Ben; Mehta, Divya

doi:10.1016/j.neubiorev.2023.105079

Cited by 16 publications

(10 citation statements)

References 93 publications

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“…The child's age is also a factor known to influence the child's epigenetic profile in response to stress, and consequently, it may also impact the degree of the resemblance between mothers and children. This consideration arises from recognizing sensitive periods for life adversity's epigenetic impact [ 23 ]. Recent research has shown that the early age of exposure to life adversity significantly explained epigenetic variability, whereas this was not the case for the accumulation or the recency of adverse events [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

“…In this study, our first aim was to identify mother and child methylation similarity for the whole epigenome, given the scant evidence on this type of analysis. We also explored the similarity in the most common and relevant genes in empathy and stress literature: NR3C1, FKPB5, OXTR, SCL6A4, and BDNF [ 1 , 23 ]. FKBP5 and NR3C1 regulate the hypothalamic–pituitary–adrenal (HPA) axis, and epigenetic changes have been frequently assessed in these genes [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Mother adversity and co-residence time impact mother–child similarity in genome-wide and gene-specific methylation profiles

Labaut,

Lage-Castellanos,

Rodrigo

et al. 2024

Clin Epigenet

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Background The effects of adverse life events on physical and psychological health, with DNA methylation (DNAm) as a critical underlying mechanism, have been extensively studied. However, the epigenetic resemblance between mother and child in the context of neglectful caregiving, and whether it may be shaped by the emotional impact of maternal stressful events and the duration of co-residence (indexed by child age), remains unknown. The present study examined mother–child similarity in methylation profiles, considering the potential effect of mother adversity, mother empathy, neglect-control group, child age (an index of years of mother–child co-residence), and mother age. Using Illumina Epic arrays, we quantified DNAm in 115 mother–child saliva samples. We obtained a methylation similarity index by computing correlation coefficients between methylation profiles within dyads, for the entire epigenome, and five specific genes related to stress and empathy: NR3C1, FKPB5, OXTR, SCL6A4, and BDNF. Results The methylation profiles of the mother–child familial pairs significantly correlated as compared to mother–child random pairs for the entire epigenome and NR3C1, FKBP5, OXTR and BDNF genes. Next, multiple linear regression models observed associations of mother adversity, child age, and neglect-control group on mother–child methylation similarity, only significant in mother–child familial pairs, after correcting for multiple comparisons. Higher mother adversity was associated with lower mother–child methylation similarity for the epigenome-wide analysis, for the BDNF gene, and in the neglect-control group for the OXTR gene. In turn, being an older child (longer co-residence) was associated with higher mother–child methylation similarity. Conclusions Mother adversity and co-residence time are modulating factors in the intergenerational methylation process that offer a window into development-dependent adaptations that can be affected by both hereditary and environmental factors, significantly observed only in biological dyads. A twofold implication for child well-being emerges, one is positive in that children of mothers exposed to life adversity or neglect did not necessarily inherit their methylation patterns. The other is concerning due to the influence of time spent living together, which affects similarity with the mother and potentially increases the risk of inheriting an epigenetic profile associated with future dysfunctional parenting patterns. This underscores the importance of the 'the earlier, the better' recommendation by the Child Protection System, which is not always followed.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mother adversity and co-residence time impact mother–child similarity in genome-wide and gene-specific methylation profiles

Labaut,

Lage-Castellanos,

Rodrigo

et al. 2024

Clin Epigenet

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“…Although promising, several former studies have been conducted with adults who have experienced childhood maltreatment, but have not been conducted with children. 4 These studies are not likely to contribute to the development of biomarkers for preventing CM given the long gap between childhood exposure to CM and adulthood. Other factors may be more relevant, and even if some methylations are identi ed, they might not be dynamic methylation in response to CM.…”

Section: Introductionmentioning

confidence: 99%

Multi-Epigenome-Wide Analyses and Meta-Analysis of Child Maltreatment in Judicial Autopsies and Intervened Children and Adolescents

Tomoda,

Nishitani,

Fujisawa

et al. 2023

Preprint

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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.

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“…The child's age is also a factor known to in uence the child's epigenetic pro le in response to stress, and consequently, it may also impact the degree of the resemblance between mothers and children. This consideration arises from recognizing sensitive periods for life adversity's epigenetic impact [23]. Recent research has shown that the early age of exposure to life adversity signi cantly explained epigenetic variability, whereas this was not the case for the accumulation or the recency of adverse events [24].…”

mentioning

confidence: 99%

“…In this study, our rst aim was to identify mother and child methylation similarity for the whole epigenome, given the scant evidence on this type of analysis. We also explored the similarity in the most common and relevant genes in empathy and stress literature: NR3C1, FKPB5, OXTR, SCL6A4, and BDNF [1,23]. FKBP5 and NR3C1 regulate the hypothalamic-pituitary-adrenal (HPA) axis, and epigenetic changes have been frequently assessed in these genes [27].…”

mentioning

confidence: 99%

Mother adversity and co-residence time impact mother-child similarity in genome-wide and gene-specific methylation profiles

Labaut-Peñalver,

Lage-Castellanos,

Rodrigo

et al. 2024

Preprint

View full text Add to dashboard Cite

Background. The effects of adverse life events on physical and psychological health, with DNA methylation (DNAm) as a critical underlying mechanism, have been extensively studied. However, the epigenetic resemblance between mother and child in the context of neglectful caregiving, and whether it may be shaped by the emotional impact of maternal stressful events and the duration of co-residence (indexed by child age), remains unknown. The present study examined mother-child similarity in methylation profiles, considering the potential effect of mother adversity, mother empathy, neglect-control group, child age (an index of years of mother-child co-residence), and mother age. We quantified DNAm in 115 mother-child saliva samples and obtained a methylation similarity index by computing correlation coefficients between methylation profiles within dyads, for the entire epigenome, and five specific genes related to stress and empathy: NR3C1, FKPB5, OXTR, SCL6A4, and BDNF. Results. The methylation profiles of the mother-child familial pairs significantly correlated as compared to mother-child random pairs for the entire epigenome and NR3C1, FKBP5, OXTR and BDNF genes. Next, multiple linear regression models observed associations of mother adversity, child age, and neglect-control group on mother-child methylation similarity, only significant in mother-child familial pairs, after correcting for multiple comparisons. Higher mother adversity was associated with lower mother-child methylation similarity for the epigenome-wide analysis, for the BDNF gene, and in the neglect-control group for the OXTR gene. In turn, being an older child (longer co-residence) was associated with higher mother-child methylation similarity. Conclusions. Mother adversity and co-residence time are modulating factors in the intergenerational methylation process that offer a window into development-dependent adaptations that can be affected by both hereditary and environmental factors, significantly observed only in biological dyads. A twofold implication for child well-being emerges, one is positive in that children of mothers exposed to life adversity or neglect did not necessarily inherit their methylation patterns. The other is worrisome, since the time living together is a crucial environmental factor with a high impact on epigenetic transmission in children, reinforcing the need for “the earlier, the better” recommendation of the Child Protection System, which is not always followed.

show abstract

Childhood maltreatment and DNA methylation: A systematic review

Cited by 16 publications

References 93 publications

Mother adversity and co-residence time impact mother–child similarity in genome-wide and gene-specific methylation profiles

Mother adversity and co-residence time impact mother–child similarity in genome-wide and gene-specific methylation profiles

Multi-Epigenome-Wide Analyses and Meta-Analysis of Child Maltreatment in Judicial Autopsies and Intervened Children and Adolescents

Mother adversity and co-residence time impact mother-child similarity in genome-wide and gene-specific methylation profiles

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