TY - JOUR
T1 - Maternal epigenetic index links early neglect to later neglectful care and other psychopathological, cognitive, and bonding effects
AU - León, Inmaculada
AU - Góngora, Daylín
AU - Rodrigo, María José
AU - Herrero-Roldán, Silvia
AU - López Rodríguez, Maykel
AU - Mitchell, Colter
AU - Fisher, Jonah
AU - Iturria-Medina, Yasser
N1 - The Data Set files analyzed during the current study are available in the supplementary material: Data Set file 1: Excel sheet 1 includes the value of the beta in each CpG for both groups that were used to calculate the EMN index; Excel sheet 2 includes the values of the covariates that were used for the EMN index; Excel sheet 3 includes the values of the variables that were used to test the SEM models. Data Set file 2: Excel sheet 1 includes the genes used in the enrichment; Excel sheets 2 and 3 include the partial and full list of annotated genes, respectively; and Excel sheets 4 and 5 present data of functional categories of the corresponding genes. The full disclosure of the raw sequencing data of mothers and their minors is subject to confidentiality restrictions of the Canary Islands Child Protection Services.
PY - 2025/3/8
Y1 - 2025/3/8
N2 - Background: Past experiences of maltreatment and life adversity induce DNA methylation changes in adults, but less is known about their impact on mothers’ maladaptive neglectful parenting and its negative effects. We performed an epigenome-wide association study to investigate the role of DNA methylation levels in mothers with neglectful care, who were exposed to childhood maltreatment and neglect, and their current negative effects. Saliva DNA methylation was determined with the Illumina Human Methylation EPIC BeadChip v1. The individual epigenome was the input to a machine learning algorithm for trajectory inference, which assigned a specific state to each mother in the progression from healthy controls to the extreme neglect condition. A compound epigenetic maternal neglect score (EMN) was derived from 138 mothers (n = 51 in the neglectful group; n = 87 in the control non-neglectful group) having young children. Differential methylation between groups was utilized to derive the EMNs adjusted for education level, age, experimental variables, and blood cell types in saliva samples. Results: Structural equation modeling: X
2 (29) = 37.81; p = 0.127; RMSEA = 0.048, confirmed that EMNs link their early experience of physical neglect to current reports of psychopathological symptoms, lower cognitive status, and observed poor mother–child emotional availability. A third of the genes annotated to the CpGs that affect EMNs are related to cognitive impairment and neurodegenerative and psychopathological disorders. Conclusions: EMNs are a novel index to assess the contribution of DNA methylations as a neglected girl to later neglectful caregiving behavior and other negative effects. The evidence provided expands the possibilities for earlier interventions on the neglect condition to prevent and ameliorate the direct or indirect epigenetic impact of maternal adversities on mother–child care, helping to break the cycle of maltreatment.
AB - Background: Past experiences of maltreatment and life adversity induce DNA methylation changes in adults, but less is known about their impact on mothers’ maladaptive neglectful parenting and its negative effects. We performed an epigenome-wide association study to investigate the role of DNA methylation levels in mothers with neglectful care, who were exposed to childhood maltreatment and neglect, and their current negative effects. Saliva DNA methylation was determined with the Illumina Human Methylation EPIC BeadChip v1. The individual epigenome was the input to a machine learning algorithm for trajectory inference, which assigned a specific state to each mother in the progression from healthy controls to the extreme neglect condition. A compound epigenetic maternal neglect score (EMN) was derived from 138 mothers (n = 51 in the neglectful group; n = 87 in the control non-neglectful group) having young children. Differential methylation between groups was utilized to derive the EMNs adjusted for education level, age, experimental variables, and blood cell types in saliva samples. Results: Structural equation modeling: X
2 (29) = 37.81; p = 0.127; RMSEA = 0.048, confirmed that EMNs link their early experience of physical neglect to current reports of psychopathological symptoms, lower cognitive status, and observed poor mother–child emotional availability. A third of the genes annotated to the CpGs that affect EMNs are related to cognitive impairment and neurodegenerative and psychopathological disorders. Conclusions: EMNs are a novel index to assess the contribution of DNA methylations as a neglected girl to later neglectful caregiving behavior and other negative effects. The evidence provided expands the possibilities for earlier interventions on the neglect condition to prevent and ameliorate the direct or indirect epigenetic impact of maternal adversities on mother–child care, helping to break the cycle of maltreatment.
KW - Childhood trauma
KW - DNA methylation
KW - Emotional availability
KW - Machine learning
KW - Neglectful parenting
KW - Humans
KW - Female
KW - DNA Methylation/genetics
KW - Adult
KW - Epigenesis, Genetic/genetics
KW - Mothers/psychology
KW - Mother-Child Relations/psychology
KW - Child Abuse/psychology
KW - Child, Preschool
KW - Male
KW - Saliva/chemistry
KW - Genome-Wide Association Study/methods
KW - Parenting/psychology
KW - Cognition
KW - Child
KW - Object Attachment
KW - Epigenome/genetics
U2 - 10.1186/s13148-025-01839-7
DO - 10.1186/s13148-025-01839-7
M3 - Article
SN - 1868-7083
VL - 17
JO - Clinical epigenetics
JF - Clinical epigenetics
IS - 1
M1 - 46
ER -