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DNA methylation and childhood maltreatment: from animal models to human studies.

ABSTRACT: Childhood maltreatment (CM) has estimated prevalence among Western societies between 10% and 15%. As CM associates with increased risk of several psychiatric disorders, early age of illness onset, increased comorbidity and negative clinical outcome, it imposes a major public health, social and economic impact. Although the clinical consequences of CM are well characterized, a major challenge remains to understand how negative early-life events can affect brain function over extended periods of time. We review here both animal and human studies indicating that the epigenetic mechanism of DNA methylation is a crucial mediator of early-life experiences, thereby maintaining life-long neurobiological sequelae of CM, and strongly determining psychopathological risk.

SUBMITTER: Lutz PE

PROVIDER: S-EPMC5293537 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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DNA methylation and childhood maltreatment: from animal models to human studies.

Lutz P-E PE Turecki G G

Neuroscience 20130808

Childhood maltreatment (CM) has estimated prevalence among Western societies between 10% and 15%. As CM associates with increased risk of several psychiatric disorders, early age of illness onset, increased comorbidity and negative clinical outcome, it imposes a major public health, social and economic impact. Although the clinical consequences of CM are well characterized, a major challenge remains to understand how negative early-life events can affect brain function over extended periods of t ...[more]

PMID: 23933308

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Project description:Offspring of persons exposed to childhood abuse are at higher risk of neurodevelopmental and physical health disparities across the life course. Animal experiments have indicated that paternal environmental stressors can affect sperm DNA methylation and gene expression in an offspring. Childhood abuse has been associated with epigenetic marks in human blood, saliva, and brain tissue, with statistically significant methylation differences ranging widely. However, no studies have examined the association of childhood abuse with DNA methylation in gametes. We examined the association of childhood abuse with DNA methylation in human sperm. Combined physical, emotional, and sexual abuse in childhood was characterized as none, medium, or high. DNA methylation was assayed in 46 sperm samples from 34 men in a longitudinal non-clinical cohort using HumanMethylation450 BeadChips. We performed principal component analysis and examined the correlation of principal components with abuse exposure. Childhood abuse was associated with a component that captured 6.2% of total variance in DNA methylation (p?<?0.05). Next, we investigated the regions differentially methylated by abuse exposure. We identified 12 DNA regions differentially methylated by childhood abuse, containing 64 probes and including sites on genes associated with neuronal function (MAPT, CLU), fat cell regulation (PRDM16), and immune function (SDK1). We examined adulthood health behaviors, mental health, and trauma exposure as potential mediators of an association between abuse and DNAm, and found that mental health and trauma exposure partly mediated the association. Finally, we constructed a parsimonious epigenetic marker for childhood abuse using a machine learning approach, which identified three probes that predicted high vs. no childhood abuse in 71% of participants. Our results suggested that childhood abuse is associated with sperm DNA methylation, which may have implications for offspring development. Larger samples are needed to identify with greater confidence specific genomic regions differentially methylated by childhood abuse.

Dataset Information

DNA methylation and childhood maltreatment: from animal models to human studies.

Publications

DNA methylation and childhood maltreatment: from animal models to human studies.

Similar Datasets

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