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ObjectiveDNA methylation has been proposed as an epigenetic mechanism by which early-life experiences become "embedded" in the genome and alter transcriptional processes to compromise health. The authors sought to investigate whether early-life victimization stress is associated with genome-wide DNA methylation.MethodThe authors tested the hypothesis that victimization is associated with DNA methylation in the Environmental Risk (E-Risk) Longitudinal Study, a nationally representative 1994-1995 birth cohort of 2,232 twins born in England and Wales and assessed at ages 5, 7, 10, 12, and 18 years. Multiple forms of victimization were ascertained in childhood and adolescence (including physical, sexual, and emotional abuse; neglect; exposure to intimate-partner violence; bullying; cyber-victimization; and crime).ResultsEpigenome-wide analyses of polyvictimization across childhood and adolescence revealed few significant associations with DNA methylation in peripheral blood at age 18, but these analyses were confounded by tobacco smoking and/or did not survive co-twin control tests. Secondary analyses of specific forms of victimization revealed sparse associations with DNA methylation that did not replicate across different operationalizations of the same putative victimization experience. Hypothesis-driven analyses of six candidate genes in the stress response (NR3C1, FKBP5, BDNF, AVP, CRHR1, SLC6A4) did not reveal predicted associations with DNA methylation in probes annotated to these genes.ConclusionsFindings from this epidemiological analysis of the epigenetic effects of early-life stress do not support the hypothesis of robust changes in DNA methylation in victimized young people. We need to come to terms with the possibility that epigenetic epidemiology is not yet well matched to experimental, nonhuman models in uncovering the biological embedding of stress.

The authors sought to determine whether the Fast Track mental health intervention delivered to individuals in childhood decreased mental health problems and the need for health services among the children of these individuals. The authors examined whether Fast Track assignment in one generation of children (generation 2; G2) from grades 1 through 10 reduced parent-reported mental health problems and health services use in these children's children (generation 3; G3) 18 years later relative to a control group. The Fast Track intervention blended parent behavior-management training, child social-cognitive skills tutoring, home visits, and classroom social-ecology changes across grades 1–10 to ameliorate emerging conduct problems among the G2 children. For this study, 1,057 G3 children of Fast Track participants (N=581 intervention group, N=476 control group) were evaluated. G3 children of G2 parents who were randomized to the Fast Track intervention group used fewer general inpatient services and fewer inpatient or outpatient mental health services compared with G3 children of G2 parents randomized to the control group. Some of these effects were mediated: randomization to Fast Track predicted fewer internalizing problems and less use of corporal punishment among G2 adults at age 25, which subsequently predicted less general inpatient service use and outpatient mental health service use among the G3 children by the time the G2 parents were 34 years old. There were no significant differences between G3 children from these two groups on the use of other health services or on mental health measures. Fast Track was associated with lower use of general inpatient services and inpatient and outpatient mental health services intergenerationally, but effects on parent-reported mental health of the children were not apparent across generations. Investing in interventions for the mental health of children could reduce service use burdens across generations. [ABSTRACT FROM AUTHOR]