Increased SERT DNA methylation is associated with bullying victimization and blunted cortisol response to stress in childhood: a longitudinal study of discordant MZ twins

Childhood adverse experiences are known to induce persistent changes in the hypothalamic–pituitary–adrenal (HPA) axis reactivity to stress. However, the mechanisms by which these experiences shape neuroendocrine response to stress remain unclear.We tested whether bullying victimization influenced SERT DNA methylation using a discordant monozygotic (MZ) twin design. A sub-sample of 28 MZ twin pairs discordant for bullying victimization, with data on cortisol and DNA methylation, was identified in the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative 1994–1995 cohort of families with twins.Bullied twins had higher SERT DNA methylation at age 10 compared to their nonbullied MZ co-twins. This group difference cannot be attributed to the children's genetic makeup or their shared familial environments because of the study design. Bullied twins also showed increasing methylation levels between age 5, prior to bullying victimization, and age 10 whereas no such increase was detected in nonbullied twins across time. Moreover, children with higher SERT methylation levels had lower cortisol responses to stress.Our study extends findings drawn from animal models, supports the hypothesis that early-life stress modifies DNA methylation at a specific CpG site in the SERT promoter and HPA functioning, and suggests that these two systems may be functionally associated.