title: Increased serotonin transporter gene (SERT) DNA methylation is associated with bullying victimization and blunted cortisol response to stress in childhood: a longitudinal study of discordant monozygotic twins.
abstract: BACKGROUND
  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 the neuroendocrine response to stress remain unclear. Method We tested whether bullying victimization influenced serotonin transporter gene (SERT) DNA methylation using a discordant monozygotic (MZ) twin design. A subsample of 28 MZ twin pairs discordant for bullying victimization, with data on cortisol and DNA methylation, were identified in the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative 1994-1995 cohort of families with twins.
  
  
  RESULTS
  Bullied twins had higher SERT DNA methylation at the age of 10 years compared with their non-bullied 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 the age of 5 years, prior to bullying victimization, and the age of 10 years whereas no such increase was detected in non-bullied twins across time. Moreover, children with higher SERT methylation levels had blunted cortisol responses to stress.
  
  
  CONCLUSIONS
  Our study extends findings drawn from animal models, supports the hypothesis that early-life stress modifies DNA methylation at a specific cytosine-phosphate-guanine (CpG) site in the SERT promoter and HPA functioning and suggests that these two systems may be functionally associated.
authors.affiliation: MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Ouellet-Morin
authors.forename: C C Y
authors.initials: CC
authors.lastname: Wong
authors.forename: A
authors.initials: A
authors.lastname: Danese
authors.forename: C M
authors.initials: CM
authors.lastname: Pariante
authors.forename: A S
authors.initials: AS
authors.lastname: Papadopoulos
authors.forename: J
authors.initials: J
authors.lastname: Mill
authors.forename: L
authors.initials: L
authors.lastname: Arseneault
mesh_terms: D058445:Bullying / Q000502:physiology*; D002648:Child; D019548:Crime Victims; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D012931:Social Environment; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism; D014430:Twins, Monozygotic / Q000235:genetics* / Q000523:psychology
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D006854:Hydrocortisone