Psychological Medicine

Original Articles

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

I. Ouellet-Morina1a2, C. C. Y. Wonga1, A. Danesea1a3, C. M. Pariantea4, A. S. Papadopoulosa5a6, J. Milla1 and L. Arseneaulta1 c1

a1 MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK

a2 School of Criminology, Université de Montréal, Mental Health Institute of Montréal Research Center and the Research Group on Child Maladjustment, Canada

a3 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, King's College London, London, UK

a4 Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK

a5 Section of Neurobiology of Mood Disorders, Institute of Psychiatry, King's College London, London, UK

a6 Affective Disorders Unit Laboratory, National Affective Disorders Unit, Bethlem Royal Hospital, Beckenham, Kent, UK

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.

(Received May 29 2012)

(Revised October 26 2012)

(Accepted October 30 2012)

(Online publication December 10 2012)

Key words

  • Bullying;
  • childhood victimization;
  • cortisol;
  • DNA methylation;
  • hypothalamic–pituitary–adrenal axis;
  • SERT

Correspondence

c1 Address for correspondence: L. Arseneault, Ph.D., MRC SGDP Centre, Institute of Psychiatry, King's College London, London SE5 8AF, UK. (Email: louise.arseneault@kcl.ac.uk)

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