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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

Published online by Cambridge University Press:  10 December 2012

I. Ouellet-Morin ,
C. C. Y. Wong ,
A. Danese ,
C. M. Pariante ,
A. S. Papadopoulos ,
J. Mill  and
L. Arseneault
I. Ouellet-Morin
Affiliation:
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK School of Criminology, Université de Montréal, Mental Health Institute of Montréal Research Center and the Research Group on Child Maladjustment, Canada
C. C. Y. Wong
Affiliation:
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK
A. Danese
Affiliation:
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK Department of Child and Adolescent Psychiatry, Institute of Psychiatry, King's College London, London, UK
C. M. Pariante
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK
A. S. Papadopoulos
Affiliation:
Section of Neurobiology of Mood Disorders, Institute of Psychiatry, King's College London, London, UK Affective Disorders Unit Laboratory, National Affective Disorders Unit, Bethlem Royal Hospital, Beckenham, Kent, UK
J. Mill
Affiliation:
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK
L. Arseneault*
Affiliation:
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK
*
*Address for correspondence: L. Arseneault, Ph.D., MRC SGDP Centre, Institute of Psychiatry, King's College London, London SE5 8AF, UK. (Email: [email protected])
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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.

Keywords

Bullyingchildhood victimizationcortisolDNA methylationhypothalamic–pituitary–adrenal axisSERT
Type
Original Articles
Information
Psychological Medicine , Volume 43 , Issue 9 , September 2013 , pp. 1813 - 1823
Copyright
Copyright © Cambridge University Press 2012 

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