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
Open accessAbstract
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.
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Overall methylation changes between the ages of five and ten were exclusively based on a single CpG island, at which methylation levels also displayed a negative correlation with the cortisol response to a psychological stress challenge.
“Overall methylation changes between the ages of five and ten were exclusively based on a single CpG island, at which methylation levels also displayed a negative correlation with the cortisol response to a psychological stress challenge”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Ouellet-Morin et al., 2013
The Results (page unavailable) report increased methylation from ages 5 to 10 at CpG8 in bullied twins, but not their non-bullied co-twins; methylation across the promoter region remained unchanged. The Discussion (page unavailable) reports lower cortisol responses in children with higher SERT methylation. The claim overstates the finding by calling CpG8 a whole CpG island and describing the change as an overall, exclusive change rather than a site-specific finding in bullied twins. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSLC6A4 methylation is increased in association with degree of bullying.
“↑ SLC6A4 methylation associated with degree of bullying”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Ouellet-Morin et al., 2013
The Results (page not provided) report higher SERT/SLC6A4 methylation in bullied twins than in their non-bullied co-twins. The Statistical analyses section compares bullied with non-bullied twins, but does not report whether methylation increases with the degree of bullying. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe serotonergic and HPA systems display a functional epigenetic connection.
“supporting the hypothesis that the serotonergic and HPA systems display a functional epigenetic connection (Ouellet-Morin et al., 2013)”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Ouellet-Morin et al., 2013
In a longitudinal study of 28 monozygotic twin pairs, bullied twins had higher SLC6A4 promoter methylation levels at age ten than non-bullied twins, while prior to any bullying experience at age five methylation levels were indistinguishable.
“A longitudinal study of 28 monozygotic twin pairs showed that bullied twins had higher SLC6A4 promoter methylation levels at age ten than non-bullied twins, while notably prior to any bullying experience at age five methylation levels were indistinguishable”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Ouellet-Morin et al., 2013
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- Authors
- Ouellet-Morin, I., Wong, C. C. Y., Danese, A., Pariante, C. M., Papadopoulos, A. S., Mill, J., & Arseneault, L.
- Affiliations
- King's College London (GB)
- Corresponding author
- Arseneault, L.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2012-12-10
- Volume
- 43
- Issue
- 9
- Pages
- 1813-1823
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- PMC
- PMC4231789
- OpenAlex
- W2165964254
- Cited by
- 207
- References
- 97
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 8 · 2023: 8 · 2022: 14 · 2021: 19 · 2020: 21 · 2019: 14 · 2018: 27 · 2017: 24 · 2016: 17 · 2015: 18 · 2014: 20 · 2013: 7
- FWCI
- 5.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institute for Health and Care Research (CSA/01/05/001)
- Jacobs Foundation
- Canadian Institutes of Health Research
- Medical Research Council (MR/J002739/1)
- Economic and Social Research Council (ES/H034897/1)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD061298, R01HD061298)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Psychology › Social Psychology › Bullying, Victimization, and Aggression
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- bullying victimization, serotonin transporter gene, hypothalamic-pituitary-adrenal axis, early life stress, childhood adversity, monozygotic twins, epigenetics, CpG methylation, Environmental Risk Longitudinal Twin Study
- MeSH terms
- Child, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Longitudinal Studies, Male, Pituitary-Adrenal System, Social Environment, Stress, Psychological, Twins, Monozygotic, DNA Methylation, Crime Victims, Serotonin Plasma Membrane Transport Proteins, Bullying
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