SLC6A4 methylation modifies the effect of the number of traumatic events on risk for posttraumatic stress disorder
Open accessAbstract
BACKGROUND: Posttraumatic stress disorder (PTSD) is a common and debilitating mental disorder that occurs following exposure to a traumatic event. However, most individuals do not develop PTSD following even a severe trauma, leading to a search for new variables, such as genetic and other molecular variation, associated with vulnerability and resilience in the face of trauma exposure. METHOD: We examined whether serotonin transporter (SLC6A4) promoter genotype and methylation status modified the association between number of traumatic events experienced and PTSD in a subset of 100 individuals from the Detroit Neighborhood Health Study. RESULTS: Number of traumatic events was strongly associated with risk of PTSD. Neither SLC6A4 genotype nor methylation status was associated with PTSD in main effects models. However, SLC6A4 methylation levels modified the effect of the number of traumatic events on PTSD after controlling for SLC6A4 genotype. Persons with more traumatic events were at increased risk for PTSD, but only at lower methylation levels. At higher methylation levels, individuals with more traumatic events were protected from this disorder. This interaction was observed whether the outcome was PTSD diagnosis, symptom severity, or number of symptoms. CONCLUSIONS: Gene-specific methylation patterns may offer potential molecular signatures of increased risk for and resilience to PTSD.
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Hypomethylation in SLC6A is associated with resilience to PTSD, while hypermethylation of SLC6A has been linked to exposure to childhood adversity and associated with the worst clinical presentation in MDD.
“With regards to the serotoninergic pathway, while hypomethylation in SLC6A is associated with resilience to PTSD (Koenen et al., 2011), hypermethylation of SLC6A has been linked to exposure to CA and associated with the worst clinical presentation in MDD (Kang et al., 2013).”
From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Koenen et al., 2011
The Results section says the opposite of the claim attributed to Koenen et al.: at low SLC6A4 methylation, more traumatic events were associated with increased PTSD risk, while at high methylation they were associated with resilience. The childhood-adversity and MDD clause is attributed to Kang et al., not to this source. (LLM, conf=0.94)
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Experimental — accuracy not yet measuredRecent studies on humans and macaque monkeys showed that higher methylation levels of the 5-HTT gene were associated with stronger effects of stress.
“recent studies on humans and macaque monkeys showed that higher methylation levels of the 5-HTT gene were associated with stronger effects of stress 133, 134.”
From Resilience in mental health: linking psychological and neurobiological perspectives. (2013) · cites this paper as [134]
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- Authors
- Koenen, K. C., Uddin, M., Chang, S.-C., Aiello, A. E., Wildman, D. E., Goldmann, E., & Galea, S.
- Affiliations
- Harvard University (US)
- University of Michigan (US)
- Wayne State University (US)
- Columbia University (US)
- Corresponding author
- Koenen, Karestan C.
- ORCID
- Venue
- Depression and Anxiety
- Publisher
- Hindawi Limited
- Published
- 2011-05-23
- Volume
- 28
- Issue
- 8
- Pages
- 639-647
- ISSN
- 1091-4269 (ISSN-L)
- PMC
- PMC3145829
- OpenAlex
- W2072260750
- Cited by
- 174
- References
- 36
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 11 · 2023: 6 · 2022: 6 · 2021: 11 · 2020: 7 · 2019: 8 · 2018: 8 · 2017: 7 · 2016: 16 · 2015: 15 · 2014: 25 · 2013: 28 · 2012: 15
- FWCI
- 24.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Depression and Anxiety (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- Wayne State University (DA022720, MH088283)
- National Institutes of Health
- National Institute of Mental Health (MH 070627, R01MH082729, R01MH078152, R01MH078928, MH 082729, RC1MH088283, MH-078928, MH088283, K08MH070627, MH 078152)
- National Institute on Drug Abuse (DA 022720, R01DA022720, DA 022720-S1)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- post-traumatic stress disorder, serotonin transporter, DNA methylation, promoter methylation, gene-environment interaction, trauma exposure, PTSD risk, resilience, PTSD symptom severity
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Depression, Genotype, Health Surveys, Humans, Interview, Psychological, Life Change Events, Male, Middle Aged, Promoter Regions, Genetic, Risk Factors, Stress Disorders, Post-Traumatic, Prevalence, DNA Methylation, Genetic Predisposition to Disease, Serotonin Plasma Membrane Transport Proteins, Young Adult
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