DNA methylation of the serotonin transporter gene (SLC6A4) is associated with brain function involved in processing emotional stimuli
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BACKGROUND: The aim of the present study was to investigate the association of fMRI blood oxygen-level dependent (BOLD) reactivity with the level of epigenetic methylation of SLC6A4 in blood DNA from a sample of healthy participants and patients with major depressive disorder (MDD). METHODS: We investigated patients with MDD and healthy controls using fMRI and an emotional attention-shifting task. We assessed site-specific DNA methylation of a previously characterized SLC6A4 region in peripheral blood DNA using pyrosequencing. RESULTS: Our study involved 25 patients with MDD and 35 healthy controls. Activation in the anterior insula elicited by negative emotional content was significantly positively associated with the degree of SLC6A4 methylation. Significantly negative associations were observed between activation in the posterior insula and the degree of SLC6A4 methylation when judging the geometry of pictures after seeing negative in contrast to positive emotional stimuli. Healthy controls with a high degree of SLC6A4 methylation depicted significantly more activity elicited by positive stimuli in limbic regions and more activity elicited by negative stimuli in limbic as well as cognitive control regions than those with a low degree of SLC6A4 methylation. LIMITATIONS: It is impossible to measure methylation directly in the brain and thus we assessed peripheral methylation of SLC6A4. Since the association was cross-sectional, no conclusion about cause and effect can be drawn. CONCLUSION: Our study provides further support to the hypothesis that particular DNA methylation states that are associated with brain function during emotion processing are detectable in the periphery.
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SLC6A4 methylation was found to be related to insula activation during the processing of emotional stimuli in major depressive disorder.
“SLC6A4 methylation was furthermore found to be related to insula activation during the processing of emotional stimuli in major depressive disorder (Frodl et al., 2015).”
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 Frodl et al., 2015
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Self-citation
- Authors
- Frodl, T., Szyf, M., Carballedo, A., Ly, V., Dymov, S., Vaisheva, F., Morris, D., Fahey, C., Meaney, J., Gill, M., & Booij, L.
- Affiliations
- Queen's University (CA)
- Department of Pharmacology and Therapeutics, McGill University, Montréal, Canada
- Venue
- Journal of Psychiatry and Neuroscience
- Publisher
- Canadian Science Publishing
- Published
- 2015-09
- Volume
- 40
- Issue
- 5
- Pages
- 296-305
- ISSN
- 1180-4882 (ISSN-L)
- 1488-2434
- PMC
- PMC4543092
- OpenAlex
- W336580706
- Cited by
- 86
- References
- 49
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 5 · 2023: 8 · 2022: 8 · 2021: 7 · 2020: 11 · 2019: 4 · 2018: 7 · 2017: 11 · 2016: 13 · 2015: 5
- FWCI
- 5.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Psychiatry and Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- 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
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- DNA methylation, serotonin transporter, major depressive disorder, epigenetics, anterior insula, posterior insula, emotional processing, blood DNA
- MeSH terms
- Adult, Brain Chemistry, Cross-Sectional Studies, Major Depressive Disorder, Depressive Disorder, Major, Emotions, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Promoter Regions, Genetic, Linear Models, Sequence Analysis, DNA, DNA Methylation, Epigenesis, Genetic, Serotonin Plasma Membrane Transport Proteins, Young Adult
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