Association of serotonin transporter gene AluJb methylation with major depression, amygdala responsiveness, 5-HTTLPR/rs25531 polymorphism, and stress
Open accessAbstract
DNA methylation profiles of the serotonin transporter gene (SLC6A4) have been shown to alter SLC6A4 expression, drive antidepressant treatment response and modify brain functions. This study investigated whether methylation of an AluJb element in the SLC6A4 promotor was associated with major depressive disorder (MDD), amygdala reactivity to emotional faces, 5-HTTLPR/rs25531 polymorphism, and recent stress. MDD patients (n=122) and healthy controls (HC, n=176) underwent fMRI during an emotional face-matching task. Individual SLC6A4 AluJb methylation profiles were ascertained and associated with MDD, amygdala reactivity, 5-HTTLPR/rs25531, and stress. SLC6A4 AluJb methylation was significantly lower in MDD compared to HC and in stressed compared to less stressed participants. Lower AluJb methylation was particularly found in 5-HTTLPR/rs25531 risk allele carriers under stress and correlated with less depressive episodes. fMRI analysis revealed a significant interaction of AluJb methylation and diagnosis in the amygdala, with MDD patients showing lower AluJb methylation associated with decreased amygdala reactivity. While no joint effect of AluJb methylation and 5-HTTLPR/rs25531 existed, risk allele carriers showed significantly increased bilateral amygdala activation. These findings suggest a role of SLC6A4 AluJb methylation in MDD, amygdala reactivity, and stress reaction, partly interwoven with 5-HTTLPR/rs25531 effects. Patients with low methylation in conjunction with a shorter MDD history and decreased amygdala reactivity might feature a more stress-adaptive epigenetic process, maybe via theoretically possible endogenous antidepressant-like effects. In contrast, patients with higher methylation might possibly suffer from impaired epigenetic adaption to chronic stress. Further, the 5-HTTLPR/rs25531 association with amygdala activation was confirmed in our large sample.
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Methylation of an AluJb element in the SLC6A4 promoter was associated with amygdala reactivity in depression.
“Methylation of an AluJb element in the SLC6A4 promoter was also associated with amygdala reactivity in depression (Schneider et al., 2018).”
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 Schneider et al., 2018
miRNA and lncRNA levels in blood distinguish depressed patients from healthy controls.
“Because miRNA and lncRNA levels in blood distinguish depressed patients from healthy controls,243,310,387”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [387]
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- Authors
- Schneider, I., Kugel, H., Redlich, R., Grotegerd, D., Bürger, C., Bürkner, P.-C., Opel, N., Dohm, K., Zaremba, D., Meinert, S., Schröder, N., Straßburg, A. M., Schwarte, K., Schettler, C., Ambrée, O., Rust, S., Domschke, K., Arolt, V., Heindel, W., Baune, B. T., Zhang, W., Dannlowski, U., & Hohoff, C.
- Affiliations
- University of Münster (DE)
- Osnabrück University (DE)
- University of Freiburg (DE)
- The University of Adelaide (AU)
- Corresponding author
- Hohoff, Christa
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2017-11-07
- Volume
- 43
- Issue
- 6
- Pages
- 1308-1316
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC5916353
- OpenAlex
- W2767520553
- Cited by
- 86
- References
- 63
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 3 · 2023: 10 · 2022: 8 · 2021: 35 · 2020: 7 · 2019: 7 · 2018: 7 · 2017: 1
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- European Commission (EU-FP7)
- Deutsche Forschungsgemeinschaft (Dan3/012/17, grant FOR2107, FOR 2107/ DA1151/5-1, TRR‐58, Project C09 to UD, DA1151/5-1, FOR 2107, SFB TRR 58)
- Bundesministerium für Bildung und Forschung
- Servier
- H. Lundbeck A/S
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- serotonin transporter gene, serotonin transporter, DNA methylation, major depressive disorder, amygdala reactivity, promoter methylation, stress, epigenetic adaptation, emotional face processing, antidepressant response
- MeSH terms
- Facial Recognition, Adult, Amygdala, Brain Mapping, Major Depressive Disorder, Emotions, Female, Heterozygote, Humans, Magnetic Resonance Imaging, Male, Promoter Regions, Genetic, Stress, Psychological, DNA Methylation, Polymorphism, Single Nucleotide, Epigenesis, Genetic, Serotonin Plasma Membrane Transport Proteins
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