Epigenetic signatures in antidepressant treatment response: a methylome-wide association study in the EMC trial
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Abstract
Although the currently available antidepressants are well established in the treatment of the major depressive disorder (MDD), there is strong variability in the response of individual patients. Reliable predictors to guide treatment decisions before or in an early stage of treatment are needed. DNA-methylation has been proven a useful biomarker in different clinical conditions, but its importance for mechanisms of antidepressant response has not yet been determined. 80 MDD patients were selected out of >500 participants from the Early Medication Change (EMC) cohort with available genetic material based on their antidepressant response after four weeks and stratified into clear responders and age- and sex-matched non-responders (N = 40, each). Early improvement after two weeks was analyzed as a secondary outcome. DNA-methylation was determined using the Illumina EPIC BeadChip. Epigenome-wide association studies were performed and differentially methylated regions (DMRs) identified using the comb-p algorithm. Enrichment was tested for hallmark gene-sets and in genome-wide association studies of depression and antidepressant response. No epigenome-wide significant differentially methylated positions were found for treatment response or early improvement. Twenty DMRs were associated with response; the strongest in an enhancer region in SORBS2, which has been related to cardiovascular diseases and type II diabetes. Another DMR was located in CYP2C18, a gene previously linked to antidepressant response. Results pointed towards differential methylation in genes associated with cardiac function, neuroticism, and depression. Linking differential methylation to antidepressant treatment response is an emerging topic and represents a step towards personalized medicine, potentially facilitating the prediction of patients' response before treatment.
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Previous EWAS sample sizes were very small and differed in sample composition and statistical approaches, limiting comparability.
“However, previous sample sizes were very small and differed both in sample composition (e.g., age, ethnicity) and statistical approaches, thus limiting comparability.”
From Epigenome-wide DNA methylation in unipolar depression: predictive biomarker of antidepressant treatment response? (2024) · cites this paper as Engelmann et al., 2022
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- Authors
- Engelmann, J., Zillich, L., Frank, J., Wagner, S., Cetin, M., Herzog, D. P., Müller, M. B., Tadic, A., Foo, J. C., Sirignano, L., Braus, D. F., Dahmen, N., Sordon, S., Riemenschneider, M., Spaniol, C., Gasparoni, G., Rietschel, M., Witt, S. H., Lieb, K., & Streit, F.
- Affiliations
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Heidelberg University (DE)
- Vitos (DE)
- Universitätsklinikum des Saarlandes (DE)
- Saarland University (DE)
- Corresponding author
- Streit, F.
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2022-07-07
- Volume
- 12
- Issue
- 1
- Pages
- 268-268
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC9259740
- OpenAlex
- W4284891643
- Cited by
- 29
- References
- 63
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 8 · 2023: 4
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Bundesministerium für Bildung und Forschung (01EW1904, 01 KG 0906)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- antidepressant response, major depressive disorder, DNA methylation, differentially methylated regions, SORBS2, CYP2C18, early improvement, treatment response prediction, personalized medicine, enhancers
- MeSH terms
- Epigenome, Antidepressive Agents, Major Depressive Disorder, Depressive Disorder, Major, Diabetes Mellitus, Type 2, DNA, Humans, Epigenesis, Genetic, Genome-Wide Association Study
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