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The potential of SLC6A4 gene methylation analysis for the diagnosis and treatment of major depression
Open accessAbstract
We examined the utility of DNA methylation profiles at the CpG island of SLC6A4 (DMS) as a diagnostic biomarker for major depression (MD). In addition, the relationship between DMS and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) allele, the severity of symptoms, number of early adversities, and therapeutic responses to antidepressants were examined. Genomic DNA was extracted from peripheral blood of Japanese healthy controls and patients with MD before and after treatment. DMS was analyzed using a MassARRAY Compact System. The severity of depression was evaluated using the Hamilton Rating Scale for Depression, and early adversity was evaluated using the Early Trauma Inventory. We were unable to distinguish between and healthy controls, or between unmedicated patients and medicated patients using DMS. The 5-HTTLPR allele had no significant effect on DMS. The methylation rates for several CpGs differed significantly after treatment. Notably, the methylation rate of CpG 3 in patients with better therapeutic responses was significantly higher than that in patients with poorer responses. Although further studies examining the function of specific CpG units of SLC6A4 are required, these results suggest that the pre-treatment methylation rate of SLC6A4 is associated with therapeutic responses to antidepressants in unmedicated patients with MD.
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“SSRIs may normalize some of these methylation changes”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [106]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“SLC6A4 methylation can be used as an indicator of treatment response to SSRIs or psychotherapy”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [106]
Experimental — accuracy not yet measuredIn the citing paper
“Methylation at a certain CpG site within SLC6A4 is significantly increased in patients with better therapeutic responses compared to those with worse responses.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [132]
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Metadata
- Authors
- Okada, S., Morinobu, S., Fuchikami, M., Segawa, M., Yokomaku, K., Kataoka, T., Okamoto, Y., Yamawaki, S., Inoue, T., Kusumi, I., Koyama, T., Tsuchiyama, K., Terao, T., Kokubo, Y., & Mimura, M.
- Affiliations
- Hiroshima University (JP)
- Hokkaido University (JP)
- Oita University (JP)
- SHOWA Medical University (JP)
- Corresponding author
- Morinobu, Shigeru
- ORCID
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 53
- Pages
- 47-53
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W2035269052
- Cited by
- 125
- References
- 48
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 9 · 2023: 10 · 2022: 13 · 2021: 37 · 2020: 8 · 2019: 8 · 2018: 4 · 2017: 9 · 2016: 9 · 2015: 7
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 355 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Journal of Psychiatric Research (acceptedVersion)
- PubMed (publishedVersion)
- Hiroshima University Acedemic Information Repository (Hiroshima University) (submittedVersion)
- Funders
- Core Research for Evolutional Science and Technology
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Science and Technology Agency
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- serotonin transporter, DNA methylation, major depressive disorder, diagnostic biomarkers, antidepressant response, 5-HTTLPR, CpG islands, childhood adversity, depression severity, epigenetics
- MeSH terms
- Adult, Antidepressive Agents, Depressive Disorder, Major, Major Depressive Disorder, Female, Genotype, Humans, Male, Middle Aged, Pharmacogenetics, Psychiatric Status Rating Scales, Statistics as Topic, Case-Control Studies, CpG Islands, DNA Methylation, Serotonin Plasma Membrane Transport Proteins
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