Cited by 134Epigenetics and DNA MethylationTreatment of Major DepressionNeurotransmitter Receptor Influence on Behavior

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The potential of SLC6A4 gene methylation analysis for the diagnosis and treatment of major depression

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Okada, Satoshi, Morinobu, Shigeru, Fuchikami, Manabu, Segawa, Masahiro, Yokomaku, Kana, Kataoka, Tsutomu, Okamoto, Yasumasa, Yamawaki, Shigeto, Inoue, Takeshi, Kusumi, Ichiro, Koyama, Tsukasa, Tsuchiyama, Kounosuke, Terao, Takeshi, Kokubo, Yosuke, Mimura, Masaru·2014·Journal of Psychiatric Research

DOI 10.1016/j.jpsychires.2014.02.002

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Abstract

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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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: Morinobu, Shigeru
Fuchikami, Manabu
Okamoto, Yasumasa
Yamawaki, Shigeto
Inoue, Takeshi
Kusumi, Ichiro
Koyama, Tsukasa
Terao, Takeshi
Mimura, Masaru
Venue: Journal of Psychiatric Research
Publisher: Elsevier BV
Published: 2014-06
Volume: 53
Pages: 47-53
ISSN: 0022-3956 (ISSN-L)
DOI: 10.1016/j.jpsychires.2014.02.002
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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The potential of SLC6A4 gene methylation analysis for the diagnosis and treatment of major depression

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