Observational studyThe international journal of neuropsychopharmacology2021
Serotonin Transporter Gene Promoter Hypomethylation as a Predictor of Antidepressant Treatment Response in Major Depression: A Replication Study.
Observational study in The international journal of neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Exploring the association between serotonin transporter promoter region methylation levels and depressive symptoms: a systematic review and multi-level meta-analysis.Translational psychiatry · 2025Pooled it
- Advances in Perinatal Depression: A Focus on Screening and Treatment.Journal of clinical medicine · 2026Review
- Antidepressant Augmentation of Antipsychotic Treatment in Schizophrenia: A Narrative Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Molecular Mechanisms of Depression: The Interplay Between Genes and Receptors.International journal of molecular sciences · 2025Review
- Mechanisms of Baishao () and Gancao () on major depressive disorder: network pharmacology and o validation.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Serotonin transporter gene methylation and cortisol reactivity to acute stress: modeling the pathogenetic and therapeutic effects of stress-related disorders?Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Pharmacogenetic Implications for Antidepressant Therapy in Major Depression: A Systematic Review Covering 2019-2024.Journal of clinical medicine · 2025Review
- Pharmaco-Multiomics: A New Frontier in Precision Psychiatry.International journal of molecular sciences · 2025Review
- Prenatal exposure to genocide and subsequent adverse childhood events are associated with DNA methylation of SLC6A4, BDNF, and PRDM8 in early adulthood in Rwanda.Scientific reports · 2024Article
- Epigenome-Wide DNA Methylation in Unipolar Depression: Predictive Biomarker of Antidepressant Treatment Response?The international journal of neuropsychopharmacology · 2024Article
- No association between peripheral serotonin-gene-related DNA methylation and brain serotonin neurotransmission in the healthy and depressed state.Clinical epigenetics · 2024Article
- The role of DNA methylation in progression of neurological disorders and neurodegenerative diseases as well as the prospect of using DNA methylation inhibitors as therapeutic agents for such disorders.IBRO neuroscience reports · 2023Review
- The Role of Pharmacogenetics in Personalizing the Antidepressant and Anxiolytic Therapy.Genes · 2023Review
- Deep phenotyping as a contribution to personalized depression therapy: the GEParD and DaCFail protocols.Journal of neural transmission (Vienna, Austria : 1996) · 2023Article
- Review
- Article
- ABSP: an automated R tool to efficiently analyze region-specific CpG methylation from bisulfite sequencing PCR.Bioinformatics (Oxford, England) · 2023Article
- Precision Medicine in Antidepressants Treatment.Handbook of experimental pharmacology · 2023Review
- DNA Methylation in Depression and Depressive-Like Phenotype: Biomarker or Target of Pharmacological Intervention?Current neuropharmacology · 2022Review
- Maternal and infant NR3C1 and SLC6A4 epigenetic signatures of the COVID-19 pandemic lockdown: when timing matters.Translational psychiatry · 2022Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe serotonin transporter gene (SLC6A4; 5-HTT; SERT) is considered a prime candidate in pharmacogenetic research in major depressive disorder (MDD). Besides genetic variation, recent advances have spotlighted the involvement of epigenetic mechanisms such as DNA methylation in predicting antidepressant treatment response in "pharmaco-epigenetic" approaches. In MDD, lower SLC6A4 promoter methylation has been suggested to predict impaired response to serotonergic antidepressants. The present study sought to replicate and extend this finding in a large, independent sample of MDD patients.
methodsThe sample comprised n = 236 Caucasian patients with MDD receiving antidepressant medication in a naturalistic treatment setting. Functional DNA methylation of 9 CpG sites located in the SLC6A4 promoter region was analyzed via direct sequencing of sodium bisulfite- treated DNA extracted from blood cells. Patients were assessed over the course of a 6-week in-patient treatment using the Hamilton Depression Scale (HAM-D).
resultsResults confirm relative SLC6A4 hypomethylation to predict impaired antidepressant response both dimensionally and categorically (HAM-D reductions < 50%) and to furthermore be indicative of nonremission (HAM-D > 7). This also held true in a homogenous subgroup of patients continuously treated with selective serotonin reuptake inhibitors or serotonin/noradrenaline reuptake inhibitors (n = 110).
conclusionsImpaired response to serotonergic antidepressants via SLC6A4 hypomethylation may be conveyed by increased gene expression and consequently decreased serotonin availability, which may counteract the effects of serotonergic antidepressants. The present results could in the future inform clinical decision-making towards a more personalized treatment of MDD.
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