Evaluation of DNA methylation in BDNF , SLC6A4 , NR3C1 and FKBP5 before and after treatment with selective serotonin-reuptake inhibitor in major depressive disorder
Abstract
Aim: To identify the DNA methylation status of related genes in major depressive disorder following selective serotonin-reuptake inhibitor treatment. Materials & methods: 45 patients with major depressive disorder and 45 healthy volunteers were considered experimental and control groups, respectively. High-resolution melting real-time PCR was implemented to evaluate DNA methylation. Results: After 100 days of selective serotonin-reuptake inhibitor treatment, methylation of promoter CpG sites of BDNF, NR3C1, FKBP5 and SLC6A4 was significantly reduced. Compared with before treatment, patients' Hamilton Depression Rating Scale scores were significantly reduced after selective serotonin-reuptake inhibitor treatment (p ≤ 0.0001). Conclusion: Based on the proven effect of antidepressants on DNA methylation and gene expression, these medications can improve the treatment process and reduce depression scores after treatment.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Methylation of BDNF, SLC6A4, and FKBP5 may predict response to SSRIs, psychotherapy, or electroconvulsive therapy.
“In the context of pharmaco-epigenetics, methylation of genes like BDNF, SLC6A4, and FKBP5 may predict response to SSRIs, psychotherapy, or electroconvulsive therapy (129).”
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 [129]
Cites
Oberlander, T. F., Weinberg, J., Papsdorf, M., Grunau, R., Misri, S., & Devlin, A. M. (2008) · Epigenetics · doi:10.4161/epi.3.2.6034 · Cited by 1,432 · see citing works
DNA Methylation-Related Chromatin Remodeling in Activity-Dependent <i>Bdnf</i> Gene Regulation
Martinowich, K., Hattori, D., Wu, H., Fouse, S., He, F., Hu, Y., Fan, G., & Sun, Y. E. (2003) · Science · doi:10.1126/science.1090842 · Cited by 1,405 · see citing works
The developmental role of serotonin: news from mouse molecular genetics
Gaspar, P., Cases, O., & Maroteaux, L. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1256 · Cited by 1,297 · see citing works
Mouse and rat <i>BDNF</i> gene structure and expression revisited
Aid, T., Kazantseva, A., Piirsoo, M., Palm, K., & Timmusk, T. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21139 · Cited by 943 · see citing works
Castrén, E., & Rantamäki, T. (2010) · Developmental Neurobiology · doi:10.1002/dneu.20758 · Cited by 864 · see citing works
Gene–Stress–Epigenetic regulation of FKBP5: clinical and translational implications
Zannas, A. S., Wiechmann, T., Gassen, N. C., & Binder, E. B. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.235 · Cited by 622 · see citing works
BDNF function and intracellular signaling in neurons.
Numakawa, T., Suzuki, S., Kumamaru, E., Adachi, N., Richards, M., & Kunugi, H. (2010) · PubMed · doi:10.14670/hh-25.237 · Cited by 598 · see citing works
Pharmacological characterization of selective serotonin reuptake inhibitors (SSRIs)
Hyttel, J. (1994) · International Clinical Psychopharmacology · doi:10.1097/00004850-199403001-00004 · Cited by 492 · see citing works
Prevalence and predictors of recurrence of major depressive disorder in the adult population
Hardeveld, F., Spijker, J., De Graaf, R., Nolen, W. A., & Beekman, A. T. F. (2010) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2009.01519.x · Cited by 486 · see citing works
Prognosis and improved outcomes in major depression: a review
Kraus, C., Kadriu, B., Lanzenberger, R., Zarate, C. A., & Kasper, S. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0460-3 · Cited by 482 · see citing works
Stress, epigenetics and depression: A systematic review
Park, C., Rosenblat, J. D., Brietzke, E., Pan, Z., Lee, Y., Cao, B., Zuckerman, H., Kalantarova, A., & McIntyre, R. S. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.04.010 · Cited by 465 · see citing works
Relative Toxicity of Selective Serotonin Reuptake Inhibitors (SSRIs) in Overdose
Isbister, G. K., Bowe, S. J., Dawson, A. H., & Whyte, I. M. (2004) · Journal of Toxicology Clinical Toxicology · doi:10.1081/clt-120037428 · Cited by 432 · see citing works
Fuchikami, M., Morinobu, S., Segawa, M., Okamoto, Y., Yamawaki, S., Ozaki, N., Inoue, T., Kusumi, I., Koyama, T., Tsuchiyama, K., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023881 · Cited by 378 · see citing works
Yehuda, R., Daskalakis, N. P., Desarnaud, F., Makotkine, I., Lehrner, A. L., Koch, E., Flory, J. D., Buxbaum, J. D., Meaney, M. J., & Bierer, L. M. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00118 · Cited by 358 · see citing works
Russo-Neustadt, A., Ha, T., Ramirez, R., & Kesslak, J. P. (2001) · Behavioural Brain Research · doi:10.1016/s0166-4328(00)00364-8 · Cited by 346 · see citing works
Weder, N., Zhang, H., Jensen, K., Yang, B. Z., Simen, A., Jackowski, A., Lipschitz, D., Douglas-Palumberi, H., Ge, M., Perepletchikova, F., et al. (2014) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2013.12.025 · Cited by 324 · see citing works
Matosin, N., Halldorsdottir, T., & Binder, E. B. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.01.021 · Cited by 226 · see citing works
Wang, Q., Shelton, R. C., & Dwivedi, Y. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.08.066 · Cited by 201 · see citing works
Serotonin transporter mRNA levels are associated with the methylation of an upstream CpG island
Philibert, R. A., Madan, A., Andersen, A. M., Cadoret, R. J., Packer, H., & Sandhu, H. K. (2006) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30414 · Cited by 191 · see citing works
Tadić, A., Müller-Engling, L., Schlicht, K. F., Kotsiari, A., Dreimüller, N., Kleimann, A., Bleich, S., Lieb, K., & Frieling, H. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.58 · Cited by 175 · see citing works
Murgatroyd, C., Quinn, J. P., Sharp, H. M., Pickles, A. R., & Hill, J. (2015) · Translational Psychiatry · doi:10.1038/tp.2014.140 · Cited by 168 · see citing works
Melas, P. A., Rogdaki, M., Lennartsson, A., Björk, K., Qi, H., Witasp, A., Werme, M., Wegener, G., Mathé, A. A., Svenningsson, P., et al. (2012) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145711000940 · Cited by 157 · see citing works
A review of DNA methylation in depression
Chen, D., Meng, L., Pei, F., Zheng, Y., & Leng, J. (2017) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2017.05.022 · Cited by 154 · see citing works
Epigenetic regulation of BDNF expression according to antidepressant response
Lopez, J. P., Mamdani, F., Labonte, B., Beaulieu, M.-M., Yang, J. P., Berlim, M. T., Ernst, C., & Turecki, G. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.38 · Cited by 146 · see citing works
Transcriptional control of the glucocorticoid receptor: CpG islands, epigenetics and more
Turner, J. D., Alt, S. R., Cao, L., Vernocchi, S., Trifonova, S. T., Battello, N., & Muller, C. P. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.06.037 · Cited by 145 · see citing works
Biomarkers in Substance Use Disorders
Volkow, N. D., Koob, G., & Baler, R. (2015) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5b00067 · Cited by 141 · see citing works
Olsson, C. A., Foley, D. L., Parkinson-Bates, M., Byrnes, G., McKenzie, M., Patton, G. C., Morley, R., Anney, R. J. L., Craig, J. M., & Saffery, R. (2010) · Biological Psychology · doi:10.1016/j.biopsycho.2009.12.003 · Cited by 137 · see citing works
Okada, S., Morinobu, S., Fuchikami, M., Segawa, M., Yokomaku, K., Kataoka, T., Okamoto, Y., Yamawaki, S., Inoue, T., Kusumi, I., et al. (2014) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2014.02.002 · Cited by 125 · see citing works
Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat
Zhang, Y., Gu, F., Chen, J., & Dong, W. (2010) · Brain Research · doi:10.1016/j.brainres.2010.09.095 · Cited by 122 · see citing works
Gassen, N. C., Fries, G. R., Zannas, A. S., Hartmann, J., Zschocke, J., Hafner, K., Carrillo‐Roa, T., Steinbacher, J., Preißinger, S. N., Hoeijmakers, L., et al. (2015) · Science Signaling · doi:10.1126/scisignal.aac7695 · Cited by 106 · see citing works
The Relationship between DNA Methylation and Antidepressant Medications: A Systematic Review
Webb, L. M., Phillips, K. E., Ho, M. C., Veldic, M., & Blacker, C. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21030826 · Cited by 84 · see citing works
The pharmacogenomics of selective serotonin reuptake inhibitors
Serretti, A., & Artioli, P. (2004) · The Pharmacogenomics Journal · doi:10.1038/sj.tpj.6500250 · Cited by 82 · see citing works
Mullins, C. D., Shaya, F. T., Meng, F., Wang, J., & Harrison, D. J. (2005) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.25.5.660.63590 · Cited by 78 · see citing works
Klinger-König, J., Hertel, J., Van der Auwera, S., Frenzel, S., Pfeiffer, L., Waldenberger, M., Golchert, J., Teumer, A., Nauck, M., Homuth, G., et al. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0319-6 · Cited by 78 · see citing works
A methylation study of long-term depression risk
Clark, S. L., Hattab, M. W., Chan, R. F., Shabalin, A. A., Han, L. K. M., Zhao, M., Smit, J. H., Jansen, R., Milaneschi, Y., Xie, L. Y., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0516-z · Cited by 77 · see citing works
Hohne, N., Poidinger, M., Merz, F., Pfister, H., Bruckl, T., Zimmermann, P., Uhr, M., Holsboer, F., & Ising, M. (2015) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyu087 · Cited by 74 · see citing works
Switzeny, O. J., Christmann, M., Renovanz, M., Giese, A., Sommer, C., & Kaina, B. (2016) · Clinical Epigenetics · doi:10.1186/s13148-016-0204-7 · Cited by 67 · see citing works
Clinical Implications of Genetic Variation in the Serotonin Transporter Promoter Region
Luddington, N. S., Mandadapu, A., Husk, M., & El‐Mallakh, R. S. (2009) · The Primary Care Companion to The Journal of Clinical Psychiatry · doi:10.4088/pcc.08r00656 · Cited by 63 · see citing works
Miller, O., Shakespeare-Finch, J., Bruenig, D., & Mehta, D. (2020) · Psychological Trauma: Theory, Research, Practice, and Policy · doi:10.1037/tra0000574 · Cited by 56 · see citing works
Shields, A. E., Wise, L. A., Ruiz-Narváez, E., Seddighzadeh, B., Byun, H., Cozier, Y. C., Rosenberg, L. A., Palmer, J. R., & Baccarelli, A. (2016) · Epigenomics · doi:10.2217/epi-2016-0074 · Cited by 56 · see citing works
Zhou, J., Li, M., Wang, X., He, Y., Xia, Y., Sweeney, J. A., Kopp, R. F., Liu, C., & Chen, C. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.674273 · Cited by 56 · see citing works
Effects of selective serotonin reuptake inhibitors on DNA damage in patients with depression
Ahmadimanesh, M., Abbaszadegan, M. R., Rad, D. M., Moallem, S. A., Mohammadpour, A. H., Ghahremani, M. H., Hosseini, F. F., Behdani, F., Manteghi, A. A., Jowsey, P. A., et al. (2019) · Journal of Psychopharmacology · doi:10.1177/0269881119874461 · Cited by 47 · see citing works
Self-citationPharmacological sex hormone manipulation as a risk model for depression
Frøkjær, V. G. (2020) · Journal of Neuroscience Research · doi:10.1002/jnr.24632 · Cited by 47 · see citing works
Schiele, M. A., Zwanzger, P., Schwarte, K., Arolt, V., Baune, B. T., & Domschke, K. (2020) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyaa081 · Cited by 47 · see citing works
Pharmacogenetics of Antidepressant Drugs: Current Clinical Practice and Future Directions
Narasimhan, S., & Lohoff, F. W. (2012) · Pharmacogenomics · doi:10.2217/pgs.12.1 · Cited by 44 · see citing works
Montirosso, R., Provenzi, L., Giorda, R., Fumagalli, M., Morandi, F., Sirgiovanni, I., Pozzoli, U., GRUNAU, R. E., Oberlander, T. F., Mosca, F., et al. (2016) · Epigenomics · doi:10.2217/epi-2016-0010 · Cited by 38 · see citing works
Brain-Derived Neurotrophic Factor: The Neurotrophin Hypothesis of Psychopathology
Stein, D. J., Daniels, W. M. U., Savitz, J. B., & Harvey, B. H. (2008) · CNS Spectrums · doi:10.1017/s1092852900013997 · Cited by 37 · see citing works
The importance of epigenetics in diagnostics and treatment of major depressive disorder
Czarny, P., Białek, K., Ziółkowska, S., Strycharz, J., Barszczewska, G., & Sliwinski, T. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11030167 · Cited by 37 · see citing works
Major depressive disorders accompanying autoimmune diseases – Response to treatment
Białek, K. I., Czarny, P. L., Strycharz, J., & Śliwiński, T. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.109678 · Cited by 32 · see citing works
Tsai, S., Hong, C., & Liou, Y. (2008) · Pharmacogenomics · doi:10.2217/14622416.9.9.1353 · Cited by 27 · see citing works
Gharraee, B., Tajrishi, K. Z., Sheybani, F., Tahmasbi, N., Mirzaei, M., Farahani, H., & Naserbakht, M. (2019) · PubMed Central · doi:10.34171/mjiri.33.151 · Cited by 27 · see citing works
Nagarajan, S., Seddighzadeh, B., Baccarelli, A., Wise, L. A., Williams, M. A., & Shields, A. E. (2016) · Epigenomics · doi:10.2217/epi.16.9 · Cited by 20 · see citing works
Dereix, A. E., Ledyard, R. F., Redhunt, A. M., Bloomquist, T. R., Brennan, K. J. M., Baccarelli, A., Hacker, M. R., & Burris, H. H. (2020) · Epigenomics · doi:10.2217/epi-2020-0022 · Cited by 20 · see citing works
Changes of BDNF exon IV DNA methylation are associated with methamphetamine dependence
Iamjan, S.-A., Thanoi, S., Watiktinkorn, P., Fachim, H., Dalton, C., Nudmamud‐Thanoi, S., & Reynolds, G. P. (2021) · Epigenomics · doi:10.2217/epi-2020-0463 · Cited by 20 · see citing works
Does DNA Methylation Influence the Effects of Psychiatric Drugs?
Reynolds, G. P., & Fachim, H. (2016) · Epigenomics · doi:10.2217/epi.15.116 · Cited by 19 · see citing works
Social determinants of late-life depression epigenetics
Lozupone, M., & Panza, F. (2020) · Epigenomics · doi:10.2217/epi-2019-0392 · Cited by 15 · see citing works
Nourian, Y. H., Beh-Pajooh, A., Aliomrani, M., et al. (2021) · NeuroToxicology · doi:10.1016/j.neuro.2021.09.008 · Cited by 13 · see citing works
Self-citationWinkler, B., Lehnert, H., Oster, H., Kirchner, H., & Harbeck, B. (2017) · Epigenomics · doi:10.2217/epi-2017-0057 · Cited by 12 · see citing works
Biomarker or Pathophysiology? The Role of DNA Methylation in Postpartum Depression
Kimmel, M., Kaminsky, Z. A., & Payne, J. L. (2013) · Epigenomics · doi:10.2217/epi.13.51 · Cited by 11 · see citing works
The Pharmacogenomics of Selective Serotonin Reuptake Inhibitors
García‐Marín, L. M., Rabinowitz, J. A., Ceja, Z., Alcauter, S., Medina-Rivera, A., & Rentería, M. E. (2022) · Pharmacogenomics · doi:10.2217/pgs-2022-0037 · Cited by 11 · see citing works
Gharraee, B., Tajrishi, K. Z., Sheybani, F., et al. (2019) · Medical Journal of the Islamic Republic of Iran · doi:10.47176/mjiri.33.151 · Cited by 9 · see citing works
Scharinger, C., Bartova, L., & Pezawas, L. (2011) · Personalized Medicine · doi:10.2217/pme.11.9 · Cited by 1 · see citing works
Pharmacogenetic Treatment of Depressive Disorders
Lee, M. (2007) · Future Neurology · doi:10.2217/14796708.2.3.329 · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Montel Hayes, R., Mason, C. E., & Miller, J. J. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1671122 · Cited by 5 · see citing works
- Authors
- Mohammadi, S., Beh-Pajooh, A., Ahmadimanesh, M., Amini, M., Ghazi-Khansari, M., Moallem, S. A., Hosseini, R., Nourian, Y. H., & Ghahremani, M. H.
- Affiliations
- Tehran University of Medical Sciences (IR)
- Mashhad University of Medical Sciences (IR)
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- ORCID
- Venue
- Epigenomics
- Publisher
- Informa UK Limited
- Published
- 2022-10
- Volume
- 14
- Issue
- 20
- Pages
- 1269-1280
- ISSN
- 1750-1911 (ISSN-L)
- 1750-192X
- OpenAlex
- W4309098941
- Semantic Scholar
- 511f0d5d194572cbc59d800e3ed1f4ec8babf40b
- Cited by
- 23
- References
- 63
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 4 · 2023: 4
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Epigenomics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Tehran University of Medical Sciences and Health Services (97-03-33-40268)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- DNA methylation, major depressive disorder, selective serotonin reuptake inhibitors, antidepressant response, brain-derived neurotrophic factor, serotonin transporter, NR3C1, FKBP5, promoter CpG sites, epigenetics, depression severity
- MeSH terms
- Tacrolimus Binding Protein 5, Major Depressive Disorder, Humans, Promoter Regions, Genetic, Receptors, Glucocorticoid, Serotonin, Selective Serotonin Reuptake Inhibitors, DNA Methylation, Brain-Derived Neurotrophic Factor, Serotonin Plasma Membrane Transport Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
