Effects of quetiapine on DNA methylation in neuroblastoma cells
Abstract
Epigenetic regulation may be involved in the pathophysiology of mental disorders, such as schizophrenia and bipolar disorder, and in the pharmacological action of drugs. Characterizing the epigenetic effects of drugs is an important step to optimal treatment. We performed comprehensive and gene-specific DNA methylation analyses of quetiapine using human neuroblastoma cells. Human neuroblastoma cells were cultured with quetiapine for 8 days, and DNA methylation analysis was performed using Infinium HumanMethylation27 BeadChip. A total of 1173 genes showed altered DNA methylation. Altered DNA methylation predominantly occurred as hypomethylation within the CpG island compared to DNA isolated from non-treated cells. Gene ontology analysis revealed that these genes were related to the cellular process of intracellular protein binding. There was no common effect of quetiapine with three mood stabilizers (lithium, valproate, and carbamazepine). However, common DNA methylation changes in eight genes, including ADRA1A, which encodes adrenoceptor alpha 1A, were found with quetiapine and lithium treatments. Finally, bisulfite-sequencing analysis revealed that quetiapine decreased the DNA methylation level of the promoter region of SLC6A4, where hypermethylation with bipolar disorder and hypomethylation with mood stabilizers have been reported.
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?
Lithium, carbamazepine and quetiapine, often prescribed for bipolar disorder, are associated with decreased methylation of SLC6A4.
“For example, Lithium, Carbamazepine and Quetiapine, often prescribed for the treatment of BD, are associated with decrease methylation of SLC6A4 (Asai et al., 2013; Sugawara et al., 2015), in contrast with the hypermethylation reported in BD in that gene (Table 2).”
From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Sugawara et al., 2015
Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
DNA methylation patterns and epigenetic memory
Bird, A. (2002) · Genes & Development · doi:10.1101/gad.947102 · Cited by 7,124 · see citing works
CpG islands in vertebrate genomes.
Gardiner-Garden, M., & Frommer, M. (1987) · Journal of Molecular Biology · doi:10.1016/0022-2836(87)90689-9 · Cited by 3,462 · see citing works
Gene Silencing in Cancer in Association with Promoter Hypermethylation
Herman, J. G., & Baylin, S. B. (2003) · New England Journal of Medicine · doi:10.1056/nejmra023075 · Cited by 3,414 · see citing works
Global epigenomic reconfiguration during mammalian brain development
Lister, R., Mukamel, E. A., Nery, J. R., Urich, M., Puddifoot, C. A., Johnson, N. D., Lucero, J., Huang, Y., Dwork, A. J., Schultz, M. D., et al. (2013) · Science · doi:10.1126/science.1237905 · Cited by 1,830 · see citing works
Calabrese, J. R., Keck, P. E., Macfadden, W., Minkwitz, M., Ketter, T. A., Weisler, R. H., Cutler, A. J., McCoy, R., Wilson, E., Mullen, J., et al. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.7.1351 · Cited by 883 · see citing works
Binding of antipsychotic drugs to human brain receptors
Richelson, E., & Souder, T. (2000) · Life Sciences · doi:10.1016/s0024-3205(00)00911-5 · Cited by 608 · see citing works
Genome-Wide Dna Methylation Profiling Using Infinium ® Assay
Bibikova, M. V., Le, J. M., Barnes, B., Saedinia-Melnyk, S., Zhou, L., Shen, R., & Gunderson, K. L. (2009) · Epigenomics · doi:10.2217/epi.09.14 · Cited by 592 · see citing works
Thase, M. E., Macfadden, W., Weisler, R. H., Chang, W., Paulsson, B., Khan, A., & Calabrese, J. R. (2006) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000248603.76231.b7 · Cited by 559 · see citing works
Senescent cells harbour features of the cancer epigenome
Cruickshanks, H. A., McBryan, T., Nelson, D. M., VanderKraats, N. D., Shah, P. P., van Tuyn, J., Singh Rai, T., Brock, C., Donahue, G., Dunican, D. S., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2879 · Cited by 358 · see citing works
Jensen, N., Rodriguiz, R. M., Caron, M. G., Wetsel, W. C., Rothman, R. B., & Roth, B. L. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301646 · Cited by 319 · see citing works
Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation
Dong, E., Nelson, M., Grayson, D. R., Costa, E., & Guidotti, A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805493105 · Cited by 284 · see citing works
HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity
Kurita, M., Holloway, T. D., García‐Bea, A., Kozlenkov, A., Friedman, A. K., Moreno, J. L., Heshmati, M., Golden, S. A., Kennedy, P., Takahashi, N., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.3181 · Cited by 278 · see citing works
Smith, L. A., Cornelius, V. R., Warnock, A., Tacchi, M. J., & Taylor, D. M. (2007) · Bipolar Disorders · doi:10.1111/j.1399-5618.2007.00468.x · Cited by 269 · see citing works
Efficacy of Antimanic Treatments: Meta-analysis of Randomized, Controlled Trials
Yıldız, A., Vieta, E., Leucht, S., & Baldessarini, R. J. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.192 · Cited by 251 · see citing works
Weisler, R. H., Nolen, W. A., Neijber, A., Hellqvist, Å., Paulsson, B., & Trial 144 Study Investigators (2011) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.11m06878 · Cited by 169 · see citing works
Sugawara, H., Iwamoto, K., Bundo, M., Ueda, J., Miyauchi, T., Komori, A., Kazuno, A., Adati, N., Kusumi, I., Okazaki, Y., et al. (2011) · Translational Psychiatry · doi:10.1038/tp.2011.26 · Cited by 121 · see citing works
Self-citationTreatment Options for Bipolar Depression
Vieta, E., Locklear, J. C., Günther, O., Ekman, M., Miltenburger, C., Chatterton, M. L., Åström, M., & Paulsson, B. (2010) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e3181f15849 · Cited by 117 · see citing works
Valproate induces DNA demethylation in nuclear extracts from adult mouse brain
Dong, E., Chen, Y., Gavin, D. P., Grayson, D., & Guidotti, A. (2010) · Epigenetics · doi:10.4161/epi.5.8.13053 · Cited by 114 · see citing works
Popkie, A. P., Zeidner, L. C., Albrecht, A. M., D’Ippolito, A. M., Eckardt, S., Newsom, D. E., Groden, J. L., Doble, B. W., Aronow, B. J., McLaughlin, K. J., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.170704 · Cited by 91 · see citing works
DNA methylation in schizophrenia: progress and challenges of epigenetic studies
Nishioka, M., Bundo, M., Kasai, K., & Iwamoto, K. (2012) · Genome Medicine · doi:10.1186/gm397 · Cited by 90 · see citing works
Self-citationEpigenetic Studies of Schizophrenia: Progress, Predicaments, and Promises for the Future
Dempster, E. L., Viana, J. F., Pidsley, R., & Mill, J. S. (2012) · Schizophrenia Bulletin · doi:10.1093/schbul/sbs139 · Cited by 78 · see citing works
Effect of mood stabilizers on DNA methylation in human neuroblastoma cells
Asai, T., Bundo, M., Sugawara, H., Sunaga, F., Ueda, J., Tanaka, G., Ishigooka, J., Kasai, K., Kato, T., & Iwamoto, K. (2013) · International Journal of Neuropsychopharmacology · doi:10.1017/s1461145713000710 · Cited by 68 · see citing works
Self-citationQuetiapine for bipolar depression: a systematic review and meta-analysis
Chiesa, A., Chierzi, F., De Ronchi, D., & Serretti, A. (2012) · International Clinical Psychopharmacology · doi:10.1097/yic.0b013e32834e4c56 · Cited by 45 · see citing works
Chernoloz, O., Mansari, M. E., & Blier, P. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.18 · Cited by 39 · see citing works
Tanibuchi, Y., Fujita, Y., Kohno, M., Ishima, T., Takatsu, Y., Iyo, M., & Hashimoto, K. (2009) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2009.07.005 · Cited by 32 · see citing works
Epigenetics of psychoactive drugs
Boyadjieva, N., & Varadinova, M. (2012) · The Journal of pharmacy and pharmacology · doi:10.1111/j.2042-7158.2012.01475.x · Cited by 28 · see citing works
Kondo, M., Tajinda, K., Colantuoni, C., Hiyama, H., Seshadri, S., Huang, B., Pou, S., Furukori, K., Hookway, C., Jaaro-Peled, H., et al. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.19 · Cited by 27 · see citing works
Schmidt, A., Krieg, J., Clement, H., Hemmeter, U., Schulz, E., Vedder, H., & Heiser, P. (2008) · Journal of Psychopharmacology · doi:10.1177/0269881108096506 · Cited by 26 · see citing works
Schmidt, A. J., Hemmeter, U., Krieg, J.-C., Vedder, H., & Heiser, P. (2008) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2008.11.005 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Xuan, P., Sun, C., Zhang, T., Ye, Y., Shen, T., & Dong, Y. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00459 · Cited by 100 · see citing works
Ovenden, E. S., McGregor, N. W., Emsley, R. A., & Warnich, L. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.10.004 · Cited by 85 · see citing works
de Bartolomeis, A., Barone, A., Begni, V., & Riva, M. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106078 · Cited by 62 · see citing works
Goud, A. C., Étain, B., Bellivier, F., & Cynthia Marie-claire, A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103026 · Cited by 68 · see citing works
Kinoshita, M., Numata, S., Tajima, A., Yamamori, H., Yasuda, Y., Fujimoto, M., Watanabe, S., Umehara, H., Shimodera, S., Nakazawa, T., et al. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18030632 · Cited by 63 · see citing works
Sun, C. Y., Xuan, P., Zhang, T., & Ye, Y. (2020) · IEEE Transactions on Computational Biology and Bioinformatics · doi:10.1109/tcbb.2020.2999084 · Cited by 60 · see citing works
Can epigenetics shine a light on the biological pathways underlying major mental disorders?
Alameda, L., Trotta, G., Quigley, H., Rodriguez, V., Gadelrab, R., Dwir, D., Dempster, E., Wong, C. C. Y., & Forti, M. D. (2022) · Psychological Medicine · doi:10.1017/s0033291721005559 · Cited by 60 · see citing works
“For example, Lithium, Carbamazepine and Quetiapine, often prescribed for the treatment of BD, are associated with decrease methylation of SLC6A4 (Asai et al., 2013; Sugawara et al., 2015), in contrast with the hypermethylation reported in BD in that gene (Table 2).”
ResultIgnácio, Z. M., Réus, G. Z., Abelaira, H. M., Maciel, A. L., de Moura, A. B., Matos, D., Demo, J. P., da Silva, J. B. I., Gava, F. F., Valvassori, S. S., et al. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.11.044 · Cited by 53 · see citing works
Epigenetic profiling of human brain differential DNA methylation networks in schizophrenia
Lee, S.-A., & Huang, K.-C. (2016) · BMC Medical Genomics · doi:10.1186/s12920-016-0229-y · Cited by 46 · see citing works
DNA methylation signature as a biomarker of major neuropsychiatric disorders
Shirvani-Farsani, Z., Maloum, Z., Bagheri‐Hosseinabadi, Z., Vilor‐Tejedor, N., & Sadeghi, I. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.06.013 · Cited by 47 · see citing works
Global Deep-Sea Biodiversity Research Trends Highlighted by Science Mapping Approach
Costa, C., Fanelli, E., Marini, S., Danovaro, R., & Aguzzi, J. (2020) · Frontiers in Marine Science · doi:10.3389/fmars.2020.00384 · Cited by 41 · see citing works
Sugawara, H., Murata, Y., Ikegame, T., Sawamura, R., Shimanaga, S., Takeoka, Y., Saito, T., Ikeda, M., Yoshikawa, A., Nishimura, F., et al. (2018) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12645 · Cited by 32 · see citing works
Self-citationWalker, R. M., Christoforou, A., McCartney, D. L., Morris, S. W., Kennedy, N. A., Morten, P., Anderson, S. M., Torrance, H. S., Macdonald, A., Sussmann, J. E., et al. (2016) · Clinical Epigenetics · doi:10.1186/s13148-016-0171-z · Cited by 30 · see citing works
Ignácio, Z. M., Calixto, A. V., da Silva, R. H., Quevedo, J., & Réus, G. Z. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.12.012 · Cited by 27 · see citing works
Marques, D., Vaziri, N., Greenway, S. C., & Bousman, C. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02735-x · Cited by 25 · see citing works
Aguilar‐Raab, C., Jarczok, M. N., Warth, M., Stoffel, M., Winter, F., Tieck, M., Berg, J., Negi, L. T., Harrison, T., Pace, T. W. W., et al. (2018) · BMJ Open · doi:10.1136/bmjopen-2017-020448 · Cited by 20 · see citing works
Hu, M., Xia, Y., Zong, X., Sweeney, J. A., Bishop, J. R., Liao, Y., Giase, G. M., Li, B., Rubin, L. H., Wang, Y., et al. (2022) · Psychiatry Research · doi:10.1016/j.psychres.2022.114789 · Cited by 19 · see citing works
The preclinical discovery and development of quetiapine for the treatment of mania and depression
de Miranda, A. S., Moreira, F. A., & Teixeira, A. L. (2017) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2017.1304378 · Cited by 16 · see citing works
Delacrétaz, A., Glatard, A., Dubath, C., Gholam‐Rezaee, M., Sanchez-Mut, J. V., Gräff, J., von Gunten, A., Conus, P., & Eap, C. B. (2019) · Clinical Epigenetics · doi:10.1186/s13148-019-0792-0 · Cited by 12 · see citing works
Mas, S., Gassó, P., & Lafuente, A. (2015) · Pharmacogenomics · doi:10.2217/pgs.15.134 · Cited by 12 · see citing works
Du, J., Nakachi, Y., Kiyono, T., Fujii, S., Kasai, K., Bundo, M., & Iwamoto, K. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.792874 · Cited by 11 · see citing works
Self-citationDNA Methylation Profiling in a Neuroblastoma Cell Line Exposed to the Antipsychotic Perospirone
Murata, Y., Bundo, M., Sunaga, F., Kasai, K., & Iwamoto, K. (2018) · Pharmacopsychiatry · doi:10.1055/s-0044-101467 · Cited by 11 · see citing works
Self-citationPharmacoepigenetics of Antipsychotic Drugs
Swathy, B., Polakkattil, B. K., & Banerjee, M. (2019) · Pharmacoepigenetics · doi:10.1016/b978-0-12-813939-4.00025-5 · Cited by 3 · see citing works
Epigenetics and Gut Microbiota in the Pathogenesis and Treatment of Bipolar Disorder (BD)
Nohesara, S., Abdolmaleky, H. M., Pirani, A., & Thiagalingam, S. (2025) · Cells · doi:10.3390/cells14141104 · Cited by 3 · see citing works
Hu, M., Xia, Y., Zong, X., Sweeney, J. A., Bishop, J. R., Liao, Y., Giase, G. M., Li, B., Rubin, L. H., Wang, Y., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.03.31.018283 · Cited by 2 · see citing works
Epigenetics of bipolar disorder
Lima, C. N. D. C., Salarda, E. M., Pinjari, O. F., & Fries, G. R. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-823577-5.00025-8 · Cited by 1 · see citing works
Drugs of Abuse and DNA Methylation in the Brain
Fragou, D., & Kovatsi, L. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800634-4.00014-7
沼田, 周., 木下, 誠., & 大森, 哲. (2015) · 日本生物学的精神医学会誌 = Japanese journal of biological psychiatry · doi:10.11249/jsbpjjpp.26.1_7
Pharmacoepigenetics of Bipolar Disorder
Fries, G. R. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813939-4.00026-7
Pharmacoepigenetics of bipolar disorder
Busogi, B. U., & Fries, G. R. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-18722-3.00016-5
Murata, Y., Fujii, A., Nakachi, Y., Du, J., Kasai, K., Bundo, M., & Iwamoto, K. (2025) · Neuroscience Research · doi:10.1016/j.neures.2025.105000
Self-citationYanagida, Y., Nakachi, Y., Kajitani, N., Kikkawa, S., Ikegame, T., Koike, S., Maikusa, N., Okada, N., Naka, I., Ohashi, J., et al. (2026) · medRxiv · doi:10.64898/2026.03.26.26349121
Self-citation
- Authors
- Sugawara, H., Bundo, M., Asai, T., Sunaga, F., Ueda, J., Ishigooka, J., Kasai, K., Kato, T., & Iwamoto, K.
- Affiliations
- Tokyo Women's Medical University (JP)
- The University of Tokyo (JP)
- RIKEN Center for Brain Science (JP)
- Corresponding author
- Iwamoto, Kazuya
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 56
- Pages
- 117-121
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W2016563708
- Cited by
- 32
- References
- 30
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 2
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (24591676)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- quetiapine, DNA methylation, neuroblastoma cells, mood stabilizers, lithium, valproic acid, carbamazepine, ADRA1A, serotonin transporter, promoter methylation, bipolar disorder, schizophrenia
- MeSH terms
- Quetiapine Fumarate, Dibenzothiazepines, Humans, Neuroblastoma, Antipsychotic Agents, Cluster Analysis, Receptors, Adrenergic, alpha-1, DNA Methylation, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Epigenesis, Genetic, Cell Line, Tumor, 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
