Moving pharmacoepigenetics tools for depression toward clinical use
Open accessAbstract
Background Major depressive disorder (MDD) is a leading cause of disability worldwide, and over half of patients do not achieve symptom remission following an initial antidepressant course. Despite evidence implicating a strong genetic basis for the pathophysiology of MDD, there are no adequately validated biomarkers of treatment response routinely used in clinical practice. Pharmacoepigenetics is an emerging field that has the potential to combine both genetic and environmental information into treatment selection and further the goal of precision psychiatry. However, this field is in its infancy compared to the more established pharmacogenetics approaches.Methods We prepared a narrative review using literature searches of studies in English pertaining to pharmacoepigenetics and treatment of depressive disorders conducted in PubMed, Google Scholar, PsychINFO, and Ovid Medicine from inception through January 2019. We reviewed studies of DNA methylation and histone modifications in both humans and animal models of depression.Results Emerging evidence from human and animal work suggests a key role for epigenetic marks, including DNA methylation and histone modifications, in the prediction of antidepressant response. The challenges of heterogeneity of patient characteristics and loci studied as well as lack of replication that have impacted the field of pharmacogenetics also pose challenges to the development of pharmacoepigenetic tools. Additionally, given the tissue specific nature of epigenetic marks as well as their susceptibility to change in response to environmental factors and aging, pharmacoepigenetic tools face additional challenges to their development.Limitations This is a narrative and not systematic review of the literature on the pharmacoepigenetics of antidepressant response. We highlight key studies pertaining to pharmacoepigenetics and treatment of depressive disorders in humans and depressive-like behaviors in animal models, regardless of sample size or methodology. While we discuss DNA methylation and histone modifications, we do not cover microRNAs, which have been reviewed elsewhere recently.Conclusions Utilization of genome-wide approaches and reproducible epigenetic assays, careful selection of the tissue assessed, and integration of genetic and clinical information into pharmacoepigenetic tools will improve the likelihood of developing clinically useful tests.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The goal of precision medicine (individually tailored treatments) is not being achieved for neurobehavioural conditions such as psychiatric disorders.
“The goal of precision medicine (individually tailored treatments) is not being achieved for neurobehavioural conditions such as psychiatric disorders.”
From Precision clinical trials: a framework for getting to precision medicine for neurobehavioural disorders (2021) · cites this paper as [28]
There is a lack of clinically validated biomarkers in mood, anxiety, psychotic, substance use and eating disorders to guide treatment.
“Evidence of this is the lack of clinically validated biomarkers in mood,28 anxiety,29 psychotic,30 substance use31 and eating disorders32 to guide treatment.”
From Precision clinical trials: a framework for getting to precision medicine for neurobehavioural disorders (2021) · cites this paper as [28]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Integrative analysis of 111 reference human epigenomes
Roadmap Epigenomics Consortium, Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., et al. (2015) · Nature · doi:10.1038/nature14248 · Cited by 6,368 · see citing works
Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Nierenberg, A. A., Stewart, J. W., Warden, D., Niederehe, G., Thase, M. E., Lavori, P. W., Lebowitz, B. D., et al. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.11.1905 · Cited by 5,643 · cited 2× · see citing works
“While successive trial and error treatment trials appear to boost cumulative remission rates to 67% (Rush et al., 2006), the prolonged process to achieve remission leaves patients suffering from illness morbidity and elevates the risk of disengaging from care.”
BackgroundNeurotrophins: Roles in Neuronal Development and Function
Huang, E. J., & Reichardt, L. F. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.677 · Cited by 4,394 · see citing works
Pharmacogenomics Knowledge for Personalized Medicine
Whirl‐Carrillo, M., McDonagh, E. M., Hebert, J. M., Gong, L., Sangkuhl, K., Thorn, C. F., Altman, R. B., & Klein, T. E. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.96 · Cited by 1,791 · see citing works
Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action
Tsankova, N. M., Berton, O., Renthal, W., Kumar, A., Neve, R. L., & Nestler, E. J. (2006) · Nature Neuroscience · doi:10.1038/nn1659 · Cited by 1,780 · see citing works
Conserved role of intragenic DNA methylation in regulating alternative promoters
Maunakea, A. K., Nagarajan, R. P., Bilenky, M., Ballinger, T. J., D’Souza, C., Fouse, S. D., Johnson, B. E., Hong, C., Nielsen, C., Zhao, Y., et al. (2010) · Nature · doi:10.1038/nature09165 · Cited by 1,743 · see citing works
Charting a dynamic DNA methylation landscape of the human genome
Ziller, M. J., Gu, H., Müller, F., Donaghey, J., Tsai, L. T.-Y., Kohlbacher, O., De Jager, P. L., Rosen, E. D., Bennett, D. A., Bernstein, B. E., et al. (2013) · Nature · doi:10.1038/nature12433 · Cited by 1,357 · see citing works
Ingelman‐Sundberg, M., Sim, S. C., Gomez, A. V., & Rodríguez‐Antona, C. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.09.004 · Cited by 1,165 · see citing works
Accounting for cellular heterogeneity is critical in epigenome-wide association studies
Jaffe, A. E., & Irizarry, R. A. (2014) · Genome Biology · doi:10.1186/gb-2014-15-2-r31 · Cited by 1,067 · see citing works
Hicks, J. K., Bishop, J., Sangkuhl, K., Dj, M., Ji, Y., Leckband, S. G., Leeder, J. S., Graham, R., Chiulli, D., LLerena, A., et al. (2015) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.147 · Cited by 1,001 · see citing works
Molecular Signals of Epigenetic States
Bonasio, R., Tu, S., & Reinberg, D. (2010) · Science · doi:10.1126/science.1191078 · Cited by 912 · see citing works
Turecki, G., & Meaney, M. J. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.11.022 · Cited by 796 · see citing works
Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain
Guo, J. U., Su, Y., Shin, J. H., Shin, J., Li, H., Xie, B., Zhong, C., Hu, S., Le, T., Fan, G., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3607 · Cited by 714 · see citing works
Hicks, J. K., Sangkuhl, K., Swen, J. J., Ellingrod, V. L., Dj, M., Shimoda, K., Bishop, J., Kharasch, E. D., Skaar, T. C., Gaedigk, A., et al. (2016) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.597 · Cited by 686 · see citing works
An epigenetic road map for histone lysine methylation
Lachner, M., O’Sullivan, R. J., & Jenuwein, T. (2003) · Journal of Cell Science · doi:10.1242/jcs.00493 · Cited by 630 · see citing works
The new field of ‘precision psychiatry’
Fernandes, B. S., Williams, L. M., Steiner, J. H., Leboyer, M., Carvalho, A. F., & Berk, M. (2017) · BMC Medicine · doi:10.1186/s12916-017-0849-x · Cited by 552 · see citing works
Molendijk, M. L., Bus, B. A. A., Spinhoven, P., Penninx, B. W. J. H., Kenis, G., Prickaerts, J., Voshaar, R. O., & Elzinga, B. M. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.98 · Cited by 437 · see citing works
Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice
Elliott, E., Ezra-Nevo, G., Regev, L., Neufeld-Cohen, A., & Chen, A. (2010) · Nature Neuroscience · doi:10.1038/nn.2642 · Cited by 436 · see citing works
CpG and non-CpG methylation in epigenetic gene regulation and brain function
Jang, H., Shin, W., Lee, J., & Do, J. (2017) · Genes · doi:10.3390/genes8060148 · Cited by 427 · see citing works
Epigenetics of the depressed brain: role of histone acetylation and methylation
Sun, H., Kennedy, P. J., & Nestler, E. J. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.73 · Cited by 413 · see citing works
Epigenetics across the human lifespan
Kanherkar, R. R., Bhatia-Dey, N., & Csoka, A. B. (2014) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2014.00049 · Cited by 407 · see citing works
Papakostas, G. I., & D, M. F. M. (2008) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2008.08.009 · Cited by 381 · see citing works
Olbrich, S., & Arns, M. (2013) · International Review of Psychiatry · doi:10.3109/09540261.2013.816269 · Cited by 371 · see citing works
Smith, A. K., Kilaru, V., Klengel, T., Mercer, K. B., Bradley, B., Conneely, K. N., Ressler, K. J., & Binder, E. B. (2015) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32278 · Cited by 355 · see citing works
Bock, C., Halbritter, F., Carmona, F. J., Tierling, S., Datlinger, P., Assenov, Y., Berdasco, M., Bergmann, A. K., Booher, K., Busato, F., et al. (2016) · Nature Biotechnology · doi:10.1038/nbt.3605 · Cited by 324 · see citing works
Williams, L. M. (2016) · Depression and Anxiety · doi:10.1002/da.22556 · Cited by 290 · see citing works
EWAS Atlas: a curated knowledgebase of epigenome-wide association studies
Li, M., Zou, D., Li, Z., Gao, R., Sang, J., Zhang, Y., Li, R., Xia, L., Zhāng, T., Niu, G., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky1027 · Cited by 286 · see citing works
Nasca, C., Xenos, D., Barone, Y., Caruso, A., Scaccianoce, S., Matrisciano, F., Battaglia, G., Mathé, A. A., Pittaluga, A., Lionetto, L., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1216100110 · Cited by 264 · see citing works
BECon: a tool for interpreting DNA methylation findings from blood in the context of brain
Edgar, R. D., Jones, M. J., Meaney, M. J., Turecki, G., & Kobor, M. S. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.171 · Cited by 261 · see citing works
Association of SLC6A4 methylation with early adversity, characteristics and outcomes in depression
Kang, H.-J., Kim, J.-M., Stewart, R., Kim, S.-Y., Bae, K.-Y., Kim, S.-W., Shin, I.-S., Shin, M.-G., & Yoon, J.-S. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2013.01.006 · Cited by 254 · see citing works
Contribution of Common Genetic Variants to Antidepressant Response
Tansey, K. E., Guipponi, M., Hu, X., Domenici, E., Lewis, G., Malafosse, A., Wendland, J. R., Lewis, C. M., McGuffin, P., & Uher, R. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.10.030 · Cited by 245 · see citing works
GENDEP Investigators, MARS Investigators, STAR*D Investigators, Uher, R., Tansey, K. E., Henigsberg, N., Wolfgang, M. C., Mors, O. N., Hauser, J., Placentino, A., et al. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.12020237 · Cited by 241 · see citing works
Csoka, A. B., & Szyf, M. (2009) · Medical Hypotheses · doi:10.1016/j.mehy.2008.10.039 · Cited by 240 · see citing works
Bousman, C., Arandjelovic, K., Mancuso, S. G., Eyre, H. A., & Dunlop, B. W. (2018) · Pharmacogenomics · doi:10.2217/pgs-2018-0142 · Cited by 204 · see citing works
Self-citationZeier, Z. R., Carpenter, L. L., Kalin, N. H., Rodríguez, C. I., McDonald, W. M., Widge, A. S., & Nemeroff, C. B. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2018.17111282 · Cited by 194 · see citing works
Iwamoto, K., Bundo, M., Ueda, J., Oldham, M. C., Ukai, W., Hashimoto, E., Saito, T., Geschwind, D. H., & Kato, T. (2011) · Genome Research · doi:10.1101/gr.112755.110 · Cited by 189 · see citing works
Wei, Y. B., Melas, P. A., Wegener, G., Mathe, A. A., & Lavebratt, C. (2015) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyu032 · Cited by 186 · see citing works
Neuroimaging biomarkers as predictors of treatment outcome in Major Depressive Disorder
Fonseka, T. M., MacQueen, G. M., & Kennedy, S. H. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.10.049 · Cited by 185 · see citing works
Perry, P. J. (1996) · Journal of Affective Disorders · doi:10.1016/0165-0327(96)00014-6 · Cited by 181 · see citing works
Serotonin transporter gene hypomethylation predicts impaired antidepressant treatment response
Domschke, K., Tidow, N., Schwarte, K., Deckert, J., Lesch, K., Arolt, V., Zwanzger, P., & Baune, B. T. (2014) · The International Journal of Neuropsychopharmacology · doi:10.1017/s146114571400039x · Cited by 179 · see citing works
Self-citationTadić, 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
Leuchter, A. F., Cook, I. A., Marangell, L. B., Gilmer, W. S., Burgoyne, K. S., Howland, R. H., Trivedi, M. H., Zisook, S., Jain, R., McCracken, J. T., et al. (2009) · Psychiatry Research · doi:10.1016/j.psychres.2009.06.004 · Cited by 175 · see citing works
Booij, L., Szyf, M., Carballedo, A., Frey, E.-M., Morris, D., Dymov, S., Vaisheva, F., Ly, V., Fahey, C., Meaney, J., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0119061 · Cited by 174 · see citing works
Jawahar, M. C., Murgatroyd, C., Harrison, E. L., & Baune, B. T. (2015) · Clinical Epigenetics · doi:10.1186/s13148-015-0156-3 · Cited by 165 · see citing works
Self-citationEarly adversity in chronic depression: clinical correlates and response to pharmacotherapy
Klein, D. N., Arnow, B. A., Barkin, J. L., Dowling, F., Kocsis, J. H., Leon, A. C., Manber, R., ROTHBAUM, B. O., Trivedi, M. H., & Wisniewski, S. R. (2009) · Depression and Anxiety · doi:10.1002/da.20577 · Cited by 164 · see citing works
Epigenetic alterations in depression and antidepressant treatment
Menke, A., & Binder, E. B. (2014) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2014.16.3/amenke · Cited by 161 · see citing works
Lowe, R., Gemma, C., Beyan, H., Hawa, M. I., Bazeos, A., Leslie, R. D., Montpetit, A., Rakyan, V. K., & Ramagopalan, S. V. (2013) · Epigenetics · doi:10.4161/epi.24362 · Cited by 160 · see citing works
Management of Patients With Treatment-Resistant Depression
Thase, M. E. (2008) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.0308e08 · Cited by 158 · 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
Atypical Depression, Panic Attacks, and Response to Imipramine and Phenelzine
Quitkin, F. M. (1990) · Archives of General Psychiatry · doi:10.1001/archpsyc.1990.01810220051006 · Cited by 153 · see citing works
Sales, A. J., Biojone, C., Terceti, M. S., Guimarães, F. S., Gomes, M. V., & Joca, S. R. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01489.x · Cited by 147 · 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
Concordant and discordant DNA methylation signatures of aging in human blood and brain
Farré, P., Jones, M. J., Meaney, M. J., Emberly, E. G., Turecki, G., & Kobor, M. S. (2015) · Epigenetics & Chromatin · doi:10.1186/s13072-015-0011-y · Cited by 145 · see citing works
Logue, M. W., Smith, A. K., Wolf, E. J., Maniates, H., Stone, A., Schichman, S. A., McGlinchey, R. E., Milberg, W., & Miller, M. W. (2017) · Epigenomics · doi:10.2217/epi-2017-0078 · Cited by 139 · see citing works
Perišić, T., Zimmermann, N., Kirmeier, T., Asmus, M., Tuorto, F., Uhr, M., Holsboer, F., Rein, T., & Zschocke, J. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.188 · Cited by 133 · 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
Roberts, S., Lester, K. J., Hudson, J. L., Rapee, R. M., Creswell, C., Cooper, P. J., Thirlwall, K. J., Coleman, J. R. I., Breen, G., Wong, C. C. Y., et al. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.83 · Cited by 118 · see citing works
Response to Phenelzine and Imipramine in Placebo Nonresponders With Atypical Depression
Quitkin, F. M. (1991) · Archives of General Psychiatry · doi:10.1001/archpsyc.1991.01810280035005 · Cited by 113 · see citing works
The potential use of histone deacetylase inhibitors in the treatment of depression
Fuchikami, M., Yamamoto, S., Morinobu, S., Okada, S., Yamawaki, Y., & Yamawaki, S. (2015) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.03.010 · Cited by 111 · 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
Self-citationDuclot, F., & Kabbaj, M. (2015) · Journal of Experimental Biology · doi:10.1242/jeb.107086 · Cited by 103 · see citing works
Pharmacometabolomic mapping of early biochemical changes induced by sertraline and placebo
Kaddurah-Daouk, R. F., Bogdanov, M. B., Wikoff, W. R., Zhu, H., Boyle, S. H., Churchill, E., Wang, Z., Rush, A. J., Krishnan, R. R., Pickering, E. H., et al. (2013) · Translational Psychiatry · doi:10.1038/tp.2012.142 · Cited by 101 · see citing works
Jin, H., Pei, L., Li, Y., Zheng, H. W., Yang, S., Wan, Y., Mao, L., Xia, Y., He, Q., Li, M., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-13929-5 · Cited by 96 · see citing works
Malhi, G. S., Outhred, T., Hamilton, A., Boyce, P. M., Bryant, R. A., Fitzgerald, P. B., Lyndon, B., Mulder, R., Murray, G., Porter, R., et al. (2018) · The Medical Journal of Australia · doi:10.5694/mja17.00659 · Cited by 93 · see citing works
Self-citationZhu, H., Bogdanov, M. B., Boyle, S. H., Matson, W. R., Sharma, S., Matson, S. A., Churchill, E., Fiehn, O., Rush, A. J., Krishnan, R. R., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068283 · Cited by 90 · see citing works
DNA methylation in interleukin-11 predicts clinical response to antidepressants in GENDEP
Powell, T. R., Smith, R. G., Hackinger, S., Schalkwyk, L. C., Uher, R., McGuffin, P., Mill, J. S., & Tansey, K. E. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.73 · Cited by 90 · see citing works
The epigenetic effects of antidepressant treatment on human prefrontal cortex BDNF expression
Chen, E. S., Ernst, C., & Turecki, G. (2011) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145710001422 · Cited by 88 · see citing works
Meylan, E. M., Halfon, O., Magistretti, P. J., & Cardinaux, J.-R. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.03.012 · Cited by 87 · see citing works
Salivary DNA Methylation Profiling: Aspects to Consider for Biomarker Identification
Langie, S. A. S., Moisse, M., Declerck, K., Koppen, G., Godderis, L., Berghe, W. V., Drury, S. S., & Boever, P. D. (2016) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.12721 · Cited by 84 · see citing works
Antidepressants inhibit DNA methyltransferase 1 through reducing G9a levels
Zimmermann, N., Zschocke, J., Perišić, T., Yu, S., Holsboer, F., & Rein, T. (2012) · Biochemical Journal · doi:10.1042/bj20120674 · Cited by 83 · see citing works
Charting oxidized methylcytosines at base resolution
Wu, H., & Zhang, Y. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3071 · Cited by 75 · see citing works
Hunter, A. M., Muthén, B., Cook, I. A., & Leuchter, A. F. (2009) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2009.06.006 · Cited by 74 · see citing works
Tadić, A., Wagner, S., Schlicht, K. F., Peetz, D., Borysenko, L., Dreimüller, N., Hiemke, C., & Lieb, K. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.08.011 · Cited by 71 · see citing works
Xu, H., Wang, J., Zhang, K., Zhao, M., Ellenbroek, B. A., Shao, F., & Wang, W. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.11.013 · Cited by 71 · see citing works
Schmauss, C. (2015) · Scientific Reports · doi:10.1038/srep08171 · Cited by 70 · see citing works
François, B. L., Soo, J., Millar, A., Daigle, M., Guisquet, A. L., Leman, S., Minier, F., Belzung, C., & Albert, P. R. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.07.002 · Cited by 70 · see citing works
Bludau, S., Bzdok, D., Gruber, O., Kohn, N., Riedl, V., Sorg, C., Palomero-Gallagher, N., Müller, V. I., Hoffstaedter, F., Amunts, K., et al. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.15030349 · Cited by 67 · see citing works
DNA Modification Study of Major Depressive Disorder: Beyond Locus-by-Locus Comparisons
Oh, G., Wang, S.-C., Pal, M., Chen, Z. F., Khare, T., Tochigi, M., Ng, C., Yang, Y. A., Kwan, A., Kaminsky, Z. A., et al. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.06.016 · Cited by 66 · see citing works
Lisoway, A. J., Zai, C. C. H., Tiwari, A. K., & Kennedy, J. L. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2016.12.071 · Cited by 66 · see citing works
Bysani, M., Perfilyev, A., de Mello, V. D., Rönn, T., Nilsson, E., Pihlajamäki, J., & Ling, C. (2016) · Epigenomics · doi:10.2217/epi-2016-0087 · Cited by 63 · see citing works
Sales, A. J., & Joca, S. R. L. (2016) · Acta Neuropsychiatrica · doi:10.1017/neu.2015.40 · Cited by 62 · see citing works
Wang, P., Zhang, C., Lv, Q., Bao, C., Sun, H., Ma, G., Fang, Y., Yi, Z., & Cai, W. (2018) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-018-2463-z · Cited by 57 · see citing works
Peterson, K., Dieperink, E., Anderson, J., Boundy, E., Ferguson, L., & Helfand, M. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4622-9 · Cited by 56 · see citing works
Etiévant, A., Manta, S., Latapy, C., Magno, L. A. V., Fecteau, S., & Beaulieu, J. (2015) · Scientific Reports · doi:10.1038/srep16873 · Cited by 53 · see citing works
Pharmacoepigenetics of depression: no major influence of MAO-A DNA methylation on treatment response
Domschke, K., Tidow, N., Schwarte, K., Ziegler, C., Lesch, K., Deckert, J., Arolt, V., Zwanzger, P., & Baune, B. T. (2014) · Journal of Neural Transmission · doi:10.1007/s00702-014-1227-x · Cited by 52 · see citing works
Self-citationFabbri, C., Zohar, J., & Serretti, A. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.05.007 · Cited by 52 · see citing works
Wang, P., Lv, Q., Mao, Y., Zhang, C., Bao, C., Sun, H., Chen, H., Yi, Z., Cai, W., & Fang, Y. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.12.010 · Cited by 51 · see citing works
Horizon Scan Of Clinical Laboratories Offering Pharmacogenetic Testing
Haga, S. B., & Kantor, A. (2018) · Health Affairs · doi:10.1377/hlthaff.2017.1564 · Cited by 50 · see citing works
de Boni, L., Gasparoni, G., Haubenreich, C., Tierling, S., Schmitt, I., Peitz, M., Koch, P., Walter, J., Wüllner, U., & Brüstle, O. (2018) · Clinical Epigenetics · doi:10.1186/s13148-018-0440-0 · Cited by 47 · see citing works
Sales, A. J., & Joca, S. R. L. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.01.022 · Cited by 47 · see citing works
Characterizing 5-hydroxymethylcytosine in human prefrontal cortex at single base resolution
Gross, J. A., Pacis, A., Chen, G. G., Barreiro, L. B., Ernst, C., & Turecki, G. (2015) · BMC Genomics · doi:10.1186/s12864-015-1875-8 · Cited by 44 · see citing works
Genipin normalizes depression-like behavior induced by prenatal stress through inhibiting DNMT1
Ye, D., Zhang, L., Fan, W., Zhang, X., & Dong, E. (2018) · Epigenetics · doi:10.1080/15592294.2018.1450033 · Cited by 43 · see citing works
Methylation of the SLC6a2 Gene Promoter in Major Depression and Panic Disorder
Bayles, R., Baker, E. K., Jowett, J. B. M., Barton, D., Esler, M., El‐Osta, A., & Lambert, G. W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083223 · Cited by 43 · see citing works
Transcriptomic and epigenomic biomarkers of antidepressant response
Belzeaux-R, R., Lin, R., Ju, C., Chay, M.-A., Fiori, L. M., Lutz, P.-É., & Turecki, G. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.08.087 · Cited by 43 · see citing works
Gassó, P., Rodríguez, N., Blázquez, A., Monteagudo, A., Boloc, D., Plana, M. T., Lafuente, A., Lázaro, L., Arnáiz, J. A., & Mas, S. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.12.003 · Cited by 39 · see citing works
Kim, J., Stewart, R. J., Kang, H., Bae, K., Kim, S., Shin, I., Hong, Y. J., Ahn, Y., Jeong, M. H., & Yoon, J. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.08.013 · Cited by 39 · see citing works
Blood-based biomarkers predicting response to antidepressants
Busch, Y., & Menke, A. (2018) · Journal of Neural Transmission · doi:10.1007/s00702-018-1844-x · Cited by 36 · see citing works
Qiao, M., Jiang, Q., Liu, Y., Hu, X.-Y., Wang, L., Zhou, Q., & Qiu, H. (2019) · Neuroreport · doi:10.1097/wnr.0000000000001191 · Cited by 31 · see citing works
Nghia, N. A., Hirasawa, T., Kasai, H., Obata, C., Moriishi, K., Mochizuki, K., Koizumi, S., & Kubota, T. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.02.010 · Cited by 26 · see citing works
Therapeutic response to paroxetine in major depressive disorder predicted by DNA Methylation
Takeuchi, N., Nonen, S., Kato, M., Wakeno, M., Takekita, Y., Kinoshita, T., & Kugawa, F. (2017) · Neuropsychobiology · doi:10.1159/000480512 · Cited by 26 · cited 1× · see citing works
“Takeuchi and colleagues conducted a genome-wide DNA methylation analysis using peripheral leukocytes in a small sample of Japanese MDD patients (n=20) treated with paroxetine for 6 weeks (Takeuchi et al., 2017).”
BackgroundEpigenetic Effects of Electroconvulsive Seizures
de Jong, J. O. Z., Arts, B. M. G., Boks, M. P., Sienaert, P. A., van den Hove, D., Kenis, G., van Os, J., & Rutten, B. P. F. (2014) · Journal of Ect · doi:10.1097/yct.0000000000000141 · Cited by 25 · see citing works
Prediction of treatment outcomes in major depressive disorder
Dunlop, B. W. (2015) · Expert Review of Clinical Pharmacology · doi:10.1586/17512433.2015.1075390 · Cited by 22 · see citing works
Self-citation(2009) · PubMed · Cited by 20 · see citing works
Self-citationHack, L. M., Dick, A. L. W., & Provençal, N. (2016) · Environmental Epigenetics · doi:10.1093/eep/dvw016 · Cited by 18 · see citing works
Self-citationUsing Epigenetic Tools to Investigate Antidepressant Response
Fiori, L. M., Lin, R., Ju, C., Belzeaux-R, R., & Turecki, G. (2018) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2018.04.004 · Cited by 17 · see citing works
Direct Induction of Human Neural Stem Cells from Peripheral Blood Hematopoietic Progenitor Cells
Wang, T., Choi, E. H., Monaco, M. C., Major, E. O., Medynets, M., & Nath, A. (2015) · Journal of Visualized Experiments · doi:10.3791/52298 · Cited by 14 · see citing works
Gadad, B. S., Raj, P., Jha, M. K., Carmody, T. J., Dozmorov, I. M., Mayes, T. L., Wakeland, E. K., & Trivedi, M. H. (2018) · Complex Psychiatry · doi:10.1159/000487321 · Cited by 12 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Papakostas GI, 2008 Tolerability of modern antidepressants. J Clin Psychiatry 69 Suppl E1, 8– 13. 18494538
Cited by
Sorted by citations
The Role of Pharmacogenetics in Personalizing the Antidepressant and Anxiolytic Therapy
Radosavljević, M., Štrac, D. Š., Jančić, J., & Samardžić, J. (2023) · Genes · doi:10.3390/genes14051095 · Cited by 62 · see citing works
Bousman, C., Maruf, A. A., Marques, D. F., Brown, L. C., & Müller, D. J. (2023) · Psychological Medicine · doi:10.1017/s0033291723002817 · Cited by 60 · see citing works
Self-citationFabbri, C., Zohar, J., & Serretti, A. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.05.007 · Cited by 52 · see citing works
Jin, J., & Zhong, X. (2023) · Drug Metabolism and Disposition · doi:10.1124/dmd.122.001007 · Cited by 47 · see citing works
Lenze, E. J., Nicol, G. E., Barbour, D. L., Kannampallil, T., Wong, A. W. K., Piccirillo, J., Drysdale, A. T., Sylvester, C. M., Haddad, R., Miller, J. P., et al. (2021) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.200042 · Cited by 43 · see citing works
Epigenetic Mechanisms in the Neurodevelopmental Theory of Depression
Talarowska, M. E. (2020) · Depression Research and Treatment · doi:10.1155/2020/6357873 · Cited by 34 · see citing works
Qiao, M., Jiang, Q., Liu, Y., Hu, X.-Y., Wang, L., Zhou, Q., & Qiu, H. (2019) · Neuroreport · doi:10.1097/wnr.0000000000001191 · Cited by 31 · see citing works
An update on antidepressant pharmacotherapy in late-life depression
Brender, R., Mulsant, B. H., & Blumberger, D. M. (2021) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2021.1921736 · Cited by 24 · see citing works
Depressive disorder and antidepressants from an epigenetic point of view
Arčan, I. Š., Kouter, K., & Paska, A. V. (2022) · World Journal of Psychiatry · doi:10.5498/wjp.v12.i9.1150 · Cited by 25 · see citing works
Research trend of epigenetics and depression: adolescents' research needs to strengthen
Yuan, D., Meng, Y., Ai, Z., & Zhou, S. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1289019 · Cited by 20 · see citing works
Xu, Z., Chen, Z., Shen, T., Chen, L., Tan, T., Gao, C., Chen, B., Yuan, Y., & Zhang, Z. (2021) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.13314 · Cited by 17 · see citing works
“Novel Psychopharmacology for Depressive Disorders”
Fornaro, M., Berardis, D. D., Anastasia, A., & Fusco, A. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-981-33-6044-0_22 · Cited by 15 · see citing works
Ding, Z., & Du, L. (2022) · Brain Research · doi:10.1016/j.brainres.2022.148113 · Cited by 15 · see citing works
Pharmacogenomic testing and antidepressant response: problems and promises
Smith, T. L., & Nemeroff, C. B. (2020) · Brazilian Journal of Psychiatry · doi:10.1590/1516-4446-2019-0799 · Cited by 13 · see citing works
Wang, T., Li, L., Yue, Y., Liu, X., Chen, S., Shen, T., Xu, Z., & Yuan, Y. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.06.042 · Cited by 10 · see citing works
Antidepressant Drug Discovery and Development: Mechanism and Drug Design Based on Small Molecules
Yao, C., Jiang, X., Ye, X., Xie, T., & Bai, R. (2022) · Advanced Therapeutics · doi:10.1002/adtp.202200007 · Cited by 10 · see citing works
Zou, Z., Zhang, Y., Huang, Y., Wang, J., Min, W., Xiang, M., Zhou, B., & Li, T. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.10.049 · Cited by 7 · see citing works
Bhuvaneshwar, K., & Gusev, Y. (2024) · Briefings in Bioinformatics · doi:10.1093/bib/bbae098 · Cited by 8 · see citing works
DNA methylation of serotonin genes as predictive biomarkers of antidepressant treatment response
Bruzzone, S. E. P., Ozenne, B., Fisher, P. M., Ortega, G., Jørgensen, M. B., Knudsen, G. M., Lesch, K., & Frøkjær, V. G. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2024.111160 · Cited by 7 · see citing works
Nozari, A., Gagné, R., Lu, C., Yauk, C. L., & Trudeau, V. L. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.847322 · Cited by 7 · see citing works
Angelin, M., Gopinath, P., Raghavan, V., THARA, R., Ahmad, F., Munirajan, A. K., & Sudesh, R. (2024) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s466502 · Cited by 7 · see citing works
Assche, E. V., Hohoff, C., Zang, J. C. S., Knight, M. J., & Baune, B. T. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1223216 · Cited by 6 · see citing works
Self-citationKhatsko, S. L., Zhdanov, A. V., Kravchenko, D. V., Nikiforova, E. V., Salimova, N. A., Kotova, M. M., Galstyan, D. S., de Abreu, M. S., Yang, L., Stewart, A., et al. (2025) · Behavioural Brain Research · doi:10.1016/j.bbr.2025.115492 · Cited by 4 · see citing works
Deciphering and manipulating the epigenome for the treatment of Parkinson’s and Alzheimer’s disease
Okechukwu, C. E. (2021) · MGM Journal of Medical Sciences · doi:10.4103/mgmj.mgmj_90_20 · Cited by 3 · see citing works
Truong, T. T. T., Lago, J., Neil, J., Wilkes, F., Barnes, R., Hopwood, M., & Singh, A. (2025) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/00048674251369625 · Cited by 3 · see citing works
Self-citationNascimento, L. V., Neto, F. L., Moreira, D. A. R., Cerutti, V., Thurow, H. S., Bastos, G. M., Ferreira, E. B., Hirata, R. D. C., & Hirata, M. H. (2022) · Epigenomics · doi:10.2217/epi-2022-0089 · Cited by 3 · see citing works
Bourdon, J. L., Davies, R. A., & Long, E. C. (2020) · Public Health Genomics · doi:10.1159/000510832 · Cited by 2 · see citing works
Sharafshah, A., Blum, K., Lewandrowski, K., Elman, I., Fuehrlein, B. S., Baron, D., Pinhasov, A., Thanos, P. K., Fiorelli, R., Schmidt, S., et al. (2025) · Journal of Personalized Medicine · doi:10.3390/jpm15120579
Pharmacogenetics of antidepressants: A step to individualized therapy
Samardžić, J. (2020) · Srpski medicinski casopis Lekarske komore · doi:10.5937/smclk2001013s · Cited by 1 · 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
Self-citationDepression management and pharmacoepigenetics
Walker, S. A., Su, A., & Kamath, J. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-823039-8.00002-2 · Cited by 1 · see citing works
Zou, Z., Zhang, Y., Huang, Y., Wang, J., Zhou, B., & Chen, H.-F. (2023) · World Journal of Psychiatry · doi:10.5498/wjp.v13.i8.524 · Cited by 1 · see citing works
- Authors
- Hack, L. M., Fries, G. R., Eyre, H. A., Bousman, C. A., Singh, A. B., Quevedo, J., John, V. P., Baune, B. T., & Dunlop, B. W.
- Affiliations
- Emory University (US)
- The University of Texas Health Science Center at Houston (US)
- Texas Medical Center (US)
- University of Calgary (CA)
- Deakin University (AU)
- The University of Melbourne (AU)
- Corresponding author
- Hack, Laura M.
- ORCID
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 249
- Pages
- 336-346
- ISSN
- 0165-0327 (ISSN-L)
- PMC
- PMC6763314
- OpenAlex
- W2914765414
- Cited by
- 33
- References
- 107
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 5 · 2022: 8 · 2021: 7 · 2020: 4 · 2019: 1 · 2018: 1
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Affective Disorders (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health (R25MH101079)
- 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
- pharmacoepigenetics, major depressive disorder, antidepressant response, DNA methylation, histone modifications, epigenetic biomarkers, precision psychiatry, animal models of depression, clinical translation
- MeSH terms
- Animals, Antidepressive Agents, Depression, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Pharmacogenetics, DNA Methylation, MicroRNAs, Precision Medicine, Epigenomics
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
