Longitudinal multi-level biomarker analysis of BDNF in major depression and bipolar disorder
Abstract
Preliminary evidence suggests that BDNF (brain derived neurotrophic factor) rs6265 genetic polymorphism, BDNF gene promotor methylation and BDNF serum levels might play an important role in the pathogenesis of affective disorders. As studies testing the BDNF system across molecular levels are sparse, this study aimed at investigating the BDNF val66met genotype, BDNF DNA methylation changes and peripheral BDNF serum levels in acute and remitted phases of MDD (major depressive disorder) and BD (bipolar disorder) and healthy controls. We found a significant difference of methylation levels at CpG site 1-1-1 and 3-1-1 between MDD and healthy controls (p < 0.003) with MDD patients showing significantly higher methylation levels. CpG 5-2-1 revealed a statistically significant difference between MDD and healthy controls and MDD and BD (p = 0.00003). Similar to the results of the methylation analysis a significant difference between MDD and healthy controls was found in BDNF serum levels (p = 0.002) with significantly lower BDNF serum levels in MDD compared to healthy controls. A difference between the samples from admission and discharge from hospital of both BDNF gene methylation and serum levels could not be detected in the present study and no influence of the BDNF val66met genotype on neither methylation nor BDNF serum level.
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Increased BDNF methylation is reported during mood episodes, where it correlates with symptom severity.
“increased BDNF methylation is reported during mood episodes, where it correlates with symptom severity”
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 [17]
Cites
Faul, F., Erdfelder, E., Lang, A.-G., & Buchner, A. (2007) · Behavior Research Methods · doi:10.3758/bf03193146 · Cited by 65,971 · see citing works
A simple salting out procedure for extracting DNA from human nucleated cells
Miller, S. A., Dykes, D. D., & Polesky, H. F. (1988) · Nucleic Acids Research · doi:10.1093/nar/16.3.1215 · Cited by 20,341 · see citing works
(1998) · The Journal of Clinical Psychiatry · Cited by 19,139 · see citing works
A new depression scale designed to be sensitive to change
Montgomery, S. A., & Åsberg, M. (1979) · British Journal of Psychiatry · doi:10.1192/bjp.134.4.382 · Cited by 13,962 · see citing works
(1998) · PubMed · Cited by 10,216 · see citing works
A Rating Scale for Mania: Reliability, Validity and Sensitivity
Young, R. C., Biggs, J. T., Ziegler, V. E., & Meyer, D. A. (1978) · British Journal of Psychiatry · doi:10.1192/bjp.133.5.429 · Cited by 8,744 · see citing works
Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework
Biomarkers Definitions Working Group (2001) · Clinical Pharmacology & Therapeutics · doi:10.1067/mcp.2001.113989 · Cited by 6,771 · see citing works
da Luz, A. C. D. D. S., Dias, G. P., Bevilaqua, M. C. D. N., Cocks, G. D., Gardino, P. F., Thuret, S., & Nardi, A. E. (2013) · Neuropsychobiology · doi:10.1159/000353269 · Cited by 4,012 · see citing works
Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., Zaitsev, E., Gold, B., Goldman, D., Dean, M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00035-7 · Cited by 3,888 · see citing works
Prevalence and Correlates of Bipolar Spectrum Disorder in the World Mental Health Survey Initiative
Merikangas, K. R., Jin, R., He, J.-P., Kessler, R. C., Lee, S., Sampson, N. A., Viana, M. C., Andrade, L. H., Hu, C., Karam, E. G., et al. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.12 · Cited by 2,627 · see citing works
Berk, M., Kapczinski, F., Andreazza, A. C., Dean, O. M., Giorlando, F., Maes, M., Yücel, M., Gama, C. S., Dodd, S., Dean, B., et al. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.10.001 · Cited by 1,178 · see citing works
Shimizu, E., Hashimoto, K., Okamura, N., Koike, K., Komatsu, N., Kumakiri, C., Nakazato, M., Watanabe, H., Shinoda, N., Okada, S.-I., et al. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00181-1 · Cited by 1,151 · see citing works
Andrade, L., Caraveo‐anduaga, J. J., Berglund, P., Bijl, R. V., Graaf, R. D., Vollebergh, W., Dragomirecka, E., Kohn, R., Keller, M., Kessler, R. C., et al. (2003) · International Journal of Methods in Psychiatric Research · doi:10.1002/mpr.138 · Cited by 1,068 · see citing works
Murer, M. G., Yan, Q., & Raisman-Vozari, R. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00014-9 · Cited by 874 · see citing works
Sklar, P. B., Gabriel, S., McInnis, M. G., Bennett, P., Lim, Y.-M., Tsan, G., Schaffner, S. F., Kirov, G., Jones, I. R., Owen, M. J., et al. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001058 · Cited by 563 · see citing works
Polyakova, M., Stuke, K., Schuemberg, K., Mueller, K., Schoenknecht, P., & Schroeter, M. L. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.11.044 · Cited by 488 · see citing works
Programming of DNA Methylation Patterns
Cedar, H., & Bergman, Y. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-052610-091920 · Cited by 439 · see citing works
Serum and plasma BDNF levels in major depression: A replication study and meta-analyses
Bocchio-Chiavetto, L., Bagnardi, V., Zanardini, R., Molteni, R., Gabriela Nielsen, M., Placentino, A., Giovannini, C., Rillosi, L., Ventriglia, M., Riva, M. A., et al. (2010) · The World Journal of Biological Psychiatry · doi:10.3109/15622971003611319 · Cited by 435 · see citing works
SNP Genotyping: The KASP Assay
He, C., Holme, J., & Anthony, J. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-0446-4_7 · Cited by 407 · see citing works
Fernandes, B. S., Gama, C. S., Maria Ceresér, K., Yatham, L. N., Fries, G. R., Colpo, G., de Lucena, D., Kunz, M., Gomes, F. A., & Kapczinski, F. (2011) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2011.03.002 · Cited by 389 · 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
Effect of treatment on serum brain–derived neurotrophic factor levels in depressed patients
Gonul, A. S., Akdeniz, F., Taneli, F., Donat, O., Eker, Ç., & Vahip, S. (2005) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-005-0578-6 · Cited by 375 · see citing works
Fernandes, B. S., Molendijk, M. L., Köhler, C. A., Soares, J. C., Leite, C. M. G. S., Machado-Vieira, R., Ribeiro, T. L., Silva, J. C., Sales, P. M. G., Quevedo, J., et al. (2015) · BMC Medicine · doi:10.1186/s12916-015-0529-7 · Cited by 291 · see citing works
Gene–environment interaction and the genetics of depression
Lesch, K. (2004) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn.0420 · Cited by 284 · see citing works
BDNF gene is a risk factor for schizophrenia in a Scottish population
Neves-Pereira, M., Cheung, J., Pasdar, A., Zhang, F., Breen, G. D., Yates, P., Sinclair, M., Crombie, C., Walker, N. P., & Clair, D. M. S. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001575 · Cited by 262 · see citing works
D'Addario, C., Dell'Osso, B., Palazzo, M. C., Benatti, B., Lietti, L., Cattaneo, E., Galimberti, D., Fenoglio, C., Cortini, F., Scarpini, E., et al. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.10 · Cited by 192 · see citing works
Geller, B., Badner, J. A., Tillman, R., Christian, S. L., Bolhofner, K., & Cook, E. H. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.9.1698 · Cited by 186 · 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
Serum BDNF levels before treatment predict SSRI response in depression
Wolkowitz, O. M., Wolf, J. S., Shelly, W. B., Rosser, R., Burke, H. M., Lerner, G. K., Reus, V. I., Nelson, J. C., Epel, E. S., & Mellon, S. H. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.06.013 · Cited by 174 · see citing works
Monteleone, P., Serritella, C., Martiadis, V., & Maj, M. (2008) · Bipolar Disorders · doi:10.1111/j.1399-5618.2008.00459.x · Cited by 162 · see citing works
Lang, U. E., Hellweg, R., Sander, T., & Gallinat, J. (2009) · Molecular Psychiatry · doi:10.1038/mp.2008.80 · Cited by 142 · see citing works
BDNF promoter methylation and genetic variation in late-life depression
Januar, V, Ancelin, M.-L., Ritchie, K., Saffery, R., & Ryan, J. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.114 · Cited by 139 · see citing works
Roy, B., Shelton, R. C., & Dwivedi, Y. (2017) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2017.02.005 · Cited by 139 · see citing works
Lee, H.-Y., & Kim, Y.-K. (2008) · Neuropsychobiology · doi:10.1159/000149817 · Cited by 132 · see citing works
Fernandes, B. S., Gama, C. S., Kauer‐Sant’Anna, M., Lobato, M. I. R., Belmonte-de-Abreu, P. S., & Kapczinski, F. P. (2009) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2009.04.010 · Cited by 124 · see citing works
Dell׳Osso, B., D׳Addario, C., Carlotta Palazzo, M., Benatti, B., Camuri, G., Galimberti, D., Fenoglio, C., Scarpini, E., Di Francesco, A., Maccarrone, M., et al. (2014) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.05.020 · Cited by 112 · see citing works
Epigenetic Modulation of BDNF Gene in Patients with Major Depressive Disorder
D’Addario, C., Dell’Osso, B. M., Galimberti, D., Palazzo, C., Benatti, B., Francesco, A. D., Scarpini, E. A., Altamura, A. C., & Maccarrone, M. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.07.009 · Cited by 96 · see citing works
A longitudinal study of BDNF promoter methylation and genotype with poststroke depression
Kim, J., Stewart, R. J., Kang, H., Kim, S., Kim, S., Shin, I., Park, M., Kim, H., Shin, M., Cho, K.-H., et al. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2013.01.008 · Cited by 91 · see citing works
Carlberg, L., Scheibelreiter, J., Hassler, M. R., Schloegelhofer, M., Schmoeger, M., Ludwig, B., Kasper, S. F., Aschauer, H. N., Egger, G., & Schosser, A. (2014) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.07.022 · Cited by 84 · see citing works
Başterzi, A. D., Yazıcı, K. U., Aslan, E., Delıalıoğlu, N., Taşdelen, B., Acar, Ş. T., & Yazıcı, A. (2008) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2008.11.016 · Cited by 80 · see citing works
Blood BDNF Level Is Gender Specific in Severe Depression
Kreinin, A., Lisson, S., Nesher, E., Schneider, J., Bergman, J., Farhat, K., Farah, J., Lejbkowicz, F., Yadid, G., Raskin, L., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0127643 · Cited by 76 · see citing works
BDNF promoter I methylation correlates between post-mortem human peripheral and brain tissues
Stenz, L., Zewdie, S., Laforge, T., Prados, J., Harpe, R. L., Dayer, A. G., Paoloni‐Giacobino, A., Perroud, N. A., & Aubry, J. (2014) · Neuroscience Research · doi:10.1016/j.neures.2014.10.003 · Cited by 73 · see citing works
Kleimann, A., Kotsiari, A., Sperling, W., Gröschl, M., Heberlein, A., Kahl, K. G., Hillemacher, T., Bleich, S., Kornhuber, J., & Frieling, H. (2015) · Journal of Neural Transmission · doi:10.1007/s00702-014-1336-6 · Cited by 70 · see citing works
Longitudinal associations between BDNF promoter methylation and late-life depression
Kang, H.-J., Kim, J.-M., Bae, K.-Y., Kim, S.-W., Shin, I.-S., Kim, H.-R., Shin, M.-G., & Yoon, J.-S. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.12.035 · Cited by 65 · see citing works
Val66met polymorphism and serum brain-derived neurotrophic factor levels in bipolar disorder
Tramontina, J., Frey, B. N., Andreazza, A. C., Zandoná, M. R., Santin, A. P., & Kapczinski, F. P. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001941 · Cited by 57 · see citing works
Brain-derived neurotrophic factor increase during treatment in severe mental illness inpatients
Nuernberg, G. L., de Aguiar, B. W., Bristot, G., Fleck, M. P. D. A., & da Rocha, N. S. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.227 · Cited by 56 · see citing works
Common Genetic and Environmental Influences on Major Depressive Disorder and Conduct Disorder
Subbarao, A., Rhee, S. H., Young, S. E., Ehringer, M. A., Corley, R. P., & Hewitt, J. K. (2007) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-007-9189-1 · Cited by 41 · see citing works
Piccinni, A., Veltri, A., Costanzo, D., Vanelli, F., Franceschini, C., Moroni, I., Domenici, L., Origlia, N., Marazziti, D., Akiskal, H. S., et al. (2014) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.08.058 · Cited by 35 · see citing works
Palazzo, C., Dell’Osso, B. M., Benatti, B., Camuri, G., D’Addario, C., Galimberti, D., Fenoglio, C., Scarpini, E. A., Francesco, A. D., Maccarrone, M., et al. (2014) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(14)70255-x · Cited by 27 · see citing works
Schuster, R., Kleimann, A., Rehme, M.-K., Taschner, L., Glahn, A., Groh, A., Frieling, H., Lichtinghagen, R., Hillemacher, T., Bleich, S., et al. (2016) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-016-0668-7 · Cited by 23 · see citing works
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“The importance of BDNF and its implications for mental health have been studied, with reports of lower serum BDNF in patients with major depressive disorder [54,55].”
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- Authors
- Schröter, K., Brum, M., Brunkhorst-Kanaan, N., Tole, F., Ziegler, C., Domschke, K., Reif, A., & Kittel-Schneider, S.
- Affiliations
- Goethe University Frankfurt (DE)
- University of Freiburg (DE)
- Venue
- European Archives of Psychiatry and Clinical Neuroscience
- Published
- 2019-03-30
- Volume
- 270
- Issue
- 2
- Pages
- 169-181
- ISSN
- 0003-9373 (ISSN-L)
- 0940-1334
- 1433-8491
- OpenAlex
- W2933196072
- Cited by
- 68
- References
- 50
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 7 · 2023: 11 · 2022: 16 · 2021: 10 · 2020: 10
- FWCI
- 5.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Archives of Psychiatry and Clinical Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- brain-derived neurotrophic factor, BDNF Val66Met polymorphism, DNA methylation, major depressive disorder, bipolar disorder, mood disorders, epigenetics, remission
- MeSH terms
- Adult, Bipolar Disorder, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Longitudinal Studies, Male, Middle Aged, Patient Admission, Patient Discharge, Promoter Regions, Genetic, Remission Induction, Biomarkers, CpG Islands, DNA Methylation, Brain-Derived Neurotrophic Factor
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