TESC gene-regulating genetic variant (rs7294919) affects hippocampal subfield volumes and parahippocampal cingulum white matter integrity in major depressive disorder
Abstract
Two recent genome-wide association studies have suggested that rs7294919 is associated with changes in hippocampal volume. rs7294919 regulates the transcriptional products of the TESC gene, which is involved in neuronal proliferation and differentiation. We investigated the interactive effect of rs7294919 and major depressive disorder (MDD) on the volume of the hippocampal subfields and the integrity of the parahippocampal cingulum (PHC). We also investigated the correlation of these structural changes with the DNA methylation status of rs7294919. A total of 105 patients with MDD and 85 healthy control subjects underwent T1-weighted structural magnetic resonance imaging and diffusion tensor imaging. The rs7294919 was genotyped and its DNA methylation status was assessed in all the participants. We analyzed the hippocampal subfield volumes and PHC integrity using FreeSurfer and the Tracts Constrained by Underlying Anatomy (TRACULA) respectively. Significant interactive effects of rs7294919 and MDD were observed in the volumes of the dentate gyrus and CA4. The patients with MDD had increased methylation in two of the three CpG loci of rs7294919, and the methylation of CpG3 was significantly correlated with right PHC integrity in the MDD group. Our results provide neurobiological evidence for the association of rs7294919 with brain structural changes in MDD.
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Patients with MDD have increased methylation in the TESC gene, negatively correlated with right parahippocampal cingulum integrity.
“a study found that patients with MDD had increased methylation in the TESC gene, negatively correlated with the right parahippocampal cingulum integrity.57”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [57]
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
The assessment and analysis of handedness: The Edinburgh inventory
Oldfield, R. C. (1971) · Neuropsychologia · doi:10.1016/0028-3932(71)90067-4 · Cited by 35,900 · see citing works
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817 · see citing works
Caspi, A., Moffitt, T. E., Cannon, M., McClay, J., Murray, R., Harrington, H., Taylor, A., Arseneault, L., Williams, B., Braithwaite, A., et al. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.01.026 · Cited by 1,409 · see citing works
Iglesias, J. E., Augustinack, J. C., Nguyen, K., Player, C. M., Player, A., Wright, M., Roy, N., Frosch, M. P., McKee, A. C., Wald, L. L., et al. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.04.042 · Cited by 1,267 · see citing works
Koolschijn, P. C. M. P., van Haren, N. E. M., Lensvelt‐Mulders, G. J. L. M., Hulshoff Pol, H. E., & Kahn, R. S. (2009) · Human Brain Mapping · doi:10.1002/hbm.20801 · Cited by 902 · see citing works
Major depressive disorder: new clinical, neurobiological, and treatment perspectives
Kupfer, D. J., Frank, E., & Phillips, M. L. (2012) · The Lancet · doi:10.1016/s0140-6736(11)60602-8 · Cited by 894 · see citing works
Teicher, M. H., Anderson, C. M., & Polcari, A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1115396109 · Cited by 639 · see citing works
Yendiki, A. (2011) · Frontiers in Neuroinformatics · doi:10.3389/fninf.2011.00023 · Cited by 590 · see citing works
Identification of common variants associated with human hippocampal and intracranial volumes
Stein, J., Medland, S., Vásquez, A., Hibar, D., Senstad, R. E., Winkler, A., Toro, R., Appel, K., Barteček, R., Bergmann, Ø., et al. (2012) · Nature Genetics · doi:10.1038/ng.2250 · Cited by 568 · see citing works
Arnone, D., McIntosh, A. M., Ebmeier, K. P., Munafò, M. R., & Anderson, I. M. (2012) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2011.05.003 · Cited by 495 · see citing works
Wray, N. R., Pergadia, M. L., Blackwood, D. H. R., Penninx, B. W. J. H., Gordon, S. D., Nyholt, D. R., Ripke, S., MacIntyre, D. J., McGhee, K. A., Maclean, A. W., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2010.109 · Cited by 444 · see citing works
Kempermann, G., & Kronenberg, G. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00319-6 · Cited by 392 · see citing works
Choi, J., Jeong, B., Rohan, M. L., Polcari, A. M., & Teicher, M. H. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.06.022 · Cited by 376 · see citing works
Widom, C. S., & Brzustowicz, L. M. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.039 · Cited by 349 · see citing works
Treadway, M. T., Waskom, M. L., Dillon, D. G., Holmes, A. J., Park, M. T. M., Chakravarty, M. M., Dutra, S. J., Polli, F. E., Iosifescu, D. V., Fava, M., et al. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.06.018 · Cited by 331 · see citing works
Serotonin: a regulator of neuronal morphology and circuitry
Daubert, E. A., & Condron, B. G. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2010.05.005 · Cited by 326 · see citing works
State-dependent changes in hippocampal grey matter in depression
Arnone, D., McKie, S., Elliott, R., Juhasz, G., Thomas, E. J., Downey, D., Williams, S., Deakin, J. F. W., & Anderson, I. M. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.150 · Cited by 287 · see citing works
Frodl, T., Jäger, M., Smajstrlova, I., Born, C., Bottlender, R., Palladino, T., Reiser, M., Möller, H.-J., & Meisenzahl, E. M. (2008) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn.0840 · Cited by 279 · see citing works
Redlich, R., Opel, N., Grotegerd, D., Dohm, K., Zaremba, D., Bürger, C., Münker, S., Mühlmann, L., Wahl, P., Heindel, W. L., et al. (2016) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2016.0316 · Cited by 267 · see citing works
Common variants at 12q14 and 12q24 are associated with hippocampal volume
Bis, J., Decarli, C., Smith, A., van der Lijn, F., Crivello, F., Fornage, M., Debette, S., Shulman, J. M., Schmidt, H., Srikanth, V., et al. (2012) · Nature Genetics · doi:10.1038/ng.2237 · Cited by 249 · see citing works
Self-citationTae, W., Kim, S. S., Lee, K. U., Nam, E., & Kim, K. W. (2008) · Neuroradiology · doi:10.1007/s00234-008-0383-9 · Cited by 242 · see citing works
Self-citationHippocampal atrophy in major depression: a function of childhood maltreatment rather than diagnosis?
Opel, N., Redlich, R., Zwanzger, P., Grotegerd, D., Arolt, V., Heindel, W., Konrad, C., Kugel, H., & Dannlowski, U. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.145 · Cited by 214 · see citing works
Childhood stress, serotonin transporter gene and brain structures in major depression
Frodl, T., Reinhold, E., Koutsouleris, N., Donohoe, G., Bondy, B., Reiser, M., Möller, H.-J., & Meisenzahl, E. M. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.8 · Cited by 200 · see citing works
Huang, Y., Coupland, N. J., Lebel, R. M., Carter, R., Seres, P., Wilman, A. H., & Malykhin, N. V. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.01.005 · Cited by 179 · see citing works
Hippocampal neuroplasticity in major depressive disorder
Malykhin, N. V., & Coupland, N. J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.04.047 · Cited by 178 · 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
Na, K., Chang, H. S., Won, E., Han, K., Choi, S., Tae, W., Yoon, H., Kim, Y., Joe, S., Jung, I., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085425 · Cited by 144 · see citing works
Self-citationIn vivo quantification of hippocampal subfields using 4.7 T fast spin echo imaging
Malykhin, N. V., Lebel, R. M., Coupland, N. J., Wilman, A. H., & Carter, R. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.09.042 · Cited by 138 · see citing works
White Matter Integrity in Highly Traumatized Adults With and Without Post-Traumatic Stress Disorder
Fani, N., King, T. Z., Jovanovic, T., Glover, E. M., Bradley, B., Choi, K., Ely, T., Gutman, D. A., & Ressler, K. J. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.146 · Cited by 135 · see citing works
Choi, S., Han, K.-M., Won, E., Yoon, B.-J., Lee, M.-S., & Ham, B.-J. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.09.042 · Cited by 111 · see citing works
Self-citationVolumetric MRI study of the insular cortex in individuals with current and past major depression
Takahashi, T., Yücel, M., Lorenzetti, V., Tanino, R., Whittle, S., Suzuki, M., Walterfang, M., Pantelis, C., & Allen, N. B. (2009) · Journal of Affective Disorders · doi:10.1016/j.jad.2009.06.003 · Cited by 104 · see citing works
Tozzi, L., Carballedo, A., Wetterling, F., McCarthy, H., O’Keane, V., Gill, M., Morris, D., Fahey, C., Meaney, J. F., & Frodl, T. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.170 · Cited by 97 · see citing works
BDNF Val66met polymorphism, white matter abnormalities and remission of geriatric depression
Alexopoulos, G. S., Glatt, C. E., Hoptman, M. J., Kanellopoulos, D., Murphy, C. F., Kelly, R. E., Morimoto, S. S., Lim, K. O., & Gunning, F. M. (2010) · Journal of Affective Disorders · doi:10.1016/j.jad.2010.02.115 · Cited by 97 · see citing works
Won, E., Choi, S., Kang, J. C., Kim, A., Han, K.-M., Chang, H.-S., Tae, W., Son, K. R., Joe, S.-H., Lee, M.-S., et al. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.137 · Cited by 97 · see citing works
Self-citationHan, K., Won, E., Sim, Y., Kang, J. C., Han, C., Kim, Y., Kim, S., Joe, S.-H., Lee, M.-S., Tae, W., et al. (2017) · Scientific Reports · doi:10.1038/srep42621 · Cited by 96 · see citing works
Self-citationCarballedo, A., Amico, F., Ugwu, I., Fagan, A. J., Fahey, C., Morris, D., Meaney, J. F., Leemans, A., & Frodl, T. (2012) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32060 · Cited by 95 · see citing works
Tract-based analysis of white matter degeneration in Alzheimer’s disease
Lee, S., Coutu, J., Wilkens, P. J., Yendiki, A., Rosas, H. D., & Salat, D. H. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.049 · Cited by 88 · see citing works
Green, M. J., Chia, T.-Y., Cairns, M. J., Wu, J. Q., Tooney, P. A., Scott, R. J., & Carr, V. J. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.10.018 · Cited by 86 · see citing works
Gönül, A. S., Kitiş, Ö., Eker, M. C., Eker, Ö. D., Ozan, E., & Coburn, K. L. (2010) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2010.507786 · Cited by 84 · see citing works
Na, K.-S., Won, E., Kang, J., Chang, H. S., Yoon, H.-K., Tae, W. S., Kim, Y.-K., Lee, M.-S., Joe, S.-H., Kim, H., et al. (2016) · Scientific Reports · doi:10.1038/srep21089 · Cited by 84 · see citing works
Self-citationKanellopoulos, D., Gunning, F. M., Morimoto, S. S., Hoptman, M. J., Murphy, C. F., Kelly, R. E., Glatt, C. E., Lim, K. O., & Alexopoulos, G. S. (2010) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3181f61d62 · Cited by 81 · see citing works
Seok, J., Choi, S., Lim, H. K., Lee, S., Kim, I. S., & Ham, B. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.04.012 · Cited by 73 · see citing works
Self-citationDentate gyrus volume and memory performance in major depressive disorder
Travis, S., Coupland, N. J., Silversone, P. H., Huang, Y., Fujiwara, E., Carter, R., Seres, P., & Malykhin, N. V. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.09.048 · Cited by 71 · see citing works
Eker, M. C., Kitiş, Ö., Okur, H., Eker, Ö. D., Ozan, E., Işıklı, S., Akarsu, N. A., & Gönül, A. S. (2010) · Neuropsychobiology · doi:10.1159/000321834 · Cited by 69 · see citing works
FKBP5 Genotype and Structural Integrity of the Posterior Cingulum
Fani, N., King, T. Z., Reiser, E., Binder, E. B., Jovanović, T., Bradley, B., & Ressler, K. J. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.322 · Cited by 68 · see citing works
Accelerated aging of the putamen in patients with major depressive disorder
Sacchet, M. D., Camacho, M. C., Livermore, E. E., Thomas, E. A. C., & Gotlib, I. H. (2017) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.160010 · Cited by 62 · see citing works
Murphy, M. L., Carballedo, A., Fagan, A. J., Morris, D. W., Fahey, C., Meaney, J. F., & Frodl, T. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.04.015 · Cited by 61 · see citing works
Serotonin transporter gene methylation is associated with hippocampal gray matter volume
Dannlowski, U., Kugel, H., Redlich, R., Halik, A., Lang, I., Opel, N., Grotegerd, D., Schwarte, K., Schettler, C., Ambrée, O., et al. (2014) · Human Brain Mapping · doi:10.1002/hbm.22555 · Cited by 56 · see citing works
Tractography reveals diffuse white matter abnormalities in Myotonic Dystrophy Type 1
Wozniak, J. R., Mueller, B. A., Lim, K. O., Hemmy, L. S., & Day, J. (2014) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2014.04.005 · Cited by 56 · see citing works
Liu, X., Watanabe, K., Kakeda, S., Yoshimura, R., Abe, O., Ide, S., Hayashi, K., Katsuki, A., Umene‐Nakano, W., Watanabe, R., et al. (2016) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.114.155689 · Cited by 53 · see citing works
The dentate mossy fibers: structural organization, development and plasticity
Blaabjerg, M., & Zimmer, J. (2007) · Progress in brain research · doi:10.1016/s0079-6123(07)63005-2 · Cited by 49 · see citing works
Dohm, K., Redlich, R., Zwitserlood, P., & Dannlowski, U. (2016) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867416661426 · Cited by 49 · see citing works
Wisse, L. E. M., Biessels, G. J., Stegenga, B. T., Kooistra, M., van der Veen, P. H., Zwanenburg, J. J. M., van der Graaf, Y., & Geerlings, M. I. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.12.052 · Cited by 48 · see citing works
Isaac, L., Main, K., Soman, S., Gotlib, I. H., Furst, A. J., Kinoshita, L. M., Fairchild, J. K., Yesavage, J. A., Ashford, J. W., Bayley, P. J., et al. (2015) · Biological Psychology · doi:10.1016/j.biopsycho.2014.12.011 · Cited by 46 · see citing works
Dannlowski, U., Grabe, H. J., Wittfeld, K., Klaus, J., Konrad, C., Grotegerd, D., Redlich, R., Suslow, T., Opel, N., Ohrmann, P., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.39 · Cited by 46 · see citing works
Choi, S., Han, K., Kang, J. C., Won, E., Chang, H. S., Tae, W., Son, K. R., Kim, S. J., Lee, M.-S., & Ham, B. (2016) · PLoS ONE · doi:10.1371/journal.pone.0164301 · Cited by 45 · see citing works
Self-citationImaging genetics studies on monoaminergic genes in major depressive disorder
Won, E., & Ham, B. (2015) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.03.014 · Cited by 39 · see citing works
Self-citationAutomated hippocampal subfields segmentation in late life depression
Lim, H. K., Hong, S., Jung, W. S., Ahn, K. J., Won, W. Y., Hahn, C., Kim, I. S., & Lee, C. U. (2012) · Journal of Affective Disorders · doi:10.1016/j.jad.2012.04.018 · Cited by 36 · see citing works
Matsuoka, K., Yasuno, F., Kishimoto, T., Yamamoto, A., Kiuchi, K., Kosaka, J., Nagatsuka, K., Iida, H., & Kudo, T. (2016) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.15m09851 · Cited by 36 · see citing works
Janowitz, D., Schwahn, C., Borchardt, U., Wittfeld, K., Schulz, A., Barnow, S., Biffar, R., Hoffmann, W. U., Habes, M., Homuth, G., et al. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.102 · Cited by 35 · see citing works
Phillips, J. L., Batten, L. A., Tremblay, P., Aldosary, F., Du, L., & Blier, P. (2015) · Acta Neuropsychiatrica · doi:10.1017/neu.2015.25 · Cited by 26 · see citing works
Jiang, W., Gong, G., Wu, F., Kong, L., Chen, K., Cui, W., Ren, L., Fan, G., Sun, W., Ma, H., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0126673 · Cited by 24 · see citing works
Expression and evolutionary conservation of the tescalcin gene during development
Bao, Y. L., Hudson, Q. J., Perera, E. M., et al. (2009) · Gene Expression Patterns · doi:10.1016/j.gep.2009.03.004 · Cited by 23 · see citing works
Won, E., Kang, J. C., Kim, A., Choi, S., Han, K., Tae, W., Chang, H. S., Son, K. R., Greenberg, T., Joe, S.-H., et al. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.07.008 · Cited by 17 · see citing works
Self-citationMa, L., Ou, J.-R., Zhang, W., Sun, F.-R., Yu, J., & Tan, L. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.12.022 · Cited by 4 · see citing works
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Yuan, M., Yang, B., Rothschild, G., Mann, J. J., Sanford, L. D., Tang, X., Huang, C., Wang, C., & Zhang, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01519-z · Cited by 246 · see citing works
“57 These studies suggest that the association between methylation changes and MDD is diverse, with no common effects throughout the genome or speci fi c genomic locations.”
BackgroundSun, Y., Hu, N., Wang, M., Lu, L., Luo, C., Tang, B., Yao, C., Sweeney, J. A., Gong, Q., Qiu, C., et al. (2023) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.220086 · Cited by 48 · see citing works
- Authors
- Han, K.-M., Won, E., Kang, J., Choi, S., Kim, A., Lee, M.-S., Tae, W.-S., & Ham, B.-J.
- Affiliations
- Korea University (KR)
- Korea University Anam Hospital (KR)
- Corresponding author
- Tae, Woo-Suk
- Ham, Byung-Joo
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 93
- Pages
- 20-29
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W2619926897
- Cited by
- 46
- References
- 66
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 25 · 2020: 4 · 2019: 3 · 2018: 2
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bio & Medical Technology Development Program of the National Research Foundation (NRF) (NRF-2016M3A9A7916996)
- Ministry of Science, ICT and Future Planning (2016M3A9A7916996)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- major depressive disorder, hippocampal subfields, dentate gyrus, CA4, white matter integrity, DNA methylation, gene-disease interaction, CpG methylation, hippocampal volume
- MeSH terms
- Adult, Aged, Analysis of Variance, Calcium-Binding Proteins, Major Depressive Disorder, Female, Genotype, Hippocampus, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, DNA Methylation, Parahippocampal Gyrus, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Young Adult, Diffusion Tensor Imaging, White Matter
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