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Remodeling of axo-spinous synapses in the pathophysiology and treatment of depression
Open accessAbstract
Dendritic spines provide a compartment for assembly and functional organization of synaptic machinery that plays a fundamental role in neuronal communication and neuroplasticity. Studies in humans as well as in animal models have demonstrated abnormal spine architecture in several psychiatric disorders, including depression and other stress-related illnesses. The negative impact of stress on the density and organization of spines is thought to contribute to the behavioral deficits caused by stress exposure. Moreover, there is now evidence that medication-induced recovery involves changes in synaptic plasticity and dendrite morphology, including increased expression of pre- and postsynaptic plasticity-related proteins, as well as the density and function of axo-spinous synapses. Here we review the evidence from brain imaging and postmortem studies demonstrating that depression is accompanied by structural and functional alterations of cortical and limbic brain regions, including the prefrontal cortex, hippocampus and amygdala. In addition, we present more direct evidence from basic research studies that exposure to stress alters spine morphology, function and plasticity and that antidepressants, particularly new rapid acting agents, reverse these effects. Elucidation of the signaling pathways and molecular mechanisms that control spine synapse assembly and plasticity will contribute to a better understanding of the pathophysiology of depression and development of novel, more effective therapeutic agents.
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“Congruent to this finding, in a postmortem analysis of MD patients, reduced densities and mean sizes of frontal cortex neurons and reduced hippocampal volume with increased numbers of glial cells are reported (Licznerski and Duman, 2013).”
From Serotonin and neuroplasticity – Links between molecular, functional and structural pathophysiology in depression (2017) · cites this paper as Licznerski and Duman, 2013
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“Studies from animal models confirm that medication-induced recovery involves changes in plasticity, dendritic morphology and density and function of synapses (for review seeLicznerski and Duman, 2013).”
From Serotonin and neuroplasticity – Links between molecular, functional and structural pathophysiology in depression (2017) · cites this paper as Licznerski and Duman, 2013
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“Congruent to this finding, in a postmortem analysis of MD patients, reduced densities and mean sizes of frontal cortex neurons and reduced hippocampal volume with increased numbers of glial cells are reported (Licznerski and Duman, 2013).”
From Serotonin and neuroplasticity – Links between molecular, functional and structural pathophysiology in depression (2017) · cites this paper as Licznerski and Duman, 2013
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“There is evidence of vmPFC gray matter loss in mood disorders7,115,116, which implies dendritic atrophy.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [115]
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Items 201–253 of 253
Barbon, A., Popoli, M., Via, L. L., Moraschi, S., Vallini, I., Tardito, D., Tiraboschi, E., Musazzi, L., Giambelli, R., Gennarelli, M., et al. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.10.018 · Cited by 96
Brain-Imaging Studies of Posttraumatic Stress Disorder
Liberzon, I., & Phan, K. L. (2003) · CNS Spectrums · doi:10.1017/s109285290000883x · Cited by 91
Qi, H., Mailliet, F., Spedding, M., Rocher, C., Zhang, X., Delagrange, P., McEwen, B. S., Jay, T. M., & Svenningsson, P. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.06.068 · Cited by 91
Bock, J., Murmu, M. S., Biala, Y., Weinstock, M., & Braun, K. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.07.048 · Cited by 86
Reduced striatal spine size in schizophrenia
Roberts, R. C., Conley, R. R., Kung, L., Peretti, F. J., & Chute, D. J. (1996) · Neuroreport · doi:10.1097/00001756-199604260-00024 · Cited by 84
Fu, Z., Lee, S. H., Simonetta, A., Hansen, J. D., Sheng, M., & Pak, D. T. S. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04195.x · Cited by 83
Norrholm, S. D., & Ouimet, C. C. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02909-7 · Cited by 82
Smit‐Rigter, L. A., Noorlander, C. W., von Oerthel, L., Chameau, P. J. P., Smidt, M. P., & van Hooft, J. A. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.09.015 · Cited by 82
Estradiol Induces Formation of Dendritic Spines in Hippocampal Neurons: Functional Correlates
Segal, M., & Murphy, D. (2001) · Hormones and Behavior · doi:10.1006/hbeh.2001.1688 · Cited by 81
Sex Steroid Hormone Gene Polymorphisms and Depressive Symptoms in Women at Midlife
Kravitz, H. M., Janssen, İ., Lotrich, F. E., Kado, D. M., & Bromberger, J. T. (2006) · The American Journal of Medicine · doi:10.1016/j.amjmed.2006.07.010 · Cited by 78
McLaughlin, K. J., Wilson, J. O., Harman, J. S., Wright, R. L., Wieczorek, L., Gomez, J. L., Korol, D. L., & Conrad, C. D. (2009) · Hippocampus · doi:10.1002/hipo.20678 · Cited by 77
Signalling pathways underlying structural plasticity of dendritic spines
Patterson, M., & Yasuda, R. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01328.x · Cited by 76
Dendritic Spine Density in Schizophrenia and Depression
Glantz, L. A., & Lewis, D. A. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.2.203 · Cited by 73
Muhammad, A., & Kolb, B. E. (2011) · Developmental Neuroscience · doi:10.1159/000324744 · Cited by 73
Neuroimaging of cortical development and brain connectivity in human newborns and animal models
Lodygensky, G. A., Vasung, L., Sizonenko, S. V., & Hüppi, P. S. (2010) · Journal of Anatomy · doi:10.1111/j.1469-7580.2010.01280.x · Cited by 71
Antidepressants and cognition: comparative effects of moclobemide, viloxazine and maprotiline
Allain, H., Lieury, A., Brunet-Bourgin, F., Mirabaud, C., Trébon, P., Coz, F. L., & Gandon, J. M. (1992) · Psychopharmacology · doi:10.1007/bf02246237 · Cited by 70
Halbach, O. V. B. U., Krause, S., Medina, D. L., Sciarretta, C., Minichiello, L., & Unsicker, K. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.08.025 · Cited by 63
Lechín, F., van der Dijs, B., & Benaim, M. (1996) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/0278-5846(96)00075-9 · Cited by 59
Fluoxetine administration modulates the cytoskeletal microtubular system in the rat hippocampus
Bianchi, M., Shah, A. J., Fone, K. C. F., Atkins, A. R., Dawson, L. A., Heidbreder, C. A., Hows, M. E., Hagan, J. J., & Marsden, C. A. (2009) · Synapse · doi:10.1002/syn.20614 · Cited by 56
Gos, T., Bock, J., Poeggel, G., & Braun, K. (2007) · Synapse · doi:10.1002/syn.20477 · Cited by 55
Conrad, C. D., McLaughlin, K. J., Huynh, T. N., El-Ashmawy, M., & Sparks, M. (2011) · Behavioral Neuroscience · doi:10.1037/a0025770 · Cited by 55
Lithium treatment prevents stress-induced dendritic remodeling in the rodent amygdala
Johnson, S. A., Wang, J., Sun, X., McEwen, B. S., Chattarji, S., & Young, L. T. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.06.005 · Cited by 54
Differential and Brain Region–Specific Regulation of Rap-1 and Epac in Depressed Suicide Victims
Dwivedi, Y., Mondal, A. C., Rizavi, H. S., Faludi, G., Palkovits, M., Sárosi, A., Conley, R. R., & Pandey, G. N. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.6.639 · Cited by 54
Mychasiuk, R., Gibb, R. L., & Kolb, B. E. (2011) · Brain Research · doi:10.1016/j.brainres.2011.07.023 · Cited by 51
Changes in rat hippocampal CA1 synapses following imipramine treatment
Chen, F., Madsen, T. M., Wegener, G., & Nyengaard, J. R. (2008) · Hippocampus · doi:10.1002/hipo.20423 · Cited by 50
Electroconvulsive seizure promotes spine maturation in newborn dentate granule cells in adult rat
Zhao, C., Warner‐Schmidt, J. L., Duman, R. S., & Gage, F. H. (2011) · Developmental Neurobiology · doi:10.1002/dneu.20986 · Cited by 49
Self-citationEffects ofBDNFPolymorphisms on Antidepressant Action
Tsai, S., Hong, C., & Liou, Y. (2010) · Psychiatry Investigation · doi:10.4306/pi.2010.7.4.236 · Cited by 48
Alcántara-González, F., Juárez, I., Solís, Ó., Martínez‐Téllez, R. I., Camacho‐Abrego, I., Masliah, E., Mena, R., & Flores, G. (2010) · Synapse · doi:10.1002/syn.20787 · Cited by 48
Almeida, O. P., Lautenschlager, N. T., Vasikaram, S., Leedman, P. J., & Flicker, L. A. (2005) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-200502000-00008 · Cited by 47
Zehle, S., Bock, J., Jezierski, G., Gruß, M., & Braun, K. (2007) · Developmental Neurobiology · doi:10.1002/dneu.20543 · Cited by 46
Marchetti, C., Tafi, E., Middei, S., Rubinacci, M. A., Restivo, L., Ammassari‐Teule, M., & Marie, H. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.017 · Cited by 42
Gibbons, A. S., Brooks, L., Scarr, E., & Dean, B. (2011) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.10.001 · Cited by 41
Electroconvulsive stimulations prevent stress-induced morphological changes in the hippocampus
Hageman, I., Nielsen, M., Wörtwein, G., Diemer, N. H., & Jørgensen, M. B. (2008) · Stress · doi:10.1080/10253890701783794 · Cited by 40
Age‐dependent effect of prenatal stress on hippocampal cell proliferation in female rats
Koehl, M., Lemaire, V., Moal, M. L., & Abrous, D. N. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.06608.x · Cited by 39
Koike, H., Iijima, M., & Chaki, S. (2011) · Neuroscience Research · doi:10.1016/j.neures.2011.07.860 · Cited by 36
Wang, M., Yang, Y., Dong, Z., Cao, J., & Xu, L. (2006) · Neuroreport · doi:10.1097/01.wnr.0000227994.07799.6c · Cited by 35
Zheng, J., Xu, D., Li, K., Wang, H., Shen, P.-C., Lin, M., Cao, X.-H., & Wang, R. (2011) · PubMed Central · Cited by 35
Rasgon, N., Carter, M. S., Elman, S., Bauer, M., Love, M., & Korenman, S. G. (2002) · Current Drug Targets - Immune Endocrine & Metabolic Disorders · doi:10.2174/1568008024606329 · Cited by 34
Age-Related Deficits in Spatial Memory and Hippocampal Spines in Virgin, Female Fischer 344 Rats
Luine, V. N., Wallace, M., & Frankfurt, M. (2011) · Current Gerontology and Geriatrics Research · doi:10.1155/2011/316386 · Cited by 31
Association study of the estrogen receptor alpha gene (ESR1) and childhood‐onset mood disorders
Mill, J. S., Kiss, E., Baji, I., Kapornai, K., Daróczy, G., Vetró, Á., Kennedy, J. L., Kovács, M., & Barr, C. L. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30751 · Cited by 30
Liao, C., & Lee, L. (2011) · Toxicology Letters · doi:10.1016/j.toxlet.2011.09.028 · Cited by 28
Gruß, M., Appenroth, D., Flubacher, A., Enzensperger, C., Bock, J., Fleck, C., Gille, G., & Braun, K. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07713.x · Cited by 26
Aberrant Extracellular Signal-Regulated Kinase (ERK) 5 Signaling in Hippocampus of Suicide Subjects
Dwivedi, Y., Rizavi, H. S., Teppen, T. L., Sasaki, N., Chen, H., Zhang, H., Roberts, R. C., Conley, R. R., & Pandey, G. N. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301372 · Cited by 25
Is fragile X mental retardation protein involved in activity-induced plasticity of dendritic spines?
Segal, M., Kreher, U., Greenberger, V., & Braun, K. A. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02410-7 · Cited by 21
Calhoun, M. E., Fletcher, B. R., Yi, S. S., Zentko, D. C., Gallagher, M., & Rapp, P. R. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.02.013 · Cited by 21
Odagiri, K., Abe, H., Kawagoe, C., Takeda, R., Ikeda, T., Matsuo, H., Nonaka, H., Ebihara, K., Nishimori, T., Ishizuka, Y., et al. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.09.028 · Cited by 21
Kao, P. F., Davis, D. A., Banigan, M. G., Vanderburg, C. R., Seshadri, S. S., & Delalle, I. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013337 · Cited by 21
Xu, F., Luk, C., Richard, M. P., Zaidi, W., Farkas, S., Getz, A. M., Lee, A. M., van Minnen, J., & Syed, N. I. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07129.x · Cited by 21
Frye, C. A., Paris, J. J., Osborne, D. M., Campbell, J. C., & Kippin, T. E. (2011) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2011.00052 · Cited by 18
Pascual, R., & Zamora-León, S. P. (2006) · Developmental Neuroscience · doi:10.1159/000096413 · Cited by 16
Ryan, M. A. K., Jacobson, I. G., Sevick, C. J., Smith, T. C., Gumbs, G. R., & Conlin, A. M. S. (2010) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.20746 · Cited by 14
Rosoklija, G., Toomayan, G., Ellis, S. P., Keilp, J., Mann, J. J., Latov, N., Hays, A. P., & Dwork, A. J. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.4.349 · Cited by 1
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- Dwyer, 2011, mTOR activation is required for the antidepressant effects of mGluR2/3 blockade, Int J Neuropsychopharmacol, 1
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Duman, R. S., Aghajanian, G. K., Sanacora, G., & Krystal, J. H. (2016) · Nature Medicine · doi:10.1038/nm.4050 · Cited by 1,750
Self-citationThe chronic mild stress (CMS) model of depression: History, evaluation and usage
Willner, P. (2017) · Neurobiology of Stress · doi:10.1016/j.ynstr.2016.08.002 · Cited by 959
Stress weakens prefrontal networks: molecular insults to higher cognition
Arnsten, A. F. T. (2015) · Nature Neuroscience · doi:10.1038/nn.4087 · Cited by 752
Kraus, C., Castrén, E., Kasper, S., & Lanzenberger, R. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.03.007 · Cited by 471
Neuroplasticity Underlying the Comorbidity of Pain and Depression
Doan, L., Manders, T. R., & Wang, J. (2015) · Neural Plasticity · doi:10.1155/2015/504691 · Cited by 304
Metadata
- Authors
- Licznerski, P., & Duman, R. S.
- Affiliations
- Yale University (US)
- Corresponding author
- Duman, R.S.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 251
- Pages
- 33-50
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC3566360
- OpenAlex
- W2065851490
- Cited by
- 157
- References
- 256
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 6 · 2023: 13 · 2022: 12 · 2021: 12 · 2020: 9 · 2019: 15 · 2018: 16 · 2017: 15 · 2016: 18 · 2015: 21 · 2014: 7 · 2013: 2
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH093897, R37MH045481)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- depression, dendritic spines, synaptic plasticity, stress, antidepressants, rapid-acting antidepressants, prefrontal cortex, hippocampus, amygdala, limbic system, neuroplasticity, dendritic spine morphology
- MeSH terms
- Animals, Brain, Depression, Humans, Neuronal Plasticity, Neurons, Stress, Physiological, Synapses, Brain-Derived Neurotrophic Factor
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