The DOI matches its Crossref record; 253 of the 256 references it cites were found in a registry or an index.
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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Cites
Antidepressant effects of ketamine in depressed patients
Berman, R. M., Cappiello, A., Anand, A., Oren, D. A., Heninger, G. R., Charney, D. S., & Krystal, J. H. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00230-9 · Cited by 3,856
A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.
Zarate, C. A., Singh, J. B., Carlson, P. J., Brutsche, N. E., Ameli, R., Luckenbaugh, D. A., Charney, D. S., & Manji, H. K. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.8.856 · Cited by 3,766
A Neurotrophic Model for Stress-Related Mood Disorders
Duman, R. S., & Monteggia, L. M. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.02.013 · Cited by 3,375
Self-citationNestler, E. J., Barrot, M., DiLeone, R. J., Eisch, A. J., Gold, S. J., & Monteggia, L. M. (2002) · Neuron · doi:10.1016/s0896-6273(02)00653-0 · Cited by 3,217
mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists
Li, N., Lee, B., Liu, R.-J., Banasr, M., Dwyer, J. M., Iwata, M., Li, X.-Y., Aghajanian, G., & Duman, R. S. (2010) · Science · doi:10.1126/science.1190287 · Cited by 2,881
Self-citationStructural basis of long-term potentiation in single dendritic spines
Matsuzaki, M., Honkura, N., Ellis-Davies, G. C. R., & Kasai, H. (2004) · Nature · doi:10.1038/nature02617 · Cited by 2,483
Mayberg, H. S., Liotti, M., Brannan, S. K., McGinnis, S., Mahurin, R. K., Jerabek, P. A., Silva, J. A., Tekell, J. L., Martin, C. C., Lancaster, J. L., et al. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.5.675 · Cited by 2,416
Synaptic Plasticity: Multiple Forms, Functions, and Mechanisms
Citri, A., & Malenka, R. C. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301559 · Cited by 2,323
Drevets, W. C., Price, J. L., & Furey, M. L. (2008) · Brain Structure and Function · doi:10.1007/s00429-008-0189-x · Cited by 2,241 · cited 2×
“…the exact functional correlates of altered hippocampal morphology in MDD. Neuroimaging studies have also reported disrupted functional correlates of the amygdala in MDD patients (Sheline et al., 2001; Siegle et al., 2002), including abnormally elevated glucose metabolism (Drevets et al., 2008).”
Kessler, R. (1993) · Journal of Affective Disorders · doi:10.1016/0165-0327(93)90026-g · Cited by 2,207 · cited 3×
“Clinical trials show that risk of developing depression is two times higher in females compared to males (Kessler et al., 1993), a phenomenon also observed in preclinical studies (Dalla et al.”
Research works printed but not linked: 1
- Dwyer, 2011, mTOR activation is required for the antidepressant effects of mGluR2/3 blockade, Int J Neuropsychopharmacol, 1
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Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants
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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