Cited by 157Treatment of Major DepressionNeuroscience and Neuropharmacology ResearchStress Responses and Cortisol

Remodeling of axo-spinous synapses in the pathophysiology and treatment of depression

Open access
Licznerski, P., Duman, R.S.·2013·Neuroscience

Abstract

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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Crossref · 10.1016/j.neuroscience.2012.09.057

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  • In postmortem major depression patients, hippocampal volume is reduced and glial cell numbers are increased.

    “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

    The postmortem studies section reports reduced hippocampal volume in MDD and a 30–35% increase in glial cell density in hippocampal cell layers. It does not report an increase in the total number of hippocampal glial cells; greater density does not establish greater numbers. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • Animal models confirm that medication-induced recovery involves changes in plasticity, dendritic morphology and density, and synaptic function.

    “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

    Section 5 (Typical Antidepressants; page not supplied) reviews animal studies showing antidepressant-related changes in dendritic branching, spine density and synaptic plasticity. Section 7 (Summary and Future Directions; page not supplied) says antidepressants may work at least in part by reversing stress-related synaptic deficits. The claim’s assertion that animal models confirm these changes as part of medication-induced recovery is stronger than the review’s qualified conclusion. (LLM, conf=0.82)

    Experimental — accuracy not yet measured
  • In postmortem major depression patients, densities and mean sizes of frontal cortex neurons are reduced.

    “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).”
  • There is evidence of vmPFC gray matter loss in mood disorders.

    “There is evidence of vmPFC gray matter loss in mood disorders7,115,116, which implies dendritic atrophy.”

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2 of the 256 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Tsai SJ Hong CJ Liou YJ 2010 Effects of BDNF polymorphisms on antidepressant action Psychiatry Investig 7 236 242 PMC3022309 21253406

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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)
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 · 2012: 2
FWCI
1.17
Type
journal article
Language
en
Open access
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 › 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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