Cited by 267Treatment of Major DepressionNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

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An excitatory synapse hypothesis of depression

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Thompson, Scott M., Kallarackal, Angy J., Kvarta, Mark D., Van Dyke, Adam M., LeGates, Tara A., Cai, Xiang·2015·Trends in Neurosciences

DOI 10.1016/j.tins.2015.03.003PMC PMC4417609

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Abstract

Depression is a common cause of mortality and morbidity, but the biological bases of the deficits in emotional and cognitive processing remain incompletely understood. Current antidepressant therapies are effective in only some patients and act slowly. Here, we propose an excitatory synapse hypothesis of depression in which chronic stress and genetic susceptibility cause changes in the strength of subsets of glutamatergic synapses at multiple locations, including the prefrontal cortex (PFC), hippocampus, and nucleus accumbens (NAc), leading to a dysfunction of corticomesolimbic reward circuitry that underlies many of the symptoms of depression. This hypothesis accounts for current depression treatments and suggests an updated framework for the development of better therapeutic compounds.

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Authors: Thompson, S. M., Kallarackal, A. J., Kvarta, M. D., Van Dyke, A. M., LeGates, T. A., & Cai, X.
Affiliations: University of Maryland, Baltimore (US)
Southern Illinois University Carbondale (US)
Corresponding author: Thompson, Scott M.
ORCID: Thompson, Scott M.
Kallarackal, Angy J.
Kvarta, Mark D.
LeGates, Tara A.
Cai, Xiang
Venue: Trends in Neurosciences
Publisher: Elsevier BV
Published: 2015-05
Volume: 38
Issue: 5
Pages: 279-294
ISSN: 0166-2236 (ISSN-L)
DOI: 10.1016/j.tins.2015.03.003
PMC: PMC4417609
OpenAlex: W2088861514
Cited by: 265
References: 203
Citations by year: 2026: 5 · 2025: 17 · 2024: 23 · 2023: 34 · 2022: 23 · 2021: 33 · 2020: 29 · 2019: 28 · 2018: 20 · 2017: 22 · 2016: 17 · 2015: 14
FWCI: 3.05
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Neurosciences (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (2t32ns063391-21)
National Institute of Mental Health (R01MH086828)
National Institute of General Medical Sciences (T32GM008181, T32GM092237)
National Institute of Neurological Disorders and Stroke (T32NS007375, T32-NS063391)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: depression, glutamatergic synapses, chronic stress, genetic susceptibility, prefrontal cortex, hippocampus, nucleus accumbens, antidepressant treatment, synaptic plasticity
MeSH terms: Animals, Antidepressive Agents, Brain, Depression, Humans, Synapses, Excitatory Postsynaptic Potentials

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An excitatory synapse hypothesis of depression

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