ReviewTrends in neurosciences2015
An excitatory synapse hypothesis of depression.
Review in Trends in neurosciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
165 citing papers in PubMed.
- A Double-Blind, Placebo-Controlled, Pilot Study of Riluzole Monotherapy for Acute Bipolar Depression.Journal of clinical psychopharmacology · 2017Trial
- Synaptic Actions of Estradiol in the Brain's Reward System: Linking Mechanisms to Behavior and Disease.Biological psychiatry global open science · 2026Review
- A Comparison of Positive and Negative Allosteric Modulators of α5-Containing GABABiological psychiatry · 2026Review
- Depression in mice causes decreased neuronal excitability and enhanced frequency adaptation in medial prefrontal cortex pyramidal neurons.Scientific reports · 2025Article
- Single-cell transcriptomics reveals Sox6 positive interneurons enriched in the prefrontal cortex of female mice vulnerable to chronic social stress.Molecular psychiatry · 2025Article
- Dissociable Neural Connectome Mapping of Reward and Punishment Responsiveness in Young Adults: Associations with Genetic Variability and Neurotransmitter Profiles.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Adaptations in Mitochondrial Function Induced by Exercise: A Therapeutic Route for Treatment-Resistant Depression.International journal of molecular sciences · 2025Review
- nNOS-expressing neurons in the mPFC mediate depression-related behaviors in mice through pPVT-mPFC projections.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- An integrated single-nucleus and spatial transcriptomics atlas reveals the molecular landscape of the human hippocampus.Nature neuroscience · 2025Article
- Bioactive ketamine metabolite exerts in vivo neuroplastogenic effects to improve hippocampal function in a treatment-resistant depression model.Cell reports · 2025Article
- Sex-specific GABAergic microcircuits that switch vulnerability into resilience to stress and reverse the effects of chronic stress exposure.Molecular psychiatry · 2025Article
- Hippocampal Zkscan4 confers resilience to chronic stress-induced depression-like behaviors.Science advances · 2025Article
- A serial mediation model of physical exercise and loneliness: the role of frailty and depression.BMC geriatrics · 2025Article
- Transcriptome signatures of the medial prefrontal cortex underlying GABAergic control of resilience to chronic stress exposure.Molecular psychiatry · 2025Article
- Astrocytic pleiotrophin deficiency in the prefrontal cortex contributes to stress-induced depressive-like responses in male mice.Nature communications · 2025Article
- Single-nucleus RNA sequencing uncovers metabolic dysregulation in the prefrontal cortex of major depressive disorder patients.Scientific reports · 2025Article
- Mitogen-activated protein kinase dependent presynaptic potentiation in the lateral habenula mediates depressive-like behaviors in rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Structural neural plasticity evoked by rapid-acting antidepressant interventions.Nature reviews. Neuroscience · 2025Review
- The Deteriorated Center-Surround Suppression in Patients With First-Episode and Drug-Naïve Major Depressive Disorder.Depression and anxiety · 2025Article
- An integrated single-nucleus and spatial transcriptomics atlas reveals the molecular landscape of the human hippocampus.bioRxiv : the preprint server for biology · 2024Article
105 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.