ReviewThe European journal of neuroscience2021
Role of BDNF in the pathophysiology and treatment of depression: Activity-dependent effects distinguish rapid-acting antidepressants.
Review in The European journal of neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 4 of them syntheses that pooled it.
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
141 citing papers in PubMed, 4 syntheses or guidelines pooled it, 301 citations in OpenAlex.
- Investigation of habenula volume in mood disorders: A meta-analytic study.Psychological medicine · 2026Pooled it
- Depressive disorders: systematic review of approved psychiatric medications (2009-April 2025) and pipeline phase 3 medications.BMC psychiatry · 2025Pooled it
- Serum Brain-derived Neurotrophic Factor Levels as a Biomarker of Treatment Response in Patients With Depression: Systematic Review and Meta-analysis.Actas espanolas de psiquiatria · 2025Pooled it
- Adaptogens on Depression-Related Outcomes: A Systematic Integrative Review and Rationale of Synergism with Physical Activity.International journal of environmental research and public health · 2023Pooled it
- Subacute effects of ketamine on neural correlates of reward processing.Translational psychiatry · 2026Trial
- Efficacy of empagliflozin as adjunctive therapy to citalopram in major depressive disorder: a randomized double-blind, placebo-controlled clinical trial.BMC psychiatry · 2024Trial
- Tai chi improves psychoemotional state, cognition, and motor learning in older adults during the COVID-19 pandemic.Experimental gerontology · 2021Trial
- Ketamine Alters Electrophysiological Responses to Emotional Faces in Major Depressive Disorder.Journal of affective disorders · 2021Trial
- PT320, a GLP-1 receptor agonist, mitigates nucleus accumbens-associated depression- and anxiety-like behaviors in MitoPark mice of Parkinson's disease.Journal of Parkinson's disease · 2026Article
- TrkB promotes the neuronal secretion of soluble Siglec-2 (CD22) to mitigate microglial activation and alleviate depression-like behaviors in male mice.Molecular psychiatry · 2026Article
- Emerging Molecular Targets and Recent Advancements for the Management of Depression.Molecular neurobiology · 2026Review
- Neurotrophin System as a Complex Set of Potential Biomarkers in Psychiatric Disorders and Therapy-Overview of Recent Advances.International journal of molecular sciences · 2026Review
- Ketamine Dosing Across Clinical Indications: A Narrative Review Organized by Proposed NMDA-Related Mechanisms.Journal of clinical pharmacology · 2026Review
- Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery.Biomedicines · 2026Review
- Glial Cells in Behavioral and Psychological Symptoms of Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Electroacupuncture Ameliorates Depressive-Like Behaviors by Enhancing Autophagy to Attenuate Hippocampal Neuroinflammation via the VEGF/AKT1/ERK Pathway in CUMS Rats.Neurochemical research · 2026Article
- Ginsenoside Rh2 Protects Against Glutamate-Induced Neurotoxicity in PC12 Cells via Activation of the VEGF-mediated PI3K/Akt/mTOR Signaling Pathway.Neurochemical research · 2026Article
- The Converging Effects of Different Categories of Antidepressants on the Brain: A Systematic Meta-Analysis of Public Transcriptional Profiling Data from the Hippocampus and Cortex.bioRxiv : the preprint server for biology · 2026Article
- Neurotrophins and Galectin-3: Hidden Keys in Neuroinflammation-A Narrative Review.International journal of molecular sciences · 2026Review
- The Antidepressant Amitriptyline Upregulates ERK1/2 Signaling and Inhibits Rho-Mediated Responses Induced by Lysophosphatidic Acid in Astroglial Cells.International journal of molecular sciences · 2026Article
81 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
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The pathophysiology and treatment of depression have been the focus of intense research and while there is much that remains unknown, modern neurobiological approaches are making progress. This work demonstrates that stress and depression are associated with atrophy of neurons and reduced synaptic connectivity in brain regions such as the hippocampus and prefrontal cortex that contribute to depressive behaviors, and conversely that antidepressant treatment can reverse these deficits. The role of neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF), has been of particular interest as these factors play a key role in activity-dependent regulation of synaptic plasticity. Here, we review the literature demonstrating that exposure to stress and depression decreases BDNF expression in the hippocampus and PFC and conversely that antidepressant treatment can up-regulate BDNF in the adult brain and reverse the effects of stress. We then focus on rapid-acting antidepressants, particularly the NMDA receptor antagonist ketamine, which produces rapid synaptic and antidepressant behavioral actions that are dependent on activity-dependent release of BDNF. This rapid release of BDNF differs from typical monoaminergic agents that require chronic administration to produce a slow induction of BDNF expression, consistent with the time lag for the therapeutic action of these agents. We review evidence that other classes of rapid-acting agents also require BDNF release, demonstrating that this is a common, convergent downstream mechanism. Finally, we discuss evidence that the actions of ketamine are also dependent on another growth factor, vascular endothelial growth factor (VEGF) and its complex interplay with BDNF.
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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.