ArticleCell2021
Antidepressant drugs act by directly binding to TRKB neurotrophin receptors.
Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 344 papers, 4 of them syntheses that pooled it.
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Who cites it
344 citing papers in PubMed, 4 syntheses or guidelines pooled it, 640 citations in OpenAlex.
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- Maintenance of Noninvasive Brain Stimulation for Preventing Relapse in Depression: A Systematic Review and Meta-Analysis.Alpha psychiatry · 2025Pooled it
- Gene expression signatures of response to fluoxetine treatment: systematic review and meta-analyses.Molecular psychiatry · 2025Pooled it
- Meta-analysis of high-intensity interval training effects on cognitive function in older adults and cognitively impaired patients.Frontiers in physiology · 2025Pooled it
- Acute effects of intranasal esketamine application on thalamic structures in healthy individuals.The international journal of neuropsychopharmacology · 2025Trial
- Therapeutic Potential of Saffron Extract in Mild Depression: A Study of Its Role on Anhedonia in Rats and Humans.Phytotherapy research : PTR · 2025Trial
- Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-Release Tablets in Depression With Anhedonia: A Single-Arm, Multicenter Clinical Study.Depression and anxiety · 2025Trial
- Spatiotemporal remodeling in habenula marks the onset of depression-related phenotypes.Nature neuroscience · 2026Article
- Article
- Enhancement of hippocampal synaptic AMPA receptor function by the antidepressant tianeptine and by opioid peptides.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- NTPDase2 suppresses hippocampal astrocyte-supplied cholesterol through hydrolyzing eATP in depression.Molecular psychiatry · 2026Article
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- Effects of SSRIs on the spatial transcriptome of dorsal raphe serotonin neurons.Molecular psychiatry · 2026Article
- [(Es)ketamine: practice update].Der Nervenarzt · 2026Review
- Signs of antidepressant-like effects of temozolomide as measured in the forced-swim test in adult rats.Pharmacological reports : PR · 2026Article
- Artesunate directly targets glucosylceramidase to suppress hepatocellular carcinoma proliferation and trigger apoptosis.Genes & diseases · 2026Article
- The NO-cGMP signaling pathway and depression: mechanisms and therapeutic prospects.Molecular biology reports · 2026Review
- In Silico and In Vitro Evaluation of Calm Supplement Constituents on Antidepressant-Related Molecular Targets and Neuroplasticity-Associated Gene Expression.Biomedicines · 2026Article
- Low Dose Ketamine Preconditions Astrocyte Mitochondria to Achieve Antidepressant Efficacy via Adenosine, Humanin, and Melatonin Upregulation and Efflux.Alpha psychiatry · 2026Article
- From Biomarkers to New Treatments for Post-Traumatic Stress Disorder.Neuroscience bulletin · 2026Review
284 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors at 3 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is unclear how binding of antidepressant drugs to their targets gives rise to the clinical antidepressant effect. We discovered that the transmembrane domain of tyrosine kinase receptor 2 (TRKB), the brain-derived neurotrophic factor (BDNF) receptor that promotes neuronal plasticity and antidepressant responses, has a cholesterol-sensing function that mediates synaptic effects of cholesterol. We then found that both typical and fast-acting antidepressants directly bind to TRKB, thereby facilitating synaptic localization of TRKB and its activation by BDNF. Extensive computational approaches including atomistic molecular dynamics simulations revealed a binding site at the transmembrane region of TRKB dimers. Mutation of the TRKB antidepressant-binding motif impaired cellular, behavioral, and plasticity-promoting responses to antidepressants in vitro and in vivo. We suggest that binding to TRKB and allosteric facilitation of BDNF signaling is the common mechanism for antidepressant action, which may explain why typical antidepressants act slowly and how molecular effects of antidepressants are translated into clinical mood recovery.
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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.