ArticleNature neuroscience2021
Sustained effects of rapidly acting antidepressants require BDNF-dependent MeCP2 phosphorylation.
Article in Nature neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
72 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- Brain-derived neurotrophic factor (BDNF) changes in rodent models of schizophrenia induced by ketamine: a systematic review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Pooled it
- A scientometric analysis of research on the role of NMDA receptor in the treatment of depression.Frontiers in pharmacology · 2024Pooled it
- Long term structural and functional neural changes following a single infusion of Ketamine in PTSD.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Trial
- The role of BDNF promoter VI in mediating protective effects of prophylactic (R,S)-ketamine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Ketamine and Evolving Neuroplasticity.Clinical drug investigation · 2026Review
- The Emerging Neurobiology of Psychedelics: Critical Periods, Metaplasticity, and Extracellular Matrix Remodeling.Annual review of neuroscience · 2026Review
- Intermittent Ketamine and Neuromodulation Treatment Evoke Synergistic Antidepressant-Relevant Action.Biological psychiatry · 2026Article
- MeCP2 regulates cell-type-specific functions of depressive-like symptoms in the nucleus accumbens.Experimental & molecular medicine · 2026Article
- Mechanism-guided identification of antidepressant G protein-coupled receptor drug targets.Cell · 2026Article
- A Time-Sensitive Plasticity Distinguishes the Rapid and Sustained Synaptic Actions of Ketamine from Its (2The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- The hippocampus as a central hub in ketamine's antidepressant action: from molecules to circuit rewiring.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- The Complex Role of Serotonin-Dopamine-Glutamate Receptors in Major Depression.Advances in experimental medicine and biology · 2026Review
- Article
- An Overview of Depression Pathogenesis: Prevailing Hypotheses and Associated Neurobiological Underpinnings Primarily Evidenced by Rodent Studies.Depression and anxiety · 2026Review
- G-protein coupled receptor kinase 2 mediates rheumatoid arthritis-induced depression-like behaviors via the hippocampal CRHR1 signaling pathway.Acta pharmacologica Sinica · 2025Article
- Review
- Genetic Mechanisms of Experience-Dependent Neuronal Plasticity.Annual review of genetics · 2025Review
- The therapeutic potential of psilocybin beyond psychedelia through shared mechanisms with ketamine.Molecular psychiatry · 2025Review
- Spontaneous glutamate release activates mGluR signaling to drive rapid antidepressant responses.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Synaptic basis of rapid antidepressant action.European archives of psychiatry and clinical neuroscience · 2025Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The rapidly acting antidepressants ketamine and scopolamine exert behavioral effects that can last from several days to more than a week in some patients. The molecular mechanisms underlying the maintenance of these antidepressant effects are unknown. Here we show that methyl-CpG-binding protein 2 (MeCP2) phosphorylation at Ser421 (pMeCP2) is essential for the sustained, but not the rapid, antidepressant effects of ketamine and scopolamine in mice. Our results reveal that pMeCP2 is downstream of BDNF, a critical factor in ketamine and scopolamine antidepressant action. In addition, we show that pMeCP2 is required for the long-term regulation of synaptic strength after ketamine or scopolamine administration. These results demonstrate that pMeCP2 and associated synaptic plasticity are essential determinants of sustained antidepressant effects.
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What OpenQuestion holds
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.