Sustained Effects of Rapidly Acting Antidepressants Require BDNF-Dependent MeCP2 Phosphorylation
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The sustained and long-term antidepressant effects of ketamine may be related to initial protein translation-dependent effects, changes in transcriptional regulation initiated by early synaptic plasticity, and the pivotal role of MeCP2.
“The sustained and long-term antidepressant effects of ketamine may be related to initial protein translation-dependent effects, changes in transcriptional regulation initiated by early synaptic plasticity, and the pivotal role of methyl CpG binding protein 2 (MeCP2) [62,78].”
From Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review (2024) · cites this paper as [78]
MeCP2 Ser421 phosphorylation is required for the long-lasting antidepressant effects of ketamine but not for the initial rapid antidepressant response.
“While MeCP2 Ser421 phosphorylation is required for these long-lasting effects, it is not required for the initial rapid antidepressant response [78,80].”
From Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review (2024) · cites this paper as [78]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,501 · see citing works
da Luz, A. C. D. D. S., Dias, G. P., Bevilaqua, M. C. D. N., Cocks, G. D., Gardino, P. F., Thuret, S., & Nardi, A. E. (2013) · Neuropsychobiology · doi:10.1159/000353269 · Cited by 4,012 · see citing works
Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., Zaitsev, E., Gold, B., Goldman, D., Dean, M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00035-7 · Cited by 3,888 · see citing works
Antidepressant effects of ketamine in depressed patients
Berman, R. M., Cappiello, A., Anand, A., Oren, D. A., Heninger, G. R., Charney, D. S., & Krystal, J. H. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00230-9 · Cited by 3,856 · see citing works
A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.
Zarate, C. A., Singh, J. B., Carlson, P. J., Brutsche, N. E., Ameli, R., Luckenbaugh, D. A., Charney, D. S., & Manji, H. K. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.8.856 · Cited by 3,766 · see citing works
mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists
Li, N., Lee, B., Liu, R.-J., Banasr, M., Dwyer, J. M., Iwata, M., Li, X.-Y., Aghajanian, G., & Duman, R. S. (2010) · Science · doi:10.1126/science.1190287 · Cited by 2,881 · see citing works
NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses
Autry, A. E., Adachi, M., Nosyreva, E., Na, E. S., Los, M. F., Cheng, P.-F., Kavalali, E. T., & Monteggia, L. M. (2011) · Nature · doi:10.1038/nature10130 · Cited by 1,926 · see citing works
Self-citationBourtchuladze, R., Frenguelli, B., Blendy, J., Cioffi, D., Schutz, G., & Silva, A. J. (1994) · Cell · doi:10.1016/0092-8674(94)90400-6 · Cited by 1,800 · see citing works
NMDAR inhibition-independent antidepressant actions of ketamine metabolites
Zanos, P., Moaddel, R., Morris, P. J., Georgiou, P., Fischell, J., Elmer, G. I., Alkondon, M., Yuan, P., Pribut, H. J., Singh, N. S., et al. (2016) · Nature · doi:10.1038/nature17998 · Cited by 1,609 · see citing works
Ca2+ Influx Regulates BDNF Transcription by a CREB Family Transcription Factor-Dependent Mechanism
Tao, X., Finkbeiner, S., Arnold, D. B., Shaywitz, A. J., & Greenberg, M. E. (1998) · Neuron · doi:10.1016/s0896-6273(00)81010-7 · Cited by 1,561 · see citing works
CREB: a Ca 2+ -Regulated Transcription Factor Phosphorylated by Calmodulin-Dependent Kinases
Sheng, M., Thompson, M. A., & Greenberg, M. E. (1991) · Science · doi:10.1126/science.1646483 · Cited by 1,498 · see citing works
MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin.
Nan, X.-S., Campoy, F., & Bird, A. (1997) · Cell · doi:10.1016/s0092-8674(00)81887-5 · Cited by 1,403 · see citing works
Derepression of BDNF Transcription Involves Calcium-Dependent Phosphorylation of MeCP2
Chen, W. G., Chang, Q., Lin, Y., Meissner, A., West, A. E., Griffith, E. C., Jaenisch, R., & Greenberg, M. E. (2003) · Science · doi:10.1126/science.1086446 · Cited by 1,232 · see citing works
Maeng, S., Zarate, C. A., Du, J., Schloesser, R. J., McCammon, J., Chen, G., & Manji, H. K. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.05.028 · Cited by 1,103 · see citing works
Transcription Factors in Long-Term Memory and Synaptic Plasticity
Alberini, C. M. (2009) · Physiological Reviews · doi:10.1152/physrev.00017.2008 · Cited by 991 · see citing works
CREB: A Major Mediator of Neuronal Neurotrophin Responses
Finkbeiner, S. M., Tavazoie, S. F., Maloratsky, A., Jacobs, K. M., Harris, K. M., & Greenberg, M. E. (1997) · Neuron · doi:10.1016/s0896-6273(00)80395-5 · Cited by 950 · see citing works
Zhou, Z., Hong, E. J., Cohen, S., Zhao, W.-N., Ho, H.-Y. H., Schmidt, L., Chen, W. G., Lin, Y., Savner, E., Griffith, E. C., et al. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.037 · Cited by 877 · see citing works
Murrough, J. W., Perez, A. M., Pillemer, S., Stern, J., Parides, M. K., aan het Rot, M., Collins, K. A., Mathew, S. J., Charney, D. S., & Iosifescu, D. V. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.06.022 · Cited by 786 · see citing works
Safety and Efficacy of Repeated-Dose Intravenous Ketamine for Treatment-Resistant Depression
aan het Rot, M., Collins, K. A., Murrough, J. W., Perez, A. M., Reich, D. L., Charney, D. S., & Mathew, S. J. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.08.038 · Cited by 690 · see citing works
Neuronal MeCP2 Is Expressed at Near Histone-Octamer Levels and Globally Alters the Chromatin State
Skene, P. J., Illingworth, R. S., Webb, S., Kerr, A. R. W., James, K. D., Turner, D. J., Andrews, R., & Bird, A. P. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.01.030 · Cited by 688 · see citing works
Essential role of brain-derived neurotrophic factor in adult hippocampal function
Monteggia, L. M., Barrot, M., Powell, C. M., Berton, O., Galanis, V., Gemelli, T., Meuth, S., Nagy, A., Greene, R. W., & Nestler, E. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402141101 · Cited by 685 · see citing works
Self-citationSustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation
Moda-Sava, R. N., Murdock, M. H., Parekh, P. K., Fetcho, R. N., Huang, B. S., Huynh, T. N., Witztum, J., Shaver, D. C., Rosenthal, D. L., Alway, E. J., et al. (2019) · Science · doi:10.1126/science.aat8078 · Cited by 643 · see citing works
Phillips, J. L., Norris, S., Talbot, J., Birmingham, M., Hatchard, T., Ortiz, A., Owoeye, O., Batten, L. A., & Blier, P. (2019) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2018.18070834 · Cited by 418 · see citing works
Furey, M. L., & Drevets, W. C. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.10.1121 · Cited by 417 · see citing works
The Role of MeCP2 in the Brain
Guy, J., Cheval, H., Selfridge, J., & Bird, A. P. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154121 · Cited by 414 · see citing works
Tissue-specific expression of four types of rat calmodulin-dependent protein kinase II mRNAs
Tobimatsu, T., & Fujisawa, H. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)84658-6 · Cited by 397 · see citing works
Mineur, Y. S., Obayemi, A., Wigestrand, M. B., Fote, G. M., Calarco, C. A., Li, A. M., & Picciotto, M. R. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219731110 · Cited by 375 · see citing works
CaM Kinase: Still Inspiring at 40
Bayer, K. U., & Schulman, H. (2019) · Neuron · doi:10.1016/j.neuron.2019.05.033 · Cited by 307 · see citing works
Barbosa, A. C., Kim, M.-S., Ertunc, M., Adachi, M., Nelson, E. D., McAnally, J., Richardson, J. A., Kavalali, E. T., Monteggia, L. M., Bassel-Duby, R., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802679105 · Cited by 303 · see citing works
Self-citationCohen, S., Gabel, H. W., Hemberg, M., Hutchinson, A. N., Sadacca, L. A., Ebert, D. H., Harmin, D. A., Greenberg, R. S., Verdine, V. K., Zhou, Z., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.08.022 · Cited by 298 · see citing works
Beurel, E., Song, L., & Jope, R. S. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.47 · Cited by 288 · see citing works
Acute suppression of spontaneous neurotransmission drives synaptic potentiation
Nosyreva, E., Szabla, K., Autry, A. E., Ryazanov, A. G., Monteggia, L. M., & Kavalali, E. T. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.4998-12.2013 · Cited by 283 · see citing works
Self-citationVoleti, B., Navarria, A., Liu, R.-J., Banasr, M., Li, N., Terwilliger, R., Sanacora, G., Eid, T., Aghajanian, G., & Duman, R. S. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.04.025 · Cited by 264 · see citing works
Drevets, W. C., & Furey, M. L. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.11.021 · Cited by 241 · see citing works
MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulants
Deng, J. V., Rodriguiz, R. M., Hutchinson, A. N., Kim, I.-H., Wetsel, W. C., & West, A. E. (2010) · Nature Neuroscience · doi:10.1038/nn.2614 · Cited by 206 · see citing works
Carreno, F. R., Donegan, J. J., Boley, A. M., Shah, A., DeGuzman, M., Frazer, A., & Lodge, D. J. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.176 · Cited by 205 · see citing works
Transgenic animals with inducible, targeted gene expression in brain.
Chen, J.-S., Kelz, M., Zeng, G., Sakai, N., Steffen, C., Shockett, P. E., Picciotto, M., Duman, R., & Nestler, E. J. (1998) · Molecular Pharmacology · doi:10.1124/mol.54.3.495 · Cited by 194 · see citing works
Use of Pattern Analysis to Identify True Drug Response
Quitkin, F. M. (1987) · Archives of General Psychiatry · doi:10.1001/archpsyc.1987.01800150071009 · Cited by 191 · see citing works
Cholinergic regulation of mood: from basic and clinical studies to emerging therapeutics
Dulawa, S. C., & Janowsky, D. S. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0219-x · Cited by 187 · see citing works
Effects of a ketamine metabolite on synaptic NMDAR function
Suzuki, K., Nosyreva, E., Hunt, K. W., Kavalali, E. T., & Monteggia, L. M. (2017) · Nature · doi:10.1038/nature22084 · Cited by 180 · see citing works
Self-citationEnhanced Long-Term Synaptic Depression in an Animal Model of Depression
Holderbach, R., Clark, K., Moreau, J., Bischofberger, J., & Normann, C. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.07.007 · Cited by 174 · see citing works
Recapitulation and Reversal of a Persistent Depression‐like Syndrome in Rodents
Gourley, S. L., & Taylor, J. R. (2009) · Current Protocols in Neuroscience · doi:10.1002/0471142301.ns0932s49 · Cited by 168 · see citing works
Functional Implications of the Subunit Composition of Neuronal CaM Kinase II
Brocke, L., Chiang, L. W., Wagner, P. D., & Schulman, H. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.32.22713 · Cited by 161 · see citing works
Navarria, A., Wohleb, E. S., Voleti, B., Ota, K. T., Dutheil, S., Lepack, A. E., Dwyer, J. M., Fuchikami, M., Becker, A., Drago, F., et al. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.06.012 · Cited by 118 · see citing works
Ghosal, S., Bang, E., Yue, W., Hare, B. D., Lepack, A. E., Girgenti, M. J., & Duman, R. S. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.06.017 · Cited by 111 · see citing works
Zhang, K., Xu, T., Yuan, Z., Wei, Z., Yamaki, V. N., Huang, M., Huganir, R. L., & Cai, X. (2016) · Science Signaling · doi:10.1126/scisignal.aai7884 · Cited by 98 · see citing works
Scheiderer, C. L., McCutchen, E., Thacker, E. E., Kolasa, K., Ward, M. K., Parsons, D. S., Harrell, L. E., Dobrunz, L. E., & McMahon, L. L. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.5507-05.2006 · Cited by 78 · see citing works
Adaikkan, C., Taha, E., Barrera, I., David, O., & Rosenblum, K. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.11.028 · Cited by 77 · see citing works
Buchthal, B., Lau, D., Weiss, U. K., Weislogel, J.-M., & Bading, H. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.382507 · Cited by 60 · see citing works
Kim, J., & Monteggia, L. M. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.112378 · Cited by 56 · see citing works
Self-citationPhosphorylation of MeCP2 at Ser421 Contributes to Chronic Antidepressant Action
Hutchinson, A. N., Deng, J. V., Cohen, S., & West, A. E. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.2156-12.2012 · Cited by 53 · see citing works
Postnatal Loss of Mef2c Results in Dissociation of Effects on Synapse Number and Learning and Memory
Adachi, M., Lin, P.-Y., Pranav, H., & Monteggia, L. M. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.09.018 · Cited by 50 · see citing works
Self-citationHill, J. J., Kolluri, N., Hashimoto, T., Wu, Q., Sampson, A. R., Monteggia, L. M., & Lewis, D. A. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.01.010 · Cited by 25 · see citing works
Self-citationMans, R. A., Warmus, B. A., Smith, C. C., et al. (2014) · Journal of Neurophysiology · doi:10.1152/jn.00048.2014 · Cited by 24 · see citing works
Scopolamine and Ketamine: Evidence of Convergence?
Monteggia, L. M., & Kavalali, E. T. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.08.011 · Cited by 18 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Brain-Derived Neurotrophic Factor in Alzheimer’s Disease and Its Pharmaceutical Potential
Gao, L., Zhang, Y., Sterling, K., & Song, W. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00279-0 · Cited by 606 · see citing works
Psychedelics reopen the social reward learning critical period
Nardou, R., Sawyer, E., Song, Y. J., Wilkinson, M., Padovan-Hernandez, Y., de Deus, J. L., Wright, N., Lama, C., Faltin, S., Goff, L. A., et al. (2023) · Nature · doi:10.1038/s41586-023-06204-3 · Cited by 358 · see citing works
Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics
Aleksandrova, L. R., & Phillips, A. G. (2021) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2021.08.003 · Cited by 276 · see citing works
Ketamine and rapid antidepressant action: New treatments and novel synaptic signaling mechanisms
Krystal, J. H., Kavalali, E. T., & Monteggia, L. M. (2024) · Neuropsychopharmacology · doi:10.1038/s41386-023-01629-w · Cited by 262 · see citing works
Self-citationMicroglial ERK-NRBP1-CREB-BDNF Signaling in Sustained Antidepressant Actions of (R)-Ketamine
Yao, W., Cao, Q., Luo, S., He, L., Yang, C., Chen, J., Qi, Q., Hashimoto, K., & Zhang, J.-C. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01377-7 · Cited by 216 · see citing works
Zanos, P., Brown, K. A., Georgiou, P., Yuan, P., Zarate, C. A., Thompson, S. M., & Gould, T. D. (2023) · The Journal of Neuroscience · doi:10.1523/jneurosci.1316-22.2022 · Cited by 115 · see citing works
Synaptic Mechanisms Regulating Mood State Transitions in Depression
Parekh, P. K., Johnson, S. B., & Liston, C. (2022) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-110920-040422 · Cited by 101 · see citing works
Bridging Rapid and Sustained Antidepressant Effects of Ketamine
Kim, J.-W., Suzuki, K., Kavalali, E. T., & Monteggia, L. M. (2023) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2023.02.003 · Cited by 59 · see citing works
Self-citationTargeting metaplasticity mechanisms to promote sustained antidepressant actions
Brown, K. A., & Gould, T. D. (2024) · Molecular Psychiatry · doi:10.1038/s41380-023-02397-1 · Cited by 49 · see citing works
Pardossi, S., Fagiolini, A., & Cuomo, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252313098 · Cited by 51 · see citing works
Troppoli, T. A., Zanos, P., Georgiou, P., Gould, T. D., Rudolph, U., & Thompson, S. M. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2021.11.024 · Cited by 29 · see citing works
Intrinsic Connectivity Networks of Glutamate-Mediated Antidepressant Response: A Neuroimaging Review
Demchenko, I., Tassone, V. K., Kennedy, S. H., Dunlop, K., & Bhat, V. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.864902 · Cited by 29 · see citing works
Rethinking the role of TRKB in the action of antidepressants and psychedelics
Brunello, C. A., Cannarozzo, C., & Castrén, E. (2024) · Trends in Neurosciences · doi:10.1016/j.tins.2024.08.011 · Cited by 31 · see citing works
Cai, M., Zhu, Y., Shanley, M. R., Morel, C., Ku, S. M., Zhang, H., Shen, Y., Friedman, A. K., & Han, M.-H. (2023) · Neurobiology of Stress · doi:10.1016/j.ynstr.2023.100565 · Cited by 18 · see citing works
MeCP2 prevents against sustained ketamine-induced synaptic depression at inhibitory synapses
Piazza, M. K., Weit, A. R., Kavalali, E. T., Neul, J. L., & Monteggia, L. M. (2025) · iScience · doi:10.1016/j.isci.2025.112485 · Cited by 3 · see citing works
Self-citation
- Authors
- Kim, J.-W., Autry, A. E., Na, E. S., Adachi, M., Björkholm, C., Kavalali, E. T., & Monteggia, L. M.
- Affiliations
- Vanderbilt University (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Monteggia, Lisa M.
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2021-06-28
- Volume
- 24
- Issue
- 8
- Pages
- 1100-1109
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC8338784
- OpenAlex
- W3175577244
- Cited by
- 113
- References
- 55
- Citations by year
- 2026: 13 · 2025: 23 · 2024: 27 · 2023: 21 · 2022: 21 · 2021: 7
- FWCI
- 11.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Research Foundation of Korea (NRF) funded by the Ministry of Education
- Elisabeth and Alfred Ahlqvist foundation within the Swedish Pharmaceutical Society and the Swedish Society for Medical Research
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (MH066198, MH081060)
- Topics
- Health Sciences › Medicine › Pharmacology › 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
- ketamine, scopolamine, brain-derived neurotrophic factor, synaptic plasticity, synaptic efficacy, MeCP2
- MeSH terms
- Animals, Antidepressive Agents, Brain, Ketamine, Mice, Inbred C57BL, Neuronal Plasticity, Phosphorylation, Scopolamine, Mice, Knockout, Brain-Derived Neurotrophic Factor, Mice, Methyl-CpG-Binding Protein 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
