D-serine for the treatment of negative symptoms in individuals at clinical high risk of schizophrenia: a pilot, double-blind, placebo-controlled, randomised parallel group mechanistic proof-of-concept trial
Abstract
Background Antagonists of N-methyl-D-aspartate-type glutamate receptors (NMDAR) induce symptoms that closely resemble those of schizophrenia, including negative symptoms. D-serine is a naturally occurring NMDAR modulator that reverses the effects of NMDAR antagonists in animal models of schizophrenia. D-serine effects have been assessed previously for treatment of established schizophrenia, but not in the early stages of the disorder. We aimed to assess effects of D-serine on negative symptoms in at risk individuals.Methods We did a double-blind, placebo-controlled, parallel-group randomised clinical trial at four academic US centres. Individuals were eligible for inclusion in the study if they were at clinical high risk of schizophrenia, aged between 13-35 years, had a total score of more than 20 on the Scale of Prodromal Symptoms (SOPS), and had an interest in participation in the clinical trial. Exclusion criteria included a history of suprathreshold psychosis symptoms (ie, no longer qualifying as prodromal) or clinical judgment that the reported symptoms from the SOPS were accounted for better by another disorder (eg, depression). Randomisation was done using a generated list with block sizes of four. Participants were stratified by site, with participants, investigators, and assessors all masked through use of identical looking placebos and centralised drug dispensation to study assignment. D-serine (60 mg/kg) was given orally in divided daily doses for 16 weeks. The primary endpoint was for negative SOPS, measured weekly for the first 6 weeks, then every 2 weeks. Participants who received at least one post-baseline assessment were included in analysis. Serum cytokine concentrations were collected at baseline, midpoint, and endpoint to assess the mechanism of action. Safety outcomes including laboratory assessments were obtained for all individuals. This trial is registered with ClinicalTrials.gov, number NCT0082620.Findings We enrolled participants between April 2, 2009, and July 23, 2012. 44 participants were randomly assigned to receive either D-serine (n=20) or placebo (n=24); 35 had assessable data (15 D-serine, 20 placebo). D-serine induced a 35·7% (SD 17·8) improvement in negative symptoms, which was significant compared with placebo (mean final SOPS negative score 7·6 [SEM 1·4] for D-serine group vs 11·3 [1·2] for placebo group; d=0·68, p=0·03). Five participants who received D-serine and nine participants who received placebo discontinued the study early because of withdrawn consent or loss to follow-up (n=8), conversion to psychosis (n=2), laboratory-confirmed adverse events (n=2), or protocol deviations (n=2).Interpretation This study supports use of NMDAR-based interventions, such as D-serine, for treatment of prodromal symptoms of schizophrenia. On the basis of observed effect sizes, future studies with sample sizes of about 40 per treatment group would be needed for confirmation of beneficial effects on symptoms and NMDAR-related inflammatory changes. Long-term studies are needed to assess effects on psychosis conversion in individuals at clinical high risk of schizophrenia.Funding National Institutes of Health.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Published studies have revealed beneficial effects of NAC in schizophrenia patients as an add-on to maintenance medication.
“Published studies have revealed beneficial effects in schizophrenia patients as an add-on to maintenance medication [100][101][102][103] and ongoing studies are following up their results and including additional metrics of efficacy such as brain GSH imaging in order to reflect the BBB permeability analyses of NAC that have been performed in rodents 104 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [100]
Cites
Statistical Power Analysis for the Behavioral Sciences
Muller, K. E., & Cohen, J. (1989) · Technometrics · doi:10.2307/1270020 · Cited by 99,588 · see citing works
Statistical power analysis for the behavioral sciences
Cohen, J. (1990) · Computers Environment and Urban Systems · doi:10.1016/0198-9715(90)90050-4 · Cited by 65,406 · see citing works
Estimating the Dimension of a Model
Schwarz, G. (1978) · The Annals of Statistics · doi:10.1214/aos/1176344136 · Cited by 47,033 · see citing works
The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research
Buysse, D. J., Reynolds, C. F., Monk, T. H., Berman, S. R., & Kupfer, D. J. (1989) · Psychiatry Research · doi:10.1016/0165-1781(89)90047-4 · Cited by 35,234 · see citing works
Krystal, J. H. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950030035004 · Cited by 3,330 · see citing works
A RATING SCALE FOR EXTRAPYRAMIDAL SIDE EFFECTS
Simpson, G. M., B., M., B., G., Angus, J. W. S., P., F. R. C., & M., D. P. (1970) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1970.tb02066.x · Cited by 3,265 · see citing works
Recent advances in the phencyclidine model of schizophrenia
(1991) · American Journal of Psychiatry · doi:10.1176/ajp.148.10.1301 · Cited by 2,904 · see citing works
Self-citationInflammation and immunity in schizophrenia: implications for pathophysiology and treatment
Khandaker, G. M., Cousins, L., Deakin, J., Lennox, B. R., Yolken, R., & Jones, P. B. (2015) · The Lancet Psychiatry · doi:10.1016/s2215-0366(14)00122-9 · Cited by 926 · see citing works
Amminger, G. P., Schäfer, M. R., Papageorgiou, K., Klier, C. M., Cotton, S. M., Harrigan, S. M., Mackinnon, A., McGorry, P. D., & Berger, G. E. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.192 · Cited by 896 · see citing works
D-Alanine Added to Antipsychotics for the Treatment of Schizophrenia
Tsai, G. E., Yang, P., Chang, Y., & Chong, M. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.06.032 · Cited by 676 · see citing works
Ruhrmann, S., Schultze-Lutter, F., Salokangas, R. K. R., Heinimaa, M., Linszen, D., Dingemans, P., Birchwood, M., Patterson, P., Juckel, G., Heinz, A., et al. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.206 · Cited by 632 · see citing works
Cannon, T. D., Chung, Y., He, G., Sun, D., Jacobson, A., van Erp, T. G. M., McEwen, S., Addington, J., Bearden, C. E., Cadenhead, K., et al. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.05.023 · Cited by 599 · see citing works
Self-citationD-serine added to antipsychotics for the treatment of schizophrenia
Tsai, G. E., Yang, P., Chung, L.-C., LANGE, N. D., & Coyle, J. T. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00279-0 · Cited by 572 · see citing works
The Psychosis-Risk Syndrome: Handbook for Diagnosis and Follow-Up
McGlashan, T. H., Walsh, B. C., & Woods, S. W. (2010) · Cited by 571 · see citing works
Self-citationBerk, M., Copolov, D., Dean, O., Lu, K., Jeavons, S., Schapkaitz, I., Anderson-Hunt, M., Judd, F., Katz, F., Katz, P., et al. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.03.004 · Cited by 552 · see citing works
Schobel, S. A., Chaudhury, N. H., Khan, U. A., Paniagua, B., Styner, M. A., Asllani, I., Inbar, B. P., Corcoran, C. M., Lieberman, J. A., Moore, H., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.02.011 · Cited by 549 · see citing works
Self-citationCytokine function in medication-naive first episode psychosis: A systematic review and meta-analysis
Upthegrove, R., Manzanares-Teson, N., & Barnes, N. M. (2014) · Schizophrenia Research · doi:10.1016/j.schres.2014.03.005 · Cited by 501 · see citing works
Gonzalez-Burgos, G., & Lewis, D. A. (2012) · Schizophrenia Bulletin · doi:10.1093/schbul/sbs010 · Cited by 478 · see citing works
Long-term Follow-up of a Group at Ultra High Risk (“Prodromal”) for Psychosis
Nelson, B., Yuen, H. P., Wood, S. J., Lin, A. P., Spiliotacopoulos, D., Bruxner, A., Broussard, C., Simmons, M. B., Foley, D. L., Brewer, W. J., et al. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.1270 · Cited by 434 · see citing works
Buchanan, R. W., Javitt, D. C., Marder, S. R., Schooler, N. R., Gold, J. M., McMahon, R. P., Heresco-Levy, U., & Carpenter, W. T. (2007) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.06081358 · Cited by 419 · see citing works
Self-citationNMDA Receptor and Schizophrenia: A Brief History
COYLE, J. T. (2012) · Schizophrenia Bulletin · doi:10.1093/schbul/sbs076 · Cited by 413 · see citing works
Kantrowitz, J. T., & Javitt, D. C. (2010) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2010.04.006 · Cited by 397 · see citing works
Self-citationHeresco‐Levy, U., Javitt, D. C., Ebstein, R. P., Vass, Á., Lichtenberg, P., Bar, G., Catinari, S., & Ermilov, M. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.12.037 · Cited by 386 · see citing works
Self-citationvan der Gaag, M., Smit, F., Bechdolf, A., French, P., Linszen, D. H., Yung, A. R., McGorry, P., & Cuijpers, P. (2013) · Schizophrenia Research · doi:10.1016/j.schres.2013.07.004 · Cited by 384 · see citing works
Glutathione Precursor, N-Acetyl-Cysteine, Improves Mismatch Negativity in Schizophrenia Patients
Lavoie, S., Murray, M. M., Deppen, P., Knyazeva, M. G., Berk, M., Boulat, O., Bovet, P., Bush, A. I., Conus, P., Copolov, D., et al. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301624 · Cited by 371 · see citing works
Schobel, S., Lewandowski, N. M., Corcoran, C. M., Moore, H. M., Brown, T. R., Malaspina, D., & Small, S. A. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.115 · Cited by 364 · see citing works
Self-citationSAFTEE: a technique for the systematic assessment of side effects in clinical trials.
Levine, J., & Schooler, N. (1986) · PubMed · Cited by 329 · see citing works
Negative symptoms in individuals at clinical high risk of psychosis
Piskulic, D., Addington, J., Cadenhead, K., Cannon, T. D., Cornblatt, B., Heinssen, R., Perkins, D., Seidman, L., Tsuang, M., Walker, E. F., et al. (2012) · Psychiatry Research · doi:10.1016/j.psychres.2012.02.018 · Cited by 298 · see citing works
Self-citationTsai, G. E., & Lin, P. (2010) · Current Pharmaceutical Design · doi:10.2174/138161210790361452 · Cited by 269 · see citing works
High dose D-serine in the treatment of schizophrenia
Kantrowitz, J. T., Malhotra, A. K., Cornblatt, B. A., Silipo, G. S., Balla, A., Suckow, R. F., D’Souza, C., Saksa, J. R., Woods, S. W., & Javitt, D. C. (2010) · Schizophrenia Research · doi:10.1016/j.schres.2010.05.012 · Cited by 253 · see citing works
Self-citationMoghaddam, B., & Krystal, J. H. (2012) · Schizophrenia Bulletin · doi:10.1093/schbul/sbs075 · Cited by 238 · see citing works
Perkins, D. O., Jeffries, C. D., Addington, J., Bearden, C. E., Cadenhead, K. S., Cannon, T. D., Cornblatt, B. A., Mathalon, D. H., McGlashan, T. H., Seidman, L. J., et al. (2015) · Schizophrenia Bulletin · doi:10.1093/schbul/sbu099 · Cited by 238 · see citing works
Self-citationEffect of Bitopertin, a Glycine Reuptake Inhibitor, on Negative Symptoms of Schizophrenia
Umbricht, D., Alberati, D., Martin‐Facklam, M., Borroni, E., Youssef, E. A., Ostland, M., Wallace, T. L., Knoflach, F., Dorflinger, E. E., Wettstein, J. G., et al. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.163 · Cited by 234 · see citing works
Addington, D. E., Addington, J., & Atkinson, M. J. (1996) · Schizophrenia Research · doi:10.1016/0920-9964(95)00070-4 · Cited by 221 · see citing works
Lin, C., Huang, C., Chang, Y., Chen, P., Lin, C.-Y., Tsai, G. E., & Lane, H. (2013) · Schizophrenia Research · doi:10.1016/j.schres.2013.02.009 · Cited by 202 · see citing works
Meta-Analysis of the Efficacy of Adjunctive NMDA Receptor Modulators in Chronic Schizophrenia
Singh, S. P., & Singh, V. (2011) · CNS Drugs · doi:10.2165/11586650-000000000-00000 · Cited by 194 · see citing works
Lane, H., Lin, C., Huang, Y.-J., Liao, C.-H., Chang, Y.-C., & Tsai, G. E. (2009) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145709990939 · Cited by 179 · see citing works
Stojanovic, A., Martorell, L., Montalvo, I., Ortega, L., Monseny, R., Vilella, E., & Labad, J. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.12.005 · Cited by 170 · see citing works
Kinon, B. J., Millen, B. A., Zhang, L., & McKinzie, D. L. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.03.016 · Cited by 169 · see citing works
Translating Glutamate: From Pathophysiology to Treatment
Javitt, D. C., Schoepp, D., Kalivas, P. W., Volkow, N. D., Zarate, C., Merchant, K., Bear, M. F., Umbricht, D., Hajos, M., Potter, W. Z., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002804 · Cited by 168 · see citing works
Self-citationBehrens, M. M., & B, T. J. S. A. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.06.002 · Cited by 160 · see citing works
Instrument for the Assessment of Prodromal Symptoms and States
McGlashan, T. H., Miller, T. J., Woods, S. W., Hoffman, R. E., & Davidson, L. (2001) · Springer eBooks · doi:10.1007/978-94-010-0892-1_7 · Cited by 159 · see citing works
Self-citationCorcoran, C. M., Kimhy, D., Parrilla-Escobar, M. A., Cressman, V. L., Stanford, A. D., Thompson, J. L., Ben‐David, S., Crumbley, A. H., Schobel, S., Moore, H. M., et al. (2010) · Psychological Medicine · doi:10.1017/s0033291710000802 · Cited by 156 · see citing works
Self-citationMeyer, E. C., Carrión, R. E., Cornblatt, B. A., Addington, J., Cadenhead, K. S., Cannon, T. D., McGlashan, T. H., Perkins, D. O., Tsuang, M. T., Walker, E. F., et al. (2014) · Schizophrenia Bulletin · doi:10.1093/schbul/sbt235 · Cited by 153 · see citing works
Self-citationBayesian Measures of Model Complexity and Fit
Spiegelhalter, D. J., Best, N. G., Carlin, B. P., & Van Der Linde, A. (2002) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/1467-9868.00353 · Cited by 151 · see citing works
Hashimoto, K., Fujita, Y., Horio, M., Kunitachi, S., Iyo, M., Ferraris, D. V., & Tsukamoto, T. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.01.002 · Cited by 128 · see citing works
Valmaggia, L. R., Stahl, D., Yung, A. R., Nelson, B., Fusar-Poli, P., McGorry, P. D., & McGuire, P. K. (2013) · Psychological Medicine · doi:10.1017/s0033291713000251 · Cited by 121 · see citing works
IV glycine and oral d-cycloserine effects on plasma and CSF amino acids in healthy humans
D’Souza, D. C., Gil, R. B., Cassello, K., Morrissey, K., Abi‐Saab, D., White, J., Sturwold, R., Bennett, A., Karper, L. P., Zuzarte, E., et al. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00133-x · Cited by 111 · see citing works
Weiser, M., Heresco‐Levy, U., Davidson, M., Javitt, D. C., Werbeloff, N., Gershon, A. A., Abramovitch, Y., Amital, D., Doron, A., Konas, S., et al. (2012) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.11m07031 · Cited by 106 · see citing works
Self-citationJavitt, D., Balla, A., Burch, S., Suckow, R., Xie, S., & Sershen, H. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300313 · Cited by 98 · see citing works
Self-citationBugarski‐Kirola, D., Wang, A., Abi‐Saab, D., & Blaettler, T. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2014.03.007 · Cited by 97 · see citing works
Glycine transport inhibitors for the treatment of schizophrenia: symptom and disease modification.
Javitt, D. C. (2009) · PubMed · Cited by 94 · see citing works
Self-citationLeiderman, E. A., Zylberman, I., Zukin, S. R., Cooper, T. B., & Javitt, D. C. (1996) · Biological Psychiatry · doi:10.1016/0006-3223(95)00585-4 · Cited by 90 · see citing works
Self-citationEarly Intervention in Psychotic Disorders
Miller, T. J., Mednick, S. A., McGlashan, T. H., Libiger, J., & Johannessen, J. O. (2001) · Springer eBooks · doi:10.1007/978-94-010-0892-1 · Cited by 80 · see citing works
Adams, D. H., Zhang, L., Millen, B. A., Kinon, B. J., & Gómez, J. (2014) · Schizophrenia Research and Treatment · doi:10.1155/2014/758212 · Cited by 74 · see citing works
Glycine treatment of the risk syndrome for psychosis: Report of two pilot studies
Woods, S. W., Walsh, B. C., Hawkins, K. A., Miller, T. J., Saksa, J. R., D’Souza, D. C., Pearlson, G. D., Javitt, D. C., McGlashan, T. H., & Krystal, J. H. (2012) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2012.09.008 · Cited by 61 · see citing works
Self-citationGozzi, A., Herdon, H. J., Schwarz, A. J., Bertani, S., Crestan, V., Turrini, G., & Bifone, A. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1271-z · Cited by 61 · see citing works
Clinical development of pomaglumetad methionil: A non-dopaminergic treatment for schizophrenia
Kinon, B. J., & Gómez, J. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.06.002 · Cited by 48 · see citing works
Balla, A., Schneider, S., Sershen, H. W., & Javitt, D. C. (2012) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2012.03.006 · Cited by 16 · see citing works
Self-citationEarly Intervention in Psychotic Disorders
Carroll, A. (2002) · Psychiatric Services · doi:10.1176/appi.ps.53.3.352 · Cited by 16 · see citing works
Arango, C., Nasrallah, H. A., Lawrie, S. M., Lohmann, T. O., Zhu, J. L., Garibaldi, G. M., Wang, A., & Bugarski‐Kirola, D. (2014) · Schizophrenia Research · doi:10.1016/j.schres.2014.07.038 · Cited by 11 · see citing works
Blaettler, T., Bugarski‐Kirola, D., Fleischhacker, W. W., Bressan, R. A., Arango, C., Abi‐Saab, D., Napieralski, J. A., Dixon, M., & Marder, S. R. (2014) · Schizophrenia Research · doi:10.1016/j.schres.2014.07.036 · Cited by 11 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Barnes, T. R. E., Drake, R., Paton, C., Cooper, S. J., Deakin, J. F. W., Ferrier, I. N., Gregory, C. J., Haddad, P. M., Howes, O. D., Jones, I. R., et al. (2019) · Journal of Psychopharmacology · doi:10.1177/0269881119889296 · Cited by 607 · see citing works
Altering the course of schizophrenia: progress and perspectives
Millan, M. J., Andrieux, A., Bartzokis, G., Cadenhead, K., Dazzan, P., Fusar-Poli, P., Gallinat, J., Giedd, J., Grayson, D. R., Heinrichs, M., et al. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.28 · Cited by 516 · see citing works
Auditory dysfunction in schizophrenia: integrating clinical and basic features
Javitt, D. C., & Sweet, R. A. (2015) · Nature reviews. Neuroscience · doi:10.1038/nrn4002 · Cited by 363 · see citing works
Self-citationLinking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis
Hardingham, G. E., & Do, K. Q. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.19 · Cited by 304 · see citing works
The NMDA Receptor and Schizophrenia
Balu, D. T. (2016) · Advances in pharmacology · doi:10.1016/bs.apha.2016.01.006 · Cited by 288 · see citing works
Detection and analysis of chiral molecules as disease biomarkers
Liu, Y., Wu, Z., Armstrong, D. W., Wolosker, H., & Zheng, Y. (2023) · Nature Reviews Chemistry · doi:10.1038/s41570-023-00476-z · Cited by 257 · see citing works
Lack of evidence to favor specific preventive interventions in psychosis: a network meta‐analysis
Davies, C., Cipriani, A., Ioannidis, J. P. A., Radua, J., Stahl, D., Provenzani, U., McGuire, P., & Fusar‐Poli, P. (2018) · World Psychiatry · doi:10.1002/wps.20526 · Cited by 229 · see citing works
Towards an Immunophenotype of Schizophrenia: Progress, Potential Mechanisms, and Future Directions
Miller, B. J., & Goldsmith, D. R. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.211 · Cited by 182 · see citing works
Treating Negative Symptoms in Schizophrenia: an Update
Remington, G. J., Foussias, G., Fervaha, G., Agid, O., Takeuchi, H., Lee, J., & Hahn, M. (2016) · Current Treatment Options in Psychiatry · doi:10.1007/s40501-016-0075-8 · Cited by 167 · see citing works
Early Detection and Preventive Intervention in Schizophrenia: From Fantasy to Reality
Lieberman, J. A., Small, S. A., & Girgis, R. R. (2019) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2019.19080865 · Cited by 158 · see citing works
Glutamatergic dysfunction in Schizophrenia
Kruse, A. O., & Bustillo, J. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02253-w · Cited by 154 · see citing works
Mei, C., van der Gaag, M., Nelson, B., Smit, F., Yuen, H. P., Berger, M., Krcmar, M., French, P., Amminger, G. P., Bechdolf, A., et al. (2021) · Clinical Psychology Review · doi:10.1016/j.cpr.2021.102005 · Cited by 143 · see citing works
Cuénod, M., Steullet, P., Cabungcal, J.-H., Dwir, D., Khadimallah, I., Klauser, P., Conus, P., & Kim, Q. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01374-w · Cited by 129 · see citing works
D-Serine: Potential Therapeutic Agent and/or Biomarker in Schizophrenia and Depression?
MacKay, M.-A. B., Kravtsenyuk, M., Thomas, R. K., Mitchell, N., Dursun, S. M., & Baker, G. B. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00025 · Cited by 128 · see citing works
Kantrowitz, J. T., Epstein, M. L., Lee, M., Lehrfeld, N., Nolan, K. A., Shope, C., Petkova, E., Silipo, G., & Javitt, D. C. (2018) · Schizophrenia Research · doi:10.1016/j.schres.2017.02.027 · Cited by 123 · see citing works
Self-citationKantrowitz, J. T., Epstein, M. L., Beggel, O., Rohrig, S. N., Lehrfeld, J. M., Revheim, N., Lehrfeld, N., Reep, J., Parker, E. M., Silipo, G. S., et al. (2016) · Brain · doi:10.1093/brain/aww262 · Cited by 114 · see citing works
Self-citationPreventive Treatments for Psychosis: Umbrella Review (Just the Evidence)
Fusar-Poli, P., Davies, C., Solmi, M., Brondino, N., De Micheli, A., Kotlicka-Antczak, M., Shin, J. I., & Radua, J. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00764 · Cited by 108 · see citing works
Davies, C., Radua, J., Cipriani, A., Stahl, D., Provenzani, U., McGuire, P., & Fusar-Poli, P. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00187 · Cited by 107 · see citing works
Interventions for prodromal stage of psychosis
Kuharić, D. B., Kekin, I., Hew, J., Kuzman, M. R., & Puljak, L. (2019) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012236.pub2 · Cited by 102 · see citing works
Foster, A. C., Farnsworth, J. C., Lind, G. E., Li, Y.-X., Yang, J., Dang, V., Penjwini, M., Viswanath, V., Staubli, U. V., & Kavanaugh, M. P. (2016) · PLoS ONE · doi:10.1371/journal.pone.0156551 · Cited by 90 · see citing works
N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease
Morland, C., & Nordengen, K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031268 · Cited by 89 · see citing works
Progress and Future Directions in Research on the Psychosis Prodrome
Woodberry, K. A., Shapiro, D. I., Bryant, C., & Seidman, L. J. (2016) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000109 · Cited by 87 · see citing works
Low d-serine levels in schizophrenia: A systematic review and meta-analysis
Cho, S., Na, K., Cho, S.-J., & Kang, S. (2016) · Neuroscience Letters · doi:10.1016/j.neulet.2016.10.006 · Cited by 83 · see citing works
Devoe, D. J. A., Peterson, A. M., & Addington, J. (2017) · Schizophrenia Bulletin · doi:10.1093/schbul/sbx139 · Cited by 79 · see citing works
Lin, C., & Lane, H. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00093 · Cited by 80 · see citing works
Devoe, D. J. A., Farris, M. S., Townes, P., & Addington, J. (2018) · Early Intervention in Psychiatry · doi:10.1111/eip.12677 · Cited by 80 · see citing works
Sleep disturbances in individuals at clinical high risk for psychosis
Poe, S.-L., Brucato, G., Bruno, N., Arndt, L. Y., Ben-David, S., Gill, K. E., Colibazzi, T., Kantrowitz, J. T., Corcoran, C. M., & Girgis, R. R. (2017) · Psychiatry Research · doi:10.1016/j.psychres.2016.12.029 · Cited by 75 · see citing works
Self-citationGirgis, R. R., Zoghbi, A. W., Javitt, D. C., & Lieberman, J. A. (2018) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2018.07.006 · Cited by 73 · see citing works
Self-citationLuo, Y., He, H., Zhang, J., Ou, Y., & Fan, N. (2019) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2019.01.003 · Cited by 70 · see citing works
d-Amino acids and kidney diseases
Kimura, T., Hesaka, A., & Isaka, Y. (2020) · Clinical and Experimental Nephrology · doi:10.1007/s10157-020-01862-3 · Cited by 70 · see citing works
The glycine site of NMDA receptors: A target for cognitive enhancement in psychiatric disorders
Peyrovian, B., Rosenblat, J. D., Pan, Z., Iacobucci, M., Brietzke, E. M., & McIntyre, R. S. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.02.001 · Cited by 70 · see citing works
Advances in D-Amino Acids in Neurological Research
Seckler, J. M., & Lewis, S. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197325 · Cited by 68 · see citing works
Astrocytic Regulation of Glutamate Transmission in Schizophrenia
Mei, Y.-Y., Wu, D., & Zhou, N. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00544 · Cited by 64 · see citing works
Inflammatory biomarkers in individuals at clinical high risk for psychosis (CHR-P): State or trait?
Khoury, R., & Nasrallah, H. A. (2018) · Schizophrenia Research · doi:10.1016/j.schres.2018.04.017 · Cited by 65 · see citing works
Potential and Challenges for the Clinical Use of d-Serine As a Cognitive Enhancer
Guercio, G. D., & Panizzutti, R. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00014 · Cited by 66 · see citing works
New discoveries for an old drug: a review of recent olanzapine research
Meftah, A. M., Deckler, E., Citrome, L., & Kantrowitz, J. T. (2019) · Postgraduate Medicine · doi:10.1080/00325481.2019.1701823 · Cited by 64 · see citing works
Self-citationUliana, D. L., Lisboa, J. R., Gomes, F. V., & Grace, A. A. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116298 · Cited by 65 · see citing works
Progression from being at-risk to psychosis: next steps
Addington, J., Farris, M., Devoe, D., & Metzak, P. D. (2020) · npj Schizophrenia · doi:10.1038/s41537-020-00117-0 · Cited by 50 · see citing works
N -Methyl-D-Aspartate (NMDA) receptor modulators: a patent review (2015-present)
Ahmed, H., Haider, A., & Ametamey, S. M. (2020) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2020.1811234 · Cited by 54 · see citing works
Wolf, G., Singh, S., Blakolmer, K., Lerer, L. A., Lifschytz, T., Heresco-Levy, U., Lotan, A., & Lerer, B. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01832-z · Cited by 33 · see citing works
Enhancing NMDA Receptor Function: Recent Progress on Allosteric Modulators
Yao, L., & Zhou, Q. (2017) · Neural Plasticity · doi:10.1155/2017/2875904 · Cited by 48 · see citing works
Avissar, M., & Javitt, D. C. (2017) · Schizophrenia Research · doi:10.1016/j.schres.2017.11.006 · Cited by 45 · see citing works
Self-citationThiebes, S., Leicht, G., Ćurić, S., Steinmann, S., Polomac, N., Andreou, C., Eichler, I., Eichler, L., Zöllner, C., Gallinat, J., et al. (2017) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.160187 · Cited by 43 · see citing works
McGorry, P. D., Mei, C., Hartmann, J., Yung, A. R., & Nelson, B. (2021) · Schizophrenia Research · doi:10.1016/j.schres.2020.12.026 · Cited by 45 · see citing works
Worthington, M., & Cannon, T. D. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.770774 · Cited by 43 · see citing works
Managing Negative Symptoms of Schizophrenia: How Far Have We Come?
Kantrowitz, J. T. (2017) · CNS Drugs · doi:10.1007/s40263-017-0428-x · Cited by 43 · see citing works
Self-citationXie, D., Shi, H., Lui, S. S. Y., Shi, C., Li, Y., Ho, K. K. Y., Hung, K. S. Y., Li, W., Yi, Z., Cheung, E. F. C., et al. (2018) · Schizophrenia Bulletin · doi:10.1093/schbul/sby013 · Cited by 42 · see citing works
The interhemispheric miscommunication theory of auditory verbal hallucinations in schizophrenia
Steinmann, S., Leicht, G., & Mulert, C. (2019) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2019.02.002 · Cited by 44 · see citing works
Pei, J.-C., Luo, D.-Z., Gau, S.-S., Chang, C., & Lai, W. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.742058 · Cited by 42 · see citing works
de Bartolomeis, A., Vellucci, L., Austin, M., Simone, G. D., & Barone, A. (2022) · Biomolecules · doi:10.3390/biom12070909 · Cited by 40 · see citing works
Kantrowitz, J. T. (2018) · Schizophrenia Research · doi:10.1016/j.schres.2018.02.003 · Cited by 41 · see citing works
Self-citationChronic d-serine supplementation impairs insulin secretion
Suwandhi, L., Hausmann, S., Braun, A., Gruber, T., Heinzmann, S. S., Gálvez, E. J. C., Buck, A., Legutko, B., Israel, A., Feuchtinger, A., et al. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.07.002 · Cited by 41 · see citing works
Neurophysiological Effects of Bitopertin in Schizophrenia
Kantrowitz, J. T., Nolan, K. A., Epstein, M. L., Lehrfeld, N., Shope, C. B., Petkova, E., & Javitt, D. C. (2017) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000722 · Cited by 40 · see citing works
Self-citationLee, M., Sehatpour, P., Dias, E. C., Silipo, G. S., Kantrowitz, J. T., Martı́nez, A., & Javitt, D. C. (2017) · Schizophrenia Research · doi:10.1016/j.schres.2017.07.032 · Cited by 40 · see citing works
Self-citationEthical and Epidemiological Dimensions of Labeling Psychosis Risk
Corcoran, C. M. (2016) · The AMA Journal of Ethic · doi:10.1001/journalofethics.2016.18.6.msoc2-1606 · Cited by 40 · see citing works
Self-citationFujita, Y., Ishima, T., & Hashimoto, K. (2016) · Scientific Reports · doi:10.1038/srep37261 · Cited by 39 · see citing works
Sershen, H. W., Hashim, A., Dunlop, D. S., Suckow, R. F., Cooper, T. B., & Javitt, D. C. (2016) · Neurochemical Research · doi:10.1007/s11064-016-1838-8 · Cited by 38 · see citing works
Self-citationThe impact of inflammation on neurocognition and risk for psychosis: a critical review
Kogan, S., Ospina, L. H., Mittal, V. A., & Kimhy, D. (2019) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-019-01073-2 · Cited by 38 · see citing works
D-Serine: A Cross Species Review of Safety
Meftah, A. M., Hasegawa, H., & Kantrowitz, J. T. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.726365 · Cited by 37 · see citing works
Self-citationFradley, R. L., Goetghebeur, P., Miller, D., Burley, R., Almond, S., Gruart, A., García, J. M. D., Zhu, B., Howley, E., Neill, J. C., et al. (2023) · Neurochemical Research · doi:10.1007/s11064-023-03956-2 · Cited by 36 · see citing works
Ghajar, A., Khoaie-Ardakani, M.-R., Shahmoradi, Z., Alavi, A.-R., Afarideh, M., Shalbafan, M., Ghazizadeh‐Hashemi, M., & Akhondzadeh, S. (2018) · Psychiatry Research · doi:10.1016/j.psychres.2018.02.012 · Cited by 35 · see citing works
Multidisciplinary Treatment for Individuals at Clinical High Risk of Developing Psychosis
Addington, J., Devoe, D. J. A., & Santesteban‐Echarri, O. (2019) · Current Treatment Options in Psychiatry · doi:10.1007/s40501-019-0164-6 · Cited by 33 · see citing works
Farris, M. S., Devoe, D. J. A., & Addington, J. (2019) · Early Intervention in Psychiatry · doi:10.1111/eip.12864 · Cited by 33 · see citing works
Polcari, D., Perry, S. C., Pollegioni, L., Geißler, M., & Mauzeroll, J. (2017) · ChemElectroChem · doi:10.1002/celc.201600766 · Cited by 29 · see citing works
Competitive Inhibitors Unveil Structure/Function Relationships in Human D-Amino Acid Oxidase
Molla, G. (2017) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2017.00080 · Cited by 29 · see citing works
Towards a neurodynamical understanding of the prodrome in schizophrenia
Mikanmaa, E., Grent-‘t-Jong, T., Hua, L., Recasens, M., Thuné, H., & Uhlhaas, P. J. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.11.026 · Cited by 29 · see citing works
Galantamine-Memantine Combination as an Antioxidant Treatment for Schizophrenia
Koola, M. M., Praharaj, S. K., & Pillai, A. (2019) · Current Behavioral Neuroscience Reports · doi:10.1007/s40473-019-00174-5 · Cited by 27 · see citing works
Wang, L., Eugenia, P., Lui, S. S. Y., Cheung, E. F. C., Cheng, K., & Chan, R. C. K. (2020) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2020.101971 · Cited by 27 · see citing works
Foster, A. C., Rangel-Diaz, N., Staubli, U. V., Yang, J., Penjwini, M., Viswanath, V., & Li, Y. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.08.010 · Cited by 27 · see citing works
Advances in the Treatment of Cognitive Impairment in Schizophrenia: Targeting NMDA Receptor Pathways
Zhang, T., Liu, C., Zhong, N., Wang, Y., Huang, Y., & Zhang, X. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910668 · Cited by 26 · see citing works
Schaefer, M., Sarkar, S., Theophil, I., Leopold, K., Heinz, A., & Gallinat, J. (2019) · Pharmacopsychiatry · doi:10.1055/a-0970-9310 · Cited by 25 · see citing works
Drugs Based on NMDAR Hypofunction Hypothesis in Schizophrenia
Wu, Q., Huang, J., & Wu, R. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.641047 · Cited by 24 · see citing works
Nasyrova, R., Khasanova, A. K., Altynbekov, K. S., Asadullin, A., Markina, E. A., Gayduk, A., Shipulin, G., Petrova, M. M., & Shnayder, N. (2022) · Nutrients · doi:10.3390/nu14235142 · Cited by 16 · see citing works
Fan, N., Luo, Y., Xu, K., Zhang, M., Ke, X., Huang, X., Ding, Y., Wang, D., Ning, Y., Deng, X., et al. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.11.006 · Cited by 22 · see citing works
Pawełczyk, T., Trafalska, E., Kotlicka‐Antczak, M., & Pawełczyk, A. M. (2016) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2016.03.010 · Cited by 22 · see citing works
de Pablo, G. S., Davies, C., Ruiz, H. D. D., Solmi, M., Shin, J. I., Carvalho, A. F., Raduà, J., & Fusar‐Poli, P. (2021) · European Psychiatry · doi:10.1192/j.eurpsy.2021.2222 · Cited by 20 · see citing works
Kurachi, M., Takahashi, T., Sumiyoshi, T., Uehara, T., & Suzuki, M. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00039 · Cited by 20 · see citing works
Raduà, J., Davies, C., & Fusar‐Poli, P. (2020) · Schizophrenia Research · doi:10.1016/j.schres.2020.05.010 · Cited by 20 · see citing works
Garip, B., Kayır, H., & Uzun, Ö. (2018) · Schizophrenia Research · doi:10.1016/j.schres.2018.12.015 · Cited by 20 · see citing works
Hauke, D. J., Charlton, C. E., Schmidt, A., Griffiths, J., Woods, S. W., Ford, J. M., Srihari, V. H., Roth, V., Diaconescu, A. O., & Mathalon, D. H. (2022) · doi:10.1101/2022.12.20.22283712 · Cited by 18 · see citing works
Self-citationMoussa, S., Murtas, G., Pollegioni, L., & Mauzeroll, J. (2021) · ACS Applied Bio Materials · doi:10.1021/acsabm.1c00409 · Cited by 18 · see citing works
Chaumette, B., Sengupta, S. M., Lepage, M., MALLA, A. K., Iyer, S. N., Kébir, O., Dion, P. A., Rouleau, G. A., Krebs, M., Shah, J. L., et al. (2020) · Schizophrenia Research · doi:10.1016/j.schres.2020.06.019 · Cited by 18 · see citing works
Zhang, T., Raballo, A., Zeng, J., Gan, R., Wu, G., Wei, Y., Xu, L., Tang, X., Hu, Y., Tang, Y., et al. (2022) · Schizophrenia · doi:10.1038/s41537-022-00254-8 · Cited by 18 · see citing works
Haider, S., Shahzad, S., Batool, Z., Sadir, S., Liaquat, L., Tabassum, S., & Perveen, T. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119417 · Cited by 18 · see citing works
Glutamate modulators for treatment of schizophrenia
Zhand, N., Attwood, D. G., & Harvey, P. D. (2019) · Personalized Medicine in Psychiatry · doi:10.1016/j.pmip.2019.02.001 · Cited by 16 · see citing works
Biotypes in Psychosis: Has the RDoC Era Arrived?
Javitt, D. C. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2016.16020140 · Cited by 15 · see citing works
Self-citationEarly Detection and Prevention of Schizophrenic Psychosis—A Review
Westhoff, M. S., Ladwig, J., Heck, J., Schülke, R., Groh, A., Deest, M., Bleich, S., Frieling, H., & Jahn, K. (2021) · Brain Sciences · doi:10.3390/brainsci12010011 · Cited by 14 · see citing works
Adraoui, F. W., Douw, L., Martens, G. J. M., & Maas, D. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24097680 · Cited by 14 · see citing works
The Time Sequence of Gene Expression Changes after Spinal Cord Injury
Mun, S., Han, K., & Hyun, J. K. (2022) · Cells · doi:10.3390/cells11142236 · Cited by 13 · see citing works
Jacobi, A. A., Halawani, S. M., Lynch, D. R., & Lin, H. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.10.055 · Cited by 12 · see citing works
Chen, C., Deng, Y., Li, Y., Zhang, M., Yu, T., Xie, K., Bao, W., Li, P., Sun, L., Zhang, T., et al. (2024) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyae014 · Cited by 12 · see citing works
Li, Z., Zhang, T., Xu, L., Wei, Y., Cui, H., Tang, Y., Liu, X., Qian, Z., Zhang, H., Liu, P., et al. (2021) · Schizophrenia Research · doi:10.1016/j.schres.2021.11.011 · Cited by 12 · see citing works
Donoso, M. V., Catalán‐Salas, V., Pulgar‐Sepúlveda, R., Eugenín, J. L., & Huidobro-Toro, J. P. (2024) · The Chemical Record · doi:10.1002/tcr.202400013 · Cited by 11 · see citing works
Gee, A., Dazzan, P., Grace, A. A., & Modinos, G. (2025) · Translational Psychiatry · doi:10.1038/s41398-024-03221-2 · Cited by 12 · see citing works
Baseline data of a sequential multiple assignment randomized trial (STEP study)
Hartmann, J., Nelson, B., Amminger, G. P., Spark, J., Yuen, H. P., Kerr, M., Polari, A. R., Wallis, N., Blasioli, J., Dixon, L. B., et al. (2022) · Early Intervention in Psychiatry · doi:10.1111/eip.13263 · Cited by 10 · see citing works
Surti, T. S., Ranganathan, M., Johannesen, J., Gueorguieva, R. V., Deaso, E., Kenney, J. G., Krystal, J. H., & D’Souza, D. C. (2023) · Schizophrenia Research · doi:10.1016/j.schres.2023.04.010 · Cited by 10 · see citing works
N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth
Gonzalez–Heydrich, J., Enlow, M. B., D’Angelo, E. J., Seidman, L. J., Gumlak, S., Kim, A., Woodberry, K. A., Rober, A., Tembulkar, S. K., O’Donnell, K., et al. (2016) · Neural Plasticity · doi:10.1155/2016/4209831 · Cited by 10 · see citing works
Hauke, D. J., Schmidt, A., Studerus, E., Andreou, C., Riecher‐Rössler, A., Raduà, J., Kambeitz, J. P., Ruef, A., Dwyer, D., Kambeitz‐Ilankovic, L., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01409-4 · Cited by 10 · see citing works
Cross species review of the physiological role of d-serine in translationally relevant behaviors
Arizanovska, D., Emodogo, J., Lally, A. P., Palavicino‐Maggio, C. B., Liebl, D. J., & Folorunso, O. O. (2023) · Amino Acids · doi:10.1007/s00726-023-03338-6 · Cited by 9 · see citing works
Bending the curve on psychosis outcomes
Light, G. A., & Swerdlow, N. R. (2015) · The Lancet Psychiatry · doi:10.1016/s2215-0366(15)00172-8 · Cited by 9 · see citing works
- Authors
- Kantrowitz, J. T., Woods, S. W., Petkova, E., Cornblatt, B., Corcoran, C. M., Chen, H., Silipo, G., & Javitt, D. C.
- Affiliations
- Nathan Kline Institute for Psychiatric Research (US)
- Yale University (US)
- Zucker Hillside Hospital (US)
- Columbia University (US)
- University of Florida (US)
- Corresponding author
- Javitt, Daniel C
- ORCID
- Venue
- The Lancet Psychiatry
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 2
- Issue
- 5
- Pages
- 403-412
- ISSN
- 2215-0366 (ISSN-L)
- OpenAlex
- W2070856797
- Cited by
- 148
- References
- 62
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 11 · 2021: 19 · 2020: 15 · 2019: 19 · 2018: 17 · 2017: 16 · 2016: 20 · 2015: 4
- FWCI
- 15.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1 TR000040)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- D-serine, negative symptoms, schizophrenia, clinical high risk, prodromal psychosis, NMDA receptor modulation, serum cytokines, mechanism of action, early intervention
- MeSH terms
- Adolescent, Adult, Double-Blind Method, Female, Humans, Male, Schizophrenia, Serine, Receptors, N-Methyl-D-Aspartate, Treatment Outcome, Risk Assessment, Young Adult
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
