2025
N-methyl-d-aspartate receptor hypofunction causes recurrent and transient failures of perceptual inference
Weilnhammer V, Rothkirch M, Yilmaz D, Fritsch M, Ptasczynski L, Reichenbach K, Roediger L, Corlett P, Sterzer P. N-methyl-d-aspartate receptor hypofunction causes recurrent and transient failures of perceptual inference. Brain 2025, 148: 1531-1539. PMID: 39821016, PMCID: PMC12073972, DOI: 10.1093/brain/awaf011.Peer-Reviewed Original ResearchN-methyl-D-aspartate receptorsN-methyl-D-aspartateN-methyl-D-aspartate receptor hypofunctionS-ketamineSymptoms of schizophreniaDissociation of perceptionsHealthy human participantsExternal sensory signalsReceptor hypofunctionSensory signalsNMDAR hypofunctionPerceptual inferenceCase-control studyInternal predictionsHuman participantsPlacebo-ControlledDouble-blindCross-over experimentHypofunctionSchizophreniaParanoidPerceptionSCZ
2024
Neuroimaging Biomarkers for Drug Discovery and Development in Schizophrenia
Preller K, Scholpp J, Wunder A, Rosenbrock H. Neuroimaging Biomarkers for Drug Discovery and Development in Schizophrenia. Biological Psychiatry 2024, 96: 666-673. PMID: 38272287, DOI: 10.1016/j.biopsych.2024.01.009.Peer-Reviewed Original ResearchNMDA receptor hypofunctionPsychosis spectrum disordersNeuroimaging data acquisitionField of neuroimagingNegative symptomsPharmacological neuroimagingPositive symptomsReceptor hypofunctionPsychotic disordersNeuroimaging resultsSpectrum disorderNeuroimaging technologiesNeuroimaging biomarkersSchizophreniaNeuroimagingPathophysiology of symptomsDrug developmentDecades of researchTarget engagementClinical drug developmentPredictive biomarkersDisordersSymptomsHealthy volunteersDose selection
2023
Randomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia
Surti T, Ranganathan M, Johannesen J, Gueorguieva R, Deaso E, Kenney J, Krystal J, D'Souza D. Randomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia. Schizophrenia Research 2023, 256: 36-43. PMID: 37141764, PMCID: PMC10257994, DOI: 10.1016/j.schres.2023.04.010.Peer-Reviewed Original ResearchConceptsGlycine transporter 1Cytochrome P450 2D6 extensive metabolizersGlyT1 inhibitorsWeeks of washoutWeeks of CTMedication adherenceReceptor hypofunctionImpaired neuroplasticityPharmacodynamic variabilityNMDAR functionExtensive metabolizersTreatment periodPsychotic symptomsStable outpatientsCognitive impairmentGlyT1 occupancyTransporter 1CTNeuroplasticityCognitive training strategiesSchizophreniaComputerized CTCognitive performanceAugmentation studiesGreater improvement
2022
Validation of ketamine as a pharmacological model of thalamic dysconnectivity across the illness course of schizophrenia
Abram SV, Roach BJ, Fryer SL, Calhoun VD, Preda A, van Erp TGM, Bustillo JR, Lim KO, Loewy RL, Stuart BK, Krystal JH, Ford JM, Mathalon DH. Validation of ketamine as a pharmacological model of thalamic dysconnectivity across the illness course of schizophrenia. Molecular Psychiatry 2022, 27: 2448-2456. PMID: 35422467, PMCID: PMC9135621, DOI: 10.1038/s41380-022-01502-0.Peer-Reviewed Original ResearchConceptsThalamic dysconnectivityHealthy controlsDysconnectivity patternsIllness courseHealthy volunteersN-methyl-D-aspartate (NMDA) receptor hypofunctionResting-state functional magnetic resonance imaging studyHallucination severityEarly illness schizophreniaExcess glutamate releaseGlutamate release inhibitorNMDAR antagonist ketaminePlacebo-controlled studyMagnetic resonance imaging studySub-anesthetic dosesSchizophrenia-like symptomsResonance imaging studyFunctional magnetic resonance imaging studyKetamine infusionGlutamate releaseNMDAR hypofunctionReceptor hypofunctionKetamine effectsThalamic connectivityRelease inhibitor
2021
Effects of Altered Excitation-Inhibition Balance on Decision Making in a Cortical Circuit Model
Lam NH, Borduqui T, Hallak J, Roque A, Anticevic A, Krystal JH, Wang XJ, Murray JD. Effects of Altered Excitation-Inhibition Balance on Decision Making in a Cortical Circuit Model. Journal Of Neuroscience 2021, 42: 1035-1053. PMID: 34887320, PMCID: PMC8824494, DOI: 10.1523/jneurosci.1371-20.2021.Peer-Reviewed Original ResearchConceptsCortical circuitsCognitive deficitsCortical circuit modelAltered excitation-inhibition balanceExcitatory pyramidal neuronsNMDA receptor hypofunctionCerebral cortical circuitsExcitation-inhibition balancePyramidal neuronsReceptor hypofunctionDistinct time coursesSynaptic excitationInhibitory interneuronsMultiple neuropsychiatric disordersBehavioral deficitsSynaptic balanceSynaptic levelLatest evidenceNeuropsychiatric disordersCognitive functionCircuit mechanismsBehavioral effectsPsychometric performanceBehavioral levelTask paradigm
2020
A circuit mechanism for decision-making biases and NMDA receptor hypofunction
Cavanagh SE, Lam NH, Murray JD, Hunt LT, Kennerley SW. A circuit mechanism for decision-making biases and NMDA receptor hypofunction. ELife 2020, 9: e53664. PMID: 32988455, PMCID: PMC7524553, DOI: 10.7554/elife.53664.Peer-Reviewed Original ResearchConceptsNMDA-R hypofunctionCortical excitation/inhibition balanceExcitation/inhibition balanceNMDA receptor hypofunctionNMDA receptor antagonismNMDA-R antagonist ketamineCircuit-level mechanismsPotential neural mechanismsNeuropsychiatric symptomsReceptor hypofunctionReceptor antagonismInhibition balanceExcitatory neuronsInhibitory neuronsPharmacological modelPharmacological manipulationNeuropsychiatric disordersCircuit mechanismsHypofunctionVariable evidenceNeural mechanismsKetamineNeuronsBehavioral psychophysicsPossible effects
2018
Early Correction of N-Methyl-D-Aspartate Receptor Function Improves Autistic-like Social Behaviors in Adult Shank2 −/− Mice
Chung C, Ha S, Kang H, Lee J, Um SM, Yan H, Yoo YE, Yoo T, Jung H, Lee D, Lee E, Lee S, Kim J, Kim R, Kwon Y, Kim W, Kim H, Duffney L, Kim D, Mah W, Won H, Mo S, Kim JY, Lim CS, Kaang BK, Boeckers TM, Chung Y, Kim H, Jiang YH, Kim E. Early Correction of N-Methyl-D-Aspartate Receptor Function Improves Autistic-like Social Behaviors in Adult Shank2 −/− Mice. Biological Psychiatry 2018, 85: 534-543. PMID: 30466882, PMCID: PMC6420362, DOI: 10.1016/j.biopsych.2018.09.025.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderSocial behaviorSpectrum disorderAutistic-like phenotypesLate pathophysiologyNMDAR hypofunctionHuman autism spectrum disorderNMDAR hyperfunctionN-methyl-D-aspartate (NMDA) receptor hypofunctionAutistic-like behaviorsNMDAR antagonist memantineAspartate Receptor FunctionEarly pathophysiologyPup stageEarly correctionAdult miceBehavioral analysisNMDAR dysfunctionPostnatal day 21Receptor hypofunctionChronic suppressionAnimal studiesDay 21HypofunctionDisorders
2017
Interactive effects of an N-methyl-d-aspartate receptor antagonist and a nicotinic acetylcholine receptor agonist on mismatch negativity: Implications for schizophrenia
Hamilton HK, D'Souza DC, Ford JM, Roach BJ, Kort NS, Ahn KH, Bhakta S, Ranganathan M, Mathalon DH. Interactive effects of an N-methyl-d-aspartate receptor antagonist and a nicotinic acetylcholine receptor agonist on mismatch negativity: Implications for schizophrenia. Schizophrenia Research 2017, 191: 87-94. PMID: 28711472, PMCID: PMC5745273, DOI: 10.1016/j.schres.2017.06.040.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptor agonistAcetylcholine receptor agonistReceptor agonistHealthy volunteersN-methyl-D-aspartate receptor antagonistPathophysiology of schizophreniaAuditory processing abnormalitiesProfile of effectsMMN amplitudeNicotine preventsNicotine administrationReceptor hypofunctionNMDAR hypofunctionNMDAR antagonistsReceptor antagonistMismatch negativity (MMN) event-related potential (ERP) componentPresent doseNicotinic agonistsSchizophrenia patientsCigarette useKetamineDeviant typesNeurophysiological effectsSecondary analysisMMN abnormalities
2015
Reciprocal Alterations in Regulator of G Protein Signaling 4 and microRNA16 in Schizophrenia
Kimoto S, Glausier J, Fish K, Volk D, Bazmi H, Arion D, Datta D, Lewis D. Reciprocal Alterations in Regulator of G Protein Signaling 4 and microRNA16 in Schizophrenia. Schizophrenia Bulletin 2015, 42: 396-405. PMID: 26424323, PMCID: PMC4753606, DOI: 10.1093/schbul/sbv139.Peer-Reviewed Original ResearchConceptsG protein-coupled receptorsDorsolateral prefrontal cortexG Protein Signaling 4Schizophrenia subjectsRGS4 mRNANMDAR hypofunctionNMDAR activityProtein levelsN-methyl-D-aspartate (NMDA) receptor hypofunctionRole of RGS4Pathology of schizophreniaHealthy comparison subjectsRGS4 mRNA levelsLevels of miR16RGS4 levelsProtein-coupled receptorsPyramidal neuronsReceptor hypofunctionPyramidal cellsComparison subjectsIncreased expressionHypofunctionPrefrontal cortexSchizophreniaMRNA levelsAbnormal Gamma Oscillations in N-Methyl-D-Aspartate Receptor Hypofunction Models of Schizophrenia
Jadi MP, Behrens MM, Sejnowski TJ. Abnormal Gamma Oscillations in N-Methyl-D-Aspartate Receptor Hypofunction Models of Schizophrenia. Biological Psychiatry 2015, 79: 716-726. PMID: 26281716, PMCID: PMC4720598, DOI: 10.1016/j.biopsych.2015.07.005.Peer-Reviewed Original ResearchConceptsInhibitory neuronsGamma-band oscillationsNMDAR hypofunctionAnimal modelsN-methyl-D-aspartate (NMDA) receptor hypofunctionParvalbumin-expressing inhibitory neuronsAbnormal gamma oscillationsReceptor hypofunctionNMDAR antagonistsHypofunctionVisual cortexSZ symptomsSchizophreniaGamma oscillationsGenetic knockoutHuman subjectsBand oscillationsSymptomsNeuronsMagnetoencephalography (MEG) signalsPatientsAntagonistN-methylCortexNeuropharmacology
2014
Effects of Nicotine on the Neurophysiological and Behavioral Effects of Ketamine in Humans
Mathalon DH, Ahn KH, Perry EB, Cho HS, Roach BJ, Blais RK, Bhakta S, Ranganathan M, Ford JM, D’Souza D. Effects of Nicotine on the Neurophysiological and Behavioral Effects of Ketamine in Humans. Frontiers In Psychiatry 2014, 5: 3. PMID: 24478731, PMCID: PMC3900858, DOI: 10.3389/fpsyt.2014.00003.Peer-Reviewed Original ResearchAuditory event-related brain potentialsEvent-related brain potentialsTest sessionsBehavioral effectsAmplitude of P3aDissociative Symptoms ScaleNicotinic acetylcholine receptor stimulationBrain potentialsP3b amplitudeMMN amplitudeP3a amplitudeNovel stimuliNeurophysiological measuresNMDA receptor hypofunctionN-methyl-D-aspartate (NMDA) receptor hypofunctionNegative Syndrome ScaleEffects of nicotineReceptor hypofunctionNeurocognitive impairmentCounterbalanced mannerP3aSchizophrenia-like effectsSyndrome ScaleInjections of nicotineInteraction of ketamine
2013
Rhythmic theta and delta activity of cortical and hippocampal neuronal networks in genetically or pharmacologically induced N-methyl-d-aspartate receptor hypofunction under urethane anesthesia
Kiss T, Feng J, Hoffmann W, Shaffer C, Hajós M. Rhythmic theta and delta activity of cortical and hippocampal neuronal networks in genetically or pharmacologically induced N-methyl-d-aspartate receptor hypofunction under urethane anesthesia. Neuroscience 2013, 237: 255-267. PMID: 23396086, DOI: 10.1016/j.neuroscience.2013.01.058.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsBiphenyl CompoundsCarrier ProteinsCerebral CortexDelta RhythmDizocilpine MaleateElectric StimulationElectroencephalographyExcitatory Amino Acid AgonistsExcitatory Amino Acid AntagonistsHippocampusMiceMice, Inbred C57BLMice, KnockoutNerve Tissue ProteinsNeuronsRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateSulfonamidesTheta RhythmUrethaneConceptsN-methyl-D-aspartate receptorsMK-801WT miceN-methyl-D-aspartate (NMDA) receptor hypofunctionTheta oscillationsMK-801 challengeWild-type miceField potentialsHippocampal field potentialsHippocampal neuronal networksPreclinical disease modelsSymptoms of schizophreniaNeuronal network oscillationsHippocampal theta oscillationsRhythmic thetaVentro-medial prefrontal cortexHippocampal theta powerNMDAR hypofunctionReceptor hypofunctionNMDAR expressionUrethane anesthesiaGlutamate neurotransmissionHealthy subjectsDelta activityHypomorphic mice
2011
The Novel Antipsychotic Drug Lurasidone Enhances N-Methyl-d-aspartate Receptor-Mediated Synaptic Responses
Yuen EY, Li X, Wei J, Horiguchi M, Meltzer HY, Yan Z. The Novel Antipsychotic Drug Lurasidone Enhances N-Methyl-d-aspartate Receptor-Mediated Synaptic Responses. Molecular Pharmacology 2011, 81: 113-119. PMID: 22072817, PMCID: PMC3263951, DOI: 10.1124/mol.111.076141.Peer-Reviewed Original ResearchConceptsAtypical antipsychotic drugsEffect of lurasidoneSynaptic responsesVivo administrationN-methyl-D-aspartate (NMDA) receptor hypofunctionShort-term administrationCortical pyramidal neuronsAtypical APDsReceptor antagonist haloperidolAtypical APD clozapineKey molecular targetsSubchronic administrationPyramidal neuronsReceptor hypofunctionReceptor antagonismReceptor antagonistAntagonist haloperidolNMDAR responsesNMDAR synaptic functionAntipsychotic drugsNR2B subunitSerotonin 5Noncompetitive antagonistLurasidoneCognitive impairment
2001
NMDA receptor regulation of memory and behavior in humans
Newcomer J, Krystal J. NMDA receptor regulation of memory and behavior in humans. Hippocampus 2001, 11: 529-542. PMID: 11732706, DOI: 10.1002/hipo.1069.Peer-Reviewed Original ResearchConceptsNMDA receptor hypofunctionReceptor hypofunctionN-methyl-D-aspartate (NMDA) receptor hypofunctionNMDA receptor antagonist drugsNMDA receptor systemAge-related decreaseNMDA receptor regulationReceptor antagonist drugsClinical syndromeNeuropathological featuresNMDA antagonistsNMDA receptorsNeurotoxic processesAntagonist drugsAdult brainHypofunctionBehavioral dysfunctionHuman studiesRange of effectsReceptor regulationReceptor systemBrain functionBrain ageAdverse effectsDisease conditions
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply