2023
Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms
Krystal J, Kavalali E, Monteggia L. Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms. Neuropsychopharmacology 2023, 49: 41-50. PMID: 37488280, PMCID: PMC10700627, DOI: 10.1038/s41386-023-01629-w.Peer-Reviewed Original ResearchConceptsMood disordersEffective treatmentN-methyl-D-aspartate receptorsGlutamatergic N-methyl-D-aspartate receptorRapid antidepressant effectsTreatment-resistant depressionKey clinical aspectsRapid antidepressant actionsNovel effective treatmentsSynaptic signaling mechanismsMore effective treatmentsSynaptic plasticity mechanismsOpen channel blockerAntidepressant actionAntidepressant effectsKetamine effectsChannel blockersClinical aspectsClinical practiceNew treatmentsNeuropsychiatric disordersCircuit mechanismsDisordersTreatmentKetamineEfficacy and Safety of Iclepertin (BI 425809) in Patients With Schizophrenia: CONNEX, A Phase III Randomized Controlled Trial Program
Wunderlich G, Blahova Z, Hake S, Ikezawa S, Marder S, Falkai P, Krystal J. Efficacy and Safety of Iclepertin (BI 425809) in Patients With Schizophrenia: CONNEX, A Phase III Randomized Controlled Trial Program. CNS Spectrums 2023, 28: 229-229. DOI: 10.1017/s1092852923001530.Peer-Reviewed Original ResearchCognitive impairmentEfficacy endpointVirtual Reality Functional Capacity Assessment ToolCognitive symptomsPlacebo-controlled parallel-group trialKey secondary efficacy endpointsN-methyl-D-aspartate receptorsSafety extension studyPrimary efficacy endpointSecondary efficacy endpointsParallel-group trialPhase II trialPoor functional outcomeComposite T-scoreMulti-center studyPhase III programRole of glutamateLong-term safetyScale total scoreDemonstration of efficacyGlycine transporter 1Industry-sponsored studiesCapacity assessment toolII trialTolerability dataEfficacy and safety of iclepertin (BI 425809) in patients with schizophrenia: CONNEX, a Phase III randomised controlled trial programme
Falkai P, Reuteman-Fowler C, Blahova Z, Ikezawa S, Marder S, Krystal J. Efficacy and safety of iclepertin (BI 425809) in patients with schizophrenia: CONNEX, a Phase III randomised controlled trial programme. European Psychiatry 2023, 66: s637-s637. PMCID: PMC10661489, DOI: 10.1192/j.eurpsy.2023.1325.Peer-Reviewed Original ResearchCognitive impairmentEfficacy endpointVirtual Reality Functional Capacity Assessment ToolCognitive symptomsJazz PharmaceuticalsPlacebo-controlled parallel-group trialBoehringer IngelheimKey secondary efficacy endpointsN-methyl-D-aspartate receptorsSafety extension studyPrimary efficacy endpointSecondary efficacy endpointsParallel-group trialPhase II trialPoor functional outcomeComposite T-scorePhase III programRole of glutamateLong-term safetyScale total scoreGrant/research supportDemonstration of efficacyGlycine transporter 1Industry-sponsored studiesCapacity assessment tool
2020
Impaired Potentiation of Theta Oscillations During a Visual Cortical Plasticity Paradigm in Individuals With Schizophrenia
Hamilton HK, Roach BJ, Cavus I, Teyler TJ, Clapp WC, Ford JM, Tarakci E, Krystal JH, Mathalon DH. Impaired Potentiation of Theta Oscillations During a Visual Cortical Plasticity Paradigm in Individuals With Schizophrenia. Frontiers In Psychiatry 2020, 11: 590567. PMID: 33391054, PMCID: PMC7772351, DOI: 10.3389/fpsyt.2020.590567.Peer-Reviewed Original ResearchLong-term potentiationN-methyl-D-aspartate receptorsHealthy controlsNeuroplastic changesPlasticity paradigmsHigh-frequency electrical stimulationExperience-dependent synaptic plasticityVisual cortical plasticityPathophysiology of schizophreniaHigh-frequency stimulationNMDA receptor dysfunctionFrequency electrical stimulationTheta oscillationsVisual stimuliImpaired potentiationGlutamatergic transmissionReceptor dysfunctionImpaired neuroplasticityEvent-related EEG oscillationsNMDAR hypofunctionCortical plasticityVEP amplitudeAnimal modelsElectrical stimulationWhite checkerboard stimuli
2016
Role of N-Methyl-D-Aspartate Receptors in Action-Based Predictive Coding Deficits in Schizophrenia
Kort NS, Ford JM, Roach BJ, Gunduz-Bruce H, Krystal JH, Jaeger J, Reinhart RM, Mathalon DH. Role of N-Methyl-D-Aspartate Receptors in Action-Based Predictive Coding Deficits in Schizophrenia. Biological Psychiatry 2016, 81: 514-524. PMID: 27647218, PMCID: PMC5203970, DOI: 10.1016/j.biopsych.2016.06.019.Peer-Reviewed Original ResearchConceptsEvent-related potentialsPredictive codingN1 suppressionN1 amplitudePredictive coding deficitsSelf-generated speechSchizophrenia patientsAuditory cortical responsesAuditory predictive codingSelf-produced vocalizationsNMDAR hypofunctionEffects of schizophreniaSpeech soundsTheorized contributionN1 componentHealthy volunteersPassive playbackCognitive deficitsN-methyl-D-aspartate receptorsPutative measureTalk/Cortical responsesHealthy control volunteersCase-control studySaline days
2013
Glutamatergic targets for new alcohol medications
Holmes A, Spanagel R, Krystal JH. Glutamatergic targets for new alcohol medications. Psychopharmacology 2013, 229: 539-554. PMID: 23995381, PMCID: PMC3811052, DOI: 10.1007/s00213-013-3226-2.Peer-Reviewed Original ResearchConceptsGlutamate systemGlycineB siteAlcohol-related behaviorsNMDA receptorsAlcohol abuseAlcohol consumptionN-methyl-D-aspartate receptorsChronic alcohol exposureElevated extracellular glutamatePathophysiology of alcoholismAMPA receptor subunitsAlcohol use disorderNovel pharmacotherapeutic approachesEffects of alcoholAlcohol medicationsBlocking NMDAHyperglutamatergic stateMetabotropic receptorsPharmacotherapeutic approachesAlcohol exposureExcess glutamateExtracellular glutamateGlutamate receptorsPreclinical studiesKainate receptors
2012
NMDA receptor function in large-scale anticorrelated neural systems with implications for cognition and schizophrenia
Anticevic A, Gancsos M, Murray JD, Repovs G, Driesen NR, Ennis DJ, Niciu MJ, Morgan PT, Surti TS, Bloch MH, Ramani R, Smith MA, Wang XJ, Krystal JH, Corlett PR. NMDA receptor function in large-scale anticorrelated neural systems with implications for cognition and schizophrenia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 16720-16725. PMID: 23012427, PMCID: PMC3478611, DOI: 10.1073/pnas.1208494109.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlgorithmsBrainCognitionDouble-Blind MethodExcitatory Amino Acid AntagonistsFemaleHumansInfusions, IntravenousKetamineMagnetic Resonance ImagingMaleMemoryModels, NeurologicalPattern Recognition, VisualPsychomotor PerformanceReceptors, N-Methyl-D-AspartateSchizophreniaSynaptic TransmissionYoung AdultConceptsNeural systemsLarge-scale brain systemsTask-dependent activationN-methyl-D-aspartate receptorsRealistic computational modelingSevere neuropsychiatric illnessNMDA glutamate receptor antagonistGlutamate receptor antagonistsBrain systemsNMDA receptor functionTask performanceMultiple interacting regionsCognitionCortical disinhibitionGlutamatergic neurotransmissionReceptor antagonistCortical computationGlutamate's roleReciprocal relationshipNeuropsychiatric illnessLocal circuitsReceptor functionSchizophreniaPresent findingsComputational modeling
2008
Relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy—a [123I]CNS-1261 SPET study
Stone JM, Erlandsson K, Arstad E, Squassante L, Teneggi V, Bressan RA, Krystal JH, Ell PJ, Pilowsky LS. Relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy—a [123I]CNS-1261 SPET study. Psychopharmacology 2008, 197: 401-408. PMID: 18176855, DOI: 10.1007/s00213-007-1047-x.Peer-Reviewed Original ResearchMeSH KeywordsAdultBrief Psychiatric Rating ScaleDose-Response Relationship, DrugGuanidinesHumansInfusions, IntravenousIodine RadioisotopesKetamineMalePrefrontal CortexPsychoses, Substance-InducedReceptors, N-Methyl-D-AspartateSchizophreniaSingle-Blind MethodTomography, Emission-Computed, Single-PhotonConceptsBrief Psychiatric Rating ScaleVolume of distributionNMDA receptorsPsychotic symptomsN-methyl-D-aspartate receptorsKetamine-induced psychotic symptomsSingle photon emission tomographyNMDA receptor bindingEffects of ketamineNegative subscaleHealthy human controlsPsychiatric Rating ScaleNegative psychotic symptomsInferior frontal cortexKetamine administrationBolus infusionHealthy controls
2005
Impact of Schizophrenia and Chronic Antipsychotic Treatment on [123I]CNS-1261 Binding to N-Methyl-D-Aspartate Receptors In Vivo
Bressan RA, Erlandsson K, Stone JM, Mulligan RS, Krystal JH, Ell PJ, Pilowsky LS. Impact of Schizophrenia and Chronic Antipsychotic Treatment on [123I]CNS-1261 Binding to N-Methyl-D-Aspartate Receptors In Vivo. Biological Psychiatry 2005, 58: 41-46. PMID: 15992521, DOI: 10.1016/j.biopsych.2005.03.016.Peer-Reviewed Original ResearchConceptsHealthy control subjectsTypical antipsychoticsControl subjectsN-methyl-D-aspartate receptor functionN-methyl-D-aspartate receptorsAntipsychotic drug discoveryChronic antipsychotic treatmentDrug-free patientsImpact of schizophreniaNMDA receptor activityHealthy normal volunteersClozapine treatmentAntipsychotic treatmentGlutamatergic systemPatient groupAntipsychotic drugsNonsignificant reductionNMDA receptorsNormal volunteersSchizophrenia patientsControl groupReceptor activityBrain regionsReceptor functionTomography radiotracer