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 ResearchMeSH KeywordsAntidepressive AgentsDepressionDepressive Disorder, Treatment-ResistantHumansKetamineReceptors, N-Methyl-D-AspartateSynapsesConceptsMood 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 mechanismsDisordersTreatmentKetamine
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 ResearchMeSH KeywordsGlutamatesHallucinationsHumansKetamineLamotrigineMagnetic Resonance ImagingReceptors, N-Methyl-D-AspartateSchizophreniaConceptsThalamic 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
2020
A New Rapid-Acting Antidepressant
Krystal JH, Charney DS, Duman RS. A New Rapid-Acting Antidepressant. Cell 2020, 181: 7. PMID: 32243798, DOI: 10.1016/j.cell.2020.02.033.Peer-Reviewed Original ResearchMeSH KeywordsAntidepressive AgentsDepressive Disorder, Treatment-ResistantDrug ApprovalGABAergic NeuronsHumansKetamineReceptors, AMPAReceptors, N-Methyl-D-Aspartate
2017
Alcohol Triggers Reemergence of Ketamine-Like Experience in a Ketamine Ex-User
Chang F, Xu K, Huang MC, Krystal JH. Alcohol Triggers Reemergence of Ketamine-Like Experience in a Ketamine Ex-User. Journal Of Clinical Psychopharmacology 2017, 37: 110-112. PMID: 28027112, PMCID: PMC5193231, DOI: 10.1097/jcp.0000000000000635.Peer-Reviewed Original ResearchAdultCentral Nervous System DepressantsEthanolExcitatory Amino Acid AntagonistsHumansKetamineMaleReceptors, N-Methyl-D-AspartateSubstance-Related DisordersNMDA Glutamate Receptor Antagonism and the Heritable Risk for Alcoholism: New Insights from a Study of Nitrous Oxide
Krystal JH, Petrakis IL, O’Malley S, Krishnan-Sarin S, Pearlson G, Yoon G. NMDA Glutamate Receptor Antagonism and the Heritable Risk for Alcoholism: New Insights from a Study of Nitrous Oxide. The International Journal Of Neuropsychopharmacology 2017, 20: 351-353. PMID: 28158462, PMCID: PMC5409033, DOI: 10.1093/ijnp/pyw118.Peer-Reviewed Original ResearchMeSH KeywordsAlcoholismGlutamic AcidHumansNitrous OxideN-MethylaspartateReceptors, N-Methyl-D-Aspartate
2016
The Role of GluN2C-Containing NMDA Receptors in Ketamine's Psychotogenic Action and in Schizophrenia Models
Khlestova E, Johnson JW, Krystal JH, Lisman J. The Role of GluN2C-Containing NMDA Receptors in Ketamine's Psychotogenic Action and in Schizophrenia Models. Journal Of Neuroscience 2016, 36: 11151-11157. PMID: 27807157, PMCID: PMC5148234, DOI: 10.1523/jneurosci.1203-16.2016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainEvidence-Based MedicineHallucinogensHumansKetaminePsychoses, Substance-InducedReceptors, N-Methyl-D-AspartateSchizophreniaConceptsNMDAR antagonistsNMDA receptor hypofunction hypothesisDifferent NMDAR subtypesHealthy human subjectsSymptoms of schizophreniaPsychotogenic effectsNMDA receptorsNMDAR subtypesSchizophrenia modelKetamine's abilityNegative symptomsKetamineMultiple subtypesPsychotic statesPreferential involvementSchizophreniaAntagonistGluN2CSubtypesReceptorsEEG powerHuman subjectsNMDARSymptomsΔ oscillationsRole 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 ResearchMeSH KeywordsAcoustic StimulationAdultCerebral CortexCross-Over StudiesElectroencephalographyEvoked PotentialsFemaleHumansKetamineMaleReceptors, N-Methyl-D-AspartateSchizophreniaSchizophrenic PsychologySpeech PerceptionConceptsEvent-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 daysKETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS
Abdallah CG, Adams TG, Kelmendi B, Esterlis I, Sanacora G, Krystal JH. KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS. Depression And Anxiety 2016, 33: 689-697. PMID: 27062302, PMCID: PMC4961540, DOI: 10.1002/da.22501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsDepressive Disorder, MajorExcitatory Amino Acid AntagonistsHumansKetamineReceptors, N-Methyl-D-AspartateConceptsMajor depressive disorderAntidepressant effectsKetamine's mechanismN-methyl-D-aspartate receptor antagonistRapid-acting antidepressant effectsPrefrontal cortexSingle subanesthetic doseRapid antidepressant effectsTreatment-resistant depressionFull therapeutic effectEfficacy of ketamineKetamine's antidepressant effectsRapid acting antidepressantsFuture clinical prospectsGlutamate surgeTraditional antidepressantsAntidepressant medicationCascade of eventsReceptor antagonistSubanesthetic doseDepressive disorderClinical dataTherapeutic effectTreatment responseLimited efficacy
2015
Deconstructing N-Methyl-D-Aspartate Glutamate Receptor Contributions to Cortical Circuit Functions to Construct Better Hypotheses About the Pathophysiology of Schizophrenia
Krystal JH. Deconstructing N-Methyl-D-Aspartate Glutamate Receptor Contributions to Cortical Circuit Functions to Construct Better Hypotheses About the Pathophysiology of Schizophrenia. Biological Psychiatry 2015, 77: 508-510. PMID: 25687430, DOI: 10.1016/j.biopsych.2014.10.010.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsAlcoholismAnimalsDrug-Seeking BehaviorGlutamic AcidHumansMolecular Targeted TherapyProtein SubunitsReceptors, AMPAReceptors, Kainic AcidReceptors, N-Methyl-D-AspartateSubstance Withdrawal SyndromeConceptsGlutamate 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 receptorsDeep resequencing of 17 glutamate system genes identifies rare variants in DISC1 and GRIN2B affecting risk of opioid dependence
Xie P, Kranzler HR, Krystal JH, Farrer LA, Zhao H, Gelernter J. Deep resequencing of 17 glutamate system genes identifies rare variants in DISC1 and GRIN2B affecting risk of opioid dependence. Addiction Biology 2013, 19: 955-964. PMID: 23855403, PMCID: PMC3815683, DOI: 10.1111/adb.12072.Peer-Reviewed Original ResearchMeSH KeywordsBlack or African AmericanCase-Control StudiesGene FrequencyHumansNerve Tissue ProteinsOpioid-Related DisordersReceptors, N-Methyl-D-AspartateSchizophreniaSequence Analysis, DNAWhite PeopleConceptsOpioid dependenceSubstance dependenceRare variantsN-methyl-D-aspartate (NMDA) glutamate receptorsCo-occurring alcohol dependenceHealthy control subjectsControl subjectsNMDA systemOpioid abuseGlutamate receptorsSchizophrenia risk genesSD riskAlcohol dependenceSignificant associationCocaine dependenceAdditional subjectsOD riskRisk genesDISC1African AmericansFirst demonstrationCommon variantsRiskSubjectsMinor allele frequencyKetamine Effects on Memory Reconsolidation Favor a Learning Model of Delusions
Corlett PR, Cambridge V, Gardner JM, Piggot JS, Turner DC, Everitt JC, Arana FS, Morgan HL, Milton AL, Lee JL, Aitken MR, Dickinson A, Everitt BJ, Absalom AR, Adapa R, Subramanian N, Taylor JR, Krystal JH, Fletcher PC. Ketamine Effects on Memory Reconsolidation Favor a Learning Model of Delusions. PLOS ONE 2013, 8: e65088. PMID: 23776445, PMCID: PMC3680467, DOI: 10.1371/journal.pone.0065088.Peer-Reviewed Original ResearchMeSH KeywordsAdultAssociation LearningCase-Control StudiesConditioning, ClassicalDelusionsFearFemaleHumansKetamineMagnetic Resonance ImagingMaleMemoryReceptors, N-Methyl-D-AspartateConceptsMemory strengthMemory reconsolidationIndividual brain responsesError-dependent learningPsychotogenic effectsSubsequent memoryFear memoryBizarre beliefsBrain responsesDelusional beliefsPrediction errorImpact of ketamineIndividual vulnerabilityBrain signalsSubject studyReconsolidationIndependent samplesLearning procedureMemoryKetamine effectsDelusionsBeliefsPlacebo administrationPsychosisNMDA receptor antagonistEffects of memantine on event-related potential, oscillations, and complexity in individuals with and without family histories of alcoholism.
Narayanan B, Stevens MC, Jiantonio RE, Krystal JH, Pearlson GD. Effects of memantine on event-related potential, oscillations, and complexity in individuals with and without family histories of alcoholism. Journal Of Studies On Alcohol And Drugs 2013, 74: 245-57. PMID: 23384372, PMCID: PMC3568163, DOI: 10.15288/jsad.2013.74.245.Peer-Reviewed Original ResearchConceptsNMDA receptor functionFHN subjectsFamily historyReceptor functionFHP individualsAlpha activityN-methyl-D-aspartate receptor functionNMDA receptor antagonist memantineEffects of memantineAuditory oddball discrimination taskPositive family historyFamily history-negative subjectsEvent-related potentialsAlcoholism family historyCortical information processingOddball discrimination taskFHN individualsMemantine administrationAcute effectsDrug interactionsP3b amplitudeFHP subjectsMemantineSeparate occasionsTheta activity
2012
Linking Microcircuit Dysfunction to Cognitive Impairment: Effects of Disinhibition Associated with Schizophrenia in a Cortical Working Memory Model
Murray JD, Anticevic A, Gancsos M, Ichinose M, Corlett PR, Krystal JH, Wang XJ. Linking Microcircuit Dysfunction to Cognitive Impairment: Effects of Disinhibition Associated with Schizophrenia in a Cortical Working Memory Model. Cerebral Cortex 2012, 24: 859-872. PMID: 23203979, PMCID: PMC3948492, DOI: 10.1093/cercor/bhs370.Peer-Reviewed Original ResearchMeSH KeywordsCerebral CortexCognition DisordersComputer SimulationHumansMemory DisordersMemory, Short-TermModels, NeurologicalNerve NetNeuronsReceptors, N-Methyl-D-AspartateConceptsWorking memoryNeural levelSpatial WM taskWorking Memory ModelSpatial working memoryPersistent activity patternsWM representationsWM taskWM maintenanceBrain mechanismsWM deficitsMicrocircuit dysfunctionPrefrontal cortexCognitive deficitsBehavioral dataMemory modelBehavioral variabilityWM deteriorationCognitive impairmentCortical disinhibitionExcitation-inhibition balanceMain model predictionsDisinhibitionBehavioral deficitsDeficitsNMDA 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 modelingCapturing the Angel in “Angel Dust”: Twenty Years of Translational Neuroscience Studies of NMDA Receptor Antagonists in Animals and Humans
Moghaddam B, Krystal JH. Capturing the Angel in “Angel Dust”: Twenty Years of Translational Neuroscience Studies of NMDA Receptor Antagonists in Animals and Humans. Schizophrenia Bulletin 2012, 38: 942-949. PMID: 22899397, PMCID: PMC3446228, DOI: 10.1093/schbul/sbs075.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAnimalsAntipsychotic AgentsBrief Psychiatric Rating ScaleCerebral CortexDisease Models, AnimalDopamineEmotionsGlutamic AcidHumansKetamineNeurosciencesPhencyclidinePsychoses, Substance-InducedReceptor, Metabotropic Glutamate 5Receptors, Dopamine D2Receptors, Metabotropic GlutamateReceptors, N-Methyl-D-AspartateSchizophreniaSynapsesTranslational Research, BiomedicalConceptsNMDA receptor antagonistReceptor antagonistDopamine hypothesisN-methyl-D-aspartate receptor antagonistGlutamate synaptic functionTranslational neuroscience studiesTreatment of schizophreniaPathophysiology of schizophreniaPotential treatment targetPotential new targetsDopamine antagonistsCortical functionAnimal studiesTreatment targetsClinical testingSynaptic functionAntagonistTranslational toolSchizophreniaTranslational research fundingTranslational researchPotential mechanismsNew targetsAngel dustSystems neuroscienceEnhancing Prolonged Exposure Therapy for Posttraumatic Stress Disorder with D-Cycloserine: Further Support for Treatments That Promote Experience-Dependent Neuroplasticity
Krystal JH. Enhancing Prolonged Exposure Therapy for Posttraumatic Stress Disorder with D-Cycloserine: Further Support for Treatments That Promote Experience-Dependent Neuroplasticity. Biological Psychiatry 2012, 71: 932-934. PMID: 22579302, DOI: 10.1016/j.biopsych.2012.03.031.Peer-Reviewed Original ResearchMeSH KeywordsAntimetabolitesCycloserineFemaleHumansImplosive TherapyMaleReceptors, N-Methyl-D-AspartateStress Disorders, Post-Traumatic
2011
Glutamatergic Modulation of Auditory Information Processing in the Human Brain
Gunduz-Bruce H, Reinhart RM, Roach BJ, Gueorguieva R, Oliver S, D'Souza DC, Ford JM, Krystal JH, Mathalon DH. Glutamatergic Modulation of Auditory Information Processing in the Human Brain. Biological Psychiatry 2011, 71: 969-977. PMID: 22036036, PMCID: PMC3290754, DOI: 10.1016/j.biopsych.2011.09.031.Peer-Reviewed Original ResearchConceptsN-acetylcysteineAuditory mismatch negativityReceptor antagonistN-methyl-D-aspartate receptor antagonistAspartate glutamate receptor antagonistOral N-acetylcysteinePlacebo-controlled studyGlutamate receptor antagonistsEffects of ketamineInfusion of salineMismatch negativityTest dayMMN amplitudeCystine-glutamate exchangerAuditory information processingP300 event-related potentialGlutamatergic modulationCognitive enhancing agentsEvent-related potentialsKetamine effectsHealthy volunteersHealthy humansSchizophrenia patientsPositive symptomsKetamine
2010
The interplay of cannabinoid and NMDA glutamate receptor systems in humans: Preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects
Hallak JE, Dursun SM, Bosi DC, de Macedo LR, Machado-de-Sousa JP, Abrão J, Crippa JA, McGuire P, Krystal JH, Baker GB, Zuardi AW. The interplay of cannabinoid and NMDA glutamate receptor systems in humans: Preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects. Progress In Neuro-Psychopharmacology And Biological Psychiatry 2010, 35: 198-202. PMID: 21062637, DOI: 10.1016/j.pnpbp.2010.11.002.Peer-Reviewed Original ResearchConceptsBrief Psychiatric Rating ScaleHealthy human subjectsGlutamate receptor systemMale healthy volunteersNMDA receptor antagonistEffects of ketamineTreatment of schizophreniaPsychiatric Rating ScaleHuman subjectsWeak partial agonistNon-significant trendKetamine administrationReceptor antagonistEndocannabinoid systemHealthy volunteersPartial agonistActivation subscalePsychiatric conditionsKetamineRandomized orderReceptor systemBehavioral effectsRating ScaleCannabidiolPreliminary evidenceN- methyl-D-aspartate Glutamate Receptor Antagonists and the Promise of Rapid-Acting Antidepressants
Krystal JH. N- methyl-D-aspartate Glutamate Receptor Antagonists and the Promise of Rapid-Acting Antidepressants. JAMA Psychiatry 2010, 67: 1110-1111. PMID: 21041611, DOI: 10.1001/archgenpsychiatry.2010.138.Peer-Reviewed Original Research