2018
2. MICROCIRCUITS, MACROCIRCUITS, AND CORTICOL DYSFUNCTION IN SCHIZOPHRENIA: A COMPUTATIONAL AND TRANSLATIONAL NEUROSCIENCE PERSPECTIVE
Krystal J. 2. MICROCIRCUITS, MACROCIRCUITS, AND CORTICOL DYSFUNCTION IN SCHIZOPHRENIA: A COMPUTATIONAL AND TRANSLATIONAL NEUROSCIENCE PERSPECTIVE. Schizophrenia Bulletin 2018, 44: s1-s1. PMCID: PMC5887654, DOI: 10.1093/schbul/sby014.001.Peer-Reviewed Original ResearchNMDA glutamate receptorsNMDA receptor antagonistCortical functional connectivityPathophysiology of schizophreniaReceptor antagonistTranslational neuroscience perspectiveGlutamate receptorsHealthy humansAnimal modelsSchizophrenia patientsMemory impairmentNeuropsychiatric disordersSynaptic signalingFunctional connectivityNovel therapeuticsSchizophreniaDisordersPresentationPatientsPathophysiologyDysfunctionKetamineAntagonistSymptomsAbnormalities
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 ResearchConceptsNMDAR antagonistsNMDA receptor hypofunction hypothesisDifferent NMDAR subtypesHealthy human subjectsSymptoms of schizophreniaPsychotogenic effectsNMDA receptorsNMDAR subtypesSchizophrenia modelKetamine's abilityNegative symptomsKetamineMultiple subtypesPsychotic statesPreferential involvementSchizophreniaAntagonistGluN2CSubtypesReceptorsEEG powerHuman subjectsNMDARSymptomsΔ oscillations
2012
Capturing 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 neuroscience
2005
Absence of behavioral sensitization in healthy human subjects following repeated exposure to ketamine
Cho HS, D’Souza D, Gueorguieva R, Perry EB, Madonick S, Karper LP, Abi-Dargham A, Belger A, Abi-Saab W, Lipschitz D, Bennet A, Seibyl JP, Krystal JH. Absence of behavioral sensitization in healthy human subjects following repeated exposure to ketamine. Psychopharmacology 2005, 179: 136-143. PMID: 15682309, DOI: 10.1007/s00213-004-2066-5.Peer-Reviewed Original ResearchConceptsHealthy human subjectsBehavioral sensitizationReceptor antagonistN-methyl-D-aspartate (NMDA) glutamate receptor antagonistBehavioral effectsHuman subjectsGlutamate receptor antagonistsNMDA receptor antagonistConclusionsThe current dataEvidence of sensitizationRetrospective studyKetamine administrationOutcome measuresNegative symptomsObjectivesThe purposePrevious exposureFirst exposureKetamineSensitizationAntagonistExposurePerceptual alterationsCurrent dataSeparate studiesSubjects
2003
NMDA receptor antagonist effects, cortical glutamatergic function, and schizophrenia: toward a paradigm shift in medication development
Krystal JH, D'Souza DC, Mathalon D, Perry E, Belger A, Hoffman R. NMDA receptor antagonist effects, cortical glutamatergic function, and schizophrenia: toward a paradigm shift in medication development. Psychopharmacology 2003, 169: 215-233. PMID: 12955285, DOI: 10.1007/s00213-003-1582-z.Peer-Reviewed Original ResearchConceptsTreatment of schizophreniaReceptor antagonistN-methyl-D-aspartate (NMDA) glutamate receptor antagonistPharmacotherapy of schizophreniaGlutamate receptor antagonistsReceptor antagonist effectsNMDA receptor antagonistNMDA receptor antagonist effectsNMDA receptor contributionTranslational Neuroscience ApproachGlutamatergic activityGlutamatergic functionNew medicationsClinical studiesReceptor contributionTherapeutic implicationsMedication developmentCortical connectivityAntagonist effectsAntagonist responseNew treatment insightsSchizophreniaModel psychosisTreatment insightsAntagonistAltered NMDA Glutamate Receptor Antagonist Response in Recovering Ethanol-Dependent Patients
Krystal JH, Petrakis IL, Limoncelli D, Webb E, Gueorgueva R, D'Souza DC, Boutros NN, Trevisan L, Charney DS. Altered NMDA Glutamate Receptor Antagonist Response in Recovering Ethanol-Dependent Patients. Neuropsychopharmacology 2003, 28: 2020-2028. PMID: 12888778, DOI: 10.1038/sj.npp.1300252.Peer-Reviewed Original ResearchConceptsEthanol-dependent patientsNMDA receptor antagonistReceptor antagonistEthanol dependenceN-methyl-D-aspartate (NMDA) glutamate receptorsDouble-blind studySelective NMDA receptor antagonistNMDA receptor functionAlcohol-dependent patientsHealthy comparison subjectsTreatment of alcoholismHealthy comparison groupExecutive cognitive functionKetamine infusionKetamine 0.5NMDA receptorsGlutamate receptorsComparison subjectsPatientsAmnestic effectsRandomized orderReceptor functionCognitive functionAntagonist responseAntagonist
1999
Glutamate and post-traumatic stress disorder: toward a psychobiology of dissociation.
Chambers RA, Bremner JD, Moghaddam B, Southwick SM, Charney DS, Krystal JH. Glutamate and post-traumatic stress disorder: toward a psychobiology of dissociation. Seminars In Clinical Neuropsychiatry 1999, 4: 274-81. PMID: 10553033, DOI: 10.153/scnp00400274.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderGlutamate releaseNMDA antagonistsStress disorderN-methyl-D-aspartate (NMDA) subtypeDevelopment of PTSDDissociative symptomsStress exposureRecent preclinical dataTraumatic stress exposureHyperglutamatergic stateNeuroprotective potentialPreclinical dataNeural toxicityClinical studiesGlutamate receptorsTraumatized individualsPerceptual effectsPerceptual alterationsNeural plasticityAntagonistBrain functionSymptomsInfluence behaviorDrugsNMDA Agonists and Antagonists as Probes of Glutamatergic Dysfunction and Pharmacotherapies in Neuropsychiatric Disorders
Krystal J, D'Souza C, Petrakis I, Belger A, Berman R, Charney D, AbiSaab W, Madonick S. NMDA Agonists and Antagonists as Probes of Glutamatergic Dysfunction and Pharmacotherapies in Neuropsychiatric Disorders. Harvard Review Of Psychiatry 1999, 7: 125-143. PMID: 10483932, DOI: 10.3109/hrp.7.3.125.Peer-Reviewed Original ResearchConceptsN-methyl-D-aspartate (NMDA) subclassChronic pain syndromePain syndromeGlutamatergic dysfunctionNMDA agonistClinical studiesMajor depressionNMDA antagonistsGlutamate receptorsCoagonist siteParkinson's diseaseHuman psychopharmacological studiesPartial agonistAlzheimer's diseaseNeuropsychiatric conditionsNeuropsychiatric disordersDiseasePsychopharmacological studiesAnxiety disordersHuntington's diseaseAgonistsAntagonistTherapeutic hypothesesDisordersAddiction disorders
1997
The role of serotonin in the pathophysiology and treatment of schizophrenia
Abi-Dargham A, Laruelle M, Aghajanian GK, Charney D, Krystal J. The role of serotonin in the pathophysiology and treatment of schizophrenia. Journal Of Neuropsychiatry 1997, 9: 1-17. PMID: 9017523, DOI: 10.1176/jnp.9.1.1.Peer-Reviewed Original ResearchConceptsRole of serotoninBeneficial effectsSubcortical dopamine activityCerebrospinal fluid studiesCortex of patientsTreatment of schizophreniaBrain tissue analysisSerotonergic hypofunctionDopaminergic antagonistsPharmacological challengeDopamine activityNegative symptomsFluid studiesSchizophreniaPathophysiologySerotoninIllnessTissue analysisTreatmentMore researchAntagonismCompelling evidenceHypofunctionPatientsAntagonist
1991
Effects of ritanserin on the behavioral, neuroendocrine, and cardiovascular responses to meta-chlorophenylpiperazine in healthy human subjects
Seibyl J, Krystal J, Price L, Woods S, D'Amico C, Heninger G, Charney D. Effects of ritanserin on the behavioral, neuroendocrine, and cardiovascular responses to meta-chlorophenylpiperazine in healthy human subjects. Psychiatry Research 1991, 38: 227-236. PMID: 1754635, DOI: 10.1016/0165-1781(91)90013-f.Peer-Reviewed Original ResearchConceptsGrowth hormone responseEffects of ritanserinHealthy male subjectsHealthy human subjectsSelf-rated anxietyMCPP infusionAgonist mCPPCardiovascular effectsHT2 receptorCardiovascular responsesNeuroendocrine responsesRitanserinHormone responseMale subjectsCortisol elevationBehavioral responsesHuman subjectsMCPPSubjectsResponsePlaceboPremedicationChlorophenylpiperazineInfusionAntagonist