2013
The Impact of NMDA Receptor Blockade on Human Working Memory-Related Prefrontal Function and Connectivity
Driesen NR, McCarthy G, Bhagwagar Z, Bloch MH, Calhoun VD, D'Souza DC, Gueorguieva R, He G, Leung HC, Ramani R, Anticevic A, Suckow RF, Morgan PT, Krystal JH. The Impact of NMDA Receptor Blockade on Human Working Memory-Related Prefrontal Function and Connectivity. Neuropsychopharmacology 2013, 38: 2613-2622. PMID: 23856634, PMCID: PMC3828532, DOI: 10.1038/npp.2013.170.Peer-Reviewed Original ResearchConceptsNMDA-RsRelationship of resting brain hyperconnectivity and schizophrenia-like symptoms produced by the NMDA receptor antagonist ketamine in humans
Driesen NR, McCarthy G, Bhagwagar Z, Bloch M, Calhoun V, D'Souza DC, Gueorguieva R, He G, Ramachandran R, Suckow RF, Anticevic A, Morgan PT, Krystal JH. Relationship of resting brain hyperconnectivity and schizophrenia-like symptoms produced by the NMDA receptor antagonist ketamine in humans. Molecular Psychiatry 2013, 18: 1199-1204. PMID: 23337947, PMCID: PMC3646075, DOI: 10.1038/mp.2012.194.Peer-Reviewed Original ResearchMeSH KeywordsAdultBrain MappingCerebral CortexDiagnostic and Statistical Manual of Mental DisordersExcitatory Amino Acid AntagonistsFemaleHealthy VolunteersHumansKetamineMaleMiddle AgedSchizophreniaConceptsFunctional connectivityNegative symptomsGamma-aminobutyric acid (GABA) neuronsNMDA receptor antagonist ketamineAspartate glutamate receptor antagonistContinuous ketamine infusionGlutamate receptor antagonistsNMDA-R antagonistsCortical functional connectivityNMDA-R antagonist ketamineSchizophrenia-like symptomsHealthy human subjectsNegative Syndrome ScaleBrain functional connectivityPrimary samplesRegion-specific mannerFunctional magnetic resonanceKetamine infusionReceptor antagonistPathological increaseSyndrome ScaleSymptomsPreclinical researchKetamineBrain oscillations
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
Capgras Syndrome Induced by Ketamine in a Healthy Subject
Corlett PR, D'Souza DC, Krystal JH. Capgras Syndrome Induced by Ketamine in a Healthy Subject. Biological Psychiatry 2010, 68: e1-e2. PMID: 20385373, PMCID: PMC3721067, DOI: 10.1016/j.biopsych.2010.02.015.Peer-Reviewed Original Research
2007
Psychiatric safety of ketamine in psychopharmacology research
Perry EB, Cramer JA, Cho HS, Petrakis IL, Karper LP, Genovese A, O’Donnell E, Krystal JH, D’Souza D. Psychiatric safety of ketamine in psychopharmacology research. Psychopharmacology 2007, 192: 253-260. PMID: 17458544, DOI: 10.1007/s00213-007-0706-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedClinical Trials as TopicDose-Response Relationship, DrugExcitatory Amino Acid AntagonistsFemaleHumansInfusions, IntravenousKetamineMaleMental DisordersMiddle AgedPsychopharmacologyRiskConceptsSubanesthetic dosesHealthy human subjectsKetamine administrationClinical research programHuman subjectsTest sessionsPsychotic spectrum disordersPsychiatric safetyResidual sequelaePlacebo infusionIntravenous infusionKetamine effectsPsychopharmacology studiesResultsFour hundredAdverse reactionsObjectiveTo reportHealthy subjectsStudy participationClinical investigationHealthy humansSide effectsKetamineInfusionDosesAdministration
2006
Greater vulnerability to the amnestic effects of ketamine in males
Morgan CJ, Perry EB, Cho HS, Krystal JH, D’Souza D. Greater vulnerability to the amnestic effects of ketamine in males. Psychopharmacology 2006, 187: 405-414. PMID: 16896964, DOI: 10.1007/s00213-006-0409-0.Peer-Reviewed Original ResearchConceptsAmnestic effectsProcessing of wordsGeneral cognitive functioningGreater performance decrementsGreater subjective senseGender differencesObjectivesThe current studyGreater vulnerabilityCognitive measuresCognitive differencesCognitive functioningPerceptual alterationsPerformance decrementsNMDA-R functionAttention dataMemory impairmentSubjective senseNegative symptomsCurrent studyFunctioningHVLTKetamine studiesAnxietyMemoryKetamine administration
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 ResearchMeSH KeywordsAdultBehaviorExcitatory Amino Acid AntagonistsFemaleHumansKetamineMaleMiddle AgedReceptors, N-Methyl-D-AspartateConceptsHealthy 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
2004
Preliminary evidence of attenuation of the disruptive effects of the NMDA glutamate receptor antagonist, ketamine, on working memory by pretreatment with the group II metabotropic glutamate receptor agonist, LY354740, in healthy human subjects
Krystal JH, Abi-Saab W, Perry E, D’Souza D, Liu N, Gueorguieva R, McDougall L, Hunsberger T, Belger A, Levine L, Breier A. Preliminary evidence of attenuation of the disruptive effects of the NMDA glutamate receptor antagonist, ketamine, on working memory by pretreatment with the group II metabotropic glutamate receptor agonist, LY354740, in healthy human subjects. Psychopharmacology 2004, 179: 303-309. PMID: 15309376, DOI: 10.1007/s00213-004-1982-8.Peer-Reviewed Original ResearchConceptsGroup II metabotropic glutamate receptor agonistMetabotropic glutamate receptor agonistHealthy human subjectsNMDA glutamate receptor antagonistGlutamate receptor agonistsGlutamate receptor antagonistsTest dayCognitive effectsPerceptual changesKetamine infusionReceptor antagonistReceptor agonistDysphoric moodMemory impairmentBehavioral consequencesSignificant dose-related improvementGroup II mGluR agonistReceptor functionHuman subjectsMemoryNegative symptomsDose-related improvementNMDA receptor functionPreliminary evidenceDisruptive effects
2003
NMDA Receptor Antagonism and the Ethanol Intoxication Signal
KRYSTAL JH, PETRAKIS IL, KRUPITSKY E, SCHÜTZ C, TREVISAN L, D'SOUZA DC. NMDA Receptor Antagonism and the Ethanol Intoxication Signal. Annals Of The New York Academy Of Sciences 2003, 1003: 176-184. PMID: 14684445, DOI: 10.1196/annals.1300.010.Peer-Reviewed Original ResearchMeSH KeywordsAlcoholic IntoxicationAlcoholismAnimalsEthanolExcitatory Amino Acid AntagonistsHumansKetaminePhenotypeReceptors, N-Methyl-D-AspartateNMDA 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 ResearchMeSH KeywordsAnimalsAntipsychotic AgentsCerebral CortexCognitionExcitatory Amino Acid AntagonistsGlutamic AcidHumansKetamineModels, NeurologicalNeural PathwaysReceptors, N-Methyl-D-AspartateSchizophreniaConceptsTreatment 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
2001
Comment on “ketamine has equal affinity for NMDA receptors and the high-affinity state of the dopamine D2 receptor”
Krystal J, D’Souza D. Comment on “ketamine has equal affinity for NMDA receptors and the high-affinity state of the dopamine D2 receptor”. Biological Psychiatry 2001, 50: 555. PMID: 11600110, DOI: 10.1016/s0006-3223(01)01258-6.Peer-Reviewed Original Research
1998
The NMDA Antagonist Model for Schizophrenia: Promise and Pitfalls
Abi-Saab W, D'Souza D, Moghaddam B, Krystal J. The NMDA Antagonist Model for Schizophrenia: Promise and Pitfalls. Pharmacopsychiatry 1998, 31: 104-109. PMID: 9754841, DOI: 10.1055/s-2007-979354.Peer-Reviewed Original ResearchAnesthetics, DissociativeExcitatory Amino Acid AntagonistsHumansKetamineReceptors, N-Methyl-D-AspartateSchizophrenia