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
2018
The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects
Abdallah CG, De Feyter HM, Averill LA, Jiang L, Averill CL, Chowdhury GMI, Purohit P, de Graaf RA, Esterlis I, Juchem C, Pittman BP, Krystal JH, Rothman DL, Sanacora G, Mason GF. The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects. Neuropsychopharmacology 2018, 43: 2154-2160. PMID: 29977074, PMCID: PMC6098048, DOI: 10.1038/s41386-018-0136-3.Peer-Reviewed Original ResearchConceptsGlutamate-glutamine cyclingGlutamate neurotransmissionAntidepressant effectsKetamine effectsRodent studiesN-methyl-D-aspartate receptor antagonistRapid antidepressant effectsClinician-Administered Dissociative States ScaleEffects of ketamineGlutamine enrichmentKetamine infusionGlutamate releaseKetamine administrationSubanesthetic dosesPsychotomimetic effectsReceptor antagonistNormal salineSchizophrenia pathophysiologyFrontal cortexMRS scansDepressed subjectsKetamineNeurotransmissionPrefrontal cortexPilot study
2016
50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate
Cavus I, Widi GA, Duckrow RB, Zaveri H, Kennard JT, Krystal J, Spencer DD. 50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate. Epilepsia 2016, 57: 288-297. PMID: 26749134, DOI: 10.1111/epi.13269.Peer-Reviewed Original ResearchConceptsBasal glutamate levelsRefractory epilepsyGlutamate effluxBasal glutamateGlutamate levelsElectrical stimulationEpileptic hippocampusGlutamate releaseSeizure groupHz stimulationBrain glutamate releaseHippocampus of patientsStimulation-induced increaseEpilepsy monitoring unitStimulation-induced changesEpileptogenic hippocampusInduced seizuresSeizure inductionSpontaneous seizuresInterictal levelsGlutamate increaseAtrophic hippocampusElectroencephalography evaluationHippocampal stimulationHippocampal electrodes
2014
In Vivo Ketamine-Induced Changes in [11C]ABP688 Binding to Metabotropic Glutamate Receptor Subtype 5
DeLorenzo C, DellaGioia N, Bloch M, Sanacora G, Nabulsi N, Abdallah C, Yang J, Wen R, Mann JJ, Krystal JH, Parsey RV, Carson RE, Esterlis I. In Vivo Ketamine-Induced Changes in [11C]ABP688 Binding to Metabotropic Glutamate Receptor Subtype 5. Biological Psychiatry 2014, 77: 266-275. PMID: 25156701, PMCID: PMC4277907, DOI: 10.1016/j.biopsych.2014.06.024.Peer-Reviewed Original ResearchConceptsSubtype 5Ketamine administrationPET scansMetabotropic glutamate receptor subtype 5Prefrontal cortexAspartate glutamate receptor antagonistIntravenous ketamine administrationKetamine-induced effectsPositron emission tomography (PET) ligandGlutamate receptor antagonistsVolume of distributionMedial prefrontal cortexNegative allosteric modulatorsKetamine initiationGlutamate releaseDorsal putamenKetamine responseSubanesthetic dosesOrbital prefrontal cortexReceptor antagonistAcute effectsBolus injectionDorsal caudateArterial bloodScan 1
2008
Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders
Sanacora G, Zarate CA, Krystal JH, Manji HK. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nature Reviews Drug Discovery 2008, 7: 426-437. PMID: 18425072, PMCID: PMC2715836, DOI: 10.1038/nrd2462.Peer-Reviewed Original ResearchConceptsGlutamatergic systemMood disordersAntidepressant effectsNMDA antagonistsDouble-blind placebo-controlled crossover studyTreatment-resistant major depressive disorderPlacebo-controlled crossover studyGlutamate release inhibitorSignificant antidepressant effectNMDA receptor expressionRecurrent mental illnessSingle intravenous doseMajor depressive disorderPotential novel therapeuticsGlutamatergic abnormalitiesCrossover studyGlutamate releaseIntravenous doseMood stabilizersDepressive disorderReceptor expressionReceptor modulatorsEvidence of alterationsCerebrospinal fluidAMPA potentiators
2003
A placebo-controlled, cross-over trial of lamotrigine in depersonalization disorder
Sierra M, Phillips ML, Ivin G, Krystal J, David AS. A placebo-controlled, cross-over trial of lamotrigine in depersonalization disorder. Journal Of Psychopharmacology 2003, 17: 103-105. PMID: 12680746, DOI: 10.1177/0269881103017001712.Peer-Reviewed Original ResearchConceptsDepersonalization disorderEfficacy of lamotrigineWeeks of treatmentCross-over trialCross-over periodCross-over designDSM-IV depersonalization disorderSole medicationGlutamate releaseLamotriginePatientsCambridge Depersonalization ScaleDisordersTreatmentDepersonalization ScalePlaceboMedicationsHyperactivityRespondersTrialsWeeks
2000
Attenuation of the Neuropsychiatric Effects of Ketamine With Lamotrigine: Support for Hyperglutamatergic Effects of N-methyl-D-aspartate Receptor Antagonists
Anand A, Charney DS, Oren DA, Berman RM, Hu XS, Cappiello A, Krystal JH. Attenuation of the Neuropsychiatric Effects of Ketamine With Lamotrigine: Support for Hyperglutamatergic Effects of N-methyl-D-aspartate Receptor Antagonists. JAMA Psychiatry 2000, 57: 270-276. PMID: 10711913, DOI: 10.1001/archpsyc.57.3.270.Peer-Reviewed Original ResearchMeSH KeywordsAdultAffectBrief Psychiatric Rating ScaleCognition DisordersDouble-Blind MethodExcitatory Amino Acid AntagonistsFemaleGlutamatesHumansKetamineLamotrigineMaleMental DisordersPerceptual DisordersPlacebosPsychiatric Status Rating ScalesReceptors, N-Methyl-D-AspartateSchizophreniaSchizophrenic PsychologyTriazinesVerbal LearningConceptsN-methyl-D-aspartate receptor antagonistNMDA receptor dysfunctionReceptor antagonistNeuropsychiatric effectsGlutamate releaseReceptor dysfunctionSymptom subscalesPlacebo 2 hoursClinician-Administered Dissociative States ScaleAdministration of lamotrigineAdministration of ketamineDouble-blind conditionsNMDA receptor antagonistMood-elevating effectsPositive symptom subscaleBrief Psychiatric RatingNovel therapeutic agentsNegative symptom subscaleHopkins Verbal Learning TestVerbal Learning TestKetamine effectsPsychiatric illnessHealthy subjectsPathophysiologic processesPreclinical studiesAttenuation of ketamine effects in healthy humans by lamotrigine, a drug that reduces glutamate release
Anand A, Berman R, Charney D, Krystal J. Attenuation of ketamine effects in healthy humans by lamotrigine, a drug that reduces glutamate release. Schizophrenia Research 2000, 41: 33. DOI: 10.1016/s0920-9964(00)90372-4.Peer-Reviewed Original Research
1999
Therapeutic Implications of the Hyperglutamatergic Effects of NMDA Antagonists
Krystal J, Belger A, D'Souza D, Anand A, Charney D, Aghajanian G, Moghaddam B. Therapeutic Implications of the Hyperglutamatergic Effects of NMDA Antagonists. Neuropsychopharmacology 1999, 21: s143-s157. DOI: 10.1016/s0893-133x(99)00102-5.Peer-Reviewed Original ResearchHealthy human subjectsNMDA antagonist effectsNMDA antagonistsClinical studiesMetabotropic glutamate receptor agonistN-methyl-D-aspartate (NMDA) subtypeD2 receptor blockadeGlutamate receptor agonistsD2 receptor stimulationDopamine 2 receptorNovel pharmacologic strategiesEffects of ketaminePathophysiology of schizophreniaCourse of schizophreniaNovel pharmacotherapeutic strategiesHuman subjectsHyperglutamatergic stateSerotonin 2AGlutamate neuronsGlutamate releaseCerebral cortexPharmacologic strategiesCurrent antipsychoticsPharmacotherapeutic strategiesSubanesthetic dosesGlutamate 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 behaviorDrugs