2020
Imaging the glutamate synapse
Krystal JH. Imaging the glutamate synapse. Nature Medicine 2020, 26: 165-167. PMID: 32015559, DOI: 10.1038/s41591-020-0760-4.Peer-Reviewed Original Research
2019
Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments
Duman RS, Sanacora G, Krystal JH. Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments. Neuron 2019, 102: 75-90. PMID: 30946828, PMCID: PMC6450409, DOI: 10.1016/j.neuron.2019.03.013.Peer-Reviewed Original ResearchConceptsAltered connectivityDepressed patientsExcitatory glutamate neuronsMajor neuronal typesRapid-acting agentsAtrophy of neuronsTreatment of depressionLimbic brain regionsChronic stress exposureStress-related disordersBrain imaging studiesImportant sex differencesNeurotransmitter deficitsGABA interneuronsImmunologic mechanismsGlutamate neuronsCurrent antidepressantsExcitotoxic effectsNeurochemical deficitsGlutamate dysfunctionPathophysiological mechanismsGABA systemInflammatory cytokinesAdrenal glucocorticoidsHippocampal regionKetamine: A Paradigm Shift for Depression Research and Treatment
Krystal JH, Abdallah CG, Sanacora G, Charney DS, Duman RS. Ketamine: A Paradigm Shift for Depression Research and Treatment. Neuron 2019, 101: 774-778. PMID: 30844397, PMCID: PMC6560624, DOI: 10.1016/j.neuron.2019.02.005.Peer-Reviewed Original Research
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 studyThe neurobiology of depression, ketamine and rapid-acting antidepressants: Is it glutamate inhibition or activation?
Abdallah CG, Sanacora G, Duman RS, Krystal JH. The neurobiology of depression, ketamine and rapid-acting antidepressants: Is it glutamate inhibition or activation? Pharmacology & Therapeutics 2018, 190: 148-158. PMID: 29803629, PMCID: PMC6165688, DOI: 10.1016/j.pharmthera.2018.05.010.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsBiomarkersDepressionDisease Models, AnimalDrug DevelopmentGlutamic AcidHumansKetamineSynaptic TransmissionConceptsRapid-acting antidepressantsNeurobiology of depressionMechanism of actionChronic stress pathologyRole of glutamateAntidepressant effectsEfficacy findingsGlutamate activationBiomarker findingsNeurobiology of stressVivo pharmacodynamicsCurrent perspective paperKetamineChronic stressReproducible biomarkersBehavioral effectsGlutamate inhibitionDepressionStress pathologyAntidepressantsNeurobiologyInhibitionActivationPharmacodynamicsPharmacokinetics
2017
Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic
Krystal JH, Abdallah CG, Averill LA, Kelmendi B, Harpaz-Rotem I, Sanacora G, Southwick SM, Duman RS. Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic. Current Psychiatry Reports 2017, 19: 74. PMID: 28844076, PMCID: PMC5904792, DOI: 10.1007/s11920-017-0829-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDisease Models, AnimalExcitatory Amino Acid AntagonistsHumansKetamineNeurobiologyStress Disorders, Post-TraumaticSynaptic TransmissionConceptsSynaptic connectivityRapid-acting treatmentPathophysiology of PTSDPotential clinical importanceTreatment of PTSDSynaptic lossPurpose of ReviewStudiesDisconnection syndromeClinical importanceNovel pharmacotherapeuticsNovel therapeuticsPTSD symptomsRecent FindingsHerePTSDPathophysiologyKetamineTreatmentDisordersTherapeutic applicationsStress-related lossesSyndromeSymptomsPharmacotherapeutics
2016
Glutamate dysregulation and glutamatergic therapeutics for PTSD: Evidence from human studies
Averill LA, Purohit P, Averill CL, Boesl MA, Krystal JH, Abdallah CG. Glutamate dysregulation and glutamatergic therapeutics for PTSD: Evidence from human studies. Neuroscience Letters 2016, 649: 147-155. PMID: 27916636, PMCID: PMC5482215, DOI: 10.1016/j.neulet.2016.11.064.Peer-Reviewed Original ResearchMeSH KeywordsBrainGamma-Aminobutyric AcidGlutamic AcidHumansReceptors, GlutamateStress Disorders, Post-TraumaticStress, PsychologicalSynaptic TransmissionConceptsPosttraumatic stress disorderPsychiatric disordersStress-related psychiatric disordersAlternative pharmacologic treatmentsPutative neurobiological underpinningsGlutamate-modulating agentsTrauma-related disordersGlutamatergic abnormalitiesGlutamate dysregulationPharmacologic treatmentPharmacologic interventionsGlutamatergic functionGlutamate neurotransmissionMillions of individualsHuman studiesCardinal featuresStress disorderDisordersNeurobiological underpinningsRelated future directionsEvidenceChronicDysfunctionNeurotransmissionSubject data
2015
Decreased SGK1 Expression and Function Contributes to Behavioral Deficits Induced by Traumatic Stress
Licznerski P, Duric V, Banasr M, Alavian KN, Ota KT, Kang HJ, Jonas EA, Ursano R, Krystal JH, Duman RS, . Decreased SGK1 Expression and Function Contributes to Behavioral Deficits Induced by Traumatic Stress. PLOS Biology 2015, 13: e1002282. PMID: 26506154, PMCID: PMC4623974, DOI: 10.1371/journal.pbio.1002282.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsBehavior, AnimalCohort StudiesDendritic SpinesDepressive Disorder, MajorEnzyme RepressionFemaleGene Transfer TechniquesHippocampusHumansImmediate-Early ProteinsMaleMiddle AgedNerve Tissue ProteinsNeuronsPrefrontal CortexProtein Serine-Threonine KinasesRats, Sprague-DawleySignal TransductionStress Disorders, Post-TraumaticSynaptic TransmissionTissue BanksConceptsMajor depressive disorderPost-traumatic stress disorderPrefrontal cortexAbnormal dendritic spine morphologyCorticolimbic brain regionsAnhedonic-like behaviorInhibition of SGK1Dendritic spine morphologyKinase 1 expressionAmygdala of individualsTraumatic stressPostmortem prefrontal cortexSynaptic dysfunctionDepressive disorderBehavioral deficitsRodent modelsPTSD subjectsFunctional alterationsBrain regionsSGK1 expressionSpine morphologyStress disorderFunction contributesBehavioral changesDisorders
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
2009
Noradrenergic and serotonergic mechanisms in the neurobiology of posttraumatic stress disorder and resilience
Krystal JH, Neumeister A. Noradrenergic and serotonergic mechanisms in the neurobiology of posttraumatic stress disorder and resilience. Brain Research 2009, 1293: 13-23. PMID: 19332037, PMCID: PMC2761677, DOI: 10.1016/j.brainres.2009.03.044.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderStress disorderOrdinary stressful life eventsEtiology of PTSDNeurobiology of PTSDSymptoms of PTSDImpact of traumaStressful life eventsTraumatic eventsNeurobiological systemsLife eventsTreatment developmentSerotonergic mechanismsNeurobiologyUse of antidepressantsDevelopment of treatmentsBasic researchResilienceMonoaminergic mechanismsAvailable treatmentsRelevant findingsHyperarousalResearchDisordersPsychopathology
2008
Capitalizing on Extrasynaptic Glutamate Neurotransmission to Treat Antipsychotic-Resistant Symptoms in Schizophrenia
Krystal JH. Capitalizing on Extrasynaptic Glutamate Neurotransmission to Treat Antipsychotic-Resistant Symptoms in Schizophrenia. Biological Psychiatry 2008, 64: 358-360. PMID: 18694665, DOI: 10.1016/j.biopsych.2008.06.011.Peer-Reviewed Original ResearchMeSH KeywordsAntipsychotic AgentsDrug ResistanceGlutamic AcidHumansSchizophreniaSynaptic Transmission
2005
Alcohol Dependence Is Associated with Blunted Dopamine Transmission in the Ventral Striatum
Martinez D, Gil R, Slifstein M, Hwang DR, Huang Y, Perez A, Kegeles L, Talbot P, Evans S, Krystal J, Laruelle M, Abi-Dargham A. Alcohol Dependence Is Associated with Blunted Dopamine Transmission in the Ventral Striatum. Biological Psychiatry 2005, 58: 779-786. PMID: 16018986, DOI: 10.1016/j.biopsych.2005.04.044.Peer-Reviewed Original ResearchConceptsAlcohol-dependent subjectsLimbic striatumPositron emission tomographyDopamine transmissionD2 receptorsDopamine releaseAD subjectsAlcohol dependenceAmphetamine-induced dopamine releaseDopamine type 2 receptorHealthy control subjectsD2 receptor availabilityMesolimbic dopamine transmissionType 2 receptorPsychostimulant challengeSensorimotor subdivisionsControl subjectsStriatal subdivisionsAssociative striatumSensorimotor striatumReceptor availabilityStriatumEmission tomographyVentral striatumReceptors
2004
Impaired GABA Neuronal Response to Acute Benzodiazepine Administration in Panic Disorder
Goddard AW, Mason GF, Appel M, Rothman DL, Gueorguieva R, Behar KL, Krystal JH. Impaired GABA Neuronal Response to Acute Benzodiazepine Administration in Panic Disorder. American Journal Of Psychiatry 2004, 161: 2186-2193. PMID: 15569888, DOI: 10.1176/appi.ajp.161.12.2186.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidPanic disorder patientsAcute benzodiazepine administrationCortical GABA levelsBenzodiazepine administrationGABA levelsPanic disorderDisorder patientsNeuronal responsesOccipital cortex GABA levelsTransmitter gamma-aminobutyric acidChronic benzodiazepine treatmentGABA neuronal functionHuman panic disorderTrait-like abnormalitiesGABA synthetic enzymeHealthy comparison subjectsStress-induced releaseCerebral cortexBenzodiazepine treatmentMedication administrationGABA responsesHealthy subjectsPathogenic factorsHuman anxiety disorders
2003
Neurobiological Correlates of the Disposition and Maintenance of Alcoholism
Heinz A, Schäfer M, Higley J, Krystal J, Goldman D. Neurobiological Correlates of the Disposition and Maintenance of Alcoholism. Pharmacopsychiatry 2003, 36: 255-258. PMID: 14677088, DOI: 10.1055/s-2003-45139.Peer-Reviewed Original ResearchConceptsAlcohol effectsMaintenance of alcoholismCurrent disease conceptsNeurobiological foundationsDispositional factorsNeurobiological correlatesMotivational therapyConsequences of alcoholismAlcohol cravingReward systemAlcohol intakeClinical withdrawalReduced controlTreatment of alcoholismChronic alcohol effectsNew treatment optionsNeuroadaptationsResearch pointsRelapse riskMonoaminergic dysfunctionPatient groupTreatment optionsGlutamatergic neurotransmissionCentral GABAergicPharmacological approachesClinical Studies Implementing Glutamate Neurotransmission in Mood Disorders
SANACORA G, ROTHMAN DL, MASON G, KRYSTAL JH. Clinical Studies Implementing Glutamate Neurotransmission in Mood Disorders. Annals Of The New York Academy Of Sciences 2003, 1003: 292-308. PMID: 14684453, DOI: 10.1196/annals.1300.018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain ChemistryDepressionGamma-Aminobutyric AcidGlutamatesHumansMagnetic Resonance SpectroscopyMood DisordersReceptors, GlutamateSynaptic Transmission
2002
Effects of NMDA receptor antagonists: implications for the pathophysiology of schizophrenia.
Krystal JH, Anand A, Moghaddam B. Effects of NMDA receptor antagonists: implications for the pathophysiology of schizophrenia. JAMA Psychiatry 2002, 59: 663-4. PMID: 12090822, DOI: 10.1001/archpsyc.59.7.663.Peer-Reviewed Original ResearchGlutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments
Krystal JH, Sanacora G, Blumberg H, Anand A, Charney DS, Marek G, Epperson CN, Goddard A, Mason GF. Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Molecular Psychiatry 2002, 7: s71-s80. PMID: 11986998, DOI: 10.1038/sj.mp.4001021.Peer-Reviewed Original ResearchMeSH KeywordsAntidepressive AgentsGamma-Aminobutyric AcidGlutamic AcidHumansModels, NeurologicalMood DisordersSynaptic TransmissionConceptsCortical GABA levelsMood-stabilizing treatmentMood disordersGABA levelsΓ-amino-butyric acid (GABA) systemMood-stabilizing agentsGlutamate receptor functionDevelopment of medicationsGABA deficitAvailable antidepressantsGABAergic modulationAntimanic effectsGlutamatergic activityClinical evidenceNovel antidepressantsGABA systemAntidepressant drugsNew agentsReceptor functionAvailable evidenceReceptor targetsAntidepressantsDisordersGlutamateTreatment
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 ResearchMeSH KeywordsAnimalsDissociative DisordersGlutamic AcidHumansStress Disorders, Post-TraumaticSynaptic TransmissionConceptsPost-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
1998
Increased Striatal Dopamine Transmission in Schizophrenia: Confirmation in a Second Cohort
Abi-Dargham A, Gil R, Krystal J, Baldwin RM, Seibyl JP, Bowers M, van Dyck CH, Charney DS, Innis RB, Laruelle M. Increased Striatal Dopamine Transmission in Schizophrenia: Confirmation in a Second Cohort. American Journal Of Psychiatry 1998, 155: 761-767. PMID: 9619147, DOI: 10.1176/ajp.155.6.761.Peer-Reviewed Original ResearchConceptsD2 receptor availabilityAcute amphetamine challengeStriatal dopamine transmissionAmphetamine challengeReceptor availabilityDopamine releaseHealthy subjectsDopamine transmissionDopamine D2 receptor availabilityExcess dopamine releaseStriatal dopamine releaseComparison groupD2 receptor radiotracerHistory of alcoholDSM-IV criteriaSingle photon emissionNew cohortUntreated patientsReceptor radiotracerSchizophrenic patientsPatientsSecond cohortParental socioeconomic statusPositive symptomsSubstance abuse
1997
Noradrenergic Alterations in Posttraumatic Stress Disorder
SOUTHWICK S, MORGAN CA, BREMNER A, GRILLON C, KRYSTAL J, NAGY L, CHARNEY D. Noradrenergic Alterations in Posttraumatic Stress Disorder. Annals Of The New York Academy Of Sciences 1997, 821: 125-141. PMID: 9238199, DOI: 10.1111/j.1749-6632.1997.tb48274.x.Peer-Reviewed Original Research