2019
Measuring the effects of ketamine on mGluR5 using [18F]FPEB and PET
Holmes SE, Gallezot JD, Davis MT, DellaGioia N, Matuskey D, Nabulsi N, Krystal JH, Javitch JA, DeLorenzo C, Carson RE, Esterlis I. Measuring the effects of ketamine on mGluR5 using [18F]FPEB and PET. Cerebrovascular And Brain Metabolism Reviews 2019, 40: 2254-2264. PMID: 31744389, PMCID: PMC7585925, DOI: 10.1177/0271678x19886316.Peer-Reviewed Original ResearchConceptsEffects of ketamineKetamine infusionGlutamate transmissionMetabotropic glutamate receptor 5Ketamine-induced effectsKetamine-induced changesGlutamate receptor 5Promising treatment targetDrug challenge studiesTwo-tissue compartment modelMGluR5 radioligandBlood pressureMGluR5 availabilityBaseline scanOutcome measuresHealthy subjectsHeart ratePsychiatric disordersReceptor 5Modulatory effectsMGluR5Treatment targetsChallenge studiesArterial input functionChallenge paradigm
2017
Prefrontal Connectivity and Glutamate Transmission: Relevance to Depression Pathophysiology and Ketamine Treatment
Abdallah CG, Averill CL, Salas R, Averill LA, Baldwin PR, Krystal JH, Mathew SJ, Mathalon DH. Prefrontal Connectivity and Glutamate Transmission: Relevance to Depression Pathophysiology and Ketamine Treatment. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2017, 2: 566-574. PMID: 29034354, PMCID: PMC5635826, DOI: 10.1016/j.bpsc.2017.04.006.Peer-Reviewed Original ResearchTreatment-resistant depressionTRD patientsHealthy subjectsHealthy controlsStudy AStudy BEffects of lamotrigineAbility of ketamineGlobal brain connectivityEffects of ketamineFunctional magnetic resonance imagingMagnetic resonance imagingSignificant reductionOral lamotrigineKetamine treatmentKetamine infusionKetamine's mechanismGlutamate transmissionGlutamate neurotransmissionDepression pathophysiologyPharmacological challengeKetamine interactionKetaminePrefrontal connectivityResonance imaging
2016
Altered Global Signal Topography in Schizophrenia
Yang GJ, Murray JD, Glasser M, Pearlson GD, Krystal JH, Schleifer C, Repovs G, Anticevic A. Altered Global Signal Topography in Schizophrenia. Cerebral Cortex 2016, 27: 5156-5169. PMID: 27702810, PMCID: PMC6075538, DOI: 10.1093/cercor/bhw297.Peer-Reviewed Original ResearchConceptsSCZ patientsGS topographyHealthy subjectsResting-state functional magnetic resonance imagingBlood oxygen level-dependent (BOLD) signalDevelopment of pharmacotherapiesGlobal signal topographyHealthy comparison subjectsFunctional magnetic resonance imagingLevel-dependent signalMagnetic resonance imagingAnti-correlated relationshipExtensive abnormalitiesComparison subjectsAssociation cortexNeural information flowResonance imagingNeuropsychiatric diseasesSensory areasPatientsSchizophreniaSensory regionsProfound alterationsSignal topographyAlterations
2015
Functional hierarchy underlies preferential connectivity disturbances in schizophrenia
Yang GJ, Murray JD, Wang XJ, Glahn DC, Pearlson GD, Repovs G, Krystal JH, Anticevic A. Functional hierarchy underlies preferential connectivity disturbances in schizophrenia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 113: e219-e228. PMID: 26699491, PMCID: PMC4720350, DOI: 10.1073/pnas.1508436113.Peer-Reviewed Original ResearchConceptsFunctional connectivityResting-state functional MRIExcitation/inhibition ratioElevated functional connectivityLarge-scale functional connectivityFronto-parietal control networkI elevationConnectivity disturbancesHealthy subjectsPreferential vulnerabilityAssociation cortexSchizophrenia patientsBipolar disorderFunctional MRIPatientsSymptom levelsSchizophreniaCortical microcircuitsInhibition ratioNeural modelControl networkNeuronal dynamicsHierarchical differencesParsimonious mechanismDysconnectivityRole of GABA Deficit in Sensitivity to the Psychotomimetic Effects of Amphetamine
Ahn KH, Sewell A, Elander J, Pittman B, Ranganathan M, Gunduz-Bruce H, Krystal J, D'Souza DC. Role of GABA Deficit in Sensitivity to the Psychotomimetic Effects of Amphetamine. Neuropsychopharmacology 2015, 40: 2822-2831. PMID: 25953357, PMCID: PMC4864658, DOI: 10.1038/npp.2015.132.Peer-Reviewed Original ResearchConceptsGABA deficitHealthy subjectsPsychotomimetic effectsIntravenous infusionSchizophrenia patientsPANSS positive symptoms subscaleDouble-blind crossover designStriatal dopamine releasePositive symptom subscaleAdministration of drugsDose of AMPHPartial inverse agonistSubclinical responsePharmacokinetic interactionsSubthreshold doseDopamine releaseBenzodiazepine receptorsSymptom subscalesCrossover designCADSS scoresPositive symptomsAMPHInverse agonistSubjective effectsTest day
2014
Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia
Xu K, Krystal JH, Ning Y, Chen da C, He H, Wang D, Ke X, Zhang X, Ding Y, Liu Y, Gueorguieva R, Wang Z, Limoncelli D, Pietrzak RH, Petrakis IL, Zhang X, Fan N. Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia. Journal Of Psychiatric Research 2014, 61: 64-72. PMID: 25560772, PMCID: PMC4445679, DOI: 10.1016/j.jpsychires.2014.12.012.Peer-Reviewed Original ResearchConceptsKetamine groupNegative Syndrome ScaleSchizophrenia groupSyndrome ScaleN-methyl-D-aspartate (NMDA) glutamate receptor antagonistGlutamate receptor antagonistsPotential confounding factorsEarly course schizophreniaSymptom dimensionsSymptoms of schizophreniaReceptor antagonistChronic schizophreniaHealthy subjectsKetamine abuseSchizophrenia psychosisSchizophrenia patientsConfounding factorsSymptom severitySymptomsInpatientsSchizophreniaPsychosisKetamine usersDissociation symptomsPrincipal component factor analysisN-Methyl-D-Aspartate Receptor Antagonist Effects on Prefrontal Cortical Connectivity Better Model Early Than Chronic Schizophrenia
Anticevic A, Corlett PR, Cole MW, Savic A, Gancsos M, Tang Y, Repovs G, Murray JD, Driesen NR, Morgan PT, Xu K, Wang F, Krystal JH. N-Methyl-D-Aspartate Receptor Antagonist Effects on Prefrontal Cortical Connectivity Better Model Early Than Chronic Schizophrenia. Biological Psychiatry 2014, 77: 569-580. PMID: 25281999, DOI: 10.1016/j.biopsych.2014.07.022.Peer-Reviewed Original ResearchConceptsHealthy volunteersFunctional connectivityKetamine effectsChronic schizophreniaIllness progressionChronic illnessHigh riskRecent pharmacologic studiesReceptor antagonist effectsAspartate glutamate receptorsStages of schizophreniaCourse of schizophreniaGlutamate dysfunctionPharmacologic modelsPrefrontal cortex functionIllness stageNMDAR antagonistsFunctional dysconnectivityGlutamate receptorsPharmacologic studiesHealthy subjectsSchizophrenia onsetFunctional alterationsDevelopment of therapeuticsAntagonist effectsAltered global brain signal in schizophrenia
Yang GJ, Murray JD, Repovs G, Cole MW, Savic A, Glasser MF, Pittenger C, Krystal JH, Wang XJ, Pearlson GD, Glahn DC, Anticevic A. Altered global brain signal in schizophrenia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 7438-7443. PMID: 24799682, PMCID: PMC4034208, DOI: 10.1073/pnas.1405289111.Peer-Reviewed Original ResearchConceptsGlobal brain signalBrain dysfunctionHealthy subjectsBipolar patientsCortical powerBipolar disorderNeuropsychiatric conditionsFunctional MRIPatient samplesBrain connectivitySchizophreniaComplex neurobiologyDiagnostic specificityPatientsBrain signalsAlterationsDysfunctionSymptomsFindingsBaselineBrainMRI
2013
Connectivity, Pharmacology, and Computation: Toward a Mechanistic Understanding of Neural System Dysfunction in Schizophrenia
Anticevic A, Cole MW, Repovs G, Savic A, Driesen NR, Yang G, Cho YT, Murray JD, Glahn DC, Wang XJ, Krystal JH. Connectivity, Pharmacology, and Computation: Toward a Mechanistic Understanding of Neural System Dysfunction in Schizophrenia. Frontiers In Psychiatry 2013, 4: 169. PMID: 24399974, PMCID: PMC3871997, DOI: 10.3389/fpsyt.2013.00169.Peer-Reviewed Original ResearchNMDA receptor antagonistFunctional neuroimaging toolsFunctional imaging studiesNeural system dysfunctionsRecent neuroimaging studiesKetamine administrationRecent findingsPharmacological treatmentSynaptic dysfunctionReceptor antagonistSystem dysfunctionPathophysiologic hypothesesBipolar illnessHealthy subjectsResting-state neuroimagingHealthy volunteersClinical investigationHealthy humansPsychiatric disordersCardinal featuresPharmacological manipulationPsychiatric conditionsLocal circuitsImaging studiesNeuropsychiatric diseases
2011
Imaging human reward processing with positron emission tomography and functional magnetic resonance imaging
Urban NB, Slifstein M, Meda S, Xu X, Ayoub R, Medina O, Pearlson GD, Krystal JH, Abi-Dargham A. Imaging human reward processing with positron emission tomography and functional magnetic resonance imaging. Psychopharmacology 2011, 221: 67-77. PMID: 22052081, DOI: 10.1007/s00213-011-2543-6.Peer-Reviewed Original ResearchConceptsPositron emission tomography studyMonetary incentive delay taskDopamine releaseVentral striatumBOLD activationVoxelwise analysisFMRI BOLD activationEndogenous dopamine releaseEmission tomography studiesROI analysisMesolimbic dopamine releaseFunctional magnetic resonance imagingMagnetic resonance imagingPositron emission tomographyReward processingBOLD signal changesFunctional neuroimaging studiesPrecommissural putamenIncentive delay taskSignal changesPosterior caudateStriatal subregionsHealthy subjectsGlutamatergic signalingPercent change
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 ResearchConceptsSubanesthetic 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
Enhanced Sensitivity to the Euphoric Effects of Alcohol in Schizophrenia
D'Souza DC, Gil RB, Madonick S, Perry EB, Forselius-Bielen K, Braley G, Donahue L, Tellioglu T, Zimolo Z, Gueorguieva R, Krystal JH. Enhanced Sensitivity to the Euphoric Effects of Alcohol in Schizophrenia. Neuropsychopharmacology 2006, 31: 2767-2775. PMID: 16985503, DOI: 10.1038/sj.npp.1301207.Peer-Reviewed Original ResearchConceptsEffects of alcoholHealthy subjectsBlood alcohol levelsPositive psychotic symptomsSmall transient increaseSelf-medication hypothesisPerceptual alterationsAlcohol administrationMotor functionAlcohol dosesElevated riskPsychotic symptomsLifetime exposureSchizophrenia patientsSchizophrenia symptomsEuphoric effectsNegative symptomsAlcohol levelsAlcohol useStimulatory effectSubjective effectsTransient increaseSchizophreniaStimulatory responseAlcohol responses
2005
Cortical Gamma-Aminobutyric Acid Levels and the Recovery from Ethanol Dependence: Preliminary Evidence of Modification by Cigarette Smoking
Mason GF, Petrakis IL, de Graaf RA, Gueorguieva R, Guidone E, Coric V, Epperson CN, Rothman DL, Krystal JH. Cortical Gamma-Aminobutyric Acid Levels and the Recovery from Ethanol Dependence: Preliminary Evidence of Modification by Cigarette Smoking. Biological Psychiatry 2005, 59: 85-93. PMID: 16289397, DOI: 10.1016/j.biopsych.2005.06.009.Peer-Reviewed Original ResearchConceptsEthanol-dependent patientsTobacco smokingEthanol dependenceHealthy subjectsN-acetylaspartateCortical gamma-aminobutyric acid (GABA) levelsGamma-aminobutyric acid (GABA) levelsCortical GABA levelsCortical GABA systemAlcohol withdrawal symptomsAcute ethanol withdrawalComorbidity of alcoholismProton magnetic resonance spectroscopyGamma-aminobutyric acidCortical GABASmoking patientsEthanol withdrawalCigarette smokingGABA systemHealthy menWithdrawal symptomsGABA levelsClinical dataNAA levelsWithdrawal severityDelta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction
D’Souza D, Abi-Saab WM, Madonick S, Forselius-Bielen K, Doersch A, Braley G, Gueorguieva R, Cooper TB, Krystal JH. Delta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction. Biological Psychiatry 2005, 57: 594-608. PMID: 15780846, DOI: 10.1016/j.biopsych.2004.12.006.Peer-Reviewed Original ResearchMeSH KeywordsAdultAkathisia, Drug-InducedArousalCognitionDose-Response Relationship, DrugDouble-Blind MethodDronabinolEndocrine SystemFemaleHumansInjections, IntravenousMaleMental RecallMiddle AgedMotor ActivityNeuropsychological TestsPerceptionPsychiatric Status Rating ScalesPsychotic DisordersPsychotropic DrugsSchizophreniaVerbal LearningConceptsSchizophrenia patientsAntipsychotic-treated schizophrenia patientsDelta-9-tetrahydrocannabinol effectsLong-term adverse eventsCognitive deficitsPlacebo-controlled studyDelta-9-THCTransient exacerbationAdverse eventsReceptor dysfunctionEndocrine effectsHealthy subjectsStudy participationPsychotic disordersPlasma prolactinSchizophrenia symptomsPatientsSchizophreniaCognitive effectsPerceptual alterationsDeficitsCannabisSubjectsAkathisiaExacerbation
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
2001
Quantitative Morphology of the Caudate and Putamen in Patients With Cocaine Dependence
Jacobsen LK, Giedd JN, Gottschalk C, Kosten TR, Krystal JH. Quantitative Morphology of the Caudate and Putamen in Patients With Cocaine Dependence. American Journal Of Psychiatry 2001, 158: 486-489. PMID: 11229995, DOI: 10.1176/appi.ajp.158.3.486.Peer-Reviewed Original ResearchConceptsCocaine dependenceDopaminergic functionStriatal dopaminergic depletionTypical neuroleptic treatmentTotal brain volumeChronic cocaine dependenceCocaine-dependent subjectsChronic cocaine useStriatal hypertrophyExtrapyramidal symptomsNeuroleptic treatmentDopaminergic depletionHealthy subjectsBrain volumePutamen volumeCocaine useStriatal structuresCaudatePatientsPutamenHypertrophyMagnetic resonanceDeficitsQuantitative morphologySubjects
2000
Similarities in the Disturbances in Cortical Information Processing in Alcoholism and Aging: A Pilot Evoked Potential Study
Boutros N, Reid M, Petrakis I, Campbell D, Torello M, Krystal J. Similarities in the Disturbances in Cortical Information Processing in Alcoholism and Aging: A Pilot Evoked Potential Study. International Psychogeriatrics 2000, 12: 513-525. PMID: 11263717, DOI: 10.1017/s1041610200006621.Peer-Reviewed Original ResearchConceptsInformation processingCortical information processingSensory gatingPaired-click paradigmOlder healthy subjectsAlcohol dependenceSensory gating deficitsStimulus classificationNovel stimuliOddball paradigmHealthy individualsYoung healthy groupEvoked potential studiesDSM-IV criteriaPotential studiesHealthy subjectsGender-matched groupAged healthy individualsGender-matched healthy individualsGating deficitsMiddle-aged individualsPsychotic symptomsOlder groupProcessingAlcoholic patientsAttenuation 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 studies
1999
Reduced Cortical γ-Aminobutyric Acid Levels in Depressed Patients Determined by Proton Magnetic Resonance Spectroscopy
Sanacora G, Mason GF, Rothman DL, Behar KL, Hyder F, Petroff OA, Berman RM, Charney DS, Krystal JH. Reduced Cortical γ-Aminobutyric Acid Levels in Depressed Patients Determined by Proton Magnetic Resonance Spectroscopy. JAMA Psychiatry 1999, 56: 1043-1047. PMID: 10565505, DOI: 10.1001/archpsyc.56.11.1043.Peer-Reviewed Original ResearchConceptsProton magnetic resonance spectroscopyDepressed patientsGABA levelsMedication-free depressed patientsOccipital cortex GABA levelsVivo proton magnetic resonance spectroscopyCortical GABA concentrationsGamma-aminobutyric acid (GABA) systemΓ-aminobutyric acid (GABA) levelsBrain GABA levelsMagnetic resonance spectroscopy protocolHealthy control subjectsDSM-IV criteriaGABA neurotransmitter systemEffect of depressionInteraction of diagnosisControl subjectsMajor depressionNeurotransmitter systemsHealthy subjectsOccipital cortexNeurobiologic processesAnalysis of covarianceGABA concentrationMental illnessCSF Monoamine Metabolite and Beta Endorphin Levels in Recently Detoxified Alcoholics and Healthy Controls
Petrakis I, Trevisan L, D'Souza C, Gil R, Krasnicki S, Webb E, Heninger G, Cooney N, Krystal J. CSF Monoamine Metabolite and Beta Endorphin Levels in Recently Detoxified Alcoholics and Healthy Controls. Alcohol Clinical And Experimental Research 1999, 23: 1336. DOI: 10.1097/00000374-199908000-00007.Peer-Reviewed Original ResearchAlcohol-dependent patientsHealthy controlsEndorphin levelsCSF levelsMonoamine metabolitesCSF measuresHealthy subjectsNorepinephrine metabolite MHPGLower CSF levelsBeta-endorphin levelsEarly-onset patientsCerebrospinal fluid levelsLate-onset patientsCentral neurotransmitter systemsCSF monoamine metabolitesDopamine metabolite HVAAlcohol cue exposureAlcohol-dependent individualsAlcohol cue reactivityLumbar punctureBackground abnormalitiesMetabolite HVANeurotransmitter systemsMonoaminergic dysregulationMetabolite MHPG