2018
Enhanced Striatal Dopamine Release to Expectation of Alcohol: A Potential Risk Factor for Alcohol Use Disorder
Kegeles LS, Horga G, Ghazzaoui R, Rosengard R, Ojeil N, Xu X, Slifstein M, Petrakis I, O’Malley S, Krystal JH, Abi-Dargham A. Enhanced Striatal Dopamine Release to Expectation of Alcohol: A Potential Risk Factor for Alcohol Use Disorder. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2018, 3: 591-598. PMID: 29803635, PMCID: PMC6953614, DOI: 10.1016/j.bpsc.2018.03.018.Peer-Reviewed Original Research
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
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
2010
Sex Differences in Striatal Dopamine Release in Young Adults After Oral Alcohol Challenge: A Positron Emission Tomography Imaging Study With [11C]Raclopride
Urban NB, Kegeles LS, Slifstein M, Xu X, Martinez D, Sakr E, Castillo F, Moadel T, O'Malley SS, Krystal JH, Abi-Dargham A. Sex Differences in Striatal Dopamine Release in Young Adults After Oral Alcohol Challenge: A Positron Emission Tomography Imaging Study With [11C]Raclopride. Biological Psychiatry 2010, 68: 689-696. PMID: 20678752, PMCID: PMC2949533, DOI: 10.1016/j.biopsych.2010.06.005.Peer-Reviewed Original ResearchConceptsDopamine releaseStriatal subregionsAlcohol-induced dopamine releasePositron emission tomography scanAlcohol challengeStriatal dopamine releaseEmission tomography scanMaximum alcohol consumptionOral alcohol challengePositron emission tomographySex differencesAlcohol administrationYoung social drinkersTomography scanAbility of alcoholOral alcoholRewarding effectsMixed model analysisAlcohol consumptionAbuse liabilitySeparate daysSignificant negative correlationEmission tomographyVentral striatumSignificant positive correlation
2007
Neural Synchrony in Schizophrenia: From Networks to New Treatments
Ford JM, Krystal JH, Mathalon DH. Neural Synchrony in Schizophrenia: From Networks to New Treatments. Schizophrenia Bulletin 2007, 33: 848-852. PMID: 17567628, PMCID: PMC2632315, DOI: 10.1093/schbul/sbm062.Peer-Reviewed Original ResearchConceptsBrain regionsNeural basisFunctional neuroanatomyNeural oscillationsTemporal synchronyNeural synchronyDifferent brain regionsNeural activityNeural assembliesNeural populationsCognitive dysfunctionDistinct neuronal populationsSchizophreniaTemporal domainPhasic relationshipSynaptic transmissionNeuronal populationsTranslational studiesNew treatmentsEmergent propertiesSynchronyNeural networkNeuroanatomyPsychosisNeurochemistry
2005
Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine: Implications for Glutamatergic and Dopaminergic Model Psychoses and Cognitive Function
Krystal JH, Perry EB, Gueorguieva R, Belger A, Madonick SH, Abi-Dargham A, Cooper TB, MacDougall L, Abi-Saab W, D’Souza D. Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine: Implications for Glutamatergic and Dopaminergic Model Psychoses and Cognitive Function. JAMA Psychiatry 2005, 62: 985-995. PMID: 16143730, DOI: 10.1001/archpsyc.62.9.985.Peer-Reviewed Original ResearchAlcohol 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
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 approaches
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 Research
2001
A neurobiological basis for substance abuse comorbidity in schizophrenia
Chambers R, Krystal J, Self D. A neurobiological basis for substance abuse comorbidity in schizophrenia. Biological Psychiatry 2001, 50: 71-83. PMID: 11526998, PMCID: PMC2913410, DOI: 10.1016/s0006-3223(01)01134-9.Peer-Reviewed Original ResearchConceptsDrug rewardLong-term substance abuseMedication side effectsPrior drug exposureSubstance abuse comorbidityNeuropathology of schizophreniaPrimary disease symptomsAddictive behaviorsDrug-seeking behaviorHippocampal dysfunctionDrug exposureFrontal cortexNucleus accumbensHippocampal formationSchizophrenic patientsSide effectsCognitive impairmentNegative symptomsSubstance abuseAltered integrationNeural circuitrySymptomsSchizophreniaMotivational changesComorbiditiesQuantitative 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
Cocaine use and the mid-latency auditory evoked responses
Boutros N, Campbell D, Petrakis I, Krystal J, Caporale M, Kosten T. Cocaine use and the mid-latency auditory evoked responses. Psychiatry Research 2000, 96: 117-126. PMID: 11063784, DOI: 10.1016/s0165-1781(00)00207-9.Peer-Reviewed Original ResearchConceptsCocaine-dependent subjectsInter-stimulus intervalMid-latency auditoryAge-matched healthy control subjectsCocaine useHealthy control subjectsDifferent inter-stimulus intervalsChronic cocaine useLong inter-stimulus intervalsPaired-click paradigmControl subjectsP50 componentN100 componentSignificant decreaseSubjectsAuditoryResponse paradigmDopamine and serotonin transporters in patients with schizophrenia: an imaging study with [123I]β-CIT
Laruelle M, Abi-Dargham A, van Dyck C, Gil R, D’Souza D, Krystal J, Seibyl J, Baldwin R, Innis R. Dopamine and serotonin transporters in patients with schizophrenia: an imaging study with [123I]β-CIT. Biological Psychiatry 2000, 47: 371-379. PMID: 10704949, DOI: 10.1016/s0006-3223(99)00257-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsBrain StemCarrier ProteinsCase-Control StudiesCocaineDopamineDopamine Plasma Membrane Transport ProteinsFemaleHumansIodine RadioisotopesMaleMembrane GlycoproteinsMembrane Transport ProteinsMiddle AgedNeostriatumNerve Tissue ProteinsSchizophreniaSerotoninSerotonin Plasma Membrane Transport ProteinsTomography, Emission-Computed, Single-PhotonConceptsAmphetamine-induced dopamine releaseStriatal dopamine transporterDopamine transporterControl subjectsDAT densityDopamine releaseNegative symptomsStriatal DAT densityDuration of illnessDopamine nerve terminalsHealthy control subjectsSerotonin transporter densityCohort of subjectsRelative deficitSingle photon emissionNeurodegenerative processesPostmortem studiesNerve terminalsSerotonin functionTrend-level associationReceptor radiotracerPatientsDopamine functionLower striatalTransporter density
1999
Toward a rational pharmacotherapy of comorbid substance abuse in schizophrenic patients
Krystal J, D'Souza D, Madonick S, Petrakis I. Toward a rational pharmacotherapy of comorbid substance abuse in schizophrenic patients. Schizophrenia Research 1999, 35: s35-s49. PMID: 10190224, DOI: 10.1016/s0920-9964(98)00162-5.Peer-Reviewed Original ResearchConceptsSchizophrenic patientsSubstance abuseTerms of rehospitalizationComorbid substance abuseExacerbation of symptomsHealth care expensesSelf-medication hypothesisBetter prognosisMedical illnessPharmacotherapeutic approachesRational pharmacotherapyNonschizophrenic populationsPatientsVocational functionIllicit substancesCare expensesAbuseVulnerability hypothesisRehospitalizationExacerbationMedicationsPharmacotherapyPrognosisPsychostimulantsIllness
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
Effect of alpha-methyl-para-tyrosine on response to cocaine challenge
Stine S, Krystal J, Petrakis I, Jatlow P, Heninger G, Kosten T, Chamey D. Effect of alpha-methyl-para-tyrosine on response to cocaine challenge. Biological Psychiatry 1997, 42: 181-190. PMID: 9232210, DOI: 10.1016/s0006-3223(96)00331-9.Peer-Reviewed Original ResearchConceptsDopamine metabolite homovanillic acidCocaine-induced euphoriaNorepinephrine metabolite 3Placebo-controlled studyBlood pressure responseMetabolite homovanillic acidReduced plasma levelsTyrosine hydroxylase inhibitorSerum cocaine levelsTuberoinfundibular dopamine systemAMPT pretreatmentAcute reductionIntranasal administrationPara-tyrosinePlasma levelsProlactin levelsCocaine challengeHomovanillic acidCatecholamine synthesisHeart rateHydroxylase inhibitorAlpha-methylDopamine systemCocaine levelsTherapeutic potential
1996
Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects.
Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D'Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 9235-9240. PMID: 8799184, PMCID: PMC38625, DOI: 10.1073/pnas.93.17.9235.Peer-Reviewed Original ResearchConceptsAmphetamine-induced dopamine releaseDopamine releaseDopaminergic transmissionPsychotic symptomsSchizophrenic groupDopamine D2 receptor availabilityAmphetamine-induced decreaseAmphetamine-induced reductionD2 receptor availabilityD2 receptor radiotracerPositive psychotic symptomsSingle photon emissionExaggerated stimulationAbnormal responsivenessDopaminergic neuronsHealthy controlsReceptor radiotracerSchizophrenic patientsDopamine hypothesisDopamine functionReceptor availabilityAmphetamine effectsControl groupSchizophrenic subjectsSchizophreniaClinical and Biochemical Effects of Catecholamine Depletion on Antidepressant-Induced Remission of Depression
Miller HL, Delgado PL, Salomon RM, Berman R, Krystal JH, Heninger GR, Charney DS. Clinical and Biochemical Effects of Catecholamine Depletion on Antidepressant-Induced Remission of Depression. JAMA Psychiatry 1996, 53: 117-128. PMID: 8629887, DOI: 10.1001/archpsyc.1996.01830020031005.Peer-Reviewed Original ResearchConceptsNorepinephrine reuptake inhibitorsReuptake inhibitorsCatecholamine depletionAlpha-methylparatyrosineTreatment groupsHamilton Depression Rating ScaleHomovanillic acid levelsSerotonin reuptake inhibitorsDepression Rating ScaleSimilar significant decreaseAntihistamine diphenhydramine hydrochlorideSeparate test sessionsFeelings of worthlessnessConsiderable sedationLoss of interestDepressed patientsDepressive relapseAntidepressant drugsInactive placeboTherapeutic effectTherapeutic mechanismDepressive symptomsCatecholamine metabolitesPlasma 3Remission
1993
Elevated CSF levels of interleukin-2 in neuroleptic-free schizophrenic patients
Licinio J, Seibyl JP, Altemus M, Charney DS, Krystal JH. Elevated CSF levels of interleukin-2 in neuroleptic-free schizophrenic patients. American Journal Of Psychiatry 1993, 150: 1408-1410. PMID: 8102512, DOI: 10.1176/ajp.150.9.1408.Peer-Reviewed Original ResearchConceptsNeuroleptic-free schizophrenic patientsInterleukin-2Dopaminergic neurotransmissionSchizophrenic patientsElevated CSF levelsAbnormal brain morphologyInterleukin-1 alphaAutoimmune phenomenaCSF levelsHealthy subjectsBrain morphologyPatientsElevated levelsNeurotransmissionCell growthAutoimmunityLevelsSchizophreniaPsychobiologic Mechanisms of Posttraumatic Stress Disorder
Charney DS, Deutch AY, Krystal JH, Southwick SM, Davis M. Psychobiologic Mechanisms of Posttraumatic Stress Disorder. JAMA Psychiatry 1993, 50: 294-305. PMID: 8466391, DOI: 10.1001/archpsyc.1993.01820160064008.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderStress disorderPathophysiology of PTSDAvoidance of stimuliFailure of extinctionFear conditioningTraumatic memoriesMemory processesAutonomic hyperarousalTraumatic eventsEffects of stressCore symptomsPersistent reexperiencingPsychobiologic mechanismsAdaptive behavioralBrain structuresNeurochemical systemsNeurobiologic mechanismsReexperiencingParallel activationHyperarousalDisordersChronic courseTrauma resultsBehavioral sensitization