2018
Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects
D’Souza D, Carson RE, Driesen N, Johannesen J, Ranganathan M, Krystal JH, Ahn K, Bielen K, Carbuto M, Deaso E, D’Souza D, Ranganathan M, Naganawa M, Ranganathan M, D’Souza D, Nabulsi N, Zheng M, Lin S, Huang Y, Carson R, Driesen N, Ahn K, Morgan P, Suckow R, He G, McCarthy G, Krystal J, Johannesen J, Kenney J, Gelernter J, Gueorguieva R, Pittman B. Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects. Biological Psychiatry 2018, 84: 413-421. PMID: 29499855, PMCID: PMC6068006, DOI: 10.1016/j.biopsych.2017.12.019.Peer-Reviewed Original ResearchMeSH KeywordsAdultAzabicyclo CompoundsBrainCognitive DysfunctionDose-Response Relationship, DrugDouble-Blind MethodFemaleGlycine Plasma Membrane Transport ProteinsHumansImidazolesKetamineLong-Term PotentiationMagnetic Resonance ImagingMaleMemory, Short-TermMiddle AgedPositron-Emission TomographySchizophreniaYoung AdultConceptsHealthy control subjectsLong-term potentiationSchizophrenia patientsControl subjectsCognitive impairmentClinical trialsGlyT1 occupancyN-methyl-D-aspartate receptor functionGlycine transporter-1 inhibitorKetamine-induced disruptionKetamine-induced effectsFunctional magnetic resonance imagingMagnetic resonance imagingPositron emission tomographyMemory-related activationF-MKSubstudy 1Schizophrenia subjectsResonance imagingReceptor functionCortical regionsEmission tomographyTarget engagementPotentiationSchizophrenia
2013
Deep resequencing of 17 glutamate system genes identifies rare variants in DISC1 and GRIN2B affecting risk of opioid dependence
Xie P, Kranzler HR, Krystal JH, Farrer LA, Zhao H, Gelernter J. Deep resequencing of 17 glutamate system genes identifies rare variants in DISC1 and GRIN2B affecting risk of opioid dependence. Addiction Biology 2013, 19: 955-964. PMID: 23855403, PMCID: PMC3815683, DOI: 10.1111/adb.12072.Peer-Reviewed Original ResearchConceptsOpioid dependenceSubstance dependenceRare variantsN-methyl-D-aspartate (NMDA) glutamate receptorsCo-occurring alcohol dependenceHealthy control subjectsControl subjectsNMDA systemOpioid abuseGlutamate receptorsSchizophrenia risk genesSD riskAlcohol dependenceSignificant associationCocaine dependenceAdditional subjectsOD riskRisk genesDISC1African AmericansFirst demonstrationCommon variantsRiskSubjectsMinor allele frequency
2012
Impaired Visual Cortical Plasticity in Schizophrenia
Çavuş I, Reinhart RM, Roach BJ, Gueorguieva R, Teyler TJ, Clapp WC, Ford JM, Krystal JH, Mathalon DH. Impaired Visual Cortical Plasticity in Schizophrenia. Biological Psychiatry 2012, 71: 512-520. PMID: 22364738, PMCID: PMC3292767, DOI: 10.1016/j.biopsych.2012.01.013.Peer-Reviewed Original ResearchConceptsHigh-frequency stimulationVisual cortical plasticityCortical plasticityVisual steady-state responseN-methyl-D-aspartate receptor functionHealthy control subjectsLong-term potentiation paradigmLong-term potentiationForm of neuroplasticityRepetitive visual stimulationSustained potentiationControl subjectsVEP assessmentSchizophrenia patientsStandard visual stimuliInfrequent target stimuliCore pathophysiologyReceptor functionPotentiationSchizophreniaVisual stimulationComponent scoresStimulationVisual stimuliBaseline
2011
Reduced Amygdala Serotonin Transporter Binding in Posttraumatic Stress Disorder
Murrough JW, Huang Y, Hu J, Henry S, Williams W, Gallezot JD, Bailey CR, Krystal JH, Carson RE, Neumeister A. Reduced Amygdala Serotonin Transporter Binding in Posttraumatic Stress Disorder. Biological Psychiatry 2011, 70: 1033-1038. PMID: 21855859, PMCID: PMC3207037, DOI: 10.1016/j.biopsych.2011.07.003.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderMontgomery-Åsberg Depression Rating Scale scoresDepression Rating Scale scoresPositron emission tomography scanStress disorderAbnormal amygdala activityEmission tomography scanHealthy control subjectsHamilton Rating ScaleRating Scale scoresBetween-group differencesSerotonin transporter bindingPositron emission tomographyControl subjectsTomography scanTransporter bindingHC groupAmygdala regionPTSD patientsLeft amygdalaScale scoreDepression symptomsEmission tomographyAmygdalaPTSD group
2010
Serotonin 1B Receptor Imaging in Alcohol Dependence
Hu J, Henry S, Gallezot JD, Ropchan J, Neumaier JF, Potenza MN, Sinha R, Krystal JH, Huang Y, Ding YS, Carson RE, Neumeister A. Serotonin 1B Receptor Imaging in Alcohol Dependence. Biological Psychiatry 2010, 67: 800-803. PMID: 20172504, PMCID: PMC3112181, DOI: 10.1016/j.biopsych.2009.12.028.Peer-Reviewed Original ResearchConceptsHealthy control subjectsAlcohol dependencePositron emission tomographyStriatal 5Emission tomographyMagnetic resonance imaging (MRI) scansIndividual magnetic resonance imaging (MRI) scansMultilinear reference tissue modelResonance imaging scansSerotonin 1B receptorReference tissue modelClinical variablesAbstinent patientsControl subjectsImaging scansAnatomical abnormalitiesHC subjectsRodent modelsAntagonist radioligandReceptor imagingAnimal modelsVivo assessmentTomographyFirst evidenceHigh-resolution research tomograph
2008
The effects of cannabinoids on serum cortisol and prolactin in humans
Ranganathan M, Braley G, Pittman B, Cooper T, Perry E, Krystal J, D’Souza D. The effects of cannabinoids on serum cortisol and prolactin in humans. Psychopharmacology 2008, 203: 737. PMID: 19083209, PMCID: PMC2863108, DOI: 10.1007/s00213-008-1422-2.Peer-Reviewed Original ResearchConceptsPlasma prolactin levelsPlasma cortisol levelsProlactin levelsNeuroendocrine effectsCannabis exposureHealthy controlsNeuroendocrine functionHormonal levelsCortisol levelsFrequent usersChronic cannabis exposureHealthy control subjectsDose-related increaseEffects of cannabinoidsBaseline hormonal levelsDose-related effectsDevelopment of toleranceLimited dose-response dataDose-dependent mannerBlunted increaseMultiple dosesControl subjectsSerum cortisolHormone levelsPlasma cortisolβ 2 Nicotinic acetylcholine receptor availability in post-traumatic stress disorder
Czermak C, Staley JK, Kasserman S, Bois F, Young T, Henry S, Tamagnan GD, Seibyl JP, Krystal JH, Neumeister A. β 2 Nicotinic acetylcholine receptor availability in post-traumatic stress disorder. The International Journal Of Neuropsychopharmacology 2008, 11: 419-424. PMID: 18190729, DOI: 10.1017/s1461145707008152.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderClinician-Administered PTSD ScaleMesiotemporal cortexPTSD patientsPathophysiology of PTSDStress disorderBeta2 nAChRsNicotinic acetylcholine receptor availabilityHistory of smokingHealthy control subjectsNicotinic acetylcholine receptorsIA bindingNovel molecular targetsSingle photon emissionSubgroup of participantsRe-experiencing symptom clusterIA-85380Symptomatic patientsControl subjectsHealthy controlsReceptor availabilityPTSD ScaleAcetylcholine receptorsSymptom clustersPrefrontal cortex
2006
Cerebral Metabolic Effects of Intravenous Glycine in Healthy Human Subjects
Neumeister A, Carson R, Henry S, Planeta-Wilson B, Binneman B, Maguire RP, Luckenbaugh DA, D'Souza C, Krystal JH, Frost JJ. Cerebral Metabolic Effects of Intravenous Glycine in Healthy Human Subjects. Journal Of Clinical Psychopharmacology 2006, 26: 595-599. PMID: 17110816, DOI: 10.1097/01.jcp.0000245558.14284.aa.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntipsychotic AgentsBehaviorBrainBrain MappingCluster AnalysisCross-Over StudiesDouble-Blind MethodFemaleFluorodeoxyglucose F18GlycineHumansInfusions, IntravenousMagnetic Resonance ImagingMaleNeuropsychological TestsPositron-Emission TomographyRadiopharmaceuticalsReference ValuesSerineConceptsN-methyl-D-aspartate receptor functionReceptor functionRegional cerebral metabolic rateAdministration of glycineCerebral metabolic effectsMagnetic resonance imaging studyPositron emission tomography studyHealthy control subjectsNMDA receptor functionCerebral metabolic rateEmission tomography studiesTest dayHealthy human subjectsResonance imaging studySignificant reductionPositron emission tomographyDorsolateral prefrontal cortexIntravenous glycinePlacebo infusionCerebral metabolismPatient populationControl subjectsGlycine administrationGlycine infusionIntravenous administration
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 striatumReceptorsImpact of Schizophrenia and Chronic Antipsychotic Treatment on [123I]CNS-1261 Binding to N-Methyl-D-Aspartate Receptors In Vivo
Bressan RA, Erlandsson K, Stone JM, Mulligan RS, Krystal JH, Ell PJ, Pilowsky LS. Impact of Schizophrenia and Chronic Antipsychotic Treatment on [123I]CNS-1261 Binding to N-Methyl-D-Aspartate Receptors In Vivo. Biological Psychiatry 2005, 58: 41-46. PMID: 15992521, DOI: 10.1016/j.biopsych.2005.03.016.Peer-Reviewed Original ResearchConceptsHealthy control subjectsTypical antipsychoticsControl subjectsN-methyl-D-aspartate receptor functionN-methyl-D-aspartate receptorsAntipsychotic drug discoveryChronic antipsychotic treatmentDrug-free patientsImpact of schizophreniaNMDA receptor activityHealthy normal volunteersClozapine treatmentAntipsychotic treatmentGlutamatergic systemPatient groupAntipsychotic drugsNonsignificant reductionNMDA receptorsNormal volunteersSchizophrenia patientsControl groupReceptor activityBrain regionsReceptor functionTomography radiotracerAbnormal hemodynamics in schizophrenia during an auditory oddball task
Kiehl KA, Stevens MC, Celone K, Kurtz M, Krystal JH. Abnormal hemodynamics in schizophrenia during an auditory oddball task. Biological Psychiatry 2005, 57: 1029-1040. PMID: 15860344, PMCID: PMC2771438, DOI: 10.1016/j.biopsych.2005.01.035.Peer-Reviewed Original ResearchConceptsAuditory oddball taskHealthy participantsOddball taskThree-stimulus auditory oddball taskDiffuse brain abnormalitiesHealthy control subjectsNovelty processingWidespread pathologic processCerebral areasControl subjectsBrain abnormalitiesMagnetic resonance imaging dataAbnormal hemodynamicsPathologic processesSchizophrenia patientsParietal cortexCognitive functionHeterogeneous disorderCerebellar circuitsSchizophreniaAbnormalitiesSignificant activationSubcortical systemsFunctional magnetic resonance imaging (fMRI) dataPatients
2004
Subtype-Specific Alterations of γ-Aminobutyric Acid and Glutamatein Patients With Major Depression
Sanacora G, Gueorguieva R, Epperson CN, Wu YT, Appel M, Rothman DL, Krystal JH, Mason GF. Subtype-Specific Alterations of γ-Aminobutyric Acid and Glutamatein Patients With Major Depression. JAMA Psychiatry 2004, 61: 705-713. PMID: 15237082, DOI: 10.1001/archpsyc.61.7.705.Peer-Reviewed Original ResearchConceptsMajor depressive disorderGamma-aminobutyric acidOccipital cortex GABA concentrationsProton magnetic resonance spectroscopyDepressed subjectsGABA concentrationHealthy controlsSubtypes of MDDCortical gamma-aminobutyric acidHealthy control subjectsMetabolite levelsCholine-containing compoundsHealthy comparison subjectsClinical research programSubtype-specific alterationsΓ-aminobutyric acidClinical correlatesMDD patientsControl subjectsDepressive disorderNeurotransmitter levelsGlutamate levelsMajor depressionMDD subtypesOccipital cortex
2003
A Functional Magnetic Resonance Imaging Study of Bipolar Disorder: State- and Trait-Related Dysfunction in Ventral Prefrontal Cortices
Blumberg HP, Leung HC, Skudlarski P, Lacadie CM, Fredericks CA, Harris BC, Charney DS, Gore JC, Krystal JH, Peterson BS. A Functional Magnetic Resonance Imaging Study of Bipolar Disorder: State- and Trait-Related Dysfunction in Ventral Prefrontal Cortices. JAMA Psychiatry 2003, 60: 601-609. PMID: 12796223, DOI: 10.1001/archpsyc.60.6.601.Peer-Reviewed Original ResearchConceptsVentral prefrontal cortexBipolar disorderPrefrontal cortexMood statesMagnetic resonance imaging studyHealthy control subjectsAcute mood statesLeft ventral prefrontal cortexResonance imaging studySignal changesDisturbances of attentionFunctional magnetic resonance imaging studyAnterior cingulate cortexBipolar disorder IDorsal anterior cingulateEvent-related functional magnetic resonanceFunctional magnetic resonanceAcute episodeControl subjectsExaggerated increaseFunctional impairmentBlunted activationMood episodesSpecific mood statesPrefrontal abnormalities
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
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 illness[123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia
Verhoeff N, Soares J, D’Souza C, Gil R, Degen K, Abi-Dargham A, Zoghbi S, Fujita M, Rajeevan N, Seibyl J, Krystal J, van Dyck C, Charney D, Innis R. [123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia. Psychiatry Research 1999, 91: 163-173. PMID: 10641580, DOI: 10.1016/s0925-4927(99)00027-x.Peer-Reviewed Original ResearchConceptsDuration of illnessHealthy control subjectsControl subjectsGamma-aminobutyric acidLeft precentral gyrusSuperior occipital gyrusPANSS scoresPrecentral gyrusOccipital gyrusSignificant differencesTotal brain uptakeNon-smoking patientsGray matter atrophyConstant infusion paradigmPathophysiology of schizophreniaCortical brain regionsSingle photon emissionTypical antipsychoticsAtypical antipsychoticsCigarette smokingInhibitory neurotransmissionBrain uptakeInfusion paradigmMatter atrophyPostmortem studies