2022
Multimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder
Smart K, Worhunsky PD, Scheinost D, Angarita GA, Esterlis I, Carson RE, Krystal JH, O'Malley SS, Cosgrove KP, Hillmer AT. Multimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder. Alcohol Clinical And Experimental Research 2022, 46: 770-782. PMID: 35342968, PMCID: PMC9117461, DOI: 10.1111/acer.14816.Peer-Reviewed Original ResearchConceptsMetabotropic glutamate 5 receptorsDefault mode networkFunctional magnetic resonance imagingReceptor availabilityPositron emission tomographyAUD groupFunctional connectivityReceptor positron emission tomographyResting-state functional magnetic resonance imagingNetwork-level functional connectivityBrain connectivityWeeks of abstinenceGlobal functional connectivityAlcohol use disorderMagnetic resonance imagingFMRI outcomesHealthy controlsSupervised abstinencePET resultsUse disordersSynaptic plasticityResonance imagingBrain regionsEmission tomographyOrbitofrontal cortexImaging the effect of ketamine on synaptic density (SV2A) in the living brain
Holmes SE, Finnema SJ, Naganawa M, DellaGioia N, Holden D, Fowles K, Davis M, Ropchan J, Emory P, Ye Y, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Imaging the effect of ketamine on synaptic density (SV2A) in the living brain. Molecular Psychiatry 2022, 27: 2273-2281. PMID: 35165397, PMCID: PMC9133063, DOI: 10.1038/s41380-022-01465-2.Peer-Reviewed Original ResearchConceptsKetamine's therapeutic effectsMajor depressive disorderTherapeutic effectPositron emission tomographyPosttraumatic stress disorderHealthy controlsSynaptic connectionsSynaptic vesicle protein 2APost-synaptic mechanismsEffects of ketamineDiscovery of ketamineNon-human primatesAntidepressant effectsDepressive disorderSingle administrationSynaptic densityPsychiatric disordersDepression severityKetamineEmission tomographyTerminal densityLiving brainStress disorderRobust reductionDissociative symptoms
2021
Imaging brain cortisol regulation in PTSD with a target for 11β-hydroxysteroid dehydrogenase type 1
Bhatt S, Hillmer AT, Rusowicz A, Nabulsi N, Matuskey D, Angarita GA, Najafzadeh S, Kapinos M, Southwick SM, Krystal JH, Carson RE, Huang Y, Cosgrove KP. Imaging brain cortisol regulation in PTSD with a target for 11β-hydroxysteroid dehydrogenase type 1. Journal Of Clinical Investigation 2021, 131: e150452. PMID: 34651587, PMCID: PMC8516462, DOI: 10.1172/jci150452.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderPositron emission tomographyVolume of distributionDehydrogenase type 1Trauma-exposed controlsPTSD groupTranslocator proteinType 1Veterans Affairs (VA) National CenterOverall PTSD severityBrain glucocorticoidBrain immuneMethodsSixteen individualsPeripheral cortisolMicroglial markersImmune suppressionTranslational Science AwardsCortisol levelsNIH National CenterTC groupCortisol regulationEmission tomographyStress disorderLower PTSD symptomsPTSD symptoms
2019
In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation
Davis MT, Hillmer A, Holmes SE, Pietrzak RH, DellaGioia N, Nabulsi N, Matuskey D, Angarita G, Carson RE, Krystal JH, Esterlis I. In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 11490-11495. PMID: 31085640, PMCID: PMC6561298, DOI: 10.1073/pnas.1818871116.Peer-Reviewed Original ResearchConceptsMGluR5 availabilitySuicidal ideationHC individualsPathophysiology of PTSDLimbic brain regionsVolume of distributionHealthy comparison controlsSuicide risk managementPositron emission tomographyReceptor 5Venous input functionsBrain regionsPTSD individualsEmission tomographyMDD individualsVivo evidenceRecent evidencePotential roleMGluR5PTSDComparison controlsDysregulationMDDIdeationIndividualsLower synaptic density is associated with depression severity and network alterations
Holmes SE, Scheinost D, Finnema SJ, Naganawa M, Davis MT, DellaGioia N, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Lower synaptic density is associated with depression severity and network alterations. Nature Communications 2019, 10: 1529. PMID: 30948709, PMCID: PMC6449365, DOI: 10.1038/s41467-019-09562-7.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPost-traumatic stress disorderLower synaptic densitySynaptic densityPositron emission tomographyFunctional connectivityNetwork alterationsSynaptic vesicle glycoprotein 2ASymptoms of depressionSynaptic lossDepressive disorderHealthy controlsNerve terminalsDepressive symptomsDepression severityUnmedicated individualsSynaptic connectionsEmission tomographyStress disorderVivo evidenceSymptomsDepressionSeverityDisordersAlterations
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
2017
Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence
Holmes SE, Girgenti MJ, Davis MT, Pietrzak RH, DellaGioia N, Nabulsi N, Matuskey D, Southwick S, Duman RS, Carson RE, Krystal JH, Esterlis I, Friedman M, Kowall N, Brady C, McKee A, Stein T, Huber B, Kaloupek D, Alvarez V, Benedek D, Ursano R, Williamson D, Cruz D, Young K, Duman R, Krystal J, Mash D, Hardegree M, Serlin G. Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 8390-8395. PMID: 28716937, PMCID: PMC5547601, DOI: 10.1073/pnas.1701749114.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderMGluR5 availabilityPositron emission tomographyGlutamate systemMetabotropic glutamate receptor 5Treatment of PTSDHuman posttraumatic stress disorderGlutamate receptor 5Mechanism-based treatmentsExpression of FKBP5Promising treatment targetHuman postmortem tissueTargeted pharmacological treatmentStress psychopathologyPharmacological treatmentExpression of proteinsReceptor 5MGluR5Treatment targetsPostmortem tissueEmission tomographyStress disorderPostmortem samplesPromising targetDisordersKetamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression
Esterlis I, DellaGioia N, Pietrzak RH, Matuskey D, Nabulsi N, Abdallah CG, Yang J, Pittenger C, Sanacora G, Krystal JH, Parsey RV, Carson RE, DeLorenzo C. Ketamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression. Molecular Psychiatry 2017, 23: 824-832. PMID: 28397841, PMCID: PMC5636649, DOI: 10.1038/mp.2017.58.Peer-Reviewed Original ResearchConceptsMajor depressive disorderMGluR5 availabilityPositron emission tomographyKetamine administrationControl groupAspartate glutamate receptor antagonistIntravenous ketamine administrationKetamine-induced reductionMetabotropic glutamatergic receptorsRapid antidepressant effectsGlutamate receptor antagonistsKetamine-induced changesEffects of ketaminePET imaging studiesMechanism of actionGlutamate surgeAntidepressant effectsAntidepressant efficacyAntidepressant responseGlutamatergic receptorsControl subjectsReceptor antagonistHealthy controlsDepressive disorderSustained decrease
2014
Evaluation of the sensitivity of the novel α4β2* nicotinic acetylcholine receptor PET radioligand 18F‐(‐)‐NCFHEB to increases in synaptic acetylcholine levels in rhesus monkeys
Gallezot J, Esterlis I, Bois F, Zheng M, Lin S, Kloczynski T, Krystal JH, Huang Y, Sabri O, Carson RE, Cosgrove KP. Evaluation of the sensitivity of the novel α4β2* nicotinic acetylcholine receptor PET radioligand 18F‐(‐)‐NCFHEB to increases in synaptic acetylcholine levels in rhesus monkeys. Synapse 2014, 68: 556-564. PMID: 25043426, PMCID: PMC4224280, DOI: 10.1002/syn.21767.Peer-Reviewed Original ResearchConceptsSynaptic acetylcholine concentrationPositron emission tomographyAcetylcholine concentrationRhesus monkeysInfusion of physostigmineSynaptic acetylcholine levelsDose-dependent reductionNicotinic acetylcholine receptorsAcetylcholine levelsBolus injectionAcetylcholine receptorsAcetylcholine dynamicsNew radioligandEmission tomographyArterial input functionAcetylcholinesterase inhibitorsRadioligandThalamusPhysostigmineDonepezilΑ4β2Promising tracerBaselineMonkeysShort scan duration
2013
Association of Posttraumatic Stress Disorder With Reduced In Vivo Norepinephrine Transporter Availability in the Locus Coeruleus
Pietrzak RH, Gallezot JD, Ding YS, Henry S, Potenza MN, Southwick SM, Krystal JH, Carson RE, Neumeister A. Association of Posttraumatic Stress Disorder With Reduced In Vivo Norepinephrine Transporter Availability in the Locus Coeruleus. JAMA Psychiatry 2013, 70: 1199-1205. PMID: 24048210, PMCID: PMC4026855, DOI: 10.1001/jamapsychiatry.2013.399.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderNorepinephrine transporter availabilityLocus coeruleusPTSD groupTransporter availabilityHC groupVeterans Affairs Medical CenterStress disorderPTSD symptomsClinician-Administered PTSD ScalePositron emission tomography studyEmission tomography studiesPositron emission tomographyAnxious arousal symptomsNoradrenergic dysfunctionMedical CenterStudy groupMAIN OUTCOMEPTSD symptom clustersPTSD ScaleHealthy adultsCoeruleusBrain regionsChronic stressEmission tomography
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 groupImaging 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 changeThe Effect of Early Trauma Exposure on Serotonin Type 1B Receptor Expression Revealed by Reduced Selective Radioligand Binding
Murrough JW, Czermak C, Henry S, Nabulsi N, Gallezot JD, Gueorguieva R, Planeta-Wilson B, Krystal JH, Neumaier JF, Huang Y, Ding YS, Carson RE, Neumeister A. The Effect of Early Trauma Exposure on Serotonin Type 1B Receptor Expression Revealed by Reduced Selective Radioligand Binding. JAMA Psychiatry 2011, 68: 892-900. PMID: 21893657, PMCID: PMC3244836, DOI: 10.1001/archgenpsychiatry.2011.91.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsBrainCarbon RadioisotopesCross-Sectional StudiesDepressive Disorder, MajorFemaleHumansMaleMiddle AgedPiperazinesPositron-Emission TomographyPsychiatric Status Rating ScalesPyrrolidinonesRadioligand AssayReceptor, Serotonin, 5-HT1BSerotonin 5-HT1 Receptor AntagonistsStress Disorders, Post-TraumaticTrauma Severity IndicesWounds and InjuriesConceptsPosttraumatic stress disorderHealthy control participantsEarly trauma exposureTrauma exposureReceptor expressionCause of PTSDVeterans Affairs Medical CenterMajor depression comorbidityPositron emission tomography studyControl participantsMain outcome measuresRecent animal modelsTrauma-exposed control participantsSevere trauma exposureEmission tomography studiesFirst trauma exposureLimbic corticostriatal circuitsAnterior cingulate cortexPositron emission tomographyPTSD symptom severityDepression comorbiditySerotonergic dysfunctionMedical CenterOutcome measuresStudy group
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 correlationSerotonin 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
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 striatumReceptors
1997
Positron Emission Tomography Measurement of Cerebral Metabolic Correlates of Tryptophan Depletion—Induced Depressive Relapse
Bremner JD, Innis RB, Salomon RM, Staib LH, Ng CK, Miller HL, Bronen RA, Krystal JH, Duncan J, Rich D, Price LH, Malison R, Dey H, Soufer R, Charney DS. Positron Emission Tomography Measurement of Cerebral Metabolic Correlates of Tryptophan Depletion—Induced Depressive Relapse. JAMA Psychiatry 1997, 54: 364-374. PMID: 9107153, DOI: 10.1001/archpsyc.1997.01830160092012.Peer-Reviewed Original ResearchConceptsCerebral metabolic correlatesDepressive relapseBrain metabolismMajor depressionMiddle frontal gyrusOrbitofrontal cortexTryptophan depletionMetabolic correlatesPositron emission tomography scanningFrontal gyrusRelapse-prone patientsPathogenesis of depressionPositron emission tomography (PET) measurementsSerotonin reuptake inhibitorsSymptoms of patientsPositron emission tomographySingle photon emissionSpecific brain regionsDorsolateral prefrontal cortexReuptake inhibitorsPlasma tryptophanLimbic regionsCaudate nucleusDepressive symptomsPatientsPositron Emission Tomography Measurement of Cerebral Metabolic Correlates of Yohimbine Administration in Combat-Related Posttraumatic Stress Disorder
Bremner JD, Innis RB, Ng CK, Staib LH, Salomon RM, Bronen RA, Duncan J, Southwick SM, Krystal JH, Rich D, Zubal G, Dey H, Soufer R, Charney DS. Positron Emission Tomography Measurement of Cerebral Metabolic Correlates of Yohimbine Administration in Combat-Related Posttraumatic Stress Disorder. JAMA Psychiatry 1997, 54: 246-254. PMID: 9075465, DOI: 10.1001/archpsyc.1997.01830150070011.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderAdministration of yohimbineNorepinephrine releaseHealthy subjectsHealthy age-matched control subjectsAge-matched control subjectsStress disorderDouble-blind fashionPositron emission tomography (PET) measurementsBrain metabolic responsesCerebral metabolic correlatesBrain norepinephrine releaseSymptoms of anxietyPositron emission tomographyBrain metabolismControl subjectsYohimbine administrationPreclinical studiesMetabolic correlatesCaudate nucleusPatientsYohimbineVietnam combat veteransEmission tomographyOrbitofrontal cortex
1987
Positron Emission Tomography and Autoradiography: Principles and Applications for the Brain and Heart
Krystal J. Positron Emission Tomography and Autoradiography: Principles and Applications for the Brain and Heart. The Yale Journal Of Biology And Medicine 1987, 60: 202-202. PMCID: PMC2590308.Peer-Reviewed Original ResearchPositron emission tomographyEmission tomography