2020
PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies
Bhatt S, Hillmer AT, Girgenti MJ, Rusowicz A, Kapinos M, Nabulsi N, Huang Y, Matuskey D, Angarita GA, Esterlis I, Davis MT, Southwick SM, Friedman MJ, Duman R, Carson R, Krystal J, Pietrzak R, Cosgrove K. PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies. Nature Communications 2020, 11: 2360. PMID: 32398677, PMCID: PMC7217830, DOI: 10.1038/s41467-020-15930-5.Peer-Reviewed Original ResearchMeSH KeywordsAcetamidesAdaptor Proteins, Signal TransducingAdultBrainCase-Control StudiesFemaleGene Expression ProfilingHealthy VolunteersHumansMaleMicrogliaMiddle AgedPositron-Emission TomographyPyridinesRadiopharmaceuticalsReceptors, GABAReceptors, Tumor Necrosis Factor, Member 14Sex FactorsStress Disorders, Post-TraumaticYoung AdultConceptsPosttraumatic stress disorderPeripheral immune activationImmune activationHigher C-reactive protein levelsC-reactive protein levelsTSPO availabilityTranslocator proteinBrain microglial activationTomography brain imagingStress-related pathophysiologyPositron emission tomography (PET) brain imagingNeuroimmune activationMicroglial activationPTSD symptom severityImmunologic regulationPostmortem studiesPTSD subgroupHealthy individualsSymptom severityTrauma exposurePTSD groupStress disorderLower relative expressionBrain imagingPET imagingImaging 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
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 paradigmIn 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 controlsDysregulationMDDIdeationIndividuals
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 targetDisorders
2014
Test–retest reliability of the novel 5-HT1B receptor PET radioligand [11C]P943
Saricicek A, Chen J, Planeta B, Ruf B, Subramanyam K, Maloney K, Matuskey D, Labaree D, Deserno L, Neumeister A, Krystal JH, Gallezot JD, Huang Y, Carson RE, Bhagwagar Z. Test–retest reliability of the novel 5-HT1B receptor PET radioligand [11C]P943. European Journal Of Nuclear Medicine And Molecular Imaging 2014, 42: 468-477. PMID: 25427881, DOI: 10.1007/s00259-014-2958-5.Peer-Reviewed Original ResearchEvaluation 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 durationIn Vivo Ketamine-Induced Changes in [11C]ABP688 Binding to Metabotropic Glutamate Receptor Subtype 5
DeLorenzo C, DellaGioia N, Bloch M, Sanacora G, Nabulsi N, Abdallah C, Yang J, Wen R, Mann JJ, Krystal JH, Parsey RV, Carson RE, Esterlis I. In Vivo Ketamine-Induced Changes in [11C]ABP688 Binding to Metabotropic Glutamate Receptor Subtype 5. Biological Psychiatry 2014, 77: 266-275. PMID: 25156701, PMCID: PMC4277907, DOI: 10.1016/j.biopsych.2014.06.024.Peer-Reviewed Original ResearchConceptsSubtype 5Ketamine administrationPET scansMetabotropic glutamate receptor subtype 5Prefrontal cortexAspartate glutamate receptor antagonistIntravenous ketamine administrationKetamine-induced effectsPositron emission tomography (PET) ligandGlutamate receptor antagonistsVolume of distributionMedial prefrontal cortexNegative allosteric modulatorsKetamine initiationGlutamate releaseDorsal putamenKetamine responseSubanesthetic dosesOrbital prefrontal cortexReceptor antagonistAcute effectsBolus injectionDorsal caudateArterial bloodScan 1
2010
Decreased Beta2*‐nicotinic acetylcholine receptor availability after chronic ethanol exposure in nonhuman primates
Cosgrove KP, Kloczynski T, Bois F, Pittman B, Tamagnan G, Seibyl JP, Krystal JH, Staley JK. Decreased Beta2*‐nicotinic acetylcholine receptor availability after chronic ethanol exposure in nonhuman primates. Synapse 2010, 64: 729-732. PMID: 20340174, PMCID: PMC2904861, DOI: 10.1002/syn.20795.Peer-Reviewed Original ResearchConceptsChronic ethanol consumptionEthanol consumptionAlcohol consumptionNicotinic acetylcholine receptor availabilityAverage daily ethanol consumptionChronic ethanol exposureDaily ethanol consumptionEthanol-induced changesNicotinic acetylcholine receptorsSelf-administer ethanolIA-85380H withdrawalEthanol exposureReceptor availabilityAcetylcholine receptorsParietal cortexMale animalsTotal gramsBaselinePercent decreasePersistent changesWithdrawalMidbrainCortexAnimalsSPECT imaging of nicotinic acetylcholine receptors in nonsmoking heavy alcohol drinking individuals
Esterlis I, Cosgrove KP, Petrakis IL, McKee SA, Bois F, Krantzler E, Stiklus SM, Perry EB, Tamagnan GD, Seibyl JP, Krystal JH, Staley JK. SPECT imaging of nicotinic acetylcholine receptors in nonsmoking heavy alcohol drinking individuals. Drug And Alcohol Dependence 2010, 108: 146-150. PMID: 20074869, PMCID: PMC2871672, DOI: 10.1016/j.drugalcdep.2009.12.006.Peer-Reviewed Original ResearchConceptsDrinks/occasionNicotinic acetylcholine receptorsControl nonsmokersAcetylcholine receptorsHeavy drinkersHeavy drinkingLast alcoholic beverageHeavy alcohol drinkersHeavy alcoholSingle photon emissionSeverity of drinkingEffect of ageTobacco smokingAlcohol drinkersAlcohol drinkingCommon neural substrateNonsmokersAlcohol consumptionReceptor availabilityLarger studyAlcohol drinksAlcohol use behaviorsAddictive disordersDrinkersNeural substrates
2009
Dopamine and Serotonin Transporter Availability During Acute Alcohol Withdrawal: Effects of Comorbid Tobacco Smoking
Cosgrove KP, Krantzler E, Frohlich EB, Stiklus S, Pittman B, Tamagnan GD, Baldwin RM, Bois F, Seibyl JP, Krystal JH, O'Malley SS, Staley JK. Dopamine and Serotonin Transporter Availability During Acute Alcohol Withdrawal: Effects of Comorbid Tobacco Smoking. Neuropsychopharmacology 2009, 34: 2218-2226. PMID: 19440191, PMCID: PMC4457331, DOI: 10.1038/npp.2009.49.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcohol DrinkingBrainBrain MappingCase-Control StudiesCocaineDopamine Plasma Membrane Transport ProteinsFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedProtein BindingRadiopharmaceuticalsSerotonin Plasma Membrane Transport ProteinsSmokingStatistics as TopicSubstance Withdrawal SyndromeTomography, Emission-Computed, Single-PhotonYoung AdultConceptsDA transporter availabilityTobacco smokingSerotonin transporter availabilityTransporter availabilityAlcohol drinkersAcute withdrawalAlcohol drinkingLast drinkCIT single photon emissionAcute alcohol withdrawalHeavy alcohol drinkingSingle photon emissionEffects of alcoholControl smokersAlcohol withdrawalSynaptic markersNeuroadaptive changesNonsmokersSmokersSmokingTotal groupBrainstemSignificant positive correlationFirst weekPrevious month
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