2024
Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia
Bonomi R, Hillmer A, Woodcock E, Bhatt S, Rusowicz A, Angarita G, Carson R, Davis M, Esterlis I, Nabulsi N, Huang Y, Krystal J, Pietrzak R, Cosgrove K. Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2406005121. PMID: 39172786, PMCID: PMC11363315, DOI: 10.1073/pnas.2406005121.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnhedoniaBrainFemaleHumansLipopolysaccharidesMaleMicrogliaMiddle AgedNeuroimmunomodulationPositron-Emission TomographyReceptors, GABAStress Disorders, Post-TraumaticConceptsPTSD groupPrefrontal-limbic circuitsNeuroimmune responseAssociated with anhedoniaPosttraumatic stress disorderPositron emission tomography brain imagingTranslocator protein availabilityBrain immune functionAnhedonic symptomsStress disorderPeripheral immune dysfunctionPTSDGroup differencesSeverity of symptomsPsychiatric diseasesTranslocator proteinBrain imagingAdministration of lipopolysaccharideSymptomsMicroglial markersLPS-induced increaseCompared to controlsImmune functionSickness symptomsAnhedonia
2023
Evaluating infusion methods and simplified quantification of synaptic density in vivo with [11C]UCB-J and [18F]SynVesT-1 PET
Asch R, Naganawa M, Nabulsi N, Huan Y, Esterlis I, Carson R. Evaluating infusion methods and simplified quantification of synaptic density in vivo with [11C]UCB-J and [18F]SynVesT-1 PET. Cerebrovascular And Brain Metabolism Reviews 2023, 43: 2120-2129. PMID: 37669455, PMCID: PMC10925870, DOI: 10.1177/0271678x231200423.Peer-Reviewed Original ResearchImaging the brain’s immune response to alcohol with [11C]PBR28 TSPO Positron Emission Tomography
Raval N, Angarita G, Matuskey D, Miller R, Drake L, Kapinos M, Nabulsi N, Huang Y, Carson R, O’Malley S, Cosgrove K, Hillmer A. Imaging the brain’s immune response to alcohol with [11C]PBR28 TSPO Positron Emission Tomography. Molecular Psychiatry 2023, 28: 3384-3390. PMID: 37532797, PMCID: PMC10743097, DOI: 10.1038/s41380-023-02198-6.Peer-Reviewed Original ResearchMeSH KeywordsBlood Alcohol ContentBrainCytokinesFemaleHumansImmunityMalePositron-Emission TomographyRadionuclide ImagingReceptors, GABAConceptsVolume of distributionBlood alcohol levelsPositron emission tomographyBrain immune responseImmune responseAlcohol challengeEmission tomographyPeak blood alcohol levelsMultilinear analysis 1Peripheral immune functionVivo human evidenceLaboratory alcohol challengeTSPO positron emission tomographyBinge levelsPlasma cytokinesImmune dysfunctionNeuroimmune systemIL-6MCP-1Cytokines TNFAcute effectsScan dayArterial bloodHuman evidenceImmune functionPrincipal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease
O'Dell R, Higgins-Chen A, Gupta D, Chen M, Naganawa M, Toyonaga T, Lu Y, Ni G, Chupak A, Zhao W, Salardini E, Nabulsi N, Huang Y, Arnsten A, Carson R, van Dyck C, Mecca A. Principal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease. NeuroImage Clinical 2023, 39: 103457. PMID: 37422964, PMCID: PMC10338149, DOI: 10.1016/j.nicl.2023.103457.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloidAmyloidogenic ProteinsBrainCognitive DysfunctionHumansPositron-Emission TomographyPrincipal Component AnalysisConceptsCognitive domainsCognitive performanceSubjects' scoresCortical regionsNeuropsychological batteryEarly Alzheimer's diseaseAD groupBilateral regionsNormal participantsNegative loadingsCognitive impairmentCN participantsAlzheimer's diseaseParticipantsStructural correlatesStrong contributionParticipant characteristicsScoresPositive loadingsData-driven approachTotal variancePrincipal component analysisSpecific spatial patternsPreclinical evaluation of a brain penetrant PARP PET imaging probe in rat glioblastoma and nonhuman primates
Chen B, Ojha D, Toyonaga T, Tong J, Pracitto R, Thomas M, Liu M, Kapinos M, Zhang L, Zheng M, Holden D, Fowles K, Ropchan J, Nabulsi N, De Feyter H, Carson R, Huang Y, Cai Z. Preclinical evaluation of a brain penetrant PARP PET imaging probe in rat glioblastoma and nonhuman primates. European Journal Of Nuclear Medicine And Molecular Imaging 2023, 50: 2081-2099. PMID: 36849748, DOI: 10.1007/s00259-023-06162-y.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainGlioblastomaPoly(ADP-ribose) Polymerase InhibitorsPositron-Emission TomographyPrimatesRatsTissue DistributionConceptsPositron emission tomographyHealthy nonhuman primatesVolume of distributionDistribution volume ratioBrain kineticsRat glioblastoma modelPreclinical evaluationBrain regionsGlioblastoma modelPET tracersNonhuman primatesTumor-bearing ratsEx vivo biodistributionPET imaging resultsActive clinical trialsTreatment of glioblastomaHigh specific uptakeDynamic PET scansNoninvasive quantificationBrain positron emission tomographyNondisplaceable volumeBrain penetrationLow nonspecific uptakePrognostic informationClinical trialsSerotonin transporter availability in physically aggressive personality disordered patients: associations with trait and state aggression, and response to fluoxetine
Rosell D, Slifstein M, Thompson J, Xu X, Perez-Rodriguez M, McClure M, Hazlett E, New A, Nabulsi N, Huang Y, Carson R, Siever L, Abi-Dargham A, Koenigsberg H. Serotonin transporter availability in physically aggressive personality disordered patients: associations with trait and state aggression, and response to fluoxetine. Psychopharmacology 2023, 240: 361-371. PMID: 36640190, DOI: 10.1007/s00213-022-06306-2.Peer-Reviewed Original ResearchMeSH KeywordsAggressionFluoxetineHumansPersonalityPersonality DisordersPositron-Emission TomographySerotonin Plasma Membrane Transport ProteinsConceptsAnterior cingulate cortexAnti-aggressive effectsIED patientsPositron emission tomographyVentral striatumTransporter availabilityChildhood traumaSerotonin transporter availabilityRational treatment selectionIntermittent explosive disorderFluoxetine 20Fluoxetine treatmentSerotonergic abnormalitiesHealthy comparison participantsTreatment selectionRisk individualsObjectivesThe aimPatientsCingulate cortexExplosive disorderEmission tomographyImpulsive aggressionNovel therapeuticsFluoxetineNeuroanatomical basis
2022
Neurotransmitter transporter occupancy following administration of centanafadine sustained-release tablets: A phase 1 study in healthy male adults
Matuskey D, Gallezot J, Nabulsi N, Henry S, Torres K, Dias M, Angarita G, Huang Y, Shoaf S, Carson R, Mehrotra S. Neurotransmitter transporter occupancy following administration of centanafadine sustained-release tablets: A phase 1 study in healthy male adults. Journal Of Psychopharmacology 2022, 37: 164-171. PMID: 36515395, PMCID: PMC9912308, DOI: 10.1177/02698811221140008.Peer-Reviewed Original ResearchDifferences in Quantification of the Metabotropic Glutamate Receptor 5 Across Bipolar Disorder and Major Depressive Disorder
Holmes S, Asch R, Davis M, DellaGioia N, Pashankar N, Gallezot J, Nabulsi N, Matuskey D, Sanacora G, Carson R, Blumberg H, Esterlis I. Differences in Quantification of the Metabotropic Glutamate Receptor 5 Across Bipolar Disorder and Major Depressive Disorder. Biological Psychiatry 2022, 93: 1099-1107. PMID: 36764853, PMCID: PMC10164841, DOI: 10.1016/j.biopsych.2022.10.018.Peer-Reviewed Original ResearchMeSH KeywordsBipolar DisorderDepressive Disorder, MajorHumansMagnetic Resonance ImagingPositron-Emission TomographyPrefrontal CortexReceptor, Metabotropic Glutamate 5ConceptsMajor depressive disorderMetabotropic glutamate receptor 5Glutamate receptor 5MGluR5 availabilityBipolar disorderPositron emission tomographyHC groupDepressive disorderReceptor 5Emission tomographyHealthy control individualsPossible treatment targetsGlutamate transmissionBD depressionTreatment strategiesBD groupMGluR5Depressive symptomsNovel treatmentsCognitive alterationsTreatment targetsSynaptic plasticityControl individualsAccurate diagnosisSignificant negative correlationAge, gender and body-mass-index relationships with in vivo CB1 receptor availability in healthy humans measured with [11C]OMAR PET
Radhakrishnan R, Worhunsky PD, Zheng MQ, Najafzadeh S, Gallezot JD, Planeta B, Henry S, Nabulsi N, Ranganathan M, Skosnik PD, Pittman B, Cyril D'Souza D, Carson RE, Huang Y, Potenza MN, Matuskey D. Age, gender and body-mass-index relationships with in vivo CB1 receptor availability in healthy humans measured with [11C]OMAR PET. NeuroImage 2022, 264: 119674. PMID: 36243269, DOI: 10.1016/j.neuroimage.2022.119674.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultBody Mass IndexBrainFemaleHumansMaleMiddle AgedPositron-Emission TomographyRadiopharmaceuticalsReceptor, Cannabinoid, CB1Young AdultSystemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers
Zakiniaeiz Y, Hoye J, Ryan Petrulli J, LeVasseur B, Stanley G, Gao H, Najafzadeh S, Ropchan J, Nabulsi N, Huang Y, Chen MK, Matuskey D, Barron DS, Kelmendi B, Fulbright RK, Hampson M, Cosgrove KP, Morris ED. Systemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers. Brain Behavior And Immunity 2022, 106: 262-269. PMID: 36058419, PMCID: PMC10097458, DOI: 10.1016/j.bbi.2022.08.016.Peer-Reviewed Original ResearchMeSH KeywordsCentral Nervous System StimulantsCorpus StriatumDopamineHumansInflammationLipopolysaccharidesMethylphenidatePositron-Emission TomographyRacloprideSmokersConceptsEffects of LPSDopamine elevationTobacco smokersHealthy controlsSystemic inflammationDopamine systemImmune-brain interactionReward-related brain regionsAdministration of placeboAdministration of LPSSmoking statusRepeated-measures ANOVAPathophysiology of addictionDrug dosingPlaceboIndependent cohortSmokersDrug reinforcementEffect size determinationImmune systemRandomized orderBrain regionsLPSMethylphenidatePBO conditionImaging the fetal nonhuman primate brain with SV2A positron emission tomography (PET)
Rossano S, Toyonaga T, Berg E, Lorence I, Fowles K, Nabulsi N, Ropchan J, Li S, Ye Y, Felchner Z, Kukis D, Huang Y, Benveniste H, Tarantal AF, Groman S, Carson RE. Imaging the fetal nonhuman primate brain with SV2A positron emission tomography (PET). European Journal Of Nuclear Medicine And Molecular Imaging 2022, 49: 3679-3691. PMID: 35633376, PMCID: PMC9826644, DOI: 10.1007/s00259-022-05825-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainMacaca mulattaMembrane GlycoproteinsNerve Tissue ProteinsPositron-Emission TomographyConceptsPositron emission tomographySynaptic densityFetal brainThird trimesterEmission tomographyBrain developmentGravid rhesus monkeysPost-mortem brain tissueEarly neonatal periodNonhuman primate brainLate gestational periodSubset of subjectsPostnatal brain developmentPost-mortem samplesGestational ageNeonatal periodPregnant monkeysSynapse numberGestational periodPrimary motorPrimate brainBrain growthSubcortical regionsBrain tissueCortical regionsSynaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [11C]UCB‐J
Mecca AP, O'Dell RS, Sharp ES, Banks ER, Bartlett HH, Zhao W, Lipior S, Diepenbrock NG, Chen M, Naganawa M, Toyonaga T, Nabulsi NB, Vander Wyk B, Arnsten AFT, Huang Y, Carson RE, van Dyck C. Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [11C]UCB‐J. Alzheimer's & Dementia 2022, 18: 2527-2536. PMID: 35174954, PMCID: PMC9381645, DOI: 10.1002/alz.12582.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseBrainCognitionCognitive DysfunctionHumansPositron-Emission TomographySynapsesConceptsSynaptic densityEarly Alzheimer's diseaseAlzheimer's diseaseCognitive performanceMajor pathological correlateGray matter volumePositron emission tomography (PET) imagingEmission Tomography ImagingPET imaging studiesIndividual cognitive domainsNeuropathologic studiesSignificant positive associationSynapse lossSynaptic alterationsPathological correlatesNeuropsychological test performanceMatter volumeCognitive impairmentSignificant associationImaging studiesDiseaseTomography imagingGlobal cognitionStrongest predictorPositive associationImaging 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 ResearchMeSH KeywordsAnimalsAntidepressive AgentsBrainDepressive Disorder, MajorHumansKetamineMacaca mulattaMembrane GlycoproteinsNerve Tissue ProteinsPositron-Emission TomographyConceptsKetamine'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 symptomsTranslational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [11C]AFM
Fang H, Rossano S, Wang X, Nabulsi N, Kelley B, Fowles K, Ropchan J, Strittmatter SM, Carson RE, Huang Y. Translational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [11C]AFM. Molecular Imaging And Biology 2022, 24: 560-569. PMID: 35020138, PMCID: PMC9550197, DOI: 10.1007/s11307-021-01698-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCitalopramHumansIndicators and ReagentsPositron-Emission TomographyRatsSerotoninSerotonin Plasma Membrane Transport ProteinsSpinal CordSpinal Cord InjuriesTissue DistributionConceptsSpinal cord injurySpinal cordHealthy ratsHuman spinal cordCord injurySerotonin transporterRat modelRodent modelsPET imagingTranslational PET imagingSCI rat modelIntact spinal cordSpinal cord caudalRodent spinal cordSerotonin transporter tracerUse of PETCervical uptakeSERT changesSCI animalsSCI patientsPresynaptic serotonin transporterCord caudalAxon damageSerotonin systemSERT radioligand
2021
Lower prefrontal cortical synaptic vesicle binding in cocaine use disorder: An exploratory 11C‐UCB‐J positron emission tomography study in humans
Angarita GA, Worhunsky PD, Naganawa M, Toyonaga T, Nabulsi NB, Li C, Esterlis I, Skosnik PD, Radhakrishnan R, Pittman B, Gueorguieva R, Potenza MN, Finnema SJ, Huang Y, Carson RE, Malison RT. Lower prefrontal cortical synaptic vesicle binding in cocaine use disorder: An exploratory 11C‐UCB‐J positron emission tomography study in humans. Addiction Biology 2021, 27: e13123. PMID: 34852401, PMCID: PMC8891080, DOI: 10.1111/adb.13123.Peer-Reviewed Original ResearchMeSH KeywordsBrainCocaineHumansNerve Tissue ProteinsPositron-Emission TomographyPrefrontal CortexPyridinesSynaptic VesiclesConceptsCocaine use disorderAnterior cingulate cortexRecent cocaine useSynaptic densityMedial orbitofrontal cortexPrefrontal cortexCocaine useOrbitofrontal cortexUse disordersVentromedial prefrontal cortexPositron emission tomography scanPositron emission tomography studyEmission tomography scanSynaptic vesicle glycoprotein 2AHealthy control subjectsVolume of distributionEmission tomography studiesAcute cocaineControl subjectsTomography scanCocaine exposurePreclinical studiesHC subjectsDendritic spinesLifetime cocaine useA metabolically stable PET tracer for imaging synaptic vesicle protein 2A: synthesis and preclinical characterization of [18F]SDM-16
Zheng C, Holden D, Zheng MQ, Pracitto R, Wilcox KC, Lindemann M, Felchner Z, Zhang L, Tong J, Fowles K, Finnema SJ, Nabulsi N, Carson RE, Huang Y, Cai Z. A metabolically stable PET tracer for imaging synaptic vesicle protein 2A: synthesis and preclinical characterization of [18F]SDM-16. European Journal Of Nuclear Medicine And Molecular Imaging 2021, 49: 1482-1496. PMID: 34761284, PMCID: PMC8940841, DOI: 10.1007/s00259-021-05597-5.Peer-Reviewed Original ResearchMeSH KeywordsAminoacridinesAnimalsBrainHumansMembrane GlycoproteinsPositron-Emission TomographyRadiopharmaceuticalsSynaptic VesiclesConceptsTest-retest variabilityVolume of distributionCentral nervous systemTime-activity curvesPET tracersCentrum semiovaleSynaptic vesicle protein 2AAbsolute test-retest variabilityWhole central nervous systemNonhuman primate brainPlasma free fractionBrain PET scansHigh specific bindingSpecific bindingNondisplaceable volumePlasma input functionNHP brainOne-tissue compartment modelArterial bloodRegional time-activity curvesPET scansNervous systemPrimate brainMonkey brainPreclinical characterizationImaging 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 ResearchMeSH Keywords11-beta-Hydroxysteroid Dehydrogenase Type 1AdultBrainFemaleHumansHydrocortisoneMaleMiddle AgedPositron-Emission TomographySeverity of Illness IndexStress Disorders, Post-TraumaticTriazolesConceptsPosttraumatic 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 symptomsImaging Pituitary Vasopressin 1B Receptor in Humans with the PET Radiotracer 11C-TASP699
Naganawa M, Nabulsi NB, Matuskey D, Henry S, Ropchan J, Lin SF, Gao H, Pracitto R, Labaree D, Zhang MR, Suhara T, Nishino I, Sabia H, Ozaki S, Huang Y, Carson RE. Imaging Pituitary Vasopressin 1B Receptor in Humans with the PET Radiotracer 11C-TASP699. Journal Of Nuclear Medicine 2021, 63: 609-614. PMID: 34385336, DOI: 10.2967/jnumed.121.262430.Peer-Reviewed Original ResearchMeSH KeywordsHumansHypothalamo-Hypophyseal SystemPituitary-Adrenal SystemPositron-Emission TomographyPyridinesPyrimidinonesReceptors, VasopressinReproducibility of ResultsConceptsMultilinear analysis 1Test-retest variabilityPlasma concentrationsHealthy subjectsR occupancyR antagonistBrain regionsMetabolite-corrected arterial input functionAbsolute test-retest variabilityAdrenal axis activityNovel PET radiotracersSubstantial specific bindingDose-dependent fashionVasopressin 1b receptorTest-retest reproducibilityHalf maximal inhibitory concentrationAdverse eventsAxis activityOutcome measuresReceptor occupancyTime-activity curvesArginine vasopressinPosterior pituitaryDistribution volumeNeuropsychiatric disordersAssessment of transient dopamine responses to smoked cannabis
Calakos KC, Liu H, Lu Y, Anderson JM, Matuskey D, Nabulsi N, Ye Y, Skosnik PD, D'Souza DC, Morris ED, Cosgrove KP, Hillmer AT. Assessment of transient dopamine responses to smoked cannabis. Drug And Alcohol Dependence 2021, 227: 108920. PMID: 34399137, PMCID: PMC8464527, DOI: 10.1016/j.drugalcdep.2021.108920.Peer-Reviewed Original ResearchMeSH KeywordsAdultCannabisCorpus StriatumDopamineHumansMarijuana SmokingPositron-Emission TomographyRacloprideVentral StriatumYoung AdultConceptsStriatal dopamine responsesDopamine responseRadiotracer uptakePositron emission tomography (PET) imaging studiesTransient reductionTomography Imaging StudyChronic cannabis useDopaminergic mechanismsCannabis smokingMesolimbic dopaminergicReceptor antagonistPlasma concentrationsRegular cannabis usersCannabis cigarettesConstant infusionDopamine DImaging studiesVentral striatumCannabis useTransient changesCannabis usersCannabisPuff protocolPreliminary dataTHC levelsIn vivo evidence of lower synaptic vesicle density in schizophrenia
Radhakrishnan R, Skosnik PD, Ranganathan M, Naganawa M, Toyonaga T, Finnema S, Hillmer AT, Esterlis I, Huang Y, Nabulsi N, Carson RE, D’Souza D. In vivo evidence of lower synaptic vesicle density in schizophrenia. Molecular Psychiatry 2021, 26: 7690-7698. PMID: 34135473, DOI: 10.1038/s41380-021-01184-0.Peer-Reviewed Original ResearchMeSH KeywordsBrainHumansNerve Tissue ProteinsPositron-Emission TomographySchizophreniaSynaptic VesiclesConceptsSynaptic vesicle densityHealthy controlsVesicle densityHigh-resolution research tomographySynaptic densitySCZ patientsVivo measuresNovel positron emission tomography (PET) ligandGender-matched healthy controlsCumulative antipsychotic exposurePositron emission tomography (PET) ligandSynaptic spine densityPsychosis symptom severityGray matter volumeJ bindingAntipsychotic exposureSpine densityDisease progressionFrontal cortexOccipital cortexTomography ligandTemporal cortexAnterior cingulateVivo findingsParietal cortex