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 ResearchConceptsPTSD 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 symptomsAnhedoniaA pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease
van Dyck C, Mecca A, O’Dell R, Bartlett H, Diepenbrock N, Huang Y, Hamby M, Grundman M, Catalano S, Caggiano A, Carson R. A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease. Alzheimer's Research & Therapy 2024, 16: 20. PMID: 38273408, PMCID: PMC10809445, DOI: 10.1186/s13195-024-01382-2.Peer-Reviewed Original ResearchConceptsMild to moderate dementiaPositron emission tomographyAlzheimer's diseaseVolumetric MRIModerate dementiaClinical rating scalesSynaptic vesicle glycoprotein 2ACerebrospinal fluidMouse model of ADPharmacodynamic effectsPlacebo-controlled phase 1 clinical trialBiomarkers of AD pathologyClinical trialsCognitive measuresNominally significant differencesPhase 1 clinical trialModel of ADHippocampal cortexPhase 1/2 studyRating ScaleParallel-group trialSynaptic densityTrial registrationThe clinical trialPlacebo-controlledSigma-2 receptor ligands
2023
Imaging 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 ResearchConceptsVolume 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 ResearchConceptsCognitive 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 patternsInvestigating CNS distribution of PF‐05212377, a P‐glycoprotein substrate, by translation of 5‐HT6 receptor occupancy from non‐human primates to humans
Sawant‐Basak A, Chen L, Lockwood P, Boyden T, Doran A, Mancuso J, Zasadny K, McCarthy T, Morris E, Carson R, Esterlis I, Huang Y, Nabulsi N, Planeta B, Fullerton T. Investigating CNS distribution of PF‐05212377, a P‐glycoprotein substrate, by translation of 5‐HT6 receptor occupancy from non‐human primates to humans. Biopharmaceutics & Drug Disposition 2023, 44: 48-59. PMID: 36825693, DOI: 10.1002/bdd.2351.Peer-Reviewed Original ResearchConceptsNon-human primatesBrain penetrationPositron emission tomographyReceptor occupancyUnbound concentrationsPre-clinical evidenceVivo brain penetrationConcentration-dependent increaseP-glycoprotein substratesPlasma ECsP-gpAlzheimer's diseaseEmission tomographyRat BBBTarget engagementCumulative evidenceDependent increaseTransporter substratesCNS distributionBBBRatsDiseasePrimatesSpecies differencesHumansIn vivo synaptic density loss correlates with impaired functional and related structural connectivity in Alzheimer’s disease
Zhang J, Wang J, Xu X, You Z, Huang Q, Huang Y, Guo Q, Guan Y, Zhao J, Liu J, Xu W, Deng Y, Xie F, Li B. In vivo synaptic density loss correlates with impaired functional and related structural connectivity in Alzheimer’s disease. Cerebrovascular And Brain Metabolism Reviews 2023, 43: 977-988. PMID: 36718002, PMCID: PMC10196742, DOI: 10.1177/0271678x231153730.Peer-Reviewed Original ResearchConceptsMiddle frontal gyrusAlzheimer's diseaseSynaptic densityMild cognitive impairmentSynapse lossCognitive impairmentCaudal middle frontal gyrusFunctional connectivityLower synaptic densityMajor pathological changesRight insular cortexStructural connectivity alterationsRight middle frontal gyrusWhite matter tractsSynaptic alterationsBilateral cortexConnectivity alterationsInsular cortexAD groupPathological changesConnectivity dysfunctionCognitive declineCognitive functionFunctional MRIDiseaseSerotonin 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 ResearchConceptsAnterior 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 basisFirst-in-Human PET Imaging of [18F]SDM-4MP3: A Cautionary Tale
Desmond K, Lindberg A, Garcia A, Tong J, Harkness M, Dobrota E, Smart K, Uribe C, Meyer J, Houle S, Strafella A, Li S, Huang Y, Vasdev N. First-in-Human PET Imaging of [18F]SDM-4MP3: A Cautionary Tale. Molecular Imaging 2023, 2023: 8826977. PMID: 37719326, PMCID: PMC10504053, DOI: 10.1155/2023/8826977.Peer-Reviewed Original Research
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 Research
2019
The Kappa Opioid Receptor Is Associated With Naltrexone-Induced Reduction of Drinking and Craving
de Laat B, Goldberg A, Shi J, Tetrault JM, Nabulsi N, Zheng MQ, Najafzadeh S, Gao H, Kapinos M, Ropchan J, O'Malley SS, Huang Y, Morris ED, Krishnan-Sarin S. The Kappa Opioid Receptor Is Associated With Naltrexone-Induced Reduction of Drinking and Craving. Biological Psychiatry 2019, 86: 864-871. PMID: 31399255, DOI: 10.1016/j.biopsych.2019.05.021.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsAlcohol use disorderOpioid receptorsUse disordersNonselective opioid receptor antagonistModest clinical effectsEfficacy of naltrexoneOpioid receptor antagonistDSM-IV criteriaPositron emission tomographyAlcohol Urge QuestionnaireNaltrexone initiationNaltrexone therapyClinical effectsReceptor antagonistTherapeutic effectCingulate cortexDrinking paradigmHeavy drinkersBilateral insulaNaltrexoneAlcohol dependenceBrain regionsEmission tomographyPrefrontal cortex
2018
Evaluation of PET Brain Radioligands for Imaging Pancreatic β-Cell Mass: Potential Utility of 11C-(+)-PHNO
Bini J, Naganawa M, Nabulsi N, Huang Y, Ropchan J, Lim K, Najafzadeh S, Herold KC, Cline GW, Carson RE. Evaluation of PET Brain Radioligands for Imaging Pancreatic β-Cell Mass: Potential Utility of 11C-(+)-PHNO. Journal Of Nuclear Medicine 2018, 59: 1249-1254. PMID: 29371405, PMCID: PMC6071501, DOI: 10.2967/jnumed.117.197285.Peer-Reviewed Original ResearchConceptsT1DM subjectsΒ-cell massHealthy controlsΒ-cellsAbdominal organsType 1 diabetes mellitusC-peptide levelsHealthy control subjectsPancreatic β-cell massDeficient insulin secretionReceptor agonist radioligandPET/CTIslets of LangerhansDynamic PET/CTCommon cellular receptorPancreatic bindingDiabetes mellitusDiabetic subjectsControl subjectsNeurologic tissueC-peptideInsulin secretionMean SUVAgonist radioligandDiabetes therapy
2017
Systemic inflammation enhances stimulant-induced striatal dopamine elevation
Petrulli J, Kalish B, Nabulsi N, Huang Y, Hannestad J, Morris E. Systemic inflammation enhances stimulant-induced striatal dopamine elevation. Translational Psychiatry 2017, 7: e1076-e1076. PMID: 28350401, PMCID: PMC5404612, DOI: 10.1038/tp.2017.18.Peer-Reviewed Original ResearchMeSH KeywordsAdultCarbon RadioisotopesCase-Control StudiesCentral Nervous System StimulantsDopamineDopamine AntagonistsFemaleHealthy VolunteersHumansInflammationInterleukin-6Interleukin-8LipopolysaccharidesMaleMethylphenidateNeostriatumPositron-Emission TomographyRacloprideRadiopharmaceuticalsReceptors, Dopamine D2Tumor Necrosis Factor-alphaYoung AdultConceptsDA elevationSystemic inflammationImmune activationTumor necrosis factor alphaAcute immune activationImmune activator lipopolysaccharideOral methylphenidate (MPH) challengeStriatal DA levelsIL-8 concentrationsNecrosis factor alphaMesolimbic dopamine systemCross-over designPositron emission tomographyNeuroimmune systemMethylphenidate challengeDA levelsDA transmissionDopamine elevationDA dysfunctionFactor alphaBaseline scanHealthy subjectsAntagonist tracersPlaceboDopamine system
2003
Imaging Human Mesolimbic Dopamine Transmission with Positron Emission Tomography. Part II: Amphetamine-Induced Dopamine Release in the Functional Subdivisions of the Striatum
Martinez D, Slifstein M, Broft A, Mawlawi O, Hwang DR, Huang Y, Cooper T, Kegeles L, Zarahn E, Abi-Dargham A, Haber SN, Laruelle M. Imaging Human Mesolimbic Dopamine Transmission with Positron Emission Tomography. Part II: Amphetamine-Induced Dopamine Release in the Functional Subdivisions of the Striatum. Cerebrovascular And Brain Metabolism Reviews 2003, 23: 285-300. PMID: 12621304, DOI: 10.1097/01.wcb.0000048520.34839.1a.Peer-Reviewed Original ResearchConceptsD2 receptor availabilityPositron emission tomographyReceptor availabilityHuman striatumFunctional subdivisionsDopamine releaseAssociative regionsSensorimotor regionsEmission tomographyAmphetamine-induced dopamine releaseIntegration of limbicMesolimbic dopamine transmissionDopamine D2 receptorsVoxel-based analysisPriming bolusSensorimotor subdivisionsAmphetamine administrationMotor functionStriatal functionD2 receptorsIntravenous administrationStriatal subregionsVentral midbrainHealthy volunteersDopamine transmission
2001
Imaging Human Mesolimbic Dopamine Transmission With Positron Emission Tomography: I. Accuracy and Precision of D2 Receptor Parameter Measurements in Ventral Striatum
Mawlawi O, Martinez D, Slifstein M, Broft A, Chatterjee R, Hwang D, Huang Y, Simpson N, Ngo K, Van Heertum R, Laruelle M. Imaging Human Mesolimbic Dopamine Transmission With Positron Emission Tomography: I. Accuracy and Precision of D2 Receptor Parameter Measurements in Ventral Striatum. Cerebrovascular And Brain Metabolism Reviews 2001, 21: 1034-1057. PMID: 11524609, DOI: 10.1097/00004647-200109000-00002.Peer-Reviewed Original ResearchConceptsPositron emission tomographyVentral striatumDopamine transmissionReceptor measurementsEmission tomographyMesolimbic dopamine transmissionHigh-resolution magnetic resonanceNonspecific partition coefficientDrugs of abuseDorsal putamenPostmortem studiesVentral putamenDorsal caudateVentral caudateNucleus accumbensConstant infusion methodReceptor availabilityPsychotic statesStriatumReceptorsPutamenCaudateSpecific bindingInfusion methodTomographyVulnerability of positron emission tomography radiotracers to endogenous competition. New insights.
Laruelle M, Huang Y. Vulnerability of positron emission tomography radiotracers to endogenous competition. New insights. Quarterly Journal Of Nuclear Medicine And Molecular Imaging 2001, 45: 124-38. PMID: 11476162.Peer-Reviewed Original ResearchConceptsTransmitter levelsSynaptic dopamine concentrationsPositron emission tomographyDA transmissionD2 receptorsNeurotransmitter systemsPharmacological challengeDevelopment of PETSynaptic transmitter levelsEmission tomographyDopamine concentrationsAcute fluctuationsReceptor traffickingHuman brainRadioligandImaging techniquesVivoEndogenous competitionPETBinding competitionNeurotransmittersBrainReceptorsAnalyses of [18F]altanserin bolus injection PET data. II: Consideration of radiolabeled metabolites in humans
Price J, Lopresti B, Meltzer C, Smith G, Mason N, Huang Y, Holt D, Gunn R, Mathis C. Analyses of [18F]altanserin bolus injection PET data. II: Consideration of radiolabeled metabolites in humans. Synapse 2001, 41: 11-21. PMID: 11354009, DOI: 10.1002/syn.1055.Peer-Reviewed Original ResearchConceptsBlood-brain barrierPositron emission tomographyPrevious animal studiesAntagonist radiotracersPET dataBolus injectionAnimal studiesReference tissue methodEmission tomographyPET studiesArterial inputTissue measuresConstant radioactivityLogan analysisFurther studiesHigh-performance liquid chromatography analysisRadiometabolitesTissue methodLiquid chromatography analysisMetabolitesInjectionBolusDifferential Occupancy of Somatodendritic and Postsynaptic 5HT1A Receptors by Pindolol: A Dose-Occupancy Study with [11C]WAY 100635 and Positron Emission Tomography in Humans
Martinez D, Hwang D, Mawlawi O, Slifstein M, Kent J, Simpson N, Parsey R, Hashimoto T, Huang Y, Shinn A, Van Heertum R, Abi-Dargham A, Caltabiano S, Malizia A, Cowley H, Mann J, Laruelle M. Differential Occupancy of Somatodendritic and Postsynaptic 5HT1A Receptors by Pindolol: A Dose-Occupancy Study with [11C]WAY 100635 and Positron Emission Tomography in Humans. Neuropsychopharmacology 2001, 24: 209-229. PMID: 11166513, DOI: 10.1016/s0893-133x(00)00187-1.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntidepressive AgentsBrainHumansKineticsMagnetic Resonance ImagingMaleMood DisordersPindololPiperazinesPyridinesRaphe NucleiReceptors, NeurotransmitterReceptors, SerotoninReceptors, Serotonin, 5-HT1Selective Serotonin Reuptake InhibitorsSynaptic TransmissionTomography, Emission-ComputedConceptsDorsal raphe nucleusPositron emission tomographyClinical studiesSelective serotonin reuptake inhibitor (SSRI) therapyPlacebo-controlled clinical studySerotonin reuptake inhibitor therapyEmission tomographyAbility of pindololPindolol augmentationAntidepressant therapyAntidepressant treatmentClinical responseInhibitor therapyRaphe nucleusScan 3Scan 4Therapeutic effectHealthy volunteersScan 2Vivo selectivityPindololAutoreceptorsSSRIsTherapyInconsistent results
2000
Positron emission tomography study of pindolol occupancy of 5-HT1A receptors in humans: preliminary analyses
Martinez D, Mawlawi O, Hwang D, Kent J, Simpson N, Parsey R, Hashimoto T, Slifstein M, Huang Y, Van Heertum R, Abi-Dargham A, Caltabiano S, Malizia A, Cowley H, Mann J, Laruelle M. Positron emission tomography study of pindolol occupancy of 5-HT1A receptors in humans: preliminary analyses. Nuclear Medicine And Biology 2000, 27: 523-527. PMID: 10962261, DOI: 10.1016/s0969-8051(00)00122-0.Peer-Reviewed Original ResearchConceptsDorsal raphe nucleusClinical studiesPositron emission tomographyPlacebo-controlled clinical studySerotonin reuptake inhibitor therapyCortical regionsAbility of pindololPositron emission tomography studyInitiation of treatmentEmission tomography studiesDRN 5Pindolol augmentationPindolol doseAntidepressant therapyAntidepressant responseInhibitor therapySerotonin transmissionRaphe nucleusScan 3SSRI effectsPostsynaptic receptorsScan 4Clinical trialsOral administrationPreclinical studies
1999
Pet imaging of serotonin 1A receptor binding in depression
Drevets W, Frank E, Price J, Kupfer D, Holt D, Greer P, Huang Y, Gautier C, Mathis C. Pet imaging of serotonin 1A receptor binding in depression. Biological Psychiatry 1999, 46: 1375-1387. PMID: 10578452, DOI: 10.1016/s0006-3223(99)00189-4.Peer-Reviewed Original ResearchConceptsFamilial mood disordersReceptor BPPostmortem studiesMood disordersMesiotemporal cortexMidbrain rapheSerotonin 1A receptor systemBrain regionsPET imagingPrevious postmortem studiesSerotonin 1A receptorMultiple brain regionsHistopathological changesHealthy controlsBP valuesMajor depressionDepressed phasePostcentral gyrusClinical conditionsOccipital cortexBipolar relativesBipolar depressivesReceptor radioligandDepressed subjectsNormal baseline
1998
Test–retest variability of serotonin 5‐HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain
Smith G, Price J, Lopresti B, Huang Y, Simpson N, Holt D, Mason N, Meltzer C, Sweet R, Nichols T, Sashin D, Mathis C. Test–retest variability of serotonin 5‐HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain. Synapse 1998, 30: 380-392. PMID: 9826230, DOI: 10.1002/(sici)1098-2396(199812)30:4<380::aid-syn5>3.0.co;2-u.Peer-Reviewed Original Research