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 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 ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBiomarkersFluorodeoxyglucose F18HumansMicePilot ProjectsPositron-Emission TomographyConceptsMild 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
Evaluation of a First PET Tracer Suitable for Imaging the Sigma‑2 Receptor in the Brain of Nonhuman Primates
Alluri S, Zheng M, Holden D, Zhang Y, Zhang L, Felchner Z, Li S, Ropchan J, Carson R, Jia H, Huang Y. Evaluation of a First PET Tracer Suitable for Imaging the Sigma‑2 Receptor in the Brain of Nonhuman Primates. Molecular Pharmaceutics 2023, 21: 194-200. PMID: 38013422, DOI: 10.1021/acs.molpharmaceut.3c00750.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainMacaca mulattaNeoplasmsPositron-Emission TomographyPrimatesRadiopharmaceuticalsConceptsAlzheimer's diseaseLimited brain uptakeNonhuman primate brainCentral nervous systemPotential therapeutic targetPositron emission tomography (PET) imagingEmission Tomography ImagingTransmembrane protein 97Sigma-2 receptorsFirst PET tracerBrain penetrantBrain uptakeTherapeutic targetNervous systemPrimate brainNeurological disordersPET tracersNonhuman primatesTomography imagingProtein 97CancerDiseaseBrainCell typesReceptorsImaging 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 patterns18F-Labeled o‑aminopyridyl alkynyl radioligands targeting colony-stimulating factor 1 receptor for neuroinflammation imaging
An X, Wang J, Tong L, Zhang X, Fu H, Zhang J, Xie H, Huang Y, Jia H. 18F-Labeled o‑aminopyridyl alkynyl radioligands targeting colony-stimulating factor 1 receptor for neuroinflammation imaging. Bioorganic & Medicinal Chemistry 2023, 83: 117233. PMID: 36933438, DOI: 10.1016/j.bmc.2023.117233.Peer-Reviewed Original ResearchConceptsBrain of lipopolysaccharideMale ICR miceModerate brain uptakeFactor 1 receptorColony-stimulating factor 1 receptorBrain uptakeICR miceGBq/Metabolic stability studiesID/Neuroinflammation imagingMouse brainBiodistribution studiesNanomolar inhibitory potencyReceptor ligandsMiceInhibitory potencySpecific bindingBrainCSF-1RRadiochemical purityMolar activityPreclinical 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 trialsCholinergic system adaptations are associated with cognitive function in people recently abstinent from smoking: a (-)-[18F]flubatine PET study
Calakos K, Hillmer A, Anderson J, LeVasseur B, Baldassarri S, Angarita G, Matuskey D, Kapinos M, Zheng M, Huang Y, Cosgrove K. Cholinergic system adaptations are associated with cognitive function in people recently abstinent from smoking: a (-)-[18F]flubatine PET study. Neuropsychopharmacology 2023, 48: 683-689. PMID: 36681758, PMCID: PMC9938267, DOI: 10.1038/s41386-023-01535-1.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAcetylcholinesteraseAnimalsBrainCholinergic AgentsCognitionFemaleMalePhysostigminePositron-Emission TomographyReceptors, NicotinicSmokingConceptsExecutive functionCholinergic systemWorse executive functionAcetylcholine levelsVerbal learningCognitive batteryPositron emission tomography brainCognitive dataAbstinent smokersCognitive functionCognitive deficitsCortical acetylcholine levelsEarly smoking cessationAcetylcholinesterase inhibitor physostigmineCognitionQuit attemptsNAChR sitesPhysostigmine administrationTomography brainSmoking statusSmoking cessationInhibitor physostigmineTreatment strategiesAgonist radioligandPhysostigmine challengeSerotonin 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 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 ResearchMeSH KeywordsAdultAlcoholismBrainBrain MappingCravingFemaleHumansMaleMiddle AgedNaltrexoneNarcotic AntagonistsPositron-Emission TomographyReceptors, Opioid, kappaYoung AdultConceptsKappa-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
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