2024
Synaptic loss and its association with symptom severity in Parkinson’s disease
Holmes S, Honhar P, Tinaz S, Naganawa M, Hilmer A, Gallezot J, Dias M, Yang Y, Toyonaga T, Esterlis I, Mecca A, Van Dyck C, Henry S, Ropchan J, Nabulsi N, Louis E, Comley R, Finnema S, Carson R, Matuskey D. Synaptic loss and its association with symptom severity in Parkinson’s disease. Npj Parkinson's Disease 2024, 10: 42. PMID: 38402233, PMCID: PMC10894197, DOI: 10.1038/s41531-024-00655-9.Peer-Reviewed Original ResearchSynaptic density lossPositron emission tomographyBinds to synaptic vesicle glycoprotein 2AAssociated with symptom severityParkinson's diseaseHigh-resolution positron emission tomographySynaptic vesicle glycoprotein 2ADuration of illnessPositron emission tomography scanBrain perfusionIllness durationSymptom severitySeverity of symptomsHC groupSubstantia nigraSynaptic densityLiving brainPD individualsClinical insightsDensity lossPD patientsEmission tomographyBrainSynaptic lossSynapse loss
2022
Differences 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 ResearchConceptsMajor 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 correlation
2019
In vivo 5-HT6 and 5-HT2A receptor availability in antipsychotic treated schizophrenia patients vs. unmedicated healthy humans measured with [11C]GSK215083 PET
Radhakrishnan R, Matuskey D, Nabulsi N, Gaiser E, Gallezot JD, Henry S, Planeta B, Lin SF, Ropchan J, Huang Y, Carson RE, D'Souza DC. In vivo 5-HT6 and 5-HT2A receptor availability in antipsychotic treated schizophrenia patients vs. unmedicated healthy humans measured with [11C]GSK215083 PET. Psychiatry Research Neuroimaging 2019, 295: 111007. PMID: 31760336, DOI: 10.1016/j.pscychresns.2019.111007.Peer-Reviewed Original ResearchConceptsHealthy male controlsPositron emission tomographyMultilinear analysis 1Antipsychotic treatmentLower BPFrontal cortexReceptor availabilityAge-matched healthy male controlsDifferent second-generation antipsychoticsSteady-state troughPeak serum levelsSecond-generation antipsychoticsPotential therapeutic targetMale patientsSerum levelsHealthy humansTherapeutic targetSchizophrenia patientsTime-activity curvesMale controlsCognitive impairmentEmission tomographyVentral striatumPatientsSchizophreniaEffects of age, BMI and sex on the glial cell marker TSPO — a multicentre [11C]PBR28 HRRT PET study
Tuisku J, Plavén-Sigray P, Gaiser EC, Airas L, Al-Abdulrasul H, Brück A, Carson RE, Chen MK, Cosgrove KP, Ekblad L, Esterlis I, Farde L, Forsberg A, Halldin C, Helin S, Kosek E, Lekander M, Lindgren N, Marjamäki P, Rissanen E, Sucksdorff M, Varrone A, Collste K, Gallezot J, Hillmer A, Huang Y, Höglund C, Johansson J, Jucaite A, Lampa J, Nabulsi N, Pittman B, Sandiego C, Stenkrona P, Rinne J, Matuskey D, Cervenka S. Effects of age, BMI and sex on the glial cell marker TSPO — a multicentre [11C]PBR28 HRRT PET study. European Journal Of Nuclear Medicine And Molecular Imaging 2019, 46: 2329-2338. PMID: 31363804, PMCID: PMC6717599, DOI: 10.1007/s00259-019-04403-7.Peer-Reviewed Original ResearchConceptsBody mass indexPositron emission tomographyEffect of ageMultilinear analysis 1PET centersGlobal gray matterMass indexSubgroup analysisClinical studiesTSPO levelsHealthy subjectsTurku PET CentreHealthy volunteersPositive correlationTemporal cortexTSPO genotypeIndividual biological propertiesMale subjectsPurposeThe purposeConclusionThese findingsLinear mixed effects modelsGray matterParietal cortexSignificant negative correlationEmission tomography
2016
OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding
Pittenger C, Adams TG, Gallezot JD, Crowley MJ, Nabulsi N, Ropchan J, Gao H, Kichuk SA, Simpson R, Billingslea E, Hannestad J, Bloch M, Mayes L, Bhagwagar Z, Carson RE. OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding. Journal Of Affective Disorders 2016, 196: 87-96. PMID: 26919057, PMCID: PMC4808438, DOI: 10.1016/j.jad.2016.02.021.Peer-Reviewed Original ResearchConceptsPrepulse inhibitionObsessive-compulsive disorderReceptor availabilitySensorimotor gatingOCD patientsImpaired sensorimotor gatingOCD-like behaviorNon-depressed OCD patientsPositron emission tomographyBasal gangliaSerotonergic regulationHealthy controlsSerotonin systemPositive correlationWidespread positive correlationsDiagnostic groupsCortical regionsEmission tomographyOrbitofrontal cortexPatientsReceptor bindingOCD diagnosisSignificant correlationSignificant main effectImportant alterations
2015
Preclinical to Clinical Translation of CNS Transporter Occupancy of TD-9855, a Novel Norepinephrine and Serotonin Reuptake Inhibitor
Smith J, Patil D, Daniels O, Ding YS, Gallezot JD, Henry S, Kim K, Kshirsagar S, Martin W, Obedencio G, Stangeland E, Tsuruda P, Williams W, Carson R, Patil. Preclinical to Clinical Translation of CNS Transporter Occupancy of TD-9855, a Novel Norepinephrine and Serotonin Reuptake Inhibitor. The International Journal Of Neuropsychopharmacology 2015, 18: pyu027. PMID: 25522383, PMCID: PMC4368888, DOI: 10.1093/ijnp/pyu027.Peer-Reviewed Original ResearchMeSH KeywordsAdultAniline CompoundsAnimalsBlood Chemical AnalysisBrainHalf-LifeHumansMagnetic Resonance ImagingMaleModels, BiologicalMorpholinesNeurotransmitter Uptake InhibitorsNorepinephrine Plasma Membrane Transport ProteinsPhenyl EthersPiperidinesPositron-Emission TomographyRadiopharmaceuticalsRats, Sprague-DawleyReboxetineSerotonin Plasma Membrane Transport ProteinsSpinal CordSulfidesConceptsReuptake inhibitorsPositron emission tomographyNorepinephrine transporterSerotonin transporterSerotonin reuptake inhibitorsSingle oral doseUnique clinical profileMonoamine reuptake inhibitorsFuture clinical evaluationRat spinal cordNET occupancySERT occupancyClinical profileOral dosePlasma levelsTransporter profilesClinical evaluationSpinal cordTransporter occupancyCNS penetrationHealthy malesPharmacodynamic modelingNorepinephrineEmission tomographyPET studiesReference Region Modeling Approaches for Amphetamine Challenge Studies with [11C]FLB 457 and PET
Sandiego CM, Gallezot JD, Lim K, Ropchan J, Lin SF, Gao H, Morris ED, Cosgrove KP. Reference Region Modeling Approaches for Amphetamine Challenge Studies with [11C]FLB 457 and PET. Cerebrovascular And Brain Metabolism Reviews 2015, 35: 623-629. PMID: 25564239, PMCID: PMC4420880, DOI: 10.1038/jcbfm.2014.237.Peer-Reviewed Original ResearchConceptsPositron emission tomographyExtrastriatal regionsBrain regionsAmphetamine-induced dopamine releaseHealthy tobacco smokersExtrastriatal brain regionsSynaptic dopamine levelsAmphetamine-induced changesSimplified reference tissue modelReference tissue modelTobacco smokersDopaminergic dysfunctionAmphetamine administrationDopamine levelsDopamine releasePsychiatric disordersChallenge studiesDistribution volumeEmission tomographyD3 bindingReference region modelCerebellumReference regionBaselineSignificant changes
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
Reductions in Brain 5-HT1B Receptor Availability in Primarily Cocaine-Dependent Humans
Matuskey D, Bhagwagar Z, Planeta B, Pittman B, Gallezot JD, Chen J, Wanyiri J, Najafzadeh S, Ropchan J, Geha P, Huang Y, Potenza MN, Neumeister A, Carson RE, Malison RT. Reductions in Brain 5-HT1B Receptor Availability in Primarily Cocaine-Dependent Humans. Biological Psychiatry 2013, 76: 816-822. PMID: 24433854, PMCID: PMC4037398, DOI: 10.1016/j.biopsych.2013.11.022.Peer-Reviewed Original ResearchConceptsRegional binding potentialPositron emission tomographyCocaine dependenceEmission tomographyFrontal cortexReceptor availabilityAge-matched healthy control subjectsSignificant gray matter reductionsYears of cocaineIllicit substance abuseHealthy control subjectsDaily tobacco useCocaine-dependent humansGray matter reductionsEffects of cocaineMagnetic resonance imagingSignificant reductionPreclinical evidenceControl subjectsPrimary addictionSerotonin receptorsHealthy subjectsTobacco useMedication developmentAnterior cingulateTracer Kinetic Modeling of [11C]AFM, a New PET Imaging Agent for the Serotonin Transporter
Naganawa M, Nabulsi N, Planeta B, Gallezot JD, Lin SF, Najafzadeh S, Williams W, Ropchan J, Labaree D, Neumeister A, Huang Y, Carson RE. Tracer Kinetic Modeling of [11C]AFM, a New PET Imaging Agent for the Serotonin Transporter. Cerebrovascular And Brain Metabolism Reviews 2013, 33: 1886-1896. PMID: 23921898, PMCID: PMC3851894, DOI: 10.1038/jcbfm.2013.134.Peer-Reviewed Original ResearchConceptsPositron emission tomographySerotonin transporterReference tissue modelArterial input functionOne-tissue modelMultilinear reference tissue modelNew PET imaging agentTwo-tissue modelPET imaging agentHealthy human brainSuitable PET radioligandNew positron emission tomographySERT densityRegional time-activity curvesTime-activity curvesEmission tomography dataRegional bindingEmission tomographyPET radioligandRoutine useInterest analysisNoninvasive methodPositron emission tomography dataImaging agentHuman brainThe neuroinflammation marker translocator protein is not elevated in individuals with mild-to-moderate depression: A [11C]PBR28 PET study
Hannestad J, DellaGioia N, Gallezot JD, Lim K, Nabulsi N, Esterlis I, Pittman B, Lee JY, O’Connor K, Pelletier D, Carson RE. The neuroinflammation marker translocator protein is not elevated in individuals with mild-to-moderate depression: A [11C]PBR28 PET study. Brain Behavior And Immunity 2013, 33: 131-138. PMID: 23850810, PMCID: PMC3899398, DOI: 10.1016/j.bbi.2013.06.010.Peer-Reviewed Original ResearchConceptsLevels of TSPOControl subjectsSystemic inflammationPositron emission tomographyModerate depressionTSPO levelsActivation of microgliaTranslocator protein 18Total ligand bindingAcute episodePrimary outcomePostmortem studiesSevere depressionMajor depressionPET scansTSPO genotypeBrain regionsEmission tomographySubject factorsPET studiesArterial input functionInflammationElevated levelsProtein 18Depression
2012
Endotoxin-induced systemic inflammation activates microglia: [11C]PBR28 positron emission tomography in nonhuman primates
Hannestad J, Gallezot JD, Schafbauer T, Lim K, Kloczynski T, Morris ED, Carson RE, Ding YS, Cosgrove KP. Endotoxin-induced systemic inflammation activates microglia: [11C]PBR28 positron emission tomography in nonhuman primates. NeuroImage 2012, 63: 232-239. PMID: 22776451, PMCID: PMC3699786, DOI: 10.1016/j.neuroimage.2012.06.055.Peer-Reviewed Original ResearchConceptsPositron emission tomographySystemic inflammationMultiple sclerosisInterleukin-6Interleukin-8Translocator proteinEndotoxin-induced systemic inflammationLevels of TSPOEmission tomographyTumor necrosis factor alphaSystemic inflammatory processActivation of microgliaSerum IL-1βIL-6 levelsCourse of diseaseEffects of LPSImportant clinical questionsNecrosis factor alphaInterleukin-1 betaNonhuman primate brainE. coli lipopolysaccharideRegional time-activity dataLocal tissue damageTwo-tissue compartmental modelTotal ligand binding
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 group
2010
Evaluation of [11C]MRB for assessment of occupancy of norepinephrine transporters: Studies with atomoxetine in non-human primates
Gallezot JD, Weinzimmer D, Nabulsi N, Lin SF, Fowles K, Sandiego C, McCarthy TJ, Maguire RP, Carson RE, Ding YS. Evaluation of [11C]MRB for assessment of occupancy of norepinephrine transporters: Studies with atomoxetine in non-human primates. NeuroImage 2010, 56: 268-279. PMID: 20869448, PMCID: PMC3710586, DOI: 10.1016/j.neuroimage.2010.09.040.Peer-Reviewed Original ResearchConceptsAttention deficit hyperactivity disorderPositron emission tomographyNorepinephrine transporterDrug occupancy studiesRhesus monkeysReference regionTreatment of depressionDose-dependent reductionVolume of distributionArterial blood samplingSuitable reference regionOccupancy studiesNon-human primatesBrain norepinephrine transportersPromising radioligandPlasma levelsTherapeutic doseOccipital cortexBlood samplingUptake inhibitorAtomoxetineEmission tomographyEffective dosePET studiesArterial input functionClinically Relevant Doses of Methylphenidate Significantly Occupy Norepinephrine Transporters in Humans In Vivo
Hannestad J, Gallezot JD, Planeta-Wilson B, Lin SF, Williams WA, van Dyck CH, Malison RT, Carson RE, Ding YS. Clinically Relevant Doses of Methylphenidate Significantly Occupy Norepinephrine Transporters in Humans In Vivo. Biological Psychiatry 2010, 68: 854-860. PMID: 20691429, PMCID: PMC3742016, DOI: 10.1016/j.biopsych.2010.06.017.Peer-Reviewed Original ResearchConceptsAttention-deficit/hyperactivity disorderNET-rich regionsPositron emission tomographyNorepinephrine transporterDopamine transporterHyperactivity disorderRelevant dosesEmission tomographySingle-blind placeboMultilinear reference tissue modelEffective dose 50Attention deficit hyperactivity disorderDose-dependent mannerMechanism of actionDeficit hyperactivity disorderBrain norepinephrine transportersReference tissue modelMaintenance doseOral methylphenidateHealthy subjectsTherapeutic effectOccipital cortexCommon treatmentPsychiatric disordersMethylphenidateSerotonin 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
2009
Decrease of Nicotinic Receptors in the Nigrostriatal System in Parkinson's Disease
Kas A, Bottlaender M, Gallezot JD, Vidailhet M, Villafane G, Grégoire MC, Coulon C, Valette H, Dollé F, Ribeiro MJ, Hantraye P, Remy P. Decrease of Nicotinic Receptors in the Nigrostriatal System in Parkinson's Disease. Cerebrovascular And Brain Metabolism Reviews 2009, 29: 1601-1608. PMID: 19491921, DOI: 10.1038/jcbfm.2009.74.Peer-Reviewed Original ResearchConceptsParkinson's diseasePositron emission tomographyDistribution volumeDopaminergic functionPD severityCerebral nicotinic acetylcholine receptorsStriatal dopaminergic functionNicotinic acetylcholine receptorsNAChR densityNeuroprotective actionNigrostriatal systemClinical scoresPD patientsSubstantia nigraHealthy controlsPD groupPostmortem studiesLower incidenceNicotinic receptorsPET markersPET scansPD stagesAcetylcholine receptorsEmission tomographyDisease