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 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 correlation
2021
Effect of age on brain metabotropic glutamate receptor subtype 5 measured with [18F]FPEB PET
Mecca AP, Rogers K, Jacobs Z, McDonald JW, Michalak HR, DellaGioia N, Zhao W, Hillmer AT, Nabulsi N, Lim K, Ropchan J, Huang Y, Matuskey D, Esterlis I, Carson RE, van Dyck CH. Effect of age on brain metabotropic glutamate receptor subtype 5 measured with [18F]FPEB PET. NeuroImage 2021, 238: 118217. PMID: 34052464, PMCID: PMC8378132, DOI: 10.1016/j.neuroimage.2021.118217.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAgingBrain ChemistryFemaleFluorine RadioisotopesFluorodeoxyglucose F18Gray MatterHippocampusHumansMagnetic Resonance ImagingMaleMiddle AgedNeuroimagingOrgan SizePositron-Emission TomographyRadiopharmaceuticalsReceptor, Metabotropic Glutamate 5Young AdultConceptsMetabotropic glutamate receptor subtype 5MGluR5 availabilityMultiple brain regionsTissue lossSubtype 5Association cortexPrimary analysisBrain regionsAge-related molecular changesBrain glutamatergic systemBrain tissue lossNon-significant trendPartial volume correctionPositron emission tomographyBrain mGluR5Effect of ageAge-related declineGlutamatergic systemInverse associationTissue alterationsDistribution volumeEmission tomographyOlder ageCognitive functionExploratory analysis
2020
Longitudinal imaging of metabotropic glutamate 5 receptors during early and extended alcohol abstinence
Hillmer AT, Angarita GA, Esterlis I, Anderson JM, Nabulsi N, Lim K, Ropchan J, Carson RE, Krystal JH, Malley S, Cosgrove KP. Longitudinal imaging of metabotropic glutamate 5 receptors during early and extended alcohol abstinence. Neuropsychopharmacology 2020, 46: 380-385. PMID: 32919411, PMCID: PMC7852514, DOI: 10.1038/s41386-020-00856-9.Peer-Reviewed Original ResearchMeSH KeywordsAlcohol AbstinenceBrainGlutamic AcidHumansPositron-Emission TomographyPyridinesReceptor, Metabotropic Glutamate 5ConceptsMetabotropic glutamate 5 receptorsSmoking statusAlcohol abstinenceEarly abstinenceMGlu5 receptor negative allosteric modulatorReceptor negative allosteric modulatorChronic alcohol useCortical brain regionsAlcohol use disorderEmission Tomography ImagingPositron emission tomography (PET) imagingNegative allosteric modulatorsDSM-5 criteriaCue-induced reinstatementHealthy controlsPreclinical literatureGlutamate systemPreclinical modelsHuman evidenceReceptor drugsPET scansUse disordersHuman studiesReceptor availabilityStudy durationPET imaging of mGluR5 in Alzheimer’s disease
Mecca AP, McDonald JW, Michalak HR, Godek TA, Harris JE, Pugh EA, Kemp EC, Chen MK, Salardini A, Nabulsi NB, Lim K, Huang Y, Carson RE, Strittmatter SM, van Dyck CH. PET imaging of mGluR5 in Alzheimer’s disease. Alzheimer's Research & Therapy 2020, 12: 15. PMID: 31954399, PMCID: PMC6969979, DOI: 10.1186/s13195-020-0582-0.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAlzheimer DiseaseBrainCognitive DysfunctionFemaleHumansMaleMiddle AgedPositron-Emission TomographyRadiopharmaceuticalsReceptor, Metabotropic Glutamate 5ConceptsEarly Alzheimer's diseaseAlzheimer's diseaseMild cognitive impairmentBrain amyloidHippocampus of ADPositron emission tomography radioligandSubtype 5 receptorsMild AD dementiaGray matter atrophyAssociation cortical regionsAmnestic mild cognitive impairmentImportant therapeutic targetCerebellum reference regionDynamic PET scansHippocampal mGluR5MethodsSixteen individualsMGluR5 bindingSynaptotoxic actionAD dementiaAD pathogenesisMatter atrophyInitial administrationAD groupSynaptic transmissionEntorhinal cortex
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 ResearchMeSH KeywordsAdultBiomarkersBrainDepressive Disorder, MajorFemaleHumansMalePositron-Emission TomographyRadiopharmaceuticalsReceptor, Metabotropic Glutamate 5Suicidal IdeationSuicide PreventionConceptsMGluR5 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 targetDisordersKetamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression
Esterlis I, DellaGioia N, Pietrzak RH, Matuskey D, Nabulsi N, Abdallah CG, Yang J, Pittenger C, Sanacora G, Krystal JH, Parsey RV, Carson RE, DeLorenzo C. Ketamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression. Molecular Psychiatry 2017, 23: 824-832. PMID: 28397841, PMCID: PMC5636649, DOI: 10.1038/mp.2017.58.Peer-Reviewed Original ResearchConceptsMajor depressive disorderMGluR5 availabilityPositron emission tomographyKetamine administrationControl groupAspartate glutamate receptor antagonistIntravenous ketamine administrationKetamine-induced reductionMetabotropic glutamatergic receptorsRapid antidepressant effectsGlutamate receptor antagonistsKetamine-induced changesEffects of ketaminePET imaging studiesMechanism of actionGlutamate surgeAntidepressant effectsAntidepressant efficacyAntidepressant responseGlutamatergic receptorsControl subjectsReceptor antagonistHealthy controlsDepressive disorderSustained decrease
2016
In vivo variation in same-day estimates of metabotropic glutamate receptor subtype 5 binding using [11C]ABP688 and [18F]FPEB
DeLorenzo C, Gallezot JD, Gardus J, Yang J, Planeta B, Nabulsi N, Ogden RT, Labaree DC, Huang YH, Mann JJ, Gasparini F, Lin X, Javitch JA, Parsey RV, Carson RE, Esterlis I. In vivo variation in same-day estimates of metabotropic glutamate receptor subtype 5 binding using [11C]ABP688 and [18F]FPEB. Cerebrovascular And Brain Metabolism Reviews 2016, 37: 2716-2727. PMID: 27742888, PMCID: PMC5536783, DOI: 10.1177/0271678x16673646.Peer-Reviewed Original ResearchConceptsMetabotropic glutamate receptor subtype 5Test-retest studySubtype 5Absolute test-retest variabilityBrain glutamatergic systemSame dayPositron emission tomography (PET) tracerTest-retest variabilityEmission tomography tracerGlutamatergic systemLarge cohortSmall cohortStudy designTomography tracerMGluR5ScansCohortVivo variationsDaysReplication studyBinding increasesResidual radioactivitySubjectsBinding differences
2014
In 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
2013
Imaging Glutamate Homeostasis in Cocaine Addiction with the Metabotropic Glutamate Receptor 5 Positron Emission Tomography Radiotracer [11C]ABP688 and Magnetic Resonance Spectroscopy
Martinez D, Slifstein M, Nabulsi N, Grassetti A, Urban NB, Perez A, Liu F, Lin SF, Ropchan J, Mao X, Kegeles LS, Shungu DC, Carson RE, Huang Y. Imaging Glutamate Homeostasis in Cocaine Addiction with the Metabotropic Glutamate Receptor 5 Positron Emission Tomography Radiotracer [11C]ABP688 and Magnetic Resonance Spectroscopy. Biological Psychiatry 2013, 75: 165-171. PMID: 24035345, PMCID: PMC4106018, DOI: 10.1016/j.biopsych.2013.06.026.Peer-Reviewed Original ResearchMeSH KeywordsAdultBrainCarbon RadioisotopesCase-Control StudiesChoice BehaviorCocaineCocaine-Related DisordersCorpus StriatumFunctional NeuroimagingGlutamic AcidGlutamineHomeostasisHumansMagnetic Resonance SpectroscopyMaleOximesPositron-Emission TomographyPyridinesReceptor, Metabotropic Glutamate 5Self AdministrationYoung AdultConceptsHealthy control subjectsCocaine addictionControl subjectsLong-term cocaine useMagnetic resonance spectroscopy measuresGlutamate-glutamine levelsMGluR5 receptor bindingCocaine self-administration sessionsPositron emission tomography (PET) radiotracerPositron emission tomographySelf-administration sessionsCocaine-seeking behaviorSelf-administer cocaineMGluR5 bindingMGluR5 availabilityLeft striatumCocaine exposurePreclinical studiesGlutamate homeostasisGlutamate turnoverSubcortical regionsStriatumCocaine useMagnetic resonance spectroscopySecondary analysisStudies of the metabotropic glutamate receptor 5 radioligand [11C]ABP688 with N‐acetylcysteine challenge in rhesus monkeys
Sandiego CM, Nabulsi N, Lin S, Labaree D, Najafzadeh S, Huang Y, Cosgrove K, Carson RE. Studies of the metabotropic glutamate receptor 5 radioligand [11C]ABP688 with N‐acetylcysteine challenge in rhesus monkeys. Synapse 2013, 67: 489-501. PMID: 23424090, PMCID: PMC3710146, DOI: 10.1002/syn.21656.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsBrainCarbon RadioisotopesFemaleMacaca mulattaMaleOximesPositron-Emission TomographyProtein BindingPyridinesReceptor, Metabotropic Glutamate 5Receptors, Metabotropic GlutamateTissue DistributionConceptsN-acetylcysteineRhesus monkeysCerebellum gray matterMetabotropic glutamate receptor 5N-acetylcysteine challengeBaboon studiesGlutamate receptor 5Non-displaceable binding potentialHigh intersubject variabilityReference regionRecent pilot studySignificant global decreaseGlutamate transmissionNAC doseEndogenous glutamatePsychiatric illnessReceptor 5Gray matterAllosteric antagonistsPilot studyReceptor bindingIntersubject variabilitySame dayDoseMonkeys