2024
11C-UCB-J PET imaging is consistent with lower synaptic density in autistic adults
Matuskey D, Yang Y, Naganawa M, Koohsari S, Toyonaga T, Gravel P, Pittman B, Torres K, Pisani L, Finn C, Cramer-Benjamin S, Herman N, Rosenthal L, Franke C, Walicki B, Esterlis I, Skosnik P, Radhakrishnan R, Wolf J, Nabulsi N, Ropchan J, Huang Y, Carson R, Naples A, McPartland J. 11C-UCB-J PET imaging is consistent with lower synaptic density in autistic adults. Molecular Psychiatry 2024, 1-7. PMID: 39367053, DOI: 10.1038/s41380-024-02776-2.Peer-Reviewed Original ResearchPositron emission tomographySynaptic densityAutistic adultsBrain regionsAutistic featuresClinical phenotype of autismNon-autistic participantsPhenotype of autismNon-autistic individualsRelationship to clinical characteristicsSynaptic vesicle glycoprotein 2AAssociated with clinical measuresPost-mortem studiesPositron emission tomography scanPrefrontal cortexClinician ratingsAutism groupNeural basisBrain areasNeural processesBetween-group differencesVolumetric differencesBinding potentialDensity of synapsesAutismMetabotropic Glutamate Receptor 5 as a Potential Biomarker of the Intersection of Trauma and Cannabis Use
Weiss E, Davis M, Asch R, D'Souza D, Cool R, Esterlis I. Metabotropic Glutamate Receptor 5 as a Potential Biomarker of the Intersection of Trauma and Cannabis Use. The International Journal Of Neuropsychopharmacology 2024, 27: pyae044. PMID: 39320043, DOI: 10.1093/ijnp/pyae044.Peer-Reviewed Original ResearchTrauma-related psychopathologyCannabis useDepressive symptomsPositron emission tomographyCross-diagnostic sampleMetabotropic glutamate receptor 5Treatment development effortsAssociated with depressive symptomsGlutamate receptor 5CU groupSample of individualsAvailability in vivoFrontolimbic regionsGlutamatergic systemGlutamatergic neurotransmissionMGlu5PsychopathologyReceptor 5Intersection of traumaExploratory analysisCannabisEmission tomographySymptomsParticipantsVmPFCChallenges and rewards of in vivo synaptic density imaging, and its application to the study of depression
Asch R, Abdallah C, Carson R, Esterlis I. Challenges and rewards of in vivo synaptic density imaging, and its application to the study of depression. Neuropsychopharmacology 2024, 50: 153-163. PMID: 39039139, PMCID: PMC11525584, DOI: 10.1038/s41386-024-01913-3.Peer-Reviewed Original ResearchStudies of depressionAnimal models of chronic stressPositron emission tomographyModel of chronic stressSV2A imagingSynaptic densitySignificant depressive symptomsDevelopment of novel radiotracersDepressive symptomsNeuropsychiatric disordersSymptom severityChronic stressDrug challengeSynaptic vesicle glycoprotein 2 ANeural markersAnimal modelsSynaptic alterationsSynaptogenesis in vivoPreliminary findingsIn vivo quantificationCentral nervous systemDepressionEmission tomographySV2ASV2A positron emission tomographyDeficits in prefrontal metabotropic glutamate receptor 5 are associated with functional alterations during emotional processing in bipolar disorder
Asch R, Worhunsky P, Davis M, Holmes S, Cool R, Boster S, Carson R, Blumberg H, Esterlis I. Deficits in prefrontal metabotropic glutamate receptor 5 are associated with functional alterations during emotional processing in bipolar disorder. Journal Of Affective Disorders 2024, 361: 415-424. PMID: 38876317, PMCID: PMC11250898, DOI: 10.1016/j.jad.2024.06.025.Peer-Reviewed Original ResearchMetabotropic glutamate receptor 5Bipolar disorderGlutamate receptor 5Positron emission tomographyFear processingEmotional processingAssociated with greater activationEmotion processing taskAssociated with impulsivityFunctional brain differencesAssociated with functional alterationsParietal brain regionsPathology of BDIncreased cortical activityAssociated with difficultiesDepressive disorderHealthy comparisonReceptor availabilityBrain differencesPre/postcentral gyriAttention difficultiesGreater activationBrain regionsPsychomotor functionTreatment developmentSynaptic 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
2023
Investigating 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 differencesHumansExamining mGlu5 Receptor Availability as a Predictor of Vulnerability to PTSD: An [18F]FPEB and PET Study in Male and Female Rats
Asch R, Fowles K, Pietrzak R, Taylor J, Esterlis I. Examining mGlu5 Receptor Availability as a Predictor of Vulnerability to PTSD: An [18F]FPEB and PET Study in Male and Female Rats. Chronic Stress 2023, 7: 24705470231215001. PMID: 38024327, PMCID: PMC10666551, DOI: 10.1177/24705470231215001.Peer-Reviewed Original ResearchPost-traumatic stress disorderReceptor availabilityFemale ratsPathophysiology of PTSDFootshock exposureMetabotropic glutamate receptor 5Recent preclinical findingsGlutamate receptor 5Positron emission tomographyPreclinical findingsClinical findingsFe ratsReceptor 5Lower baselineEmission tomographyGreater riskPET studiesRatsStress disorderDifferential involvementPassive copingSex differencesMalesPTSD susceptibilityBaseline
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 correlationImaging synaptic density in depression
Holmes SE, Abdallah C, Esterlis I. Imaging synaptic density in depression. Neuropsychopharmacology 2022, 48: 186-190. PMID: 35768568, PMCID: PMC9700860, DOI: 10.1038/s41386-022-01368-4.Peer-Reviewed Original ResearchConceptsMagnetic resonance imagingPositron emission tomographySynaptic restorationSynaptic densityAdministration of ketamineMajor depressive disorderUnderstanding of depressionSynaptic alterationsSynaptic involvementDepressive disorderMonoamine systemsPreclinical workTreatment resistanceEffective treatmentDendritic spinesResonance imagingEmission tomographyHeterogeneous disorderDepressionDisordersMore researchInitial studyGliaKetamineBoutonsMultimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder
Smart K, Worhunsky PD, Scheinost D, Angarita GA, Esterlis I, Carson RE, Krystal JH, O'Malley SS, Cosgrove KP, Hillmer AT. Multimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder. Alcohol Clinical And Experimental Research 2022, 46: 770-782. PMID: 35342968, PMCID: PMC9117461, DOI: 10.1111/acer.14816.Peer-Reviewed Original ResearchConceptsMetabotropic glutamate 5 receptorsDefault mode networkFunctional magnetic resonance imagingReceptor availabilityPositron emission tomographyAUD groupFunctional connectivityReceptor positron emission tomographyResting-state functional magnetic resonance imagingNetwork-level functional connectivityBrain connectivityWeeks of abstinenceGlobal functional connectivityAlcohol use disorderMagnetic resonance imagingFMRI outcomesHealthy controlsSupervised abstinencePET resultsUse disordersSynaptic plasticityResonance imagingBrain regionsEmission tomographyOrbitofrontal cortexImaging 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 ResearchConceptsKetamine'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 symptoms
2021
Lower synaptic density is associated with psychiatric and cognitive alterations in obesity
Asch RH, Holmes SE, Jastreboff AM, Potenza MN, Baldassarri SR, Carson RE, Pietrzak RH, Esterlis I. Lower synaptic density is associated with psychiatric and cognitive alterations in obesity. Neuropsychopharmacology 2021, 47: 543-552. PMID: 34294874, PMCID: PMC8674236, DOI: 10.1038/s41386-021-01111-5.Peer-Reviewed Original ResearchConceptsStress-related psychiatric disordersBody mass indexLower synaptic densitySynaptic densityPsychiatric disordersPsychiatric diagnosisOverweight/obesityNormal-weight individualsNormal-weight participantsSerious medical conditionPositron emission tomographyStress-related psychopathologyDorsolateral prefrontal cortexOverweight/Mass indexWeight participantsWeight individualsHealthy controlsTension/anxietyAssociated symptomatologyMedical conditionsIntervention development effortsObesityCognitive alterationsPsychiatric groupsEffect 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 analysisMacro- and Microscale Stress–Associated Alterations in Brain Structure: Translational Link With Depression
Banasr M, Sanacora G, Esterlis I. Macro- and Microscale Stress–Associated Alterations in Brain Structure: Translational Link With Depression. Biological Psychiatry 2021, 90: 118-127. PMID: 34001371, DOI: 10.1016/j.biopsych.2021.04.004.Peer-Reviewed Original ResearchConceptsMajor depressive disorderStress-related disordersCytoarchitectural alterationsPathophysiology of MDDChronic stress pathologyDepressive-like behaviorChronic stress modelAnimal stress modelsPositron emission tomographyHuman brain tissueAstroglial alterationsSynaptic deficitsNeurochemical changesDepressive disorderBehavioral deficitsRodent modelsBrain tissueEmission tomographyDepression symptomatologyLiving brainBrain structuresNovel drugsTranslational linkStress pathologyDisorders
2020
PET Imaging of Synaptic Vesicle Protein 2A
Finnema S, Li S, Cai Z, Naganawa M, Chen M, Matuskey D, Nabulsi N, Esterlis I, Holmes S, Radhakrishnan R, Toyonaga T, Huang Y, Carson R. PET Imaging of Synaptic Vesicle Protein 2A. 2020, 993-1019. DOI: 10.1007/978-3-030-53176-8_29.ChaptersSynaptic vesicle protein 2APositron emission tomographyAntiepileptic drug levetiracetamInitial PET studiesPET imagingPET studiesSynaptic densityDrug levetiracetamHigh-affinity SV2A ligandsBrain regionsSynaptic density lossNeuropathological diseasesDisease-modifying therapiesLarge patient cohortMajor depressive disorderProtein 2APET imaging resultsPosttraumatic stress disorderPatient groupPatient cohortDepressive disorderClinical valueParkinson's diseaseEfficacy assessmentSynaptic vesicle proteins