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 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
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
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 ResearchConceptsMGluR5 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 controlsDysregulationMDDIdeationIndividualsLower synaptic density is associated with depression severity and network alterations
Holmes SE, Scheinost D, Finnema SJ, Naganawa M, Davis MT, DellaGioia N, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Lower synaptic density is associated with depression severity and network alterations. Nature Communications 2019, 10: 1529. PMID: 30948709, PMCID: PMC6449365, DOI: 10.1038/s41467-019-09562-7.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPost-traumatic stress disorderLower synaptic densitySynaptic densityPositron emission tomographyFunctional connectivityNetwork alterationsSynaptic vesicle glycoprotein 2ASymptoms of depressionSynaptic lossDepressive disorderHealthy controlsNerve terminalsDepressive symptomsDepression severityUnmedicated individualsSynaptic connectionsEmission tomographyStress disorderVivo evidenceSymptomsDepressionSeverityDisordersAlterations
2017
Ketamine-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
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
The 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 18DepressionChanges in the Cholinergic System between Bipolar Depression and Euthymia as Measured with [123I]5IA Single Photon Emission Computed Tomography
Hannestad JO, Cosgrove KP, DellaGioia NF, Perkins E, Bois F, Bhagwagar Z, Seibyl JP, McClure-Begley TD, Picciotto MR, Esterlis I. Changes in the Cholinergic System between Bipolar Depression and Euthymia as Measured with [123I]5IA Single Photon Emission Computed Tomography. Biological Psychiatry 2013, 74: 768-776. PMID: 23773793, PMCID: PMC3805761, DOI: 10.1016/j.biopsych.2013.04.004.Peer-Reviewed Original ResearchConceptsBipolar depressionControl subjectsCholinergic systemSingle photon emissionBipolar disorderAge-matched control subjectsEndogenous acetylcholine levelsNew treatment targetsNicotinic acetylcholine receptorsPhoton emissionLow receptor numbersClinical characteristicsEndogenous acetylcholineDepressive episodeAcetylcholine levelsTomography scanMajor depressionReceptor numberTemporal cortexNAChR numbersTreatment targetsAcetylcholine receptorsControl groupBrain regionsLower β2
2012
Bupropion pre-treatment of endotoxin-induced depressive symptoms
DellaGioia N, Devine L, Pittman B, Hannestad J. Bupropion pre-treatment of endotoxin-induced depressive symptoms. Brain Behavior And Immunity 2012, 31: 197-204. PMID: 23064079, DOI: 10.1016/j.bbi.2012.10.008.Peer-Reviewed Original ResearchConceptsVisual analog scaleInflammatory cytokinesDepressive symptomsSerum levelsMontgomery-Åsberg Depression Rating ScaleSerotonin reuptake inhibitor citalopramLow-dose lipopolysaccharideReuptake inhibitor citalopramCross-over studyDepression Rating ScaleTotal MADRS scoreDopamine reuptake inhibitorInnate immune responseInnate immune systemIntravenous LPSLPS administrationReuptake inhibitorsAnalog scaleMADRS scoresHealthy subjectsImmune responseBupropionImmune systemCytokinesLPSGlucose Metabolism in the Insula and Cingulate Is Affected by Systemic Inflammation in Humans
Hannestad J, Subramanyam K, Dellagioia N, Planeta-Wilson B, Weinzimmer D, Pittman B, Carson RE. Glucose Metabolism in the Insula and Cingulate Is Affected by Systemic Inflammation in Humans. Journal Of Nuclear Medicine 2012, 53: 601-607. PMID: 22414635, PMCID: PMC3717572, DOI: 10.2967/jnumed.111.097014.Peer-Reviewed Original ResearchConceptsNormalized glucose metabolismMontgomery-Åsberg Depression Rating ScalePeak cytokine levelsSystemic inflammationDepression Rating ScaleDepressive symptomsGlucose metabolismCytokine levelsFDG-PETRating ScaleSystemic inflammatory responseCerebral metabolic rateMild depressive symptomsRight anterior cingulateTumor necrosis factorRight anterior insulaSerum levelsInflammatory cytokinesEndotoxin administrationInterleukin-6Inflammatory responseNecrosis factorCingulate subregionsHealthy subjectsInflammation
2011
The Effect of Antidepressant Medication Treatment on Serum Levels of Inflammatory Cytokines: A Meta-Analysis
Hannestad J, DellaGioia N, Bloch M. The Effect of Antidepressant Medication Treatment on Serum Levels of Inflammatory Cytokines: A Meta-Analysis. Neuropsychopharmacology 2011, 36: 2452-2459. PMID: 21796103, PMCID: PMC3194072, DOI: 10.1038/npp.2011.132.Peer-Reviewed Original ResearchConceptsMajor depressive disorderInflammatory cytokinesSerum levelsAntidepressant treatmentInterleukin-6Depressive symptomsIL-1βCytokine levelsDepressive episodeDiagnosis of MDDTumor necrosis factor alphaPharmacological antidepressant treatmentAntidepressant medication treatmentClasses of antidepressantsStratified subgroup analysisIL-1 betaNecrosis factor alphaNormalization of levelsReuptake inhibitorsMedication treatmentPharmacological treatmentSubgroup analysisBrain dysfunctionDepressive disorderFactor alpha
2010
Citalopram reduces endotoxin-induced fatigue
Hannestad J, DellaGioia N, Ortiz N, Pittman B, Bhagwagar Z. Citalopram reduces endotoxin-induced fatigue. Brain Behavior And Immunity 2010, 25: 256-259. PMID: 20955776, PMCID: PMC3025065, DOI: 10.1016/j.bbi.2010.10.013.Peer-Reviewed Original ResearchConceptsTumor necrosis factorMADRS total scoreDepressive-like symptomsInterleukin-6Serum levelsImmune responseMontgomery-Åsberg Depression Rating ScaleTotal scorePeripheral immune responseLow-dose endotoxinCross-over studyVisual analog scaleDepression Rating ScaleImmune system activationInnate immune responseInnate immune systemEffect sizeTrait Anxiety InventoryModerate effect sizeAnalog scaleInflammatory cytokinesEndotoxin administrationPreventive treatmentNecrosis factorHealthy subjects
2009
A critical review of human endotoxin administration as an experimental paradigm of depression
DellaGioia N, Hannestad J. A critical review of human endotoxin administration as an experimental paradigm of depression. Neuroscience & Biobehavioral Reviews 2009, 34: 130-143. PMID: 19666048, PMCID: PMC2795398, DOI: 10.1016/j.neubiorev.2009.07.014.Peer-Reviewed Original ResearchConceptsImmune system activationEndotoxin administrationSystem activationImmune stimuliDepressive symptomsInnate immune system activationElicit depressive symptomsInterferon-alpha treatmentCommon final pathwayPotential molecular pathwaysImmunologic abnormalitiesImmune depressionVaccine administrationInflammatory cytokinesDepression paradigmDepressed patientsFinal pathwaySymptomsDepression researchAdministrationDepressionMolecular pathwaysBehavioral changesActivationRodents