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 ResearchConceptsPTSD 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 symptomsAnhedonia
2022
Imaging 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
Imaging brain cortisol regulation in PTSD with a target for 11β-hydroxysteroid dehydrogenase type 1
Bhatt S, Hillmer AT, Rusowicz A, Nabulsi N, Matuskey D, Angarita GA, Najafzadeh S, Kapinos M, Southwick SM, Krystal JH, Carson RE, Huang Y, Cosgrove KP. Imaging brain cortisol regulation in PTSD with a target for 11β-hydroxysteroid dehydrogenase type 1. Journal Of Clinical Investigation 2021, 131: e150452. PMID: 34651587, PMCID: PMC8516462, DOI: 10.1172/jci150452.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderPositron emission tomographyVolume of distributionDehydrogenase type 1Trauma-exposed controlsPTSD groupTranslocator proteinType 1Veterans Affairs (VA) National CenterOverall PTSD severityBrain glucocorticoidBrain immuneMethodsSixteen individualsPeripheral cortisolMicroglial markersImmune suppressionTranslational Science AwardsCortisol levelsNIH National CenterTC groupCortisol regulationEmission tomographyStress disorderLower PTSD symptomsPTSD symptoms
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 proteinsPTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies
Bhatt S, Hillmer AT, Girgenti MJ, Rusowicz A, Kapinos M, Nabulsi N, Huang Y, Matuskey D, Angarita GA, Esterlis I, Davis MT, Southwick SM, Friedman MJ, Duman R, Carson R, Krystal J, Pietrzak R, Cosgrove K. PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies. Nature Communications 2020, 11: 2360. PMID: 32398677, PMCID: PMC7217830, DOI: 10.1038/s41467-020-15930-5.Peer-Reviewed Original ResearchMeSH KeywordsAcetamidesAdaptor Proteins, Signal TransducingAdultBrainCase-Control StudiesFemaleGene Expression ProfilingHealthy VolunteersHumansMaleMicrogliaMiddle AgedPositron-Emission TomographyPyridinesRadiopharmaceuticalsReceptors, GABAReceptors, Tumor Necrosis Factor, Member 14Sex FactorsStress Disorders, Post-TraumaticYoung AdultConceptsPosttraumatic stress disorderPeripheral immune activationImmune activationHigher C-reactive protein levelsC-reactive protein levelsTSPO availabilityTranslocator proteinBrain microglial activationTomography brain imagingStress-related pathophysiologyPositron emission tomography (PET) brain imagingNeuroimmune activationMicroglial activationPTSD symptom severityImmunologic regulationPostmortem studiesPTSD subgroupHealthy individualsSymptom severityTrauma exposurePTSD groupStress disorderLower relative expressionBrain imagingPET imaging
2019
Imaging the Enzyme 11β-Hydroxysteroid Dehydrogenase Type 1 with PET: Evaluation of the Novel Radiotracer 11C-AS2471907 in Human Brain
Gallezot JD, Nabulsi N, Henry S, Pracitto R, Planeta B, Ropchan J, Lin SF, Labaree D, Kapinos M, Shirali A, Lara-Jaime T, Gao H, Matuskey D, Walzer M, Marek GJ, Bellaire S, Yuan N, Carson RE, Huang Y. Imaging the Enzyme 11β-Hydroxysteroid Dehydrogenase Type 1 with PET: Evaluation of the Novel Radiotracer 11C-AS2471907 in Human Brain. Journal Of Nuclear Medicine 2019, 60: 1140-1146. PMID: 30877174, DOI: 10.2967/jnumed.118.219766.Peer-Reviewed Original ResearchConceptsTest-retest variabilityNondisplaceable distribution volumeOccipital cortexEnzyme 11β-hydroxysteroid dehydrogenase type 1White matterDistribution volumeTreatment of depressionDehydrogenase type 1Large cortical regionsPosttraumatic stress disorderHuman brainAdditional scansIntraclass correlation coefficientAge-related cognitive functionBolus administrationFrontal cortexCaudate nucleusAdipose tissueTime-activity curvesNovel radiotracersGlucocorticoid levelsParietal cortexCortical regionsPattern of uptakeType 1
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 targetDisorders
2011
The Effect of Early Trauma Exposure on Serotonin Type 1B Receptor Expression Revealed by Reduced Selective Radioligand Binding
Murrough JW, Czermak C, Henry S, Nabulsi N, Gallezot JD, Gueorguieva R, Planeta-Wilson B, Krystal JH, Neumaier JF, Huang Y, Ding YS, Carson RE, Neumeister A. The Effect of Early Trauma Exposure on Serotonin Type 1B Receptor Expression Revealed by Reduced Selective Radioligand Binding. JAMA Psychiatry 2011, 68: 892-900. PMID: 21893657, PMCID: PMC3244836, DOI: 10.1001/archgenpsychiatry.2011.91.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsBrainCarbon RadioisotopesCross-Sectional StudiesDepressive Disorder, MajorFemaleHumansMaleMiddle AgedPiperazinesPositron-Emission TomographyPsychiatric Status Rating ScalesPyrrolidinonesRadioligand AssayReceptor, Serotonin, 5-HT1BSerotonin 5-HT1 Receptor AntagonistsStress Disorders, Post-TraumaticTrauma Severity IndicesWounds and InjuriesConceptsPosttraumatic stress disorderHealthy control participantsEarly trauma exposureTrauma exposureReceptor expressionCause of PTSDVeterans Affairs Medical CenterMajor depression comorbidityPositron emission tomography studyControl participantsMain outcome measuresRecent animal modelsTrauma-exposed control participantsSevere trauma exposureEmission tomography studiesFirst trauma exposureLimbic corticostriatal circuitsAnterior cingulate cortexPositron emission tomographyPTSD symptom severityDepression comorbiditySerotonergic dysfunctionMedical CenterOutcome measuresStudy group