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 ResearchMeSH KeywordsAdultAnhedoniaBrainFemaleHumansLipopolysaccharidesMaleMicrogliaMiddle AgedNeuroimmunomodulationPositron-Emission TomographyReceptors, GABAStress Disorders, Post-TraumaticConceptsPTSD 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 symptomsAnhedoniaDoes seasonal variation affect the neuroimmune system? A retrospective [11C]PBR28 PET study in healthy individuals
Ibrahim W, An J, Yang Y, Cosgrove K, Matuskey D. Does seasonal variation affect the neuroimmune system? A retrospective [11C]PBR28 PET study in healthy individuals. Neuroscience Letters 2024, 828: 137766. PMID: 38583505, PMCID: PMC11073647, DOI: 10.1016/j.neulet.2024.137766.Peer-Reviewed Original ResearchMeSH KeywordsBrainCarrier ProteinsHumansPositron-Emission TomographyReceptors, GABARetrospective StudiesSeasonsConceptsTranslocator protein levelsPositron emission tomographyNeuroimmune systemHealthy individualsHuman studiesPositron emission tomography scanTranslocator proteinTest-retest variabilityBrain TSPO levelsVolume of distributionPositron emission tomography imagingBrain regionsCentral nervous systemTranslocator protein expressionGene polymorphismsCell markersHealthy subjectsTSPO levelsInterindividual variabilityNeuropsychiatric disordersEmission tomographyPET studiesNervous systemMonthsNo significant effect
2023
Imaging the brain’s immune response to alcohol with [11C]PBR28 TSPO Positron Emission Tomography
Raval N, Angarita G, Matuskey D, Miller R, Drake L, Kapinos M, Nabulsi N, Huang Y, Carson R, O’Malley S, Cosgrove K, Hillmer A. Imaging the brain’s immune response to alcohol with [11C]PBR28 TSPO Positron Emission Tomography. Molecular Psychiatry 2023, 28: 3384-3390. PMID: 37532797, PMCID: PMC10743097, DOI: 10.1038/s41380-023-02198-6.Peer-Reviewed Original ResearchMeSH KeywordsBlood Alcohol ContentBrainCytokinesFemaleHumansImmunityMalePositron-Emission TomographyRadionuclide ImagingReceptors, GABAConceptsVolume of distributionBlood alcohol levelsPositron emission tomographyBrain immune responseImmune responseAlcohol challengeEmission tomographyPeak blood alcohol levelsMultilinear analysis 1Peripheral immune functionVivo human evidenceLaboratory alcohol challengeTSPO positron emission tomographyBinge levelsPlasma cytokinesImmune dysfunctionNeuroimmune systemIL-6MCP-1Cytokines TNFAcute effectsScan dayArterial bloodHuman evidenceImmune functionClustering of KOR PET images separates people with AUD into distinct responses to naltrexone
Hoye J, Key J, de Laat B, Cosgrove K, Krishnan-Sarin S, Papademetris X, Morris E. Clustering of KOR PET images separates people with AUD into distinct responses to naltrexone. Brain Imaging And Behavior 2023, 17: 367-371. PMID: 36695971, DOI: 10.1007/s11682-023-00758-6.Peer-Reviewed Original ResearchAlcohol DrinkingAlcoholismHumansMagnetic Resonance ImagingNaltrexonePositron-Emission TomographyReceptors, Opioid, kappaCholinergic system adaptations are associated with cognitive function in people recently abstinent from smoking: a (-)-[18F]flubatine PET study
Calakos K, Hillmer A, Anderson J, LeVasseur B, Baldassarri S, Angarita G, Matuskey D, Kapinos M, Zheng M, Huang Y, Cosgrove K. Cholinergic system adaptations are associated with cognitive function in people recently abstinent from smoking: a (-)-[18F]flubatine PET study. Neuropsychopharmacology 2023, 48: 683-689. PMID: 36681758, PMCID: PMC9938267, DOI: 10.1038/s41386-023-01535-1.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAcetylcholinesteraseAnimalsBrainCholinergic AgentsCognitionFemaleMalePhysostigminePositron-Emission TomographyReceptors, NicotinicSmokingConceptsExecutive functionCholinergic systemWorse executive functionAcetylcholine levelsVerbal learningCognitive batteryPositron emission tomography brainCognitive dataAbstinent smokersCognitive functionCognitive deficitsCortical acetylcholine levelsEarly smoking cessationAcetylcholinesterase inhibitor physostigmineCognitionQuit attemptsNAChR sitesPhysostigmine administrationTomography brainSmoking statusSmoking cessationInhibitor physostigmineTreatment strategiesAgonist radioligandPhysostigmine challenge
2022
Lower Dopamine D2/3 Receptor Availability is Associated With Worse Verbal Learning and Memory in People Who Smoke Cigarettes
Zakiniaeiz Y, Gueorguieva R, Peltier M, Roberts W, Verplaetse T, Burke C, Morris E, McKee S, Cosgrove K. Lower Dopamine D2/3 Receptor Availability is Associated With Worse Verbal Learning and Memory in People Who Smoke Cigarettes. Nicotine & Tobacco Research 2022, 25: 1047-1051. PMID: 36107715, PMCID: PMC10077933, DOI: 10.1093/ntr/ntac215.Peer-Reviewed Original ResearchMeSH KeywordsAmphetamineCigarette SmokingDopamineFemaleHumansMalePositron-Emission TomographyPrefrontal CortexVerbal LearningConceptsCognitive functionVerbal learningPrefrontal cortexCognitive deficitsWorse verbal learningBrain-behavior relationshipsD2R availabilityDorsolateral prefrontal cortexCognitive performanceComputerized testsTask performanceCogState batteryInhibitory controlNeurocognitive testsReceptor availabilityMesocortical dopaminePositron emission tomographyDopamine D2/3 receptor availabilityMemoryCognitionD2/3 receptor availabilityDopamine releaseSmoking variablesSubject samplesDeficitsSystemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers
Zakiniaeiz Y, Hoye J, Ryan Petrulli J, LeVasseur B, Stanley G, Gao H, Najafzadeh S, Ropchan J, Nabulsi N, Huang Y, Chen MK, Matuskey D, Barron DS, Kelmendi B, Fulbright RK, Hampson M, Cosgrove KP, Morris ED. Systemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers. Brain Behavior And Immunity 2022, 106: 262-269. PMID: 36058419, PMCID: PMC10097458, DOI: 10.1016/j.bbi.2022.08.016.Peer-Reviewed Original ResearchMeSH KeywordsCentral Nervous System StimulantsCorpus StriatumDopamineHumansInflammationLipopolysaccharidesMethylphenidatePositron-Emission TomographyRacloprideSmokersConceptsEffects of LPSDopamine elevationTobacco smokersHealthy controlsSystemic inflammationDopamine systemImmune-brain interactionReward-related brain regionsAdministration of placeboAdministration of LPSSmoking statusRepeated-measures ANOVAPathophysiology of addictionDrug dosingPlaceboIndependent cohortSmokersDrug reinforcementEffect size determinationImmune systemRandomized orderBrain regionsLPSMethylphenidatePBO conditionRelationships between dopamine D2/3 receptor availability and social-environmental factors in humans
Calakos KC, Rusowicz A, Pittman B, Gallezot JD, Potenza MN, Cosgrove KP, Matuskey D. Relationships between dopamine D2/3 receptor availability and social-environmental factors in humans. Neuroscience Letters 2022, 771: 136463. PMID: 35051435, PMCID: PMC8821418, DOI: 10.1016/j.neulet.2022.136463.Peer-Reviewed Original Research
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 ResearchMeSH Keywords11-beta-Hydroxysteroid Dehydrogenase Type 1AdultBrainFemaleHumansHydrocortisoneMaleMiddle AgedPositron-Emission TomographySeverity of Illness IndexStress Disorders, Post-TraumaticTriazolesConceptsPosttraumatic 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 symptomsRecently Abstinent Smokers Exhibit Mood-Associated Dopamine Dysfunction in the Ventral Striatum Compared to Nonsmokers: A [11C]-(+)-PHNO PET Study
Calakos KC, Hillmer AT, Angarita GA, Baldassarri SR, Najafzadeh S, Emery PR, Matuskey D, Huang Y, Cosgrove KP. Recently Abstinent Smokers Exhibit Mood-Associated Dopamine Dysfunction in the Ventral Striatum Compared to Nonsmokers: A [11C]-(+)-PHNO PET Study. Nicotine & Tobacco Research 2021, 24: 745-752. PMID: 34628508, PMCID: PMC8962719, DOI: 10.1093/ntr/ntab208.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarbon RadioisotopesDopamineFemaleHumansNon-SmokersPositron-Emission TomographySmokersVentral StriatumConceptsSmoking cessationAbstinent smokersDopamine releaseVentral striatumPercent changeTobacco smokersDopamine dysfunctionDopamine functionPHNO scansPositron emission tomography brainHigher CES-D scoresAbstinent tobacco smokersEarly quit attemptsHuman tobacco smokersPHNO PET StudyStriatal dopamine dysfunctionEpidemiologic Studies Depression ScaleStriatal dopamine releaseChronic nicotine exposureCES-D scoresSmoking cessation attemptNegative mood symptomsReceptor agonist radioligandStriatal dopamine functionLong-term abstinenceAssessment of transient dopamine responses to smoked cannabis
Calakos KC, Liu H, Lu Y, Anderson JM, Matuskey D, Nabulsi N, Ye Y, Skosnik PD, D'Souza DC, Morris ED, Cosgrove KP, Hillmer AT. Assessment of transient dopamine responses to smoked cannabis. Drug And Alcohol Dependence 2021, 227: 108920. PMID: 34399137, PMCID: PMC8464527, DOI: 10.1016/j.drugalcdep.2021.108920.Peer-Reviewed Original ResearchMeSH KeywordsAdultCannabisCorpus StriatumDopamineHumansMarijuana SmokingPositron-Emission TomographyRacloprideVentral StriatumYoung AdultConceptsStriatal dopamine responsesDopamine responseRadiotracer uptakePositron emission tomography (PET) imaging studiesTransient reductionTomography Imaging StudyChronic cannabis useDopaminergic mechanismsCannabis smokingMesolimbic dopaminergicReceptor antagonistPlasma concentrationsRegular cannabis usersCannabis cigarettesConstant infusionDopamine DImaging studiesVentral striatumCannabis useTransient changesCannabis usersCannabisPuff protocolPreliminary dataTHC levelsPET Imaging Estimates of Regional Acetylcholine Concentration Variation in Living Human Brain
Smart K, Naganawa M, Baldassarri SR, Nabulsi N, Ropchan J, Najafzadeh S, Gao H, Navarro A, Barth V, Esterlis I, Cosgrove KP, Huang Y, Carson RE, Hillmer AT. PET Imaging Estimates of Regional Acetylcholine Concentration Variation in Living Human Brain. Cerebral Cortex 2021, 31: 2787-2798. PMID: 33442731, PMCID: PMC8355478, DOI: 10.1093/cercor/bhaa387.Peer-Reviewed Original ResearchConceptsACh concentrationHuman volunteersHigh ACh concentrationsMuscarinic antagonist scopolamineHealthy human volunteersHuman brainCholinergic receptorsNicotine challengeAntagonist scopolaminePreclinical studiesStriatal regionsPET scansEndogenous neurotransmittersNeuropsychiatric diseasesNonhuman primatesWhole-brain imagesDrug occupancyNicotinic ligandsClinical populationsBrainAcetylcholineDistinct functional rolesStriatumVolunteersFunctional role
2020
Acute neuroimmune stimulation impairs verbal memory in adults: A PET brain imaging study
Woodcock EA, Hillmer AT, Sandiego CM, Maruff P, Carson RE, Cosgrove KP, Pietrzak RH. Acute neuroimmune stimulation impairs verbal memory in adults: A PET brain imaging study. Brain Behavior And Immunity 2020, 91: 784-787. PMID: 33002632, PMCID: PMC7749814, DOI: 10.1016/j.bbi.2020.09.027.Peer-Reviewed Original ResearchConceptsMemory processesCognitive dysfunctionHippocampal memory processesBrain imaging studiesExecutive processesVerbal learningVerbal memoryExperimental paradigmCognitive deficitsPositron emission tomographyGreater decrementNeuroinflammatory dysfunctionNeurologic disordersPrevious findingsHealthy adultsDevelopment studiesMarker of microgliaImaging studiesNeuroimmune responseLPS administrationNeuroinflammatory signalingAdultsPreclinical findingsExperimental inductionDisordersLongitudinal 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 durationPTSD 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 imagingTobacco Smoking in People Is Not Associated with Altered 18-kDa Translocator Protein Levels: A PET Study
Hillmer AT, Matuskey D, Huang Y, Nabulsi N, Ropchan J, Carson RE, O'Malley SS, Cosgrove KP. Tobacco Smoking in People Is Not Associated with Altered 18-kDa Translocator Protein Levels: A PET Study. Journal Of Nuclear Medicine 2020, 61: 1200-1204. PMID: 32005773, PMCID: PMC7413239, DOI: 10.2967/jnumed.119.237735.Peer-Reviewed Original ResearchMeSH KeywordsAdultFemaleHumansMaleMiddle AgedPositron-Emission TomographyReceptors, GABATobacco SmokingYoung AdultConceptsTobacco smokingTobacco smokersTSPO levelsImmune systemPET studiesBrain immune systemBrain TSPO levelsPrimary immunocompetent cellsPrevious PET studiesTranslocator proteinTranslocator protein (TSPO) levelsInflammatory effectsImmunocompetent cellsArterial bloodTobacco smokePET scansNonsmokersSmokersRadiotracer concentrationMedium effect sizeSmokingPET imagingBrainProtein levelsSignificant differences
2019
Sex differences in amphetamine-induced dopamine release in the dorsolateral prefrontal cortex of tobacco smokers
Zakiniaeiz Y, Hillmer AT, Matuskey D, Nabulsi N, Ropchan J, Mazure CM, Picciotto MR, Huang Y, McKee SA, Morris ED, Cosgrove KP. Sex differences in amphetamine-induced dopamine release in the dorsolateral prefrontal cortex of tobacco smokers. Neuropsychopharmacology 2019, 44: 2205-2211. PMID: 31269510, PMCID: PMC6897943, DOI: 10.1038/s41386-019-0456-y.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAdultAmphetamineDopamineFemaleHumansMalePositron-Emission TomographyPrefrontal CortexReceptors, Dopamine D2Sex CharacteristicsSmokersConceptsDA releasePositron emission tomographyD2R availabilityDorsolateral prefrontal cortexMale smokersFemale smokersTobacco smokingPrefrontal cortexAmphetamine-induced DA releaseAmphetamine-induced dopamine releaseCortical DA releaseMesocortical DA systemEffects of nicotineSmoking-related behaviorsMesolimbic dopamine systemLong-term abstinenceSex differencesGender-specific treatmentFemale nonsmokersTobacco smokersAmphetamine administrationDopamine releaseNeurochemical mechanismsNonsmokersSmokersFirst in-human PET study and kinetic evaluation of [18F]AS2471907 for imaging 11β-hydroxysteroid dehydrogenase type 1
Bhatt S, Nabulsi NB, Li S, Cai Z, Matuskey D, Bini J, Najafzadeh S, Kapinos M, Ropchan JR, Carson RE, Cosgrove KP, Huang Y, Hillmer AT. First in-human PET study and kinetic evaluation of [18F]AS2471907 for imaging 11β-hydroxysteroid dehydrogenase type 1. Cerebrovascular And Brain Metabolism Reviews 2019, 40: 695-704. PMID: 30895878, PMCID: PMC7168798, DOI: 10.1177/0271678x19838633.Peer-Reviewed Original Research
2017
The Effect of Treatment with Guanfacine, an Alpha2 Adrenergic Agonist, on Dopaminergic Tone in Tobacco Smokers: An [11C]FLB457 PET Study
Sandiego CM, Matuskey D, Lavery M, McGovern E, Huang Y, Nabulsi N, Ropchan J, Picciotto MR, Morris ED, McKee SA, Cosgrove KP. The Effect of Treatment with Guanfacine, an Alpha2 Adrenergic Agonist, on Dopaminergic Tone in Tobacco Smokers: An [11C]FLB457 PET Study. Neuropsychopharmacology 2017, 43: 1052-1058. PMID: 28944773, PMCID: PMC5854798, DOI: 10.1038/npp.2017.223.Peer-Reviewed Original ResearchConceptsTobacco smokersGuanfacine treatmentPositron emission tomographyTobacco smokingDA releaseDopaminergic toneDopamine releaseAmphetamine-induced DA releaseTobacco smoking cessationCortical dopamine releaseExtrastriatal brain regionsAlpha2-adrenergic agonistExtrastriatal dopamine releaseEffect of treatmentBaseline BPNDSmoking cessationReceptor radiotracerAdrenergic agonistsPET scansAnimal modelsBrain regionsEmission tomographyPET studiesDopamine signalingSmokersIn vivo imaging of translocator protein, a marker of activated microglia, in alcohol dependence
Hillmer AT, Sandiego CM, Hannestad J, Angarita GA, Kumar A, McGovern EM, Huang Y, O'Connor KC, Carson RE, O'Malley SS, Cosgrove KP. In vivo imaging of translocator protein, a marker of activated microglia, in alcohol dependence. Molecular Psychiatry 2017, 22: 1759-1766. PMID: 28242869, PMCID: PMC5573660, DOI: 10.1038/mp.2017.10.Peer-Reviewed Original ResearchMeSH KeywordsAcetamidesAdultAlcoholismBrainBrain MappingCarbon RadioisotopesCells, CulturedCytokinesFemaleHumansInflammationLipopolysaccharidesMaleMicrogliaMonocytesNeuroimagingPolymorphism, Single NucleotidePositron-Emission TomographyPyridinesRadiopharmaceuticalsReceptors, GABASeverity of Illness IndexConceptsAlcohol-dependent subjectsAlcohol dependenceTSPO levelsTranslocator proteinProinflammatory cytokine interleukin-6Peripheral immune profilePeripheral immune responseCytokine interleukin-6Absence of lipopolysaccharideSubset of subjectsAlcohol use disorderPositron emission tomographyAlcohol-dependent individualsMicroglial activationImmune profileNeuroimmune systemCytokine expressionBrain levelsProinflammatory responseInterleukin-6Healthy controlsInterleukin-8Immune responseLast drinkUse disorders