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 symptomsAnhedonia
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 functionCholinergic 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
2021
Assessment 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
Nondisplaceable Binding Is a Potential Confounding Factor in 11C-PBR28 Translocator Protein PET Studies
Laurell G, Plavén-Sigray P, Jucaite A, Varrone A, Cosgrove KP, Svarer C, Knudsen G, Consortium K, Ogden R, Zanderigo F, Cervenka S, Hillmer A, Schain M. Nondisplaceable Binding Is a Potential Confounding Factor in 11C-PBR28 Translocator Protein PET Studies. Journal Of Nuclear Medicine 2020, 62: 412-417. PMID: 32680926, PMCID: PMC8049343, DOI: 10.2967/jnumed.120.243717.Peer-Reviewed Original ResearchMeSH KeywordsArtifactsBrainHumansPositron-Emission TomographyProtein BindingPyrimidinesReceptors, GABAConceptsAlcohol use disorderDistribution volumePET studiesParkinson's diseaseFirst-episode psychosis patientsTranslocator proteinAdministration of lipopolysaccharideNondisplaceable bindingFirst-episode psychosisPotential confounding factorsTotal distribution volumeC-PBR28Patient groupPsychosis patientsLipopolysaccharide challengeClinical studiesOutcome measuresTSPO PET studiesUse disordersPET ligandConfounding factorsCorresponding controlsDiseaseDisordersGroup
2019
Effects of age, BMI and sex on the glial cell marker TSPO — a multicentre [11C]PBR28 HRRT PET study
Tuisku J, Plavén-Sigray P, Gaiser EC, Airas L, Al-Abdulrasul H, Brück A, Carson RE, Chen MK, Cosgrove KP, Ekblad L, Esterlis I, Farde L, Forsberg A, Halldin C, Helin S, Kosek E, Lekander M, Lindgren N, Marjamäki P, Rissanen E, Sucksdorff M, Varrone A, Collste K, Gallezot J, Hillmer A, Huang Y, Höglund C, Johansson J, Jucaite A, Lampa J, Nabulsi N, Pittman B, Sandiego C, Stenkrona P, Rinne J, Matuskey D, Cervenka S. Effects of age, BMI and sex on the glial cell marker TSPO — a multicentre [11C]PBR28 HRRT PET study. European Journal Of Nuclear Medicine And Molecular Imaging 2019, 46: 2329-2338. PMID: 31363804, PMCID: PMC6717599, DOI: 10.1007/s00259-019-04403-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overAgingBody Mass IndexFemaleGenotypeHumansMaleMiddle AgedPositron-Emission TomographyPyrimidinesReceptors, GABASex FactorsYoung AdultConceptsBody mass indexPositron emission tomographyEffect of ageMultilinear analysis 1PET centersGlobal gray matterMass indexSubgroup analysisClinical studiesTSPO levelsHealthy subjectsTurku PET CentreHealthy volunteersPositive correlationTemporal cortexTSPO genotypeIndividual biological propertiesMale subjectsPurposeThe purposeConclusionThese findingsLinear mixed effects modelsGray matterParietal cortexSignificant negative correlationEmission tomographyQuantification of PET infusion studies without true equilibrium: A tissue clearance correction
Hillmer AT, Carson RE. Quantification of PET infusion studies without true equilibrium: A tissue clearance correction. Cerebrovascular And Brain Metabolism Reviews 2019, 40: 860-874. PMID: 31088233, PMCID: PMC7168787, DOI: 10.1177/0271678x19850000.Peer-Reviewed Original Research
2017
In 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