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
Relationships 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 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 symptomsAssessment 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 ResearchConceptsStriatal 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 inductionDisordersPTSD 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 ResearchConceptsTobacco 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 StatementsConceptsDA 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
2015
Imaging robust microglial activation after lipopolysaccharide administration in humans with PET
Sandiego CM, Gallezot JD, Pittman B, Nabulsi N, Lim K, Lin SF, Matuskey D, Lee JY, O’Connor K, Huang Y, Carson RE, Hannestad J, Cosgrove KP. Imaging robust microglial activation after lipopolysaccharide administration in humans with PET. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 12468-12473. PMID: 26385967, PMCID: PMC4603509, DOI: 10.1073/pnas.1511003112.Peer-Reviewed Original ResearchConceptsMicroglial activationBrain microglial activationLPS administrationInflammatory cytokinesLPS challengeRobust microglial activationSystemic LPS challengeActivation of microgliaInnate immune cellsVital sign changesHealthy male subjectsEscherichia coli lipopolysaccharidePositron emission tomography (PET) radiotracerNeuroinflammatory responseSystemic inflammationLipopolysaccharide administrationAntiinflammatory effectsBlood levelsImmune cellsNew medicationsSystemic administrationColi lipopolysaccharidePET scansPsychiatric diseasesMale subjects
2014
Sex Differences in the Brain's Dopamine Signature of Cigarette Smoking
Cosgrove KP, Wang S, Kim SJ, McGovern E, Nabulsi N, Gao H, Labaree D, Tagare HD, Sullivan JM, Morris ED. Sex Differences in the Brain's Dopamine Signature of Cigarette Smoking. Journal Of Neuroscience 2014, 34: 16851-16855. PMID: 25505336, PMCID: PMC4261105, DOI: 10.1523/jneurosci.3661-14.2014.Peer-Reviewed Original ResearchConceptsCigarette smokingVentral striatumCigarette smoking differsEffect of smokingEarly PET studiesMesolimbic dopamine systemRight ventral striatumSex differencesDopaminergic eventsMale smokersNicotine patchCessation treatmentFemale smokersDorsal putamenDopaminergic responseBrain scanningSmoking differsDrug effectsDopamine systemSmokingNeurotransmitter releasePublic health dangerPET studiesCue reactivityWomen
2012
Sex Differences in Availability of β2*-Nicotinic Acetylcholine Receptors in Recently Abstinent Tobacco Smokers
Cosgrove KP, Esterlis I, McKee SA, Bois F, Seibyl JP, Mazure CM, Krishnan-Sarin S, Staley JK, Picciotto MR, O’Malley S. Sex Differences in Availability of β2*-Nicotinic Acetylcholine Receptors in Recently Abstinent Tobacco Smokers. JAMA Psychiatry 2012, 69: 418-427. PMID: 22474108, PMCID: PMC3508698, DOI: 10.1001/archgenpsychiatry.2011.1465.Peer-Reviewed Original ResearchMeSH KeywordsAdultAzetidinesBehavior, AddictiveBrainDepressionEstradiolFemaleFunctional NeuroimagingHumansIodine RadioisotopesMaleNicotinic AntagonistsProgesteronePyridinesRadioligand AssayReceptors, NicotinicSex CharacteristicsSmokingSubstance Withdrawal SyndromeTomography, Emission-Computed, Single-PhotonConceptsNAChR availabilityFemale smokersTobacco smokersNicotinic acetylcholine receptorsFemale nonsmokersProgesterone levelsAcetylcholine receptorsFemale sex steroid hormonesSex differencesSex steroid hormone levelsAbstinent tobacco smokersSex-matched nonsmokersTobacco smoking effectsMagnetic resonance imaging studyAge-matched malesEquilibrium distribution volumeEffects of nicotineSex steroid hormonesSteroid hormone levelsUnderlying neurochemical mechanismsResonance imaging studySingle photon emissionDays of abstinenceIA SPECTNicotine therapy
2009
β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking
Cosgrove KP, Batis J, Bois F, Maciejewski PK, Esterlis I, Kloczynski T, Stiklus S, Krishnan-Sarin S, O’Malley S, Perry E, Tamagnan G, Seibyl JP, Staley JK. β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking. JAMA Psychiatry 2009, 66: 666-676. PMID: 19487632, PMCID: PMC2796827, DOI: 10.1001/archgenpsychiatry.2009.41.Peer-Reviewed Original ResearchMeSH KeywordsAdultAzetidinesBrainBrain MappingDominance, CerebralFemaleFollow-Up StudiesHumansImage Processing, Computer-AssistedIodine RadioisotopesMagnetic Resonance ImagingMaleMiddle AgedNicotineReceptors, NicotinicSmokingSmoking CessationSubstance Withdrawal SyndromeTobacco Use DisorderTomography, Emission-Computed, Single-PhotonConceptsWeeks of abstinenceTobacco smokingTobacco smokersAbstinent tobacco smokersAge-matched nonsmokersMagnetic resonance imaging studyMain outcome measuresCourse of abstinenceResonance imaging studyNicotinic acetylcholine receptorsMonths of abstinenceSingle photon emissionDays of abstinenceIA SPECTNonsmoker levelsClinical featuresTobacco cessationNicotine withdrawalTomography scanOutcome measuresSPECT scansSmokersReceptor availabilityAcetylcholine receptorsSmoking
2006
Human Tobacco Smokers in Early Abstinence Have Higher Levels of β2* Nicotinic Acetylcholine Receptors than Nonsmokers
Staley JK, Krishnan-Sarin S, Cosgrove KP, Krantzler E, Frohlich E, Perry E, Dubin JA, Estok K, Brenner E, Baldwin RM, Tamagnan GD, Seibyl JP, Jatlow P, Picciotto MR, London ED, O'Malley S, van Dyck CH. Human Tobacco Smokers in Early Abstinence Have Higher Levels of β2* Nicotinic Acetylcholine Receptors than Nonsmokers. Journal Of Neuroscience 2006, 26: 8707-8714. PMID: 16928859, PMCID: PMC6674379, DOI: 10.1523/jneurosci.0546-06.2006.Peer-Reviewed Original ResearchConceptsNAChR availabilityNicotinic acetylcholine receptorsEarly abstinenceAbstinent smokersHuman smokersAcetylcholine receptorsExpired carbon monoxide levelsAbility of smokersHuman tobacco smokersProperties of nicotineSingle photon emissionIA-85380Agonist radiotracerUrinary cotinineTobacco smokingTobacco smokersCerebral cortexLast cigaretteNicotine withdrawalWithdrawal symptomsPrevalent subtypeTobacco smokeAddictive chemicalNicotine dependenceSmokers