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
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 ResearchConceptsVolume 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 functionDeveloping Researchers with Expertise in Sex as a Biological Variable through SCORE Career Enhancement Core Center Programs
Zakiniaeiz Y, Peltier M, Mineur Y, Gueorguieva R, Picciotto M, Petrakis I, Cosgrove K, McKee S. Developing Researchers with Expertise in Sex as a Biological Variable through SCORE Career Enhancement Core Center Programs. Journal Of Women's Health 2023, 32: 852-857. PMID: 37585509, PMCID: PMC10457604, DOI: 10.1089/jwh.2023.0015.Peer-Reviewed Original ResearchCholinergic 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 ResearchConceptsExecutive 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 ResearchConceptsCognitive 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 samplesDeficitsNicotine Patch Alters Patterns of Cigarette Smoking-Induced Dopamine Release: Patterns Relate to Biomarkers Associated With Treatment Response
Zakiniaeiz Y, Liu H, Gao H, Najafzadeh S, Ropchan J, Nabulsi N, Huang Y, Matuskey D, Chen MK, Cosgrove KP, Morris ED. Nicotine Patch Alters Patterns of Cigarette Smoking-Induced Dopamine Release: Patterns Relate to Biomarkers Associated With Treatment Response. Nicotine & Tobacco Research 2022, 24: 1597-1606. PMID: 35100429, PMCID: PMC9575980, DOI: 10.1093/ntr/ntac026.Peer-Reviewed Original ResearchConceptsNicotine replacement therapyDopamine releasePlacebo patchDorsal striatumTobacco smokingReplacement therapyFirst-line pharmacological treatmentVentral striatumMajor public health burdenPositron emission tomography scanEmission tomography scanPublic health burdenNicotine dependence levelNicotine metabolism rateNicotinic acetylcholine receptorsCounter-balanced orderTobacco smokersCigarette smokingSmoking cessationDopamine terminalsPharmacological treatmentDependent smokersFast metabolizersSlow metabolizersNicotine actsRelationships 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 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 ResearchConceptsSmoking 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 abstinenceSex differences in progestogen- and androgen-derived neurosteroids in vulnerability to alcohol and stress-related disorders
Peltier MR, Verplaetse TL, Mineur YS, Gueorguieva R, Petrakis I, Cosgrove KP, Picciotto MR, McKee SA. Sex differences in progestogen- and androgen-derived neurosteroids in vulnerability to alcohol and stress-related disorders. Neuropharmacology 2021, 187: 108499. PMID: 33600842, PMCID: PMC7992136, DOI: 10.1016/j.neuropharm.2021.108499.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsStress-related disordersAlcohol useMajor depressive disorderAlcohol-related disordersAlcohol use disorderPosttraumatic stress disorderStress regulation systemComplex comorbiditiesDepressive disorderProblematic alcohol useUse disordersAlcohol misuseTherapeutic potentialTrauma exposureSubstance abuseStress disorderAnxiety disordersDisordersExposure resultsProgestogensNeurosteroidsNegative affectWomenComorbiditiesMale counterpartsPET 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
PTSD 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 imagingSex/gender differences in brain function and structure in alcohol use: A narrative review of neuroimaging findings over the last 10 years
Verplaetse TL, Cosgrove KP, Tanabe J, McKee SA. Sex/gender differences in brain function and structure in alcohol use: A narrative review of neuroimaging findings over the last 10 years. Journal Of Neuroscience Research 2020, 99: 309-323. PMID: 32333417, PMCID: PMC7584757, DOI: 10.1002/jnr.24625.Peer-Reviewed Original ResearchConceptsAlcohol use disorderAlcohol consumptionNarrative reviewBrain functionAlcohol useRisk of AUDMagnetic resonance imagingPositron emission tomographyDiffusion tensor imagingHigh-risk drinkingFunctional magnetic resonanceImaging outcomesSex/genderProblematic alcohol consumptionUse disordersResonance imagingEmission tomographySex/gender differencesRobust increaseTensor imagingBrain imaging researchRecent neuroimaging literatureWomenEvent-related potentialsNeurobiological underpinningsTobacco 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
2014
Tobacco smoking interferes with GABAA receptor neuroadaptations during prolonged alcohol withdrawal
Cosgrove KP, McKay R, Esterlis I, Kloczynski T, Perkins E, Bois F, Pittman B, Lancaster J, Glahn DC, O’Malley S, Carson RE, Krystal JH. Tobacco smoking interferes with GABAA receptor neuroadaptations during prolonged alcohol withdrawal. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 18031-18036. PMID: 25453062, PMCID: PMC4273348, DOI: 10.1073/pnas.1413947111.Peer-Reviewed Original ResearchConceptsGABAA receptor levelsAlcohol withdrawalTobacco smokingReceptor levelsGABAA receptorsAlcohol-dependent smokersGABAA receptor availabilityMo of abstinenceProlonged alcohol withdrawalGABAA receptor systemCombination of alcoholNicotine blocksComorbid alcoholSustained elevationAlcohol abstinenceNicotine dependenceRobust elevationReceptor availabilityNicotine consumptionSmokingReceptor systemFirst weekNonhuman primatesControl levelsWithdrawalSex 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