2022
ABCB1 variants and sex affect serotonin transporter occupancy in the brain
Silberbauer LR, Rischka L, Vraka C, Hartmann AM, Godbersen GM, Philippe C, Pacher D, Nics L, Klöbl M, Unterholzner J, Stimpfl T, Wadsak W, Hahn A, Hacker M, Rujescu D, Kasper S, Lanzenberger R, Gryglewski G. ABCB1 variants and sex affect serotonin transporter occupancy in the brain. Molecular Psychiatry 2022, 27: 4502-4509. PMID: 36071112, PMCID: PMC7613909, DOI: 10.1038/s41380-022-01733-1.Peer-Reviewed Original ResearchConceptsMinor allele carriersTransporter occupancyAllele carriersABCB1 single nucleotide polymorphismsBasic clinical variablesCitalopram plasma concentrationsYears of ageMajor allele homozygotesCross-over designPET/MRISERT occupancyClinical variablesTreatment promisesClinical algorithmMajor depressionPlasma concentrationsPrecision pharmacotherapyABCB1 variantsHealthy volunteersABCB1 geneAllele homozygotesSame dosageDrug-target engagementTarget engagementSingle nucleotide polymorphismsSimultaneous radiomethylation of [11C]harmine and [11C]DASB and kinetic modeling approach for serotonergic brain imaging in the same individual
Vraka C, Murgaš M, Rischka L, Geist BK, Lanzenberger R, Gryglewski G, Zenz T, Wadsak W, Mitterhauser M, Hacker M, Philippe C, Pichler V. Simultaneous radiomethylation of [11C]harmine and [11C]DASB and kinetic modeling approach for serotonergic brain imaging in the same individual. Scientific Reports 2022, 12: 3283. PMID: 35228586, PMCID: PMC8885643, DOI: 10.1038/s41598-022-06906-0.Peer-Reviewed Original Research
2021
Coexpression of Gene Transcripts with Monoamine Oxidase A Quantified by Human In Vivo Positron Emission Tomography
Godbersen GM, Murgaš M, Gryglewski G, Klöbl M, Unterholzner J, Rischka L, Spies M, Baldinger-Melich P, Winkler D, Lanzenberger R. Coexpression of Gene Transcripts with Monoamine Oxidase A Quantified by Human In Vivo Positron Emission Tomography. Cerebral Cortex 2021, 32: 3516-3524. PMID: 34952543, DOI: 10.1093/cercor/bhab430.Peer-Reviewed Original ResearchMeSH KeywordsAdultBrainCarbon RadioisotopesFemaleHarmineHumansMonoamine OxidasePositron-Emission TomographyConceptsExact testPositron emission tomography scanCerebral distribution volumeMonoamine oxidaseEmission tomography scanNovel therapeutic targetVivo positron emission tomographyFisher's exact testPositron emission tomographyFalse discovery rate correctionVivo MAOTomography scanHealthy subjectsSubcortical areasCortical areasTherapeutic targetMAOA expressionDistribution volumeEmission tomographyNeuropsychiatric disordersNeuron projectionsNeuron developmentNeuron differentiationSpearman's ρCell-cell signalingFirst-in-Humans Brain PET Imaging of the GluN2B-Containing N-methyl-d-aspartate Receptor with (R)-11C-Me-NB1
Rischka L, Vraka C, Pichler V, Rasul S, Nics L, Gryglewski G, Handschuh P, Murgaš M, Godbersen GM, Silberbauer LR, Unterholzner J, Wotawa C, Haider A, Ahmed H, Schibli R, Mindt T, Mitterhauser M, Wadsak W, Hahn A, Lanzenberger R, Hacker M, Ametamey SM. First-in-Humans Brain PET Imaging of the GluN2B-Containing N-methyl-d-aspartate Receptor with (R)-11C-Me-NB1. Journal Of Nuclear Medicine 2021, 63: 936-941. PMID: 34620732, PMCID: PMC9157734, DOI: 10.2967/jnumed.121.262427.Peer-Reviewed Original Research
2020
Topologically Guided Prioritization of Candidate Gene Transcripts Coexpressed with the 5-HT1A Receptor by Combining In Vivo PET and Allen Human Brain Atlas Data
Unterholzner J, Gryglewski G, Philippe C, Seiger R, Pichler V, Godbersen GM, Berroterán-Infante N, Murgaš M, Hahn A, Wadsak W, Mitterhauser M, Kasper S, Lanzenberger R. Topologically Guided Prioritization of Candidate Gene Transcripts Coexpressed with the 5-HT1A Receptor by Combining In Vivo PET and Allen Human Brain Atlas Data. Cerebral Cortex 2020, 30: 3771-3780. PMID: 31989157, PMCID: PMC7232988, DOI: 10.1093/cercor/bhz341.Peer-Reviewed Original ResearchConceptsMRNA expressionRole of BDNFSerotonin 1A receptorEfficacy of drugsTreatment of disordersReceptor subtypesHealthy subjectsPsychiatric drugsBrain tissueCortical regionsVivo PETSerotonergic functioningViable targetDrugsSpearman's rhoCandidate gene transcriptsReceptorsCoexpression patternsRelative inaccessibility
2019
Association of norepinephrine transporter methylation with in vivo NET expression and hyperactivity–impulsivity symptoms in ADHD measured with PET
Sigurdardottir HL, Kranz GS, Rami-Mark C, James GM, Vanicek T, Gryglewski G, Berroterán-Infante N, Kautzky A, Hienert M, Traub-Weidinger T, Mitterhauser M, Wadsak W, Hartmann AM, Hacker M, Rujescu D, Kasper S, Lanzenberger R. Association of norepinephrine transporter methylation with in vivo NET expression and hyperactivity–impulsivity symptoms in ADHD measured with PET. Molecular Psychiatry 2019, 26: 1009-1018. PMID: 31383926, PMCID: PMC7910214, DOI: 10.1038/s41380-019-0461-x.Peer-Reviewed Original ResearchModeling the acute pharmacological response to selective serotonin reuptake inhibitors in human brain using simultaneous PET/MR imaging
Gryglewski G, Klöbl M, Berroterán-Infante N, Rischka L, Balber T, Vanicek T, Pichler V, Kautzky A, Klebermass EM, Reed MB, Vraka C, Hienert M, James GM, Silberbauer L, Godbersen GM, Unterholzner J, Michenthaler P, Hartenbach M, Winkler-Pjrek E, Wadsak W, Mitterhauser M, Hahn A, Hacker M, Kasper S, Lanzenberger R. Modeling the acute pharmacological response to selective serotonin reuptake inhibitors in human brain using simultaneous PET/MR imaging. European Neuropsychopharmacology 2019, 29: 711-719. PMID: 31076187, DOI: 10.1016/j.euroneuro.2019.04.001.Peer-Reviewed Original ResearchConceptsSelective serotonin reuptake inhibitorsSerotonin reuptake inhibitorsReuptake inhibitorsPharmacological responsePharmacological imagingFunctional MRIRandomized double-blind designResting-state functional MRIAcute pharmacological responsesCitalopram plasma concentrationsPrevalent neuropsychiatric conditionsDouble-blind designMechanism of actionPlacebo scansInfusion paradigmPlasma levelsSSRI effectsDrug challengePatient outcomesPlasma concentrationsDrug infusionInfluence treatmentConstant infusionLarger sample sizePET/MR scansEpistasis of HTR1A and BDNF risk genes alters cortical 5-HT1A receptor binding: PET results link genotype to molecular phenotype in depression
Kautzky A, James GM, Philippe C, Baldinger-Melich P, Kraus C, Kranz GS, Vanicek T, Gryglewski G, Hartmann AM, Hahn A, Wadsak W, Mitterhauser M, Rujescu D, Kasper S, Lanzenberger R. Epistasis of HTR1A and BDNF risk genes alters cortical 5-HT1A receptor binding: PET results link genotype to molecular phenotype in depression. Translational Psychiatry 2019, 9: 5. PMID: 30664620, PMCID: PMC6341100, DOI: 10.1038/s41398-018-0308-2.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factor (BDNF) geneAffective disordersReceptor bindingSingle nucleotide polymorphismsPhenotype of depressionNeurotrophic factor geneSerotonin 1A receptor geneFunctional single nucleotide polymorphismsReceptor profileHealthy subjectsPET resultsRisk genotypesRs6265Multifactorial riskCortical regionsMixed modelsRisk allelesRs6295DisordersCortical surfaceReceptor geneReceptorsMolecular phenotypesHTR1ADepressionThe effect of electroconvulsive therapy on cerebral monoamine oxidase A expression in treatment-resistant depression investigated using positron emission tomography
Baldinger-Melich P, Gryglewski G, Philippe C, James GM, Vraka C, Silberbauer L, Balber T, Vanicek T, Pichler V, Unterholzner J, Kranz GS, Hahn A, Winkler D, Mitterhauser M, Wadsak W, Hacker M, Kasper S, Frey R, Lanzenberger R. The effect of electroconvulsive therapy on cerebral monoamine oxidase A expression in treatment-resistant depression investigated using positron emission tomography. Brain Stimulation 2019, 12: 714-723. PMID: 30635228, DOI: 10.1016/j.brs.2018.12.976.Peer-Reviewed Original ResearchMeSH KeywordsAdultBrainDepressive Disorder, Treatment-ResistantElectroconvulsive TherapyFemaleHumansMaleMiddle AgedMonoamine OxidasePositron-Emission TomographyConceptsElectroconvulsive therapyTRD patientsMAO-A levelsHealthy subjectsPositron emission tomographyTest-retest variabilityMechanism of actionEffective antidepressant treatment strategiesSex-matched healthy subjectsEmission tomographyAntidepressant treatment strategiesMonoamine oxidaseTreatment-resistant depressionTreatment-resistant patientsSerotonin 1A receptorUnmedicated depressed patientsCerebral monoamine oxidasesCerebral MAOAntidepressant pharmacotherapyECT sessionsAntidepressant treatmentDepressed patientsMajor depressionSerotonergic systemTreatment strategies
2018
Parcellation of the Human Cerebral Cortex Based on Molecular Targets in the Serotonin System Quantified by Positron Emission Tomography In vivo
James GM, Gryglewski G, Vanicek T, Berroterán-Infante N, Philippe C, Kautzky A, Nics L, Vraka C, Godbersen GM, Unterholzner J, Sigurdardottir HL, Spies M, Seiger R, Kranz GS, Hahn A, Mitterhauser M, Wadsak W, Bauer A, Hacker M, Kasper S, Lanzenberger R. Parcellation of the Human Cerebral Cortex Based on Molecular Targets in the Serotonin System Quantified by Positron Emission Tomography In vivo. Cerebral Cortex 2018, 29: 372-382. PMID: 30357321, PMCID: PMC6294402, DOI: 10.1093/cercor/bhy249.Peer-Reviewed Original ResearchConceptsPositron emission tomographyEmission tomographySerotonin neurotransmitter systemSerotonin 1ACerebral cortexEnzyme monoamine oxidase AMonoamine oxidase ANeurotransmitter systemsSerotonin systemPsychotropic drugsNeuropsychiatric disordersBrain functionHealthy participantsSerotonin transporterMolecular imaging dataMolecular targetsMolecular profileOxidase AWhole-brain coverageCortexParcellationTomographyDefined clustersClose associationImaging dataBrain monoamine oxidase A in seasonal affective disorder and treatment with bright light therapy
Spies M, James GM, Vraka C, Philippe C, Hienert M, Gryglewski G, Komorowski A, Kautzky A, Silberbauer L, Pichler V, Kranz GS, Nics L, Balber T, Baldinger-Melich P, Vanicek T, Spurny B, Winkler-Pjrek E, Wadsak W, Mitterhauser M, Hacker M, Kasper S, Lanzenberger R, Winkler D. Brain monoamine oxidase A in seasonal affective disorder and treatment with bright light therapy. Translational Psychiatry 2018, 8: 198. PMID: 30242221, PMCID: PMC6155094, DOI: 10.1038/s41398-018-0227-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultBrainCarbon RadioisotopesFemaleHarmineHumansMaleMonoamine OxidasePhototherapyPositron-Emission TomographySeasonal Affective DisorderTreatment OutcomeConceptsBright light therapyMAO-A levelsBrain MAO-A levelsSeasonal affective disorderPositron emission tomographyMAO-A VTNon-seasonal depressionHealthy controlsLight therapyAffective disordersTreatment of SADMajor depressive disorderBrain monoamine oxidaseCerebral MAODepressive disorderSerotonergic systemPET scansHC groupMilder symptomsPatientsDistribution volumeEmission tomographyMonoamine oxidaseDisordersSignificant reductionStriatal dopaminergic alterations in Tourette’s syndrome: a meta-analysis based on 16 PET and SPECT neuroimaging studies
Hienert M, Gryglewski G, Stamenkovic M, Kasper S, Lanzenberger R. Striatal dopaminergic alterations in Tourette’s syndrome: a meta-analysis based on 16 PET and SPECT neuroimaging studies. Translational Psychiatry 2018, 8: 143. PMID: 30072700, PMCID: PMC6072751, DOI: 10.1038/s41398-018-0202-y.Peer-Reviewed Original ResearchConceptsTourette patientsTourette syndromeDopamine transporterDopaminergic alterationsDopamine systemCurrent pathophysiological hypothesesStriatal dopaminergic alterationsStriatal dopamine receptorsStudy population characteristicsStriatal dopamine transporterStriatal dopamine functionFree patientsHealthy controlsPathophysiological hypothesesDopamine receptorsMolecular imaging studiesNonsignificant trendDopamine functionPatientsSPECT studiesSystematic reviewImaging studiesSyndromeNeuroimaging studiesReceptor bindingReduced task durations in functional PET imaging with [18F]FDG approaching that of functional MRI
Rischka L, Gryglewski G, Pfaff S, Vanicek T, Hienert M, Klöbl M, Hartenbach M, Haug A, Wadsak W, Mitterhauser M, Hacker M, Kasper S, Lanzenberger R, Hahn A. Reduced task durations in functional PET imaging with [18F]FDG approaching that of functional MRI. NeuroImage 2018, 181: 323-330. PMID: 29966719, DOI: 10.1016/j.neuroimage.2018.06.079.Peer-Reviewed Original ResearchConceptsFunctional MRIPercent signal changeTask-specific changesMotor cortexGlucose metabolismIpsilateral motor cortexImaging modalitiesSupplementary motor areaSecondary visual cortexHybrid PET/MRI scannerConstant infusion protocolTask-specific activationInfusion protocolDifferent activation patternsHealthy subjectsMotor areaArterial samplesCMRgluConstant infusionDifferent imaging modalitiesTracer uptakeVisual cortexSignificant associationUnspecific activationPET/MRI scannerSpatial analysis and high resolution mapping of the human whole-brain transcriptome for integrative analysis in neuroimaging
Gryglewski G, Seiger R, James GM, Godbersen GM, Komorowski A, Unterholzner J, Michenthaler P, Hahn A, Wadsak W, Mitterhauser M, Kasper S, Lanzenberger R. Spatial analysis and high resolution mapping of the human whole-brain transcriptome for integrative analysis in neuroimaging. NeuroImage 2018, 176: 259-267. PMID: 29723639, DOI: 10.1016/j.neuroimage.2018.04.068.Peer-Reviewed Original Research
2017
Task-relevant brain networks identified with simultaneous PET/MR imaging of metabolism and connectivity
Hahn A, Gryglewski G, Nics L, Rischka L, Ganger S, Sigurdardottir H, Vraka C, Silberbauer L, Vanicek T, Kautzky A, Wadsak W, Mitterhauser M, Hartenbach M, Hacker M, Kasper S, Lanzenberger R. Task-relevant brain networks identified with simultaneous PET/MR imaging of metabolism and connectivity. Brain Structure And Function 2017, 223: 1369-1378. PMID: 29134288, PMCID: PMC5869947, DOI: 10.1007/s00429-017-1558-0.Peer-Reviewed Original ResearchConceptsTask performanceBrain networksFunctional connectivityTask-relevant brain networksBrain regionsSimple task performanceDefault mode networkHuman brain functionResting-state networksTask-specific changesCognitive tasksMode networkFunctional MRICertain brain regionsWhite matter microstructureEntire brain networkGlucose metabolismRecent methodological advancementsBrain functionTaskYields important insightsCertain tasksRight fingerMethodological advancementsMotor cortexAssessment of Ketamine Binding of the Serotonin Transporter in Humans with Positron Emission Tomography
Spies M, James GM, Berroterán-Infante N, Ibeschitz H, Kranz GS, Unterholzner J, Godbersen M, Gryglewski G, Hienert M, Jungwirth J, Pichler V, Reiter B, Silberbauer L, Winkler D, Mitterhauser M, Stimpfl T, Hacker M, Kasper S, Lanzenberger R. Assessment of Ketamine Binding of the Serotonin Transporter in Humans with Positron Emission Tomography. The International Journal Of Neuropsychopharmacology 2017, 21: 145-153. PMID: 29045739, PMCID: PMC5793827, DOI: 10.1093/ijnp/pyx085.Peer-Reviewed Original ResearchConceptsKetamine plasma levelsPositron emission tomographyAntidepressant effectsPlasma levelsSerotonin transporterEmission tomographyAntidepressant dosePositron emission tomography scanReal-life patient cohortEmission tomography scanHigh-dose ketamineSerotonin transporter bindingTest-retest variabilityWhole brain regionsAntidepressant dosesAntidepressant mechanismPatient cohortTomography scanSerotonergic systemTransporter bindingHealthy subjectsAnimal studiesHigh dosesKetamineAdministrationThe influence of the rs6295 gene polymorphism on serotonin-1A receptor distribution investigated with PET in patients with major depression applying machine learning
Kautzky A, James GM, Philippe C, Baldinger-Melich P, Kraus C, Kranz GS, Vanicek T, Gryglewski G, Wadsak W, Mitterhauser M, Rujescu D, Kasper S, Lanzenberger R. The influence of the rs6295 gene polymorphism on serotonin-1A receptor distribution investigated with PET in patients with major depression applying machine learning. Translational Psychiatry 2017, 7: e1150-e1150. PMID: 28608854, PMCID: PMC5537636, DOI: 10.1038/tp.2017.108.Peer-Reviewed Original ResearchSimple and rapid quantification of serotonin transporter binding using [11C]DASB bolus plus constant infusion
Gryglewski G, Rischka L, Philippe C, Hahn A, James GM, Klebermass E, Hienert M, Silberbauer L, Vanicek T, Kautzky A, Berroterán-Infante N, Nics L, Traub-Weidinger T, Mitterhauser M, Wadsak W, Hacker M, Kasper S, Lanzenberger R. Simple and rapid quantification of serotonin transporter binding using [11C]DASB bolus plus constant infusion. NeuroImage 2017, 149: 23-32. PMID: 28119137, DOI: 10.1016/j.neuroimage.2017.01.050.Peer-Reviewed Original Research
2016
Association of Protein Distribution and Gene Expression Revealed by PET and Post-Mortem Quantification in the Serotonergic System of the Human Brain
Komorowski A, James GM, Philippe C, Gryglewski G, Bauer A, Hienert M, Spies M, Kautzky A, Vanicek T, Hahn A, Traub-Weidinger T, Winkler D, Wadsak W, Mitterhauser M, Hacker M, Kasper S, Lanzenberger R. Association of Protein Distribution and Gene Expression Revealed by PET and Post-Mortem Quantification in the Serotonergic System of the Human Brain. Cerebral Cortex 2016, 27: 117-130. PMID: 27909009, PMCID: PMC5939202, DOI: 10.1093/cercor/bhw355.Peer-Reviewed Original ResearchQuantification of Task-Specific Glucose Metabolism with Constant Infusion of 18F-FDG
Hahn A, Gryglewski G, Nics L, Hienert M, Rischka L, Vraka C, Sigurdardottir H, Vanicek T, James GM, Seiger R, Kautzky A, Silberbauer L, Wadsak W, Mitterhauser M, Hacker M, Kasper S, Lanzenberger R. Quantification of Task-Specific Glucose Metabolism with Constant Infusion of 18F-FDG. Journal Of Nuclear Medicine 2016, 57: 1933-1940. PMID: 27390156, DOI: 10.2967/jnumed.116.176156.Peer-Reviewed Original ResearchConceptsBaseline glucose metabolismTask-specific changesGlucose metabolismTime-activity curvesConstant infusionBolus applicationF-FDGBlood samplingBaseline metabolismPatlak plotVenous blood samplesCerebral metabolic rateVenous blood samplingGeneral linear modelHigh intrasubject variabilityMultimodal brain imagingArterial blood samplingMotor cortexHealthy subjectsCMRgluRegional time-activity curvesRight thumbArterial samplesBlood samplesDefault mode regions