2023
Impact of genetic variants within serotonin turnover enzymes on human cerebral monoamine oxidase A in vivo
Spies M, Murgaš M, Vraka C, Philippe C, Gryglewski G, Nics L, Balber T, Baldinger-Melich P, Hartmann A, Rujescu D, Hacker M, Winkler-Pjrek E, Winkler D, Lanzenberger R. Impact of genetic variants within serotonin turnover enzymes on human cerebral monoamine oxidase A in vivo. Translational Psychiatry 2023, 13: 208. PMID: 37322010, PMCID: PMC10272199, DOI: 10.1038/s41398-023-02506-2.Peer-Reviewed Original ResearchConceptsMAO-A levelsMAO-A VTSerotonin turnoverCerebral serotonin systemPositron emission tomography studyGenetic variantsEmission tomography studiesTryptophan hydroxylase 2 geneCerebral MAODepressed cohortBrain MAOMonoamine oxidase ASerotonin systemRelated clinical phenomenaRs1386494Distribution volumeTPH2 polymorphismsTomography studyClinical phenomenaMonoamine oxidase
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 polymorphismsRegional gene expression patterns are associated with task‐specific brain activation during reward and emotion processing measured with functional MRI
Komorowski A, Murgaš M, Vidal R, Singh A, Gryglewski G, Kasper S, Wiltfang J, Lanzenberger R, Goya‐Maldonado R. Regional gene expression patterns are associated with task‐specific brain activation during reward and emotion processing measured with functional MRI. Human Brain Mapping 2022, 43: 5266-5280. PMID: 35796185, PMCID: PMC9812247, DOI: 10.1002/hbm.26001.Peer-Reviewed Original ResearchCorrelation of receptor density and mRNA expression patterns in the human cerebral cortex
Murgaš M, Michenthaler P, Reed MB, Gryglewski G, Lanzenberger R. Correlation of receptor density and mRNA expression patterns in the human cerebral cortex. NeuroImage 2022, 256: 119214. PMID: 35452805, DOI: 10.1016/j.neuroimage.2022.119214.Peer-Reviewed Original ResearchConceptsMRNA expression patternsExpression patternsPost-translational processesGene expression patternsRNA sequencing dataComprehensive proteomic studyMolecular targetsMulti-receptor systemsMessenger ribonucleic acid transcriptsRibonucleic acid transcriptsTranscriptome dataProteomic informationProteomic dataProteomic studiesMost proteinsSequencing dataVivo linkMicroarray dataAllen Human Brain AtlasMRNA expressionProtein densitySubunits α3ProteinHuman Brain AtlasHigh-resolution topologySimultaneous 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 ResearchEscitalopram administration, relearning, and neuroplastic effects: A diffusion tensor imaging study in healthy individuals
Vanicek T, Reed MB, Unterholzner J, Klöbl M, Godbersen GM, Handschuh PA, Spurny-Dworak B, Ritter V, Gryglewski G, Kraus C, Winkler D, Lanzenberger R, Seiger R. Escitalopram administration, relearning, and neuroplastic effects: A diffusion tensor imaging study in healthy individuals. Journal Of Affective Disorders 2022, 301: 426-432. PMID: 35016914, DOI: 10.1016/j.jad.2021.12.135.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 ResearchConceptsExact 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 ResearchDifferential patterns of gray matter volumes and associated gene expression profiles in cognitively-defined Alzheimer’s disease subgroups
Groot C, Grothe MJ, Mukherjee S, Jelistratova I, Jansen I, van Loenhoud AC, Risacher SL, Saykin AJ, Mac Donald C, Mez J, Trittschuh EH, Gryglewski G, Lanzenberger R, Pijnenburg YAL, Barkhof F, Scheltens P, van der Flier WM, Crane PK, Ossenkoppele R. Differential patterns of gray matter volumes and associated gene expression profiles in cognitively-defined Alzheimer’s disease subgroups. NeuroImage Clinical 2021, 30: 102660. PMID: 33895633, PMCID: PMC8186562, DOI: 10.1016/j.nicl.2021.102660.Peer-Reviewed Original ResearchConceptsGray matter volumeRegional GM volumeAd memoryAd executivesGM volumeMatter volumeRegional gray matter volumeVoxel-wise contrastsAlzheimer’s disease subgroupsCognitive domainsCognitive profileNeuropsychological assessmentNeurobiological mechanismsNeurobiological differencesPsychometric frameworkAd languageRelative impairmentTemporal lobeHuman brainAllen Human Brain AtlasDifferential patternsStructural MRILower GM volumeHuman Brain AtlasPosterior areasEnrichment of Disease-Associated Genes in Cortical Areas Defined by Transcriptome-Based Parcellation
Gryglewski G, Murgaš M, Klöbl M, Reed MB, Unterholzner J, Michenthaler P, Lanzenberger R. Enrichment of Disease-Associated Genes in Cortical Areas Defined by Transcriptome-Based Parcellation. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2021, 7: 10-23. PMID: 33711548, DOI: 10.1016/j.bpsc.2021.02.012.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGene setsEnrichment analysisAssociation studiesDistinct gene expression profilesCortical areasDisease-associated genesGene expression profilesEnrichment patternsSimilar enrichment patternsExpert-curated databasesNovel disease mechanismsTranscriptome dataBrain disordersPleiotropic genesSpecific genesExpression profilesGenesMicroarray dataSpecific cortical areasAmyotrophic lateral sclerosisInferior parietal lobuleFunctional differentiationTranscriptomeRegional enrichmentEffects of SSRI treatment on GABA and glutamate levels in an associative relearning paradigm
Spurny B, Vanicek T, Seiger R, Reed MB, Klöbl M, Ritter V, Unterholzner J, Godbersen GM, Silberbauer LR, Pacher D, Klug S, Konadu ME, Gryglewski G, Trattnig S, Bogner W, Lanzenberger R. Effects of SSRI treatment on GABA and glutamate levels in an associative relearning paradigm. NeuroImage 2021, 232: 117913. PMID: 33657450, PMCID: PMC7610796, DOI: 10.1016/j.neuroimage.2021.117913.Peer-Reviewed Original ResearchConceptsSelective serotonin reuptake inhibitorsGamma-aminobutyric acidMajor depressive disorderSerotonin reuptake inhibitorsSSRI treatmentPlacebo administrationReuptake inhibitorsGlutamatergic functionGlutamatergic neurotransmissionDepressive disorderNeuroplastic effectsSerotonergic systemNeurotransmitter systemsHealthy subjectsPsychiatric disordersImpaired cognitive flexibilityBrain regionsNeurotransmitter concentrationsCognitive functionWidespread symptomsMemory formationLast dayDisordersDownstream effectsTreatment
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 ResearchConceptsElectroconvulsive 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
Brain 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 ResearchConceptsBright 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 reductionSpatial 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 cortexThe 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 Research