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 polymorphismsSerotonergic modulation of effective connectivity in an associative relearning network during task and rest
Reed MB, Klöbl M, Godbersen GM, Handschuh PA, Ritter V, Spurny-Dworak B, Unterholzner J, Kraus C, Gryglewski G, Winkler D, Seiger R, Vanicek T, Hahn A, Lanzenberger R. Serotonergic modulation of effective connectivity in an associative relearning network during task and rest. NeuroImage 2022, 249: 118887. PMID: 34999203, DOI: 10.1016/j.neuroimage.2022.118887.Peer-Reviewed Original ResearchConceptsRight angular gyrusAnterior cingulate cortexEffective connectivityRight insulaCognitive flexibilityAngular gyrusCingulate cortexAssociative learning taskAssociative learningLearning taskTask connectivityLearning phaseInsulaGray matter volume changesSelective serotonin reuptake inhibitor escitalopramDouble-blind designNeuroplastic changesGyrusTaskParticipantsSSRI intakeCortexEffective connectionSerotonergic modulationConnectivity
2021
Escitalopram modulates learning content-specific neuroplasticity of functional brain networks
Klöbl M, Seiger R, Vanicek T, Handschuh P, Reed MB, Spurny-Dworak B, Ritter V, Godbersen GM, Gryglewski G, Kraus C, Hahn A, Lanzenberger R. Escitalopram modulates learning content-specific neuroplasticity of functional brain networks. NeuroImage 2021, 247: 118829. PMID: 34923134, DOI: 10.1016/j.neuroimage.2021.118829.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexSelective serotonin reuptake inhibitorsPrefrontal cortexBroca's areaLingual gyrusFunctional connectivityFunctional magnetic resonance imagingResting-state functional magnetic resonance imagingFunctional brain networksBrain functional connectivityFear extinctionComplexity of learningSerotonin reuptake inhibitorsHuman neuroplasticityBrain networksMagnetic resonance imagingEscitalopram intakeComparable modulationClinical improvementSSRI escitalopramDaily doseReuptake inhibitorsNeuroplastic changesHealthy subjectsNeuroplasticityFirst-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 ResearchNeuroplastic effects of a selective serotonin reuptake inhibitor in relearning and retrieval
Reed MB, Vanicek T, Seiger R, Klöbl M, Spurny B, Handschuh P, Ritter V, Unterholzner J, Godbersen GM, Gryglewski G, Kraus C, Winkler D, Hahn A, Lanzenberger R. Neuroplastic effects of a selective serotonin reuptake inhibitor in relearning and retrieval. NeuroImage 2021, 236: 118039. PMID: 33852940, PMCID: PMC7610799, DOI: 10.1016/j.neuroimage.2021.118039.Peer-Reviewed Original ResearchConceptsLeft angular gyrusAngular gyrusMemory retrievalAssociative learningLearning taskAssociative learning taskFunctional MRI sessionsRetrieval tasksTime interactionFunctional brain activationInsula activationExecutive functionCognitive functioningBrain activationGreater deactivationTask performanceTime interaction effectsMRI scanning sessionsRight insulaSubsequent retrievalNeuroplastic effectsLearning phaseScanning sessionSelective serotonin reuptake inhibitorsNeuroplastic processesDifferential 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 areasThe Influence of Acute SSRI Administration on White Matter Microstructure in Patients Suffering From Major Depressive Disorder and Healthy Controls
Seiger R, Gryglewski G, Klöbl M, Kautzky A, Godbersen GM, Rischka L, Vanicek T, Hienert M, Unterholzner J, Silberbauer LR, Michenthaler P, Handschuh P, Hahn A, Kasper S, Lanzenberger R. The Influence of Acute SSRI Administration on White Matter Microstructure in Patients Suffering From Major Depressive Disorder and Healthy Controls. The International Journal Of Neuropsychopharmacology 2021, 24: 542-550. PMID: 33667309, PMCID: PMC8299824, DOI: 10.1093/ijnp/pyab008.Peer-Reviewed Original ResearchConceptsSelective serotonin reuptake inhibitorsMajor depressive disorderSSRI administrationDepressive disorderAxial diffusivityRadial diffusivityMean diffusivityFractional anisotropySerotonin transporterInterventional longitudinal studySerotonin reuptake inhibitorsLevels of serotoninWM microstructureAcute SSRI administrationTract-based spatial statisticsWhite matter alterationsAnterior corona radiataBrain WM microstructureCross-over designAntidepressant therapySSRI treatmentReuptake inhibitorsWhite matter microstructureRepeated-measures ANOVA modelsExternal capsuleEffects 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
Changes in White Matter Microstructure After Electroconvulsive Therapy for Treatment-Resistant Depression
Gryglewski G, Seiger R, Baldinger-Melich P, Unterholzner J, Spurny B, Vanicek T, Hahn A, Kasper S, Frey R, Lanzenberger R. Changes in White Matter Microstructure After Electroconvulsive Therapy for Treatment-Resistant Depression. The International Journal Of Neuropsychopharmacology 2019, 23: 20-25. PMID: 31740958, PMCID: PMC7064047, DOI: 10.1093/ijnp/pyz059.Peer-Reviewed Original ResearchConceptsTreatment-resistant depressionElectroconvulsive therapyWhite matter microstructureRight unilateral electroconvulsive therapyDiffusivity metricsUnipolar treatment-resistant depressionPoor antidepressant responseEffective therapeutic optionUnilateral electroconvulsive therapyDiffusion tensor imaging sequencesElectrode placementTract-based spatial statisticsAntidepressant responseClinical outcomesTherapeutic optionsInternal capsuleRepeated-measures ANOVAPosterior limbTreatment responseMagnetic resonanceElectrical stimulationTherapyAxial diffusivityLeft hemisphereWarrants investigationHippocampal GABA levels correlate with retrieval performance in an associative learning paradigm
Spurny B, Seiger R, Moser P, Vanicek T, Reed MB, Heckova E, Michenthaler P, Basaran A, Gryglewski G, Klöbl M, Trattnig S, Kasper S, Bogner W, Lanzenberger R. Hippocampal GABA levels correlate with retrieval performance in an associative learning paradigm. NeuroImage 2019, 204: 116244. PMID: 31606475, PMCID: PMC7610791, DOI: 10.1016/j.neuroimage.2019.116244.Peer-Reviewed Original ResearchConceptsHippocampal GABA levelsGABA levelsLong-term depressionLong-term potentiationHealthy participantsChanges of GABAMain inhibitory neurotransmitterMulti-voxel magnetic resonance spectroscopyMemory formationBaseline GABA levelsLongitudinal study designGlutamatergic systemInhibitory neurotransmitterNeuroplastic processesGlutamate concentrationNeural plasticityStudy designGABAAssociative learning paradigmThalamusHippocampusHuman brainInsulaNeurochemical underpinningsBrainHippocampal Subfields in Acute and Remitted Depression—an Ultra-High Field Magnetic Resonance Imaging Study
Kraus C, Seiger R, Pfabigan D, Sladky R, Tik M, Paul K, Woletz M, Gryglewski G, Vanicek T, Komorowski A, Kasper S, Lamm C, Windischberger C, Lanzenberger R. Hippocampal Subfields in Acute and Remitted Depression—an Ultra-High Field Magnetic Resonance Imaging Study. The International Journal Of Neuropsychopharmacology 2019, 22: 513-522. PMID: 31175352, PMCID: PMC6672627, DOI: 10.1093/ijnp/pyz030.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAffectAntidepressive Agents, Second-GenerationAustriaCitalopramDepressive Disorder, MajorDrug SubstitutionFemaleHippocampusHumansMagnetic Resonance ImagingMaleMiddle AgedPredictive Value of TestsRemission InductionSelective Serotonin Reuptake InhibitorsSerotonin and Noradrenaline Reuptake InhibitorsTreatment OutcomeVenlafaxine HydrochlorideYoung AdultConceptsMajor depressive disorderDepressive disorderHippocampal subfieldsSubfield volumesAntidepressant treatmentHealthy controlsHippocampal-amygdaloid transition areaMajor depressive disorder patientsOpen-label studyMagnetic resonance imaging studyDepressive disorder patientsHippocampal formation volumeStructural magnetic resonance imagingHippocampal volume changesLower baseline volumesTreatment-related changesResonance imaging studyMagnetic resonance imagingMeasurement time pointsSerotonergic antidepressantsWeeks treatmentAcute patientsRight subiculumUnmedicated patientsBaseline volumeModeling 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
Structural changes in amygdala nuclei, hippocampal subfields and cortical thickness following electroconvulsive therapy in treatment-resistant depression: longitudinal analysis
Gryglewski G, Baldinger-Melich P, Seiger R, Godbersen GM, Michenthaler P, Klöbl M, Spurny B, Kautzky A, Vanicek T, Kasper S, Frey R, Lanzenberger R. Structural changes in amygdala nuclei, hippocampal subfields and cortical thickness following electroconvulsive therapy in treatment-resistant depression: longitudinal analysis. The British Journal Of Psychiatry 2018, 214: 159-167. PMID: 30442205, PMCID: PMC6383756, DOI: 10.1192/bjp.2018.224.Peer-Reviewed Original ResearchConceptsTreatment-resistant depressionElectroconvulsive therapyMagnetic resonance imagingCortical thicknessHippocampal subfieldsAmygdala nucleiHippocampal-amygdaloid transition areaRight unilateral electroconvulsive therapyEffects of ECTHigh-resolution structural magnetic resonance imagingUnipolar treatment-resistant depressionCorticoamygdaloid transition areaPathophysiology of depressionPre-post study designCorrelation of imagingUnilateral electroconvulsive therapyTreatment of choiceStructural magnetic resonance imagingSpecific hippocampal subfieldsSevere mental illnessGrant/research supportStress-related disordersClinical parametersRepeated-measures ANOVADentate gyrusParcellation 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 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 reductionReduced 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 scanner
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 cortex