2025
Role of Serotonin on Gene Expression and Physiology in Human Cytotrophoblasts and Placenta
Morris N, Guller S, Tang Z, Zhang Y, Siegman E, Milano K, Rudnick G, Kliman H. Role of Serotonin on Gene Expression and Physiology in Human Cytotrophoblasts and Placenta. Endocrinology 2025, 166: bqaf124. PMID: 40898405, PMCID: PMC12399332, DOI: 10.1210/endocr/bqaf124.Peer-Reviewed Original ResearchConceptsExogenous 5-HTCytotrophoblast nucleiUptake of 5-HTHistone 3Differentiation in vitroMaternal 5-HTTransglutaminase 2Fetal growthIntact placentaPlacental explantsHuman cytotrophoblastsGene expressionSerotonin transporterHuman placentaPlacentaSerotoninRNA expressionWestern blottingCell survivalCell proliferationEscitalopramTrophoblastProtective pathwaysSERTSerotonylationPhenotyping extracellular vesicles and their serotonin transporter cargo in major depressive disorder
Zadka Ł, Eggerstorfer B, Buzalewicz I, Vraka C, Rusak A, Godbersen G, Opalińska A, Unterholzner J, Ulatowska-Jarża A, Philippe C, Haczkiewicz-Leśniak K, Silberbauer L, Murgaš M, Nics L, Hahn A, Hacker M, Gomułkiewicz A, Rujescu D, Podhorska-Okołów M, Lanzenberger R, Gryglewski G. Phenotyping extracellular vesicles and their serotonin transporter cargo in major depressive disorder. Journal Of Affective Disorders 2025, 389: 119740. PMID: 40550277, DOI: 10.1016/j.jad.2025.119740.Peer-Reviewed Original ResearchSerotonin transporterDepressive disorderPresence of serotonin transporterAntidepressant treatment responseSerotonin transporter levelsMDD patientsNanoparticle tracking analysisMood disordersPsychiatric disordersMDDBinding potentialExtracellular vesiclesTreatment response predictionPositron emission tomographyTreatment responseDisordersHealthy controlsExosome markers CD63Blood-brain barrierEmission tomographyStudy intercellular communicationPrognostic valueConcentration of extracellular vesiclesPatient stratificationExosomal markersA large-scale multimodal investigation of the interplay between the serotonergic system and emotion processing
Klöbl M, Murgaš M, Reed M, Silberbauer L, Hartmann A, Godbersen G, Gryglewski G, Nics L, Hahn A, Rujescu D, Hacker M, Lanzenberger R. A large-scale multimodal investigation of the interplay between the serotonergic system and emotion processing. Translational Psychiatry 2025, 15: 196. PMID: 40500269, PMCID: PMC12159172, DOI: 10.1038/s41398-025-03407-2.Peer-Reviewed Original ResearchConceptsAnterior cingulate cortex activationAnterior cingulate cortexMajor depressive disorderFunctional magnetic resonance imagingSerotonin transporter availabilitySerotonin transporterEmotional processingSerotonergic systemDiagnosis of major depressive disorderAnxiolytic effect of citalopramFacial emotion processing taskMonths of antidepressant treatmentViewing fearful facesAcute anxiolytic effectsEmotion processing taskEffect of citalopramReduced fMRI activationSuperior frontal sulcusSERT availabilityFearful facesHappy facesAntidepressant treatmentFear processingNeutral facesDepressive disorderSimplified methods for SERT occupancy estimation measured with [11C]DASB PET bolus plus infusion
Ponce de León M, Murgaš M, Silberbauer L, Hacker M, Gryglewski G, Hahn A, Lanzenberger R. Simplified methods for SERT occupancy estimation measured with [11C]DASB PET bolus plus infusion. NeuroImage 2025, 311: 121208. PMID: 40221064, DOI: 10.1016/j.neuroimage.2025.121208.Peer-Reviewed Original ResearchSerotonin transporterBolus plus constant infusionSerotonin transporter occupancyDepressive disorderBinding potentialBolus plus infusionReference regionCitalopramHealthy controlsArterial blood samplesPET/MRI scansPET scansOccupational valuesIntravenous applicationConstant infusionBlood samplesIn vivoAntidepressantsInfusionSaline solutionSerotoninHighest agreementDisordersRadioligandPlaceboTHE ANTERIOR CINGULATE CORTEX LINKS SEROTONIN TRANSPORTER GENETICS AND EMOTION PROCESSING
Kloebl *, Murgaš M, Reed M, Silberbauer L, Hartmann A, Godbersen G, Hahn A, Gryglewski G, Rujescu D, Lanzenberger R. THE ANTERIOR CINGULATE CORTEX LINKS SEROTONIN TRANSPORTER GENETICS AND EMOTION PROCESSING. The International Journal Of Neuropsychopharmacology 2025, 28: i18-i19. PMCID: PMC11814669, DOI: 10.1093/ijnp/pyae059.032.Peer-Reviewed Original ResearchAnterior cingulate cortex activationAnterior cingulate cortexEmotional processingSerotonin reuptake inhibitorsSerotonin transporterSerotonin transporter expressionBrain functionHappy facesNeutral facesCingulate cortexReuptake inhibitorsBrain activitySerotonin transporter binding potentialMeasures of emotional processingSingle nucleotide polymorphism rs25531Anterior cingulate cortex connectivityImpact of 5-HTTLPRAssess attributional styleSituational Attributions QuestionnaireAcute tryptophan depletionFacial emotion processingIncreased amygdala activationSerotonin transporter bindingSerotonin transporter polymorphismEffect of citalopramEXTRACELLULAR VESICLES IN MAJOR DEPRESSIVE DISORDER AND THEIR RELATIONSHIP TO TREATMENT OUTCOME
Eggerstorfer *, Zadka Ł, Rusak A, Godbersen G, Opalińska A, Unterholzner J, Haczkiewicz-Leśniak K, Silberbauer L, Hahn A, Murgaš M, Gomułkiewicz A, Rujescu D, Podhorska-Okołów M, Lanzenberger R, Gryglewski G. EXTRACELLULAR VESICLES IN MAJOR DEPRESSIVE DISORDER AND THEIR RELATIONSHIP TO TREATMENT OUTCOME. The International Journal Of Neuropsychopharmacology 2025, 28: i32-i33. PMCID: PMC11815236, DOI: 10.1093/ijnp/pyae059.056.Peer-Reviewed Original ResearchMDD patientsPathophysiology of psychiatric disordersPlasma of MDD patientsOutcome of MDDAntidepressant treatment responseSerotonin transporter occupancyDepression Rating ScaleTreated with escitalopramHealthy controlsExpression of SLC6A4Expression of exosome markersAntidepressant treatmentDepressive disorderSerotonin transporterExosomal markersPsychiatric disordersTransporter occupancyNanoparticle tracking analysisMDDMental disordersMRNA expressionDiverse neurotransmittersRating ScaleCD9 expressionExtracellular vesicles
2024
Electroencephalography (EEG) spectral signatures of selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs) and vortioxetine in major depressive disorder: A systematic review
Le G, Wong S, Lu A, Vasudeva S, Gill H, Badulescu S, Portelles D, Zheng Y, Teopiz K, Meshkat S, Kwan A, Ho R, Rhee T, Rosenblat J, Mansur R, McIntyre R. Electroencephalography (EEG) spectral signatures of selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs) and vortioxetine in major depressive disorder: A systematic review. Journal Of Affective Disorders 2024, 368: 798-819. PMID: 39299586, DOI: 10.1016/j.jad.2024.09.081.Peer-Reviewed Original ResearchReuptake inhibitorsDepressive disorderPathophysiology of depressive disordersSystematic reviewAssociated with SSRIsClass of SSRIsNorepinephrine reuptake inhibitorsDoses of antidepressantsSerotonin reuptake inhibitorsFDA-approved agentsVortioxetine treatmentBlock reuptakeAntidepressant exposureSerotonin transporterSNRISSRIsVortioxetineDatabase inceptionConverging evidenceFunctional connectivitySerotoninNeural activityElectroencephalography signaturesStudy investigated changesInhibitorsIdentification of the potassium-binding site in serotonin transporter
Hellsberg E, Boytsov D, Chen Q, Niello M, Freissmuth M, Rudnick G, Zhang Y, Sandtner W, Forrest L. Identification of the potassium-binding site in serotonin transporter. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319384121. PMID: 38652746, PMCID: PMC11067047, DOI: 10.1073/pnas.2319384121.Peer-Reviewed Original ResearchConceptsSerotonin transporterSite-directed mutagenesis of residuesMutagenesis of residuesSite-directed mutagenesisHeterologous expression systemStudy of vesiclesNa2 siteClearance of serotoninPatch-clamp recordingsExpression systemBinding residuesSequential bindingMolecular dynamics simulationsBinding sitesPotassium binding siteSubstrate accumulationClamp recordingsVesiclesResiduesTurnover rateBindingStructural studiesChemical gradientsBinding configurationsSynaptic cleftLong COVID-19 and Peripheral Serotonin: A Commentary and Reconsideration
Anderson G, Cook E, Blakely R, Sutcliffe J, Veenstra-VanderWeele J. Long COVID-19 and Peripheral Serotonin: A Commentary and Reconsideration. Journal Of Inflammation Research 2024, 17: 2169-2172. PMID: 38628604, PMCID: PMC11019386, DOI: 10.2147/jir.s456000.Peer-Reviewed Original ResearchPlatelet serotoninSerotonin valuesTrials of SSRIsSerotonin reuptake inhibitorsPlatelet serotonin transportersSerotonin reductionSSRI administrationSSRI treatmentReuptake inhibitorsSerotonin transporterMemory impairmentSerotonin levelsSSRIsSerotoninDepletion of plateletsPlasma serotoninPeripheral serotoninSequelae of COVID-19Viremia patientsCardiovascular sequelaeCirculating serotoninHyperaggregable stateTreatment of COVID-19Clinical trialsLong COVID
2023
Mephedrone induces partial release at human dopamine transporters but full release at human serotonin transporters
Mayer F, Niello M, Bulling S, Zhang Y, Li Y, Kudlacek O, Holy M, Kooti F, Sandtner W, Rudnick G, Schmid D, Sitte H. Mephedrone induces partial release at human dopamine transporters but full release at human serotonin transporters. Neuropharmacology 2023, 240: 109704. PMID: 37703919, DOI: 10.1016/j.neuropharm.2023.109704.Peer-Reviewed Original ResearchSerotonin transporterCarrier-mediated releaseProtein kinase C inhibitor GF109203X.Human embryonic kidney 293Empathogenic effectsAbuse liabilityGreater efficacyElectrophysiological recordingsDopamine transporterHuman DATReverse transportEntactogenic effectsStimulating propertiesHuman serotonin transporterHuman dopamine transporterMephedroneDopamineMolecular mechanismsHDATReleaserTransportersHigh-affinity transporterDATReleasePrevious studiesAntibiotic-induced microbial depletion enhances murine small intestinal epithelial growth in a serotonin-dependent manner
Salvi P, Shaughnessy M, Sumigray K, Cowles R. Antibiotic-induced microbial depletion enhances murine small intestinal epithelial growth in a serotonin-dependent manner. AJP Gastrointestinal And Liver Physiology 2023, 325: g80-g91. PMID: 37158470, DOI: 10.1152/ajpgi.00113.2022.Peer-Reviewed Original ResearchConceptsSerotonin activitySERT protein expressionSerotonin potentiationEpithelial proliferationSerotonin transporterEndogenous serotoninVillus heightMicrobial depletionIntestinal epithelial growthProtein expressionEpithelial growthSerotonin-dependent mechanismIntestinal villus heightSmall intestine resultsIntestinal surface areaSmall intestinal villiSmall intestinal cryptsIntestinal pathologyPara-chlorophenylalanineISC numbersSerotonin synthesisIntestinal homeostasisEpithelial expressionMouse modelAnimal modelsStructure-based discovery of conformationally selective inhibitors of the serotonin transporter
Singh I, Seth A, Billesbølle C, Braz J, Rodriguiz R, Roy K, Bekele B, Craik V, Huang X, Boytsov D, Pogorelov V, Lak P, O'Donnell H, Sandtner W, Irwin J, Roth B, Basbaum A, Wetsel W, Manglik A, Shoichet B, Rudnick G. Structure-based discovery of conformationally selective inhibitors of the serotonin transporter. Cell 2023, 186: 2160-2175.e17. PMID: 37137306, PMCID: PMC10306110, DOI: 10.1016/j.cell.2023.04.010.Peer-Reviewed Original Research
2022
Systematic review of studies using platelet serotonin content to assess bioeffect of serotonin reuptake inhibitors at the serotonin transporter
Anderson G, Bruno-Pacella I. Systematic review of studies using platelet serotonin content to assess bioeffect of serotonin reuptake inhibitors at the serotonin transporter. Psychopharmacology 2022, 240: 1-13. PMID: 36399187, DOI: 10.1007/s00213-022-06276-5.Peer-Reviewed Original ResearchConceptsSerotonin reuptake inhibitorsSerotonin transporterPlatelet serotonin transporterSERT occupancyReuptake inhibitorsSystematic reviewClinical implicationsPlatelet serotonin contentMeasurement of plateletPlatelet serotonin uptakePractical clinical implicationsStudy of plateletsSerotonin uptakeHealthy controlsSerotonin contentDifferent SSRIsClinical practicePlateletsInhibitorsUptakeSNRIsSSRIsPatientsReviewTransportersTranslational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [11C]AFM
Fang H, Rossano S, Wang X, Nabulsi N, Kelley B, Fowles K, Ropchan J, Strittmatter SM, Carson RE, Huang Y. Translational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [11C]AFM. Molecular Imaging And Biology 2022, 24: 560-569. PMID: 35020138, PMCID: PMC9550197, DOI: 10.1007/s11307-021-01698-7.Peer-Reviewed Original ResearchConceptsSpinal cord injurySpinal cordHealthy ratsHuman spinal cordCord injurySerotonin transporterRat modelRodent modelsPET imagingTranslational PET imagingSCI rat modelIntact spinal cordSpinal cord caudalRodent spinal cordSerotonin transporter tracerUse of PETCervical uptakeSERT changesSCI animalsSCI patientsPresynaptic serotonin transporterCord caudalAxon damageSerotonin systemSERT radioligand
2021
The response to prolonged fasting in hypothalamic serotonin transporter availability is blunted in obesity
van Galen KA, Booij J, Schrantee A, Adriaanse SM, Unmehopa UA, Fliers E, Schwartz GJ, DiLeone RJ, Horst K, la Fleur SE, Serlie MJ. The response to prolonged fasting in hypothalamic serotonin transporter availability is blunted in obesity. Metabolism 2021, 123: 154839. PMID: 34331964, PMCID: PMC8994212, DOI: 10.1016/j.metabol.2021.154839.Peer-Reviewed Original ResearchConceptsStriatal DAT availabilityLean menSERT availabilityDAT availabilityThalamic serotonin transportersSerotonin transporterDopaminergic systemTransporter availabilityStriatal dopamine transporter availabilityPeripheral metabolic signalsFree fatty acid concentrationsCross-over trialSerotonin transporter availabilityFasting-induced increaseDopamine transporter availabilitySystemic energy metabolismHypothalamus/thalamusLean subjectsPlasma insulinFatty acid concentrationsStriatal DATFood intakeObesityInter-individual variationHigh inter-individual variationThe 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 capsule
2020
Neuroimaging of Obsessive-Compulsive Disorder: Insights into Serotonergic Mechanisms
Lissemore J, Booij L, Leyton M, Gravel P, Sookman D, Nordahl T, Benkelfat C. Neuroimaging of Obsessive-Compulsive Disorder: Insights into Serotonergic Mechanisms. 2020, 457-478. DOI: 10.1007/978-3-030-57231-0_13.Peer-Reviewed Original ResearchSelective serotonin reuptake inhibitorsObsessive-compulsive disorderSerotonin synthesis capacityPositron emission tomographyHealthy controlsPET studiesOCD patientsSerotonin reuptake inhibitorsMost PET studiesBorderline personality disorderCognitive behavior therapySymptom onsetSerotonergic mechanismsClinical benefitSerotonergic toneSerotonergic alterationsSynthesis capacityEmission tomographySuicide attemptsSerotonin transporterPersonality disorderBehavior therapyGroup differencesDisordersPatientsAssociation of antibody titers and 5-HTTLPR gene polymorphisms in pediatric autoimmune neuropsychiatric disorder associated with streptococci
Genis-Mendoza A, Nicolini H, Manrique V, López-Canovas L, Cabrera-Mendoza B, Bobes M, Lanzagorta N, Santana D. Association of antibody titers and 5-HTTLPR gene polymorphisms in pediatric autoimmune neuropsychiatric disorder associated with streptococci. Salud Mental 2020, 43: 181-187. DOI: 10.17711/sm.0185-3325.2020.025.Peer-Reviewed Original ResearchPediatric autoimmune neuropsychiatric disordersAutoimmune neuropsychiatric disordersPANDAS patientsAntibody titersAntibody levelsHealthy controlsImmune responseNeuropsychiatric disordersAbnormal immune responseImmune abnormalitiesStreptococcal infectionSerum antibodiesSerotonergic systemImmunological processesPatientsEtiology resultsGene polymorphismsSerotonin transporterTitersDisordersGenotype frequenciesSerotonergic genesOCD symptomsAssociationPolymorphismAnalysis of DNA Methylation Changes in Mice Mediated by Early‐life Exposure to the Antidepressant S‐citalopram
Rodriquez M, Shetty M, Black E, Kretschmar M, Perley D, De Kumar B, Henry L. Analysis of DNA Methylation Changes in Mice Mediated by Early‐life Exposure to the Antidepressant S‐citalopram. The FASEB Journal 2020, 34: 1-1. DOI: 10.1096/fasebj.2020.34.s1.06398.Peer-Reviewed Original ResearchMethylation changesSelective serotonin reuptake inhibitorsGenome-wide scaleDNA methylation changesSingle amino acid substitutionDNA methylation analysisSpecific methylation changesAmino acid substitutionsExpression changesMolecular mechanismsAcid substitutionsMethylation analysisSerotonin transporter blockadeSerotonin reuptake inhibitorsEarly life exposurePost-analysis methodsEarly developmentMice MediatedTransgenic miceReuptake inhibitorsTransporter blockadeMale miceS-citalopramSerotonin transporterSignificant risk
2019
Serotonin transport in the 21st century
Rudnick G, Sandtner W. Serotonin transport in the 21st century. Journal Of General Physiology 2019, 151: 1248-1264. PMID: 31570504, PMCID: PMC6829555, DOI: 10.1085/jgp.201812066.Peer-Reviewed Original Research
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