2022
An HPA-1a–positive platelet–depleting agent for prevention of fetal and neonatal alloimmune thrombocytopenia: a randomized, single-blind, placebo–controlled, single-center, phase 1/2 proof-of-concept study
Geisen C, Kjaer M, Fleck E, Skogen B, Armstrong R, Behrens F, Bhagwagar Z, Braeuninger S, Mortberg A, Olsen K, Gastón Schäfer S, Walter C, Seifried E, Wikman A, Kjeldsen-Kragh J, Koehm M. An HPA-1a–positive platelet–depleting agent for prevention of fetal and neonatal alloimmune thrombocytopenia: a randomized, single-blind, placebo–controlled, single-center, phase 1/2 proof-of-concept study. Journal Of Thrombosis And Haemostasis 2022, 21: 838-849. PMID: 36696185, DOI: 10.1016/j.jtha.2022.11.041.Peer-Reviewed Original ResearchConceptsFetal/Neonatal Alloimmune ThrombocytopeniaNeonatal alloimmune thrombocytopeniaHPA-1aAlloimmune thrombocytopeniaHuman platelet antigen 1aTreatment-emergent adverse eventsPlacebo 1 hourHPA-1a antibodiesFNAIT casesHyperimmune IgGPrimary endpointAdverse eventsFetus/Healthy menSingle doseAntigen 1aHLA-A2Concept studyCohort 1PlaceboFlow cytometryThrombocytopeniaPlateletsAdministrationWeeks
2011
Abnormal prefrontal activity subserving attentional control of emotion in remitted depressed patients during a working memory task with emotional distracters
Kerestes R, Ladouceur CD, Meda S, Nathan PJ, Blumberg HP, Maloney K, Ruf B, Saricicek A, Pearlson GD, Bhagwagar Z, Phillips ML. Abnormal prefrontal activity subserving attentional control of emotion in remitted depressed patients during a working memory task with emotional distracters. Psychological Medicine 2011, 42: 29-40. PMID: 21733287, DOI: 10.1017/s0033291711001097.Peer-Reviewed Original ResearchConceptsVentrolateral prefrontal cortexNegative emotional informationFunctional magnetic resonance imagingEmotional distractersAttentional controlEmotional informationMemory taskMemory loadEmotional Face N-Back (EFNBACK) taskOrbitofrontal cortexNegative emotional distractersN-back taskInterface of cognitionAccurate task performanceKey neural circuitsBlood oxygen level-dependent functional magnetic resonance imagingRMDD patientsLevel-dependent functional magnetic resonance imagingAttentional biasesFacial emotionsEmotion processingDepressed patientsDistracter stimuliTrait-like abnormalitiesRight DLPFC
2010
Increased peripheral blood expression of electron transport chain genes in bipolar depression
Beech RD, Lowthert L, Leffert JJ, Mason PN, Taylor MM, Umlauf S, Lin A, Lee JY, Maloney K, Muralidharan A, Lorberg B, Zhao H, Newton SS, Mane S, Epperson CN, Sinha R, Blumberg H, Bhagwagar Z. Increased peripheral blood expression of electron transport chain genes in bipolar depression. Bipolar Disorders 2010, 12: 813-824. PMID: 21176028, PMCID: PMC3076072, DOI: 10.1111/j.1399-5618.2010.00882.x.Peer-Reviewed Original ResearchConceptsBipolar disorderBipolar depressionPeripheral bloodDepressed subjectsGeneGo MetaCore softwarePeripheral blood expressionHealthy control subjectsReal-time reverse transcription-polymerase chain reactionEffects of medicationReverse transcription-polymerase chain reactionQuantitative real-time reverse transcription-polymerase chain reactionTranscription-polymerase chain reactionMitochondrial electron transport chainControl subjectsPolymerase chain reactionUnmedicated subjectsHealthy controlsBlood expressionBPD subjectsSpecific genetic pathwaysElectron transport chain genesMetaCore softwareA totalAltered expressionQRT-PCRLevetiracetam in the management of bipolar depression: a randomized, double-blind, placebo-controlled trial.
Saricicek A, Maloney K, Muralidharan A, Ruf B, Blumberg HP, Sanacora G, Lorberg B, Pittman B, Bhagwagar Z. Levetiracetam in the management of bipolar depression: a randomized, double-blind, placebo-controlled trial. The Journal Of Clinical Psychiatry 2010, 72: 744-50. PMID: 21034692, DOI: 10.4088/jcp.09m05659gre.Peer-Reviewed Original ResearchConceptsDepression Rating ScaleRating ScaleMean changeWeek 6Clinical Global Impression-Bipolar Version ScaleBipolar disorderHamilton Depression Rating Scale scoresMontgomery-Åsberg Depression Rating ScalePlacebo-controlled clinical trialDepression Rating Scale scoresHamilton Depression Rating ScaleYoung Mania Rating ScaleAdjunctive levetiracetam therapyLevetiracetam adjunctive therapySecondary efficacy assessmentsBipolar disorder type IPlacebo-controlled trialHamilton Anxiety Rating ScalePrimary efficacy measureSecondary outcome measuresMajor depressive episodeRating Scale scoresMania Rating ScaleShort-term treatmentSignificant differences
2005
Increased salivary cortisol after waking in depression
Bhagwagar Z, Hafizi S, Cowen P. Increased salivary cortisol after waking in depression. Psychopharmacology 2005, 182: 54-57. PMID: 15991000, DOI: 10.1007/s00213-005-0062-z.Peer-Reviewed Original ResearchConceptsSalivary cortisolMedication-free subjectsMorning cortisol secretionCommunity-based sampleExaggerated releaseCortisol secretionAcute depressionHealthy controlsMajor depressionCortisol levelsDepressed subjectsCortisolMore cortisolDepressionPatientsRecent studiesSubjectsHypersecretionPathophysiologyObjectiveToMinMethodsWeResultsInControlSecretion
2004
Preferential 5-HT1A Autoreceptor Occupancy by Pindolol is Attenuated in Depressed Patients: Effect of Treatment or an Endophenotype of Depression?
Rabiner E, Bhagwagar Z, Gunn R, Cowen P, Grasby P. Preferential 5-HT1A Autoreceptor Occupancy by Pindolol is Attenuated in Depressed Patients: Effect of Treatment or an Endophenotype of Depression? Neuropsychopharmacology 2004, 29: 1688-1698. PMID: 15127080, DOI: 10.1038/sj.npp.1300472.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic beta-AntagonistsAdultAutoreceptorsDepressive DisorderDose-Response Relationship, DrugFemaleHumansMaleMiddle AgedPhenotypePindololPiperazinesPsychiatric Status Rating ScalesPyridinesRadiopharmaceuticalsReceptor, Serotonin, 5-HT1ASerotonin AntagonistsTomography, Emission-ComputedPersistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [11C]WAY-100635
Bhagwagar Z, Rabiner E, Sargent P, Grasby P, Cowen P. Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [11C]WAY-100635. Molecular Psychiatry 2004, 9: 386-392. PMID: 15042104, DOI: 10.1038/sj.mp.4001401.Peer-Reviewed Original ResearchConceptsMajor depressionDepressed menDepressed subjectsAcute major depressionPositron emission tomography studyPotentials of brainEmission tomography studiesRecurrent major depressionPositron emission tomographyStatistical parametric mappingReceptor BPReference tissue modelAntidepressant medicationPersistent dysfunctionRaphe nucleusUnmedicated subjectsHealthy controlsBP valuesCortical areasTrait abnormalityMale subjectsEmission tomographyPersistent reductionTomography studyReceptor bindingIncreased Brain GABA Concentrations Following Acute Administration of a Selective Serotonin Reuptake Inhibitor
Bhagwagar Z, Wylezinska M, Taylor M, Jezzard P, Matthews P, Cowen P. Increased Brain GABA Concentrations Following Acute Administration of a Selective Serotonin Reuptake Inhibitor. American Journal Of Psychiatry 2004, 161: 368-370. PMID: 14754790, DOI: 10.1176/appi.ajp.161.2.368.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidBrain GABA concentrationsAcute administrationGABA concentrationSelective serotonin reuptake inhibitor citalopramSelective serotonin reuptake inhibitorsSerotonin reuptake inhibitor citalopramCortical gamma-aminobutyric acidActions of SSRIsGABA/creatine ratiosReuptake inhibitor citalopramSerotonin reuptake inhibitorsGABA neuronsSSRI treatmentReuptake inhibitorsIntravenous citalopramDepressed patientsCreatine ratioHealthy volunteersCortical levelOccipital cortexCrossover designMean increaseMagnetic resonance spectroscopyMood improvementEffects of beta-adrenoceptor blockade on components of human decision-making
Rogers R, Lancaster M, Wakeley J, Bhagwagar Z. Effects of beta-adrenoceptor blockade on components of human decision-making. Psychopharmacology 2004, 172: 157-164. PMID: 14716472, DOI: 10.1007/s00213-003-1641-5.Peer-Reviewed Original ResearchConceptsProbabilistic rewardsCortico-limbic systemsBrain imaging studiesSeries of choicesOrbitofrontal cortexEmotional aspectsSubjective stateSubjects designPunishment signalsCingulate cortexNegative ratingsProbability of losingNeurological patientsSubjective changesHealthy volunteersMoodRewardBeta-adrenoceptor blockadeCatecholamine systemsBeta-adrenoceptor blockersVisual analog scaleImaging studiesSlower heart rateCortexConclusionsThese results
2003
Lack of effect of a single dose of hydrocortisone on serotonin1A receptors in recovered depressed patients measured by positron emission tomography with [11C]WAY-100635
Bhagwagar Z, Montgomery A, Grasby P, Cowen P. Lack of effect of a single dose of hydrocortisone on serotonin1A receptors in recovered depressed patients measured by positron emission tomography with [11C]WAY-100635. Biological Psychiatry 2003, 54: 890-895. PMID: 14573316, DOI: 10.1016/s0006-3223(03)00466-9.Peer-Reviewed Original ResearchConceptsReceptor BPMajor depressionPositron emission tomographySerotonin-1A receptor bindingEmission tomographyPositron emission tomography scanAcute major depressionEmission tomography scanCertain brain areasElevated cortisol levelsLack of effectCortisol hypersecretionAcute administrationSingle doseHydrocortisone treatmentDepressed patientsTomography scanHealthy volunteersBrain areasCrossover designCortisol levelsSerotonin1A receptorsMale subjectsFemale subjectsPatientsIncrease in Concentration of Waking Salivary Cortisol in Recovered Patients With Depression
Bhagwagar Z, Hafizi S, Cowen P. Increase in Concentration of Waking Salivary Cortisol in Recovered Patients With Depression. American Journal Of Psychiatry 2003, 160: 1890-1891. PMID: 14514508, DOI: 10.1176/appi.ajp.160.10.1890.Peer-Reviewed Original ResearchConceptsSalivary cortisol levelsCortisol levelsDepressed patientsAcute major depressionComorbid medical conditionsHPA axis abnormalitiesWithdrawal of medicationCoronary heart diseaseElevated plasma cortisol levelsHPA axis activityHealthy comparison subjectsPlasma cortisol levelsHealthy comparison groupClinical recoveryAxis abnormalitiesRecovered patientsAdrenal axisFurther episodesAxis activityHeart diseaseMajor depressionMedical conditionsComparison subjectsPatientsDepressed subjectsContrasting effects of citalopram and reboxetine on waking salivary cortisol
Harmer C, Bhagwagar Z, Shelley N, Cowen P. Contrasting effects of citalopram and reboxetine on waking salivary cortisol. Psychopharmacology 2003, 167: 112-114. PMID: 12605289, DOI: 10.1007/s00213-003-1417-y.Peer-Reviewed Original ResearchConceptsHPA axis activitySalivary cortisolAxis activitySelective noradrenaline re-uptake inhibitorNoradrenaline re-uptake inhibitorSelective serotonin re-uptake inhibitor citalopramConclusionsShort-term treatmentDifferent antidepressant medicationsHPA axis functionEffect of citalopramRe-uptake inhibitorsDouble-blind designShort-term treatmentBasal salivary cortisol levelsDiurnal salivary cortisolSalivary free cortisolSalivary cortisol levelsAntidepressant administrationRationaleAcute administrationReboxetine treatmentAntidepressant medicationAntidepressant treatmentAxis functionHPA axisAdrenal axisRisperidone augmentation decreases rapid eye movement sleep and decreases wake in treatment-resistant depressed patients.
Sharpley A, Bhagwagar Z, Hafizi S, Whale W, Gijsman H, Cowen P. Risperidone augmentation decreases rapid eye movement sleep and decreases wake in treatment-resistant depressed patients. The Journal Of Clinical Psychiatry 2003, 64: 192-6. PMID: 12633128, DOI: 10.4088/jcp.v64n0212.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAntidepressive AgentsAntipsychotic AgentsCross-Over StudiesDepressive DisorderDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansMaleMiddle AgedPersonality InventoryPlacebosPolysomnographyPsychiatric Status Rating ScalesRisperidoneSleep, REMTreatment OutcomeWakefulnessConceptsRapid eye movement (REM) sleepEye movement sleepDepressed patientsHealthy volunteersRisperidone treatmentMovement sleepREM sleepMedication-resistant depressed patientsTreatment-resistant depressed patientsConventional antidepressant medicationAntidepressant-like effectsAntipsychotic agent risperidoneDepression Rating ScaleMajor depressive disorderDSM-IV criteriaPatients meritRisperidone additionRisperidone augmentationAntidepressant medicationRisperidone administrationSingle doseTherapeutic dosesAugmentation agentsDepressive disorderHealthy subjects
2002
Cortisol modulation of 5-HT-mediated growth hormone release in recovered depressed patients
Bhagwagar Z, Hafizi S, Cowen P. Cortisol modulation of 5-HT-mediated growth hormone release in recovered depressed patients. Journal Of Affective Disorders 2002, 72: 249-255. PMID: 12450642, DOI: 10.1016/s0165-0327(01)00467-0.Peer-Reviewed Original ResearchConceptsGrowth hormone releaseDepressed patientsMajor depressionHormone releaseStress-induced cortisol secretionBrain serotonin functionPlasma GH levelsEffects of cortisolEffect of hydrocortisoneCross-over designStressful life eventsGH responseGH levelsSingle doseCortisol secretionGH releaseHealthy controlsSerotonin functionRecurrent depressionTRP infusionHealthy volunteersCortisol modulationDepressive symptomatologyDepressed subjectsEuthymic subjectsAcute citalopram administration produces correlated increases in plasma and salivary cortisol
Bhagwagar Z, Hafizi S, Cowen P. Acute citalopram administration produces correlated increases in plasma and salivary cortisol. Psychopharmacology 2002, 163: 118-120. PMID: 12185409, DOI: 10.1007/s00213-002-1149-4.Peer-Reviewed Original ResearchConceptsSalivary cortisol levelsCortisol levelsSelective serotonin re-uptake inhibitorsSalivary cortisolSerotonin re-uptake inhibitorsAcute citalopram administrationRe-uptake inhibitorsCross-over designSalivary cortisol concentrationsCitalopram administrationIntravenous administrationCortisol releaseHealthy volunteersCortisol concentrationsSaliva cortisolCitalopramCortisolParallel increaseAdministrationCorrelated increaseAcceptable meansTryptophan Depletion Alters the Decision-Making of Healthy Volunteers through Altered Processing of Reward Cues
Rogers R, Tunbridge E, Bhagwagar Z, Drevets W, Sahakian B, Carter C. Tryptophan Depletion Alters the Decision-Making of Healthy Volunteers through Altered Processing of Reward Cues. Neuropsychopharmacology 2002, 28: 153-162. PMID: 12496952, DOI: 10.1038/sj.npp.1300001.Peer-Reviewed Original ResearchConceptsAmino acid drinkReward cuesOrbitofrontal cortexNegative outcomesReduced discriminationAltered processingTryptophan depletionHuman choiceCuesMonoamine neurotransmitter systemsAltered discriminationNeurotransmitter systemsBiasesDiscriminationCortexGamblesProcessingPsychiatric illnessCognitionHealthy volunteersAnhedoniaMoodFunctioningPresent studyLittle evidenceState and trait abnormalities in serotonin function in major depression
Bhagwagar Z, Whale R, Cowen P. State and trait abnormalities in serotonin function in major depression. The British Journal Of Psychiatry 2002, 180: 24-28. PMID: 11772847, DOI: 10.1192/bjp.180.1.24.Peer-Reviewed Original ResearchConceptsCortisol responseHealthy controlsMajor depressionSerotonin functionRecovered subjectsAdrenal axis dysfunctionBrain serotonin functionPlacebo-controlled designMarker of vulnerabilityAxis dysfunctionClinical recoveryReuptake inhibitorsUnmedicated subjectsProlactin responseDepressed patientsEndocrine responsesNeuroendocrine studiesDepressed subjectsCitalopramDepressionPatientsSubjectsResponseDysfunctionNeurotransmission
2001
Pindolol Augmentation of Selective Serotonin Reuptake Inhibitors: PET Evidence That the Dose Used in Clinical Trials Is Too Low
Rabiner E, Bhagwagar Z, Gunn R, Sargent P, Bench C, Cowen P, Grasby P. Pindolol Augmentation of Selective Serotonin Reuptake Inhibitors: PET Evidence That the Dose Used in Clinical Trials Is Too Low. American Journal Of Psychiatry 2001, 158: 2080-2082. PMID: 11729033, DOI: 10.1176/appi.ajp.158.12.2080.Peer-Reviewed Original ResearchMeSH KeywordsAdultBrainDepressive Disorder, MajorDose-Response Relationship, DrugDrug Administration ScheduleDrug Therapy, CombinationFemaleHumansMaleMiddle AgedPindololReceptors, SerotoninReceptors, Serotonin, 5-HT1Selective Serotonin Reuptake InhibitorsTomography, Emission-ComputedTreatment OutcomeConceptsPositron emission tomographyDose of pindololClinical trialsDepressed patientsSelective serotonin reuptake inhibitorsSignificant occupancyPresent clinical trialSerotonin reuptake inhibitorsPindolol augmentationAntidepressant medicationReuptake inhibitorsPET evidenceEmission tomographyPindololTrialsDoseAutoreceptorsMedicationsPatientsInconsistent resultsEfficacyVast majorityDosesPET measurement of the influence of corticosteroids on serotonin-1A receptor number
Montgomery A, Bench C, Young A, Hammers A, Gunn R, Bhagwagar Z, Grasby P. PET measurement of the influence of corticosteroids on serotonin-1A receptor number. Biological Psychiatry 2001, 50: 668-676. PMID: 11704073, DOI: 10.1016/s0006-3223(01)01205-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnti-Inflammatory AgentsBinding, CompetitiveDose-Response Relationship, DrugDouble-Blind MethodDrug Administration ScheduleFemaleHippocampusHumansHydrocortisoneHypothalamo-Hypophyseal SystemMaleMiddle AgedPituitary-Adrenal SystemReceptors, SerotoninReceptors, Serotonin, 5-HT1Tomography, Emission-ComputedConceptsPositron emission tomographyReceptor numberReceptor bindingPlacebo-controlled designInfluence of corticosteroidsSingle doseSerotonergic systemPreclinical studiesCorticosteroidsNormal subjectsModulatory effectsAlters 5Corticosteroid levelsBrain regionsEmission tomographyElevated levelsPET measurementsHippocampusHuman brainPatientsHydrocortisoneDoseBrainReceptorsDecreased sensitivity of 5-HT1D receptors in melancholic depression
Whale R, Clifford E, Bhagwagar Z, Cowen P. Decreased sensitivity of 5-HT1D receptors in melancholic depression. The British Journal Of Psychiatry 2001, 178: 454-457. PMID: 11331562, DOI: 10.1192/bjp.178.5.454.Peer-Reviewed Original ResearchConceptsSelective serotonin reuptake inhibitorsGrowth hormone responseGrowth hormone releaseSSRI treatmentMajor depressionHormone releaseMelancholic depressionHormone responseBrain serotonin functionSerotonin reuptake inhibitorsReuptake inhibitorsDepressive syndromeReceptor agonistReceptor subtypesSerotonin functionHealthy subjectsReceptor sensitivityPatientsControl groupMarked reductionZolmitriptanDepressionReceptorsTreatmentSelective ligands