2024
Illusory generalizability of clinical prediction models
Chekroud A, Hawrilenko M, Loho H, Bondar J, Gueorguieva R, Hasan A, Kambeitz J, Corlett P, Koutsouleris N, Krumholz H, Krystal J, Paulus M. Illusory generalizability of clinical prediction models. Science 2024, 383: 164-167. PMID: 38207039, DOI: 10.1126/science.adg8538.Peer-Reviewed Original Research
2023
Randomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia
Surti T, Ranganathan M, Johannesen J, Gueorguieva R, Deaso E, Kenney J, Krystal J, D'Souza D. Randomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia. Schizophrenia Research 2023, 256: 36-43. PMID: 37141764, PMCID: PMC10257994, DOI: 10.1016/j.schres.2023.04.010.Peer-Reviewed Original ResearchConceptsGlycine transporter 1Cytochrome P450 2D6 extensive metabolizersGlyT1 inhibitorsWeeks of washoutWeeks of CTMedication adherenceReceptor hypofunctionImpaired neuroplasticityPharmacodynamic variabilityNMDAR functionExtensive metabolizersTreatment periodPsychotic symptomsStable outpatientsCognitive impairmentGlyT1 occupancyTransporter 1CTNeuroplasticityCognitive training strategiesSchizophreniaComputerized CTCognitive performanceAugmentation studiesGreater improvement
2021
Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia
Abi-Dargham A, Javitch JA, Slifstein M, Anticevic A, Calkins ME, Cho YT, Fonteneau C, Gil R, Girgis R, Gur RE, Gur RC, Grinband J, Kantrowitz J, Kohler C, Krystal J, Murray J, Ranganathan M, Santamauro N, Van Snellenberg J, Tamayo Z, Wolf D, D’Souza D, Srihari V, Gueorguieva R, Patel P, Forselius-Bielen K, Lu J, Butler A, Fram G, Afriyie-Agyemang Y, Selloni A, Cadavid L, Gomez-Luna S, Gupta A, Radhakrishnan R, Rashid A, Aker R, Abrahim P, Nia A, Surti T, Kegeles L, Carlson M, Goldberg T, Gangwisch J, Benedict E, Govil P, Brazis S, Mayer M, de la Garrigue N, Fallon N, Baumvoll T, Abeykoon S, Perlman G, Bobchin K, Elliott M, Schmidt L, Rush S, Port A, Heffernan Z, Laney N, Kantor J, Hohing T, Gray D, Lieberman J. Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia. Schizophrenia Bulletin 2021, 48: 199-210. PMID: 34423843, PMCID: PMC8781338, DOI: 10.1093/schbul/sbab095.Peer-Reviewed Original ResearchConceptsCortical dopamine neurotransmissionPositive allosteric modulationImportant therapeutic targetPF-06412562Dopaminergic receptorsD1R stimulationDA levelsTolerable dosesLevel of stimulationDopamine neurotransmissionReceptor stimulationTherapeutic targetPartial agonistCognitive deficitsBiased agonismFull agonismTarget engagementAllosteric modulationNew drugsStimulationPoor bioavailabilitySchizophreniaOptimal stimulationDrugsExpression levels
2019
Altered functional connectivity and low-frequency signal fluctuations in early psychosis and genetic high risk
Tang Y, Zhou Q, Chang M, Chekroud A, Gueorguieva R, Jiang X, Zhou Y, He G, Rowland M, Wang D, Fu S, Yin Z, Leng H, Wei S, Xu K, Wang F, Krystal JH, Driesen NR. Altered functional connectivity and low-frequency signal fluctuations in early psychosis and genetic high risk. Schizophrenia Research 2019, 210: 172-179. PMID: 30685394, DOI: 10.1016/j.schres.2018.12.041.Peer-Reviewed Original ResearchConceptsFunctional connectivityHigh-risk individualsAltered functional connectivityHealthy comparison subjectsGenetic high riskGenetic high-risk individualsLow-frequency signal fluctuationsFunctional magnetic resonanceALFF abnormalitiesALFF measuresFunctional connectivity measuresBasal gangliaFirst episodeHigh riskEarly psychosisComparison subjectsSchizophrenia diathesisSchizophrenia vulnerabilityFESzGenetic riskLow-frequency fluctuationsIllnessSchizophreniaVoxel connectivityGHR
2018
Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects
D’Souza D, Carson RE, Driesen N, Johannesen J, Ranganathan M, Krystal JH, Ahn K, Bielen K, Carbuto M, Deaso E, D’Souza D, Ranganathan M, Naganawa M, Ranganathan M, D’Souza D, Nabulsi N, Zheng M, Lin S, Huang Y, Carson R, Driesen N, Ahn K, Morgan P, Suckow R, He G, McCarthy G, Krystal J, Johannesen J, Kenney J, Gelernter J, Gueorguieva R, Pittman B. Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects. Biological Psychiatry 2018, 84: 413-421. PMID: 29499855, PMCID: PMC6068006, DOI: 10.1016/j.biopsych.2017.12.019.Peer-Reviewed Original ResearchMeSH KeywordsAdultAzabicyclo CompoundsBrainCognitive DysfunctionDose-Response Relationship, DrugDouble-Blind MethodFemaleGlycine Plasma Membrane Transport ProteinsHumansImidazolesKetamineLong-Term PotentiationMagnetic Resonance ImagingMaleMemory, Short-TermMiddle AgedPositron-Emission TomographySchizophreniaYoung AdultConceptsHealthy control subjectsLong-term potentiationSchizophrenia patientsControl subjectsCognitive impairmentClinical trialsGlyT1 occupancyN-methyl-D-aspartate receptor functionGlycine transporter-1 inhibitorKetamine-induced disruptionKetamine-induced effectsFunctional magnetic resonance imagingMagnetic resonance imagingPositron emission tomographyMemory-related activationF-MKSubstudy 1Schizophrenia subjectsResonance imagingReceptor functionCortical regionsEmission tomographyTarget engagementPotentiationSchizophrenia
2014
Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia
Xu K, Krystal JH, Ning Y, Chen da C, He H, Wang D, Ke X, Zhang X, Ding Y, Liu Y, Gueorguieva R, Wang Z, Limoncelli D, Pietrzak RH, Petrakis IL, Zhang X, Fan N. Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia. Journal Of Psychiatric Research 2014, 61: 64-72. PMID: 25560772, PMCID: PMC4445679, DOI: 10.1016/j.jpsychires.2014.12.012.Peer-Reviewed Original ResearchConceptsKetamine groupNegative Syndrome ScaleSchizophrenia groupSyndrome ScaleN-methyl-D-aspartate (NMDA) glutamate receptor antagonistGlutamate receptor antagonistsPotential confounding factorsEarly course schizophreniaSymptom dimensionsSymptoms of schizophreniaReceptor antagonistChronic schizophreniaHealthy subjectsKetamine abuseSchizophrenia psychosisSchizophrenia patientsConfounding factorsSymptom severitySymptomsInpatientsSchizophreniaPsychosisKetamine usersDissociation symptomsPrincipal component factor analysis
2012
Efficacy of pimozide augmentation for clozapine partial responders with schizophrenia
Gunduz-Bruce H, Oliver S, Gueorguieva R, Forselius-Bielen K, D'Souza DC, Zimolo Z, Tek C, Kaliora S, Ray S, Petrides G. Efficacy of pimozide augmentation for clozapine partial responders with schizophrenia. Schizophrenia Research 2012, 143: 344-347. PMID: 23219861, DOI: 10.1016/j.schres.2012.11.008.Peer-Reviewed Original ResearchConceptsBrief Psychiatric Rating ScaleTreatment-resistant schizophreniaClinical trialsNegative symptomsDouble-blind placeboAdequate blood levelsPsychiatric Rating ScaleNeurocognitive measuresAttention/executive functionBPRS totalPartial respondersPartial responseStudy entryQTc intervalBlood levelsClozapine's effectSide effectsNeurocognitive functionPatientsWeekly assessmentsClozapineNeurocognitive testsRating ScaleSchizophreniaTrialsImpaired Visual Cortical Plasticity in Schizophrenia
Çavuş I, Reinhart RM, Roach BJ, Gueorguieva R, Teyler TJ, Clapp WC, Ford JM, Krystal JH, Mathalon DH. Impaired Visual Cortical Plasticity in Schizophrenia. Biological Psychiatry 2012, 71: 512-520. PMID: 22364738, PMCID: PMC3292767, DOI: 10.1016/j.biopsych.2012.01.013.Peer-Reviewed Original ResearchConceptsHigh-frequency stimulationVisual cortical plasticityCortical plasticityVisual steady-state responseN-methyl-D-aspartate receptor functionHealthy control subjectsLong-term potentiation paradigmLong-term potentiationForm of neuroplasticityRepetitive visual stimulationSustained potentiationControl subjectsVEP assessmentSchizophrenia patientsStandard visual stimuliInfrequent target stimuliCore pathophysiologyReceptor functionPotentiationSchizophreniaVisual stimulationComponent scoresStimulationVisual stimuliBaseline
2011
Using Computational Patients to Evaluate Illness Mechanisms in Schizophrenia
Hoffman RE, Grasemann U, Gueorguieva R, Quinlan D, Lane D, Miikkulainen R. Using Computational Patients to Evaluate Illness Mechanisms in Schizophrenia. Biological Psychiatry 2011, 69: 997-1005. PMID: 21397213, PMCID: PMC3105006, DOI: 10.1016/j.biopsych.2010.12.036.Peer-Reviewed Original ResearchConceptsPrediction-error signallingStory recall taskIllness mechanismsEpisodic memoryRecall taskAssociated emotionsNarrative memoryNarrative languageDopamine neuromodulationDisparate symptomsNarrative understandingHealthy control subjectsDisorganized speechMemorySchizoaffective disorderComputational modelNeural network modelParental educationSchizophreniaCrime storiesPrediction errorDelusionsControl subjectsEmotionsNetwork model
2008
Impairment of Working Memory Maintenance and Response in Schizophrenia: Functional Magnetic Resonance Imaging Evidence
Driesen NR, Leung HC, Calhoun VD, Constable RT, Gueorguieva R, Hoffman R, Skudlarski P, Goldman-Rakic PS, Krystal JH. Impairment of Working Memory Maintenance and Response in Schizophrenia: Functional Magnetic Resonance Imaging Evidence. Biological Psychiatry 2008, 64: 1026-1034. PMID: 18823880, PMCID: PMC2650279, DOI: 10.1016/j.biopsych.2008.07.029.Peer-Reviewed Original ResearchConceptsMemory taskPrefrontal activityMemory maintenanceBrain activationFunctional Magnetic Resonance Imaging EvidenceWorking Memory MaintenanceCognitive impairmentHealthy comparison participantsPrefrontal cortical activityFunctional magnetic resonanceMemory loadComparison participantsTask accuracyDistinct neurobiologyCortical activityHealthy participantsBasic research insightsImaging EvidenceMemoryCortical deficitsCortical functionPoor performanceTaskSchizophreniaResponse phase
2007
Cortisol levels in relation to hippocampal sub-regions in subjects with first episode schizophrenia
Gunduz-Bruce H, Szeszko PR, Gueorguieva R, Ashtari M, Robinson DG, Kane JM, Bilder RM. Cortisol levels in relation to hippocampal sub-regions in subjects with first episode schizophrenia. Schizophrenia Research 2007, 94: 281-287. PMID: 17490857, DOI: 10.1016/j.schres.2007.03.025.Peer-Reviewed Original ResearchConceptsFirst-episode schizophreniaHippocampal volumeRegional hippocampal volumesCortisol levelsEpisode schizophreniaAnterior hippocampal volumeDiurnal salivary cortisol levelsSalivary cortisol levelsCoronal MR imagesHigher cortisol levelsCushing's syndromeFirst admissionPatient groupHealthy controlsCortisol exposureHealthy adolescentsSignificant associationSchizophreniaVolumetric reductionCortisol measuresLarge-scale studiesGenetic factorsSchizophrenia sampleSyndromeCortisolCSF sub-compartments in relation to plasma osmolality in healthy controls and in patients with first episode schizophrenia
Gunduz-Bruce H, Narr KL, Gueorguieva R, Toga AW, Szeszko PR, Ashtari M, Robinson DG, Sevy S, Kane JM, Bilder RM. CSF sub-compartments in relation to plasma osmolality in healthy controls and in patients with first episode schizophrenia. Psychiatry Research 2007, 155: 57-66. PMID: 17398079, PMCID: PMC3299193, DOI: 10.1016/j.pscychresns.2006.12.006.Peer-Reviewed Original ResearchConceptsFirst-episode schizophreniaHealthy controlsEpisode schizophreniaMagnetic resonance imagingVentricle sizePlasma osmolalityHealthy control groupSignificant group effectVentricular morphologyCSF concentrationsLateral ventricleHealthy volunteersBlood samplesPatientsControl groupHigher plasmaWhite matterResonance imagingSuperior hornBrain morphologyTesla scannerSchizophreniaSignificant correlationOsmolalityPreliminary evidence
2006
Enhanced Sensitivity to the Euphoric Effects of Alcohol in Schizophrenia
D'Souza DC, Gil RB, Madonick S, Perry EB, Forselius-Bielen K, Braley G, Donahue L, Tellioglu T, Zimolo Z, Gueorguieva R, Krystal JH. Enhanced Sensitivity to the Euphoric Effects of Alcohol in Schizophrenia. Neuropsychopharmacology 2006, 31: 2767-2775. PMID: 16985503, DOI: 10.1038/sj.npp.1301207.Peer-Reviewed Original ResearchConceptsEffects of alcoholHealthy subjectsBlood alcohol levelsPositive psychotic symptomsSmall transient increaseSelf-medication hypothesisPerceptual alterationsAlcohol administrationMotor functionAlcohol dosesElevated riskPsychotic symptomsLifetime exposureSchizophrenia patientsSchizophrenia symptomsEuphoric effectsNegative symptomsAlcohol levelsAlcohol useStimulatory effectSubjective effectsTransient increaseSchizophreniaStimulatory responseAlcohol responsesEffects of Naltrexone on Cognition in a Treatment Study of Patients with Schizophrenia and Comorbid Alcohol Dependence
Ralevski E, Balachandra K, Gueorguieva R, Limoncelli D, Petrakis I. Effects of Naltrexone on Cognition in a Treatment Study of Patients with Schizophrenia and Comorbid Alcohol Dependence. Journal Of Dual Diagnosis 2006, 2: 53-69. DOI: 10.1300/j374v02n04_05.Peer-Reviewed Original ResearchCognitive functioningAlcohol dependenceFrontal lobe functioningComorbid alcohol dependenceSymptoms of schizophreniaAlcohol useFunctioningCognitionTreatment studiesSchizophreniaEffects of naltrexoneAlcohol reductionMemoryDrinking patternsAlcohol consumptionAttentionSecond objectiveWeeks of treatmentDeficitsFirst objectiveWeek 24Naltrexone treatmentWeek 12NaltrexonePatients
2005
Delta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction
D’Souza D, Abi-Saab WM, Madonick S, Forselius-Bielen K, Doersch A, Braley G, Gueorguieva R, Cooper TB, Krystal JH. Delta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction. Biological Psychiatry 2005, 57: 594-608. PMID: 15780846, DOI: 10.1016/j.biopsych.2004.12.006.Peer-Reviewed Original ResearchMeSH KeywordsAdultAkathisia, Drug-InducedArousalCognitionDose-Response Relationship, DrugDouble-Blind MethodDronabinolEndocrine SystemFemaleHumansInjections, IntravenousMaleMental RecallMiddle AgedMotor ActivityNeuropsychological TestsPerceptionPsychiatric Status Rating ScalesPsychotic DisordersPsychotropic DrugsSchizophreniaVerbal LearningConceptsSchizophrenia patientsAntipsychotic-treated schizophrenia patientsDelta-9-tetrahydrocannabinol effectsLong-term adverse eventsCognitive deficitsPlacebo-controlled studyDelta-9-THCTransient exacerbationAdverse eventsReceptor dysfunctionEndocrine effectsHealthy subjectsStudy participationPsychotic disordersPlasma prolactinSchizophrenia symptomsPatientsSchizophreniaCognitive effectsPerceptual alterationsDeficitsCannabisSubjectsAkathisiaExacerbationMazindol Augmentation of Antipsychotic Treatment for Schizophrenic Patients with Comorbid Cocaine Abuse or Dependence
Perry E, Gil R, Miles D, Brenner L, Macdougall L, Johnson R, Degen K, Gueorguieva R, Petrakis I, Krystal J, D'Souza D. Mazindol Augmentation of Antipsychotic Treatment for Schizophrenic Patients with Comorbid Cocaine Abuse or Dependence. Journal Of Dual Diagnosis 2005, 1: 37-47. DOI: 10.1300/j374v01n01_04.Peer-Reviewed Original ResearchCocaine abusePsychiatric symptomsCocaine cravingCatecholamine reuptake inhibitorCurrent antipsychotic medicationsCocaine consumptionPlacebo groupAntipsychotic pharmacotherapyReuptake inhibitorsAntipsychotic medicationAntipsychotic treatmentComorbid schizophreniaSchizoaffective patientsSubstance abuse issuesSchizophrenic patientsPatientsSchizoaffective disorderSchizophrenia patientsNatural historyMazindolPilot studyGroup therapySchizophreniaSymptomsAbuse issues
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