2023
Efficacy and safety of iclepertin (BI 425809) in patients with schizophrenia: CONNEX, a Phase III randomised controlled trial programme
Reuteman-Fowler C, Blahova Z, Ikezawa S, Marder S, Falkai P, Krystal J. Efficacy and safety of iclepertin (BI 425809) in patients with schizophrenia: CONNEX, a Phase III randomised controlled trial programme. Neuroscience Applied 2023, 2: 102592. DOI: 10.1016/j.nsa.2023.102592.Peer-Reviewed Original Research
2022
mTORC1 inhibitor effects on rapid ketamine-induced reductions in suicidal ideation in patients with treatment-resistant depression
Averill LA, Averill CL, Gueorguieva R, Fouda S, Sherif M, Ahn KH, Ranganathan M, D'Souza DC, Southwick SM, Sanacora G, Duman RS, Krystal JH, Abdallah CG. mTORC1 inhibitor effects on rapid ketamine-induced reductions in suicidal ideation in patients with treatment-resistant depression. Journal Of Affective Disorders 2022, 303: 91-97. PMID: 35101523, DOI: 10.1016/j.jad.2022.01.104.Peer-Reviewed Original ResearchConceptsAntisuicidal effectsAntidepressant effectsSuicidal ideationKetamine-induced reductionTreatment-resistant depressionLimited treatment optionsCross-over trialMajor depressive episodeOral rapamycinPublic health crisisKetamine administrationTreatment optionsDepressive episodeParent studyOverall severityKetamineTwo weeksBeck ScaleRapamycin complex 1Mechanistic targetPatientsSignificant main effectHealth crisisRobust improvementFuture studiesPrefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans
Averill LA, Jiang L, Purohit P, Coppoli A, Averill CL, Roscoe J, Kelmendi B, De Feyter HM, de Graaf RA, Gueorguieva R, Sanacora G, Krystal JH, Rothman DL, Mason GF, Abdallah CG. Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans. Chronic Stress 2022, 6: 24705470221092734. PMID: 35434443, PMCID: PMC9008809, DOI: 10.1177/24705470221092734.Peer-Reviewed Original ResearchGlutamatergic synaptic strengthSynaptic strengthPathophysiology of PTSDNovel putative biomarkersTrauma-related psychopathologyMagnetic resonance spectroscopyGlutamate neurotransmissionHealthy controlsNew treatmentsChronic stressPatientsPutative biomarkersEffects of sexPTSDNeurotransmissionPosttraumatic stressAgePsychopathologyEPCPathophysiologyStudy resultsTraumaBiomarkersEfficacy and safety of BI 425809 in patients with schizophrenia: CONNEX, a Phase III randomised controlled trial programme
Wunderlich G, Blahova Z, Hake S, Ikezawa S, Marder S, Falkai P, Krystal J. Efficacy and safety of BI 425809 in patients with schizophrenia: CONNEX, a Phase III randomised controlled trial programme. Neuroscience Applied 2022, 1: 100342. DOI: 10.1016/j.nsa.2022.100342.Peer-Reviewed Original Research
2020
Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis
Wang X, Xie H, Chen T, Cotton AS, Salminen LE, Logue MW, Clarke-Rubright EK, Wall J, Dennis EL, O’Leary B, Abdallah CG, Andrew E, Baugh LA, Bomyea J, Bruce SE, Bryant R, Choi K, Daniels JK, Davenport ND, Davidson RJ, DeBellis M, deRoon-Cassini T, Disner SG, Fani N, Fercho KA, Fitzgerald J, Forster GL, Frijling JL, Geuze E, Gomaa H, Gordon EM, Grupe D, Harpaz-Rotem I, Haswell CC, Herzog JI, Hofmann D, Hollifield M, Hosseini B, Hudson AR, Ipser J, Jahanshad N, Jovanovic T, Kaufman ML, King AP, Koch SBJ, Koerte IK, Korgaonkar MS, Krystal JH, Larson C, Lebois LAM, Levy I, Li G, Magnotta VA, Manthey A, May G, McLaughlin KA, Mueller SC, Nawijn L, Nelson SM, Neria Y, Nitschke JB, Olff M, Olson EA, Peverill M, Phan K, Rashid FM, Ressler K, Rosso IM, Sambrook K, Schmahl C, Shenton ME, Sierk A, Simons JS, Simons RM, Sponheim SR, Stein MB, Stein DJ, Stevens JS, Straube T, Suarez-Jimenez B, Tamburrino M, Thomopoulos SI, van der Wee NJA, van der Werff SJA, van Erp TGM, van Rooij SJH, van Zuiden M, Varkevisser T, Veltman DJ, Vermeiren RRJM, Walter H, Wang L, Zhu Y, Zhu X, Thompson PM, Morey RA, Liberzon I. Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis. Molecular Psychiatry 2020, 26: 4331-4343. PMID: 33288872, PMCID: PMC8180531, DOI: 10.1038/s41380-020-00967-1.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderLateral orbitofrontal gyrusPTSD patientsCortical regionsComorbid depressionCortical volumeVolume abnormalitiesStress disorderSuperior parietal gyrusRegional cortical volumesSuperior temporal gyrusPrefrontal regulatory regionsCerebral cortexControl subjectsRight insularLimbic regionsParietal gyrusPosttraumatic stress symptom severityStress symptom severityDepression symptomsOrbitofrontal gyrusSymptom severityTemporal gyrusPatientsAbnormalitiesAssociation of a Prior Psychiatric Diagnosis With Mortality Among Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Infection
Li L, Li F, Fortunati F, Krystal JH. Association of a Prior Psychiatric Diagnosis With Mortality Among Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Infection. JAMA Network Open 2020, 3: e2023282. PMID: 32997123, PMCID: PMC7527869, DOI: 10.1001/jamanetworkopen.2020.23282.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAgedAged, 80 and overBetacoronavirusCerebrovascular DisordersCohort StudiesComorbidityCoronavirus InfectionsCOVID-19Diabetes MellitusFemaleHeart FailureHIV InfectionsHospitalizationHumansKaplan-Meier EstimateKidney DiseasesLiver DiseasesMaleMental DisordersMiddle AgedMyocardial InfarctionNeoplasmsPandemicsPneumonia, ViralProportional Hazards ModelsRisk FactorsSARS-CoV-2United StatesKetamine and rapid acting antidepressants: Are we ready to cure, rather than treat depression?
Abdallah CG, Krystal JH. Ketamine and rapid acting antidepressants: Are we ready to cure, rather than treat depression? Behavioural Brain Research 2020, 390: 112628. PMID: 32407817, PMCID: PMC7316409, DOI: 10.1016/j.bbr.2020.112628.Peer-Reviewed Original ResearchConceptsChronic stress pathologyRapid acting antidepressantsHigh treatment resistanceActing antidepressantsChronic courseClinical evidenceLeading causeTreatment resistancePsychiatric disordersStress pathologyDepressionLarge proportionAntidepressantsPatientsReviewKetamineIllnessPathologyComprehensive review
2019
Schizophrenia Exhibits Bi-directional Brain-Wide Alterations in Cortico-Striato-Cerebellar Circuits
Ji JL, Diehl C, Schleifer C, Tamminga CA, Keshavan MS, Sweeney JA, Clementz BA, Hill SK, Pearlson G, Yang G, Creatura G, Krystal JH, Repovs G, Murray J, Winkler A, Anticevic A. Schizophrenia Exhibits Bi-directional Brain-Wide Alterations in Cortico-Striato-Cerebellar Circuits. Cerebral Cortex 2019, 29: 4463-4487. PMID: 31157363, PMCID: PMC6917525, DOI: 10.1093/cercor/bhy306.Peer-Reviewed Original ResearchConceptsBrain-wide alterationsResting-state functional magnetic resonanceSensory-motor cortexFunctional magnetic resonanceNeural dysconnectivityPolysynaptic connectionsCortico-striatoFunctional disturbancesChronic patientsAssociation cortexFocal disruptionNeural effectsCerebellar circuitsPatientsDysconnectivityStriatal componentsSchizophreniaCortexSpecific alterationsHallmark featureCognitive performanceAlterationsFunctional pathwaysQuestion accountsMagnetic resonanceAssociation of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder
Yoon G, Petrakis IL, Krystal JH. Association of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder. JAMA Psychiatry 2019, 76: 337-338. PMID: 30624551, PMCID: PMC6439824, DOI: 10.1001/jamapsychiatry.2018.3990.Peer-Reviewed Original ResearchA multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms
Fleming LM, Javitt DC, Carter CS, Kantrowitz JT, Girgis RR, Kegeles LS, Ragland JD, Maddock RJ, Lesh TA, Tanase C, Robinson J, Potter WZ, Carlson M, Wall MM, Choo TH, Grinband J, Lieberman J, Krystal JH, Corlett PR. A multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms. NeuroImage Clinical 2019, 22: 101739. PMID: 30852397, PMCID: PMC6411494, DOI: 10.1016/j.nicl.2019.101739.Peer-Reviewed Original ResearchConceptsDorsolateral prefrontal cortexN-methyl-D-aspartate (NMDA) glutamate receptor antagonistFunctional connectivityKetamine-induced alterationsGlutamate receptor antagonistsAltered brain functionState functional connectivityRsfMRI connectivityRisk patientsMulticenter studyKetamine effectsReceptor antagonistDLPFC connectivityMimic symptomsHealthy individualsKetamine usePositive symptomsCertain biomarkersBrain functionPrefrontal cortexPatientsConnectivity signaturesSeed-based measuresSchizophreniaKetamine
2018
Predicting Barriers to Treatment for Depression in a U.S. National Sample: A Cross-Sectional, Proof-of-Concept Study
Chekroud AM, Foster D, Zheutlin AB, Gerhard DM, Roy B, Koutsouleris N, Chandra A, Esposti MD, Subramanyan G, Gueorguieva R, Paulus M, Krystal JH. Predicting Barriers to Treatment for Depression in a U.S. National Sample: A Cross-Sectional, Proof-of-Concept Study. Psychiatric Services 2018, 69: 927-934. PMID: 29962307, PMCID: PMC7232987, DOI: 10.1176/appi.ps.201800094.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overCross-Sectional StudiesDepressive DisorderFemaleHealth Services AccessibilityHumansLogistic ModelsMaleMiddle AgedPatient Acceptance of Health CarePrimary Health CareProof of Concept StudyPsychotherapySampling StudiesSelf-AssessmentSurveys and QuestionnairesTreatment RefusalUnited StatesYoung AdultConceptsDiagnosis of depressionHealth care providersSelf-report survey itemsImplementation of interventionsDerivation cohortUntreated depressionCare providersEffective treatmentU.S. national sampleDrug useDepressionDiagnosisTreatmentU.S. National SurveyPatientsCohortNational surveyNational sampleConcept studySurvey itemsBalanced accuracyIndividualsRetention rateIndependent responsesPrevalence2. MICROCIRCUITS, MACROCIRCUITS, AND CORTICOL DYSFUNCTION IN SCHIZOPHRENIA: A COMPUTATIONAL AND TRANSLATIONAL NEUROSCIENCE PERSPECTIVE
Krystal J. 2. MICROCIRCUITS, MACROCIRCUITS, AND CORTICOL DYSFUNCTION IN SCHIZOPHRENIA: A COMPUTATIONAL AND TRANSLATIONAL NEUROSCIENCE PERSPECTIVE. Schizophrenia Bulletin 2018, 44: s1-s1. PMCID: PMC5887654, DOI: 10.1093/schbul/sby014.001.Peer-Reviewed Original ResearchNMDA glutamate receptorsNMDA receptor antagonistCortical functional connectivityPathophysiology of schizophreniaReceptor antagonistTranslational neuroscience perspectiveGlutamate receptorsHealthy humansAnimal modelsSchizophrenia patientsMemory impairmentNeuropsychiatric disordersSynaptic signalingFunctional connectivityNovel therapeuticsSchizophreniaDisordersPresentationPatientsPathophysiologyDysfunctionKetamineAntagonistSymptomsAbnormalities
2017
Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression
Su TP, Chen MH, Li CT, Lin WC, Hong CJ, Gueorguieva R, Tu PC, Bai YM, Cheng CM, Krystal JH. Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression. Neuropsychopharmacology 2017, 42: 2482-2492. PMID: 28492279, PMCID: PMC5686503, DOI: 10.1038/npp.2017.94.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntidepressive AgentsAsian PeopleBlood PressureBrain-Derived Neurotrophic FactorDepressive Disorder, MajorDepressive Disorder, Treatment-ResistantDose-Response Relationship, DrugDouble-Blind MethodFemaleHeart RateHumansKetamineMaleMiddle AgedPolymorphism, GeneticPsychiatric Status Rating ScalesTaiwanTreatment OutcomeConceptsTreatment-resistant depressionHamilton Depression Rating ScaleAntidepressant effectsKetamine effectsBDNF genotypeBrain-derived neurotrophic factor (BDNF) genotypeChinese populationDose-related efficacyPlacebo-controlled trialSignificant dose-related effectsDepression Rating ScaleNeurotrophic factor genotypeDose-related effectsSingle ketamine infusionMost patientsKetamine infusionTaiwanese patientsAdjunctive ketamineResponder analysisBDNF geneS-ketamineKetamine levelsPatientsMet alleleRating Scale
2016
Altered Global Signal Topography in Schizophrenia
Yang GJ, Murray JD, Glasser M, Pearlson GD, Krystal JH, Schleifer C, Repovs G, Anticevic A. Altered Global Signal Topography in Schizophrenia. Cerebral Cortex 2016, 27: 5156-5169. PMID: 27702810, PMCID: PMC6075538, DOI: 10.1093/cercor/bhw297.Peer-Reviewed Original ResearchConceptsSCZ patientsGS topographyHealthy subjectsResting-state functional magnetic resonance imagingBlood oxygen level-dependent (BOLD) signalDevelopment of pharmacotherapiesGlobal signal topographyHealthy comparison subjectsFunctional magnetic resonance imagingLevel-dependent signalMagnetic resonance imagingAnti-correlated relationshipExtensive abnormalitiesComparison subjectsAssociation cortexNeural information flowResonance imagingNeuropsychiatric diseasesSensory areasPatientsSchizophreniaSensory regionsProfound alterationsSignal topographyAlterationsCross-trial prediction of treatment outcome in depression: a machine learning approach
Chekroud AM, Zotti RJ, Shehzad Z, Gueorguieva R, Johnson MK, Trivedi MH, Cannon TD, Krystal JH, Corlett PR. Cross-trial prediction of treatment outcome in depression: a machine learning approach. The Lancet Psychiatry 2016, 3: 243-250. PMID: 26803397, DOI: 10.1016/s2215-0366(15)00471-x.Peer-Reviewed Original ResearchConceptsTreatment outcomesTreatment groupsEscitalopram treatment groupSpecific antidepressantsPatient-reported dataSequenced Treatment AlternativesClinical trial dataIndependent clinical trialsClinical remissionSymptomatic remissionClinical trialsTreatment efficacyPatientsProspective identificationTreatment alternativesTrial dataDepressionRemissionAntidepressantsOutcomesGroupLevel 1CitalopramCohortClinicians
2015
Functional hierarchy underlies preferential connectivity disturbances in schizophrenia
Yang GJ, Murray JD, Wang XJ, Glahn DC, Pearlson GD, Repovs G, Krystal JH, Anticevic A. Functional hierarchy underlies preferential connectivity disturbances in schizophrenia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 113: e219-e228. PMID: 26699491, PMCID: PMC4720350, DOI: 10.1073/pnas.1508436113.Peer-Reviewed Original ResearchConceptsFunctional connectivityResting-state functional MRIExcitation/inhibition ratioElevated functional connectivityLarge-scale functional connectivityFronto-parietal control networkI elevationConnectivity disturbancesHealthy subjectsPreferential vulnerabilityAssociation cortexSchizophrenia patientsBipolar disorderFunctional MRIPatientsSymptom levelsSchizophreniaCortical microcircuitsInhibition ratioNeural modelControl networkNeuronal dynamicsHierarchical differencesParsimonious mechanismDysconnectivityEarly-Course Unmedicated Schizophrenia Patients Exhibit Elevated Prefrontal Connectivity Associated with Longitudinal Change
Anticevic A, Hu X, Xiao Y, Hu J, Li F, Bi F, Cole MW, Savic A, Yang GJ, Repovs G, Murray JD, Wang XJ, Huang X, Lui S, Krystal JH, Gong Q. Early-Course Unmedicated Schizophrenia Patients Exhibit Elevated Prefrontal Connectivity Associated with Longitudinal Change. Journal Of Neuroscience 2015, 35: 267-286. PMID: 25568120, PMCID: PMC4287147, DOI: 10.1523/jneurosci.2310-14.2015.Peer-Reviewed Original ResearchConceptsEarly course schizophreniaFunctional connectivityPrefrontal cortexImmediate symptom improvementSevere mental illnessEarly course patientsHealthy human subjectsHuman subjectsWhole-brain levelFunctional connectivity patternsResting-state fMRIIllness onsetSymptom improvementChronic illnessFunctional impairmentTherapeutic implicationsPFC connectivityOverall connection strengthMental illnessLongitudinal progressionLongitudinal changesSchizophrenia studiesSchizophreniaDiagnostic classificationPatients
2014
Altered global brain signal in schizophrenia
Yang GJ, Murray JD, Repovs G, Cole MW, Savic A, Glasser MF, Pittenger C, Krystal JH, Wang XJ, Pearlson GD, Glahn DC, Anticevic A. Altered global brain signal in schizophrenia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 7438-7443. PMID: 24799682, PMCID: PMC4034208, DOI: 10.1073/pnas.1405289111.Peer-Reviewed Original ResearchConceptsGlobal brain signalBrain dysfunctionHealthy subjectsBipolar patientsCortical powerBipolar disorderNeuropsychiatric conditionsFunctional MRIPatient samplesBrain connectivitySchizophreniaComplex neurobiologyDiagnostic specificityPatientsBrain signalsAlterationsDysfunctionSymptomsFindingsBaselineBrainMRIVentral Anterior Cingulate Connectivity Distinguished Nonpsychotic Bipolar Illness From Psychotic Bipolar Disorder and Schizophrenia
Anticevic A, Savic A, Repovs G, Yang G, McKay DR, Sprooten E, Knowles EE, Krystal JH, Pearlson GD, Glahn DC. Ventral Anterior Cingulate Connectivity Distinguished Nonpsychotic Bipolar Illness From Psychotic Bipolar Disorder and Schizophrenia. Schizophrenia Bulletin 2014, 41: 133-143. PMID: 24782562, PMCID: PMC4266289, DOI: 10.1093/schbul/sbu051.Peer-Reviewed Original ResearchConceptsVentral anterior cingulate cortexBipolar illnessPsychosis historyWhole-brain connectivityBipolar patientsConnectivity alterationsBrain connectivityCo-occurring psychosisChronic schizophrenia patientsHealthy comparison subjectsBipolar disorder patientsPsychotic bipolar disorder patientsBipolar disorder groupAnterior cingulate cortexFunctional connectivity studiesPsychotic bipolar disorderLifetime psychosisChronic schizophreniaPsychotic symptomsDisorder patientsPatientsComparison subjectsSchizophrenia patientsBipolar disorderCingulate cortexSymptom structure and severity: A comparison of responses to the positive and negative syndrome scale (PANSS) between patients with PTSD or schizophrenia
Stefanovics EA, Krystal JH, Rosenheck RA. Symptom structure and severity: A comparison of responses to the positive and negative syndrome scale (PANSS) between patients with PTSD or schizophrenia. Comprehensive Psychiatry 2014, 55: 887-895. PMID: 24602497, DOI: 10.1016/j.comppsych.2014.01.014.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntipsychotic AgentsChronic DiseaseCombat DisordersDiagnosis, DifferentialDouble-Blind MethodFemaleHumansMaleMiddle AgedPsychiatric Status Rating ScalesPsychometricsRisperidoneSchizophreniaSchizophrenic PsychologyStress Disorders, Post-TraumaticVeteransYoung AdultConceptsPost-traumatic stress disorderNegative Syndrome ScaleSyndrome ScalePTSD samplePlacebo-controlled trialPsychosis-related factorsClinical trial patientsClinical Antipsychotic TrialsT-testSchizophrenia sampleExploratory factor analysisSymptoms of schizophreniaMilitary-related post-traumatic stress disorderSymptom structureAdjunctive risperidoneTrial patientsTraumatic Stress DisorderAntipsychotic TrialsSecondary data analysisSevere symptomsIndependent factorsDepressive factorsPatientsSymptom ratingsStress disorder