2020
A Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia
Koblan KS, Kent J, Hopkins SC, Krystal JH, Cheng H, Goldman R, Loebel A. A Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia. New England Journal Of Medicine 2020, 382: 1497-1506. PMID: 32294346, DOI: 10.1056/nejmoa1911772.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdministration, OralAdultAntipsychotic AgentsDouble-Blind MethodDrug Administration ScheduleFemaleHumansLeast-Squares AnalysisMaleReceptors, Dopamine D2Receptors, G-Protein-CoupledSchizophreniaSchizophrenic PsychologySerotonin 5-HT1 Receptor AgonistsSeverity of Illness IndexTreatment OutcomeConceptsTrace amine-associated receptor 1Week 4Negative Symptom ScaleAcute exacerbationPlacebo groupBrief Negative Symptom ScaleTotal scoreSymptom ScaleClinical Global Impression-Severity ScaleEnd pointPrimary end pointSecondary end pointsSudden cardiac deathPANSS total scoreTreatment of schizophreniaDopamine D2 receptorsTreatment of psychosisType 1A receptorMean total scoreLevels of lipidsGastrointestinal symptomsAdverse eventsCardiac deathExtrapyramidal symptomsPrimary outcome
2018
Similar psychotic and cognitive profile between ketamine dependence with persistent psychosis and schizophrenia
Cheng WJ, Chen CH, Chen CK, Huang MC, Pietrzak RH, Krystal JH, Xu K. Similar psychotic and cognitive profile between ketamine dependence with persistent psychosis and schizophrenia. Schizophrenia Research 2018, 199: 313-318. PMID: 29510925, DOI: 10.1016/j.schres.2018.02.049.Peer-Reviewed Original ResearchMeSH KeywordsAdultCognitionCognitive DysfunctionExcitatory Amino Acid AntagonistsFemaleHumansKetamineMalePsychotic DisordersSchizophrenic PsychologySubstance-Related DisordersConceptsSZ patientsCognitive impairmentCognitive functionSocial-emotional cognitionCogstate Brief BatteryPsychomotor processing speedTreatment-seeking patientsSpatial problemsSymptom profilesSevere symptom profileVerbal memoryCognitive profileKetamine-dependent patientsVisual learningBrief batteryProcessing speedNegative Syndrome ScaleBiology of psychosisKetamine usersCognitive dysfunctionPersistent psychosisMemorySubscale scoresKetamine abuseMinority of users
2016
Schizophrenia is associated with a pattern of spatial working memory deficits consistent with cortical disinhibition
Starc M, Murray JD, Santamauro N, Savic A, Diehl C, Cho YT, Srihari V, Morgan PT, Krystal JH, Wang XJ, Repovs G, Anticevic A. Schizophrenia is associated with a pattern of spatial working memory deficits consistent with cortical disinhibition. Schizophrenia Research 2016, 181: 107-116. PMID: 27745755, PMCID: PMC5901719, DOI: 10.1016/j.schres.2016.10.011.Peer-Reviewed Original ResearchConceptsHealthy comparison subjectsSpatial WM taskSchizophrenia patientsSevere cognitive deficitsSpecific spatial locationsComputational modelContinuous response measuresWM precisionWM representationsSpatial WMWM taskDistractor distanceWM impairmentWM tracesNeural mechanismsCognitive deficitsMemory deficitsBehavioral consequencesDelay periodDelay durationCortical disinhibitionSpatial locationComparison subjectsMicrocircuit modelDistractibilityShall we really say goodbye to first rank symptoms?
Heinz A, Voss M, Lawrie SM, Mishara A, Bauer M, Gallinat J, Juckel G, Lang U, Rapp M, Falkai P, Strik W, Krystal J, Abi-Dargham A, Galderisi S. Shall we really say goodbye to first rank symptoms? European Psychiatry 2016, 37: 8-13. PMID: 27429167, DOI: 10.1016/j.eurpsy.2016.04.010.Peer-Reviewed Original ResearchRole of N-Methyl-D-Aspartate Receptors in Action-Based Predictive Coding Deficits in Schizophrenia
Kort NS, Ford JM, Roach BJ, Gunduz-Bruce H, Krystal JH, Jaeger J, Reinhart RM, Mathalon DH. Role of N-Methyl-D-Aspartate Receptors in Action-Based Predictive Coding Deficits in Schizophrenia. Biological Psychiatry 2016, 81: 514-524. PMID: 27647218, PMCID: PMC5203970, DOI: 10.1016/j.biopsych.2016.06.019.Peer-Reviewed Original ResearchConceptsEvent-related potentialsPredictive codingN1 suppressionN1 amplitudePredictive coding deficitsSelf-generated speechSchizophrenia patientsAuditory cortical responsesAuditory predictive codingSelf-produced vocalizationsNMDAR hypofunctionEffects of schizophreniaSpeech soundsTheorized contributionN1 componentHealthy volunteersPassive playbackCognitive deficitsN-methyl-D-aspartate receptorsPutative measureTalk/Cortical responsesHealthy control volunteersCase-control studySaline days
2015
Early-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 ResearchMeSH KeywordsAdolescentAdultEarly DiagnosisFemaleFollow-Up StudiesHumansLongitudinal StudiesMaleNerve NetPrefrontal CortexSchizophreniaSchizophrenic PsychologyYoung AdultConceptsEarly 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
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 analysisSymptom 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 disorderGoing up in smoke? A review of nAChRs-based treatment strategies for improving cognition in schizophrenia.
Boggs DL, Carlson J, Cortes-Briones J, Krystal JH, D'Souza DC. Going up in smoke? A review of nAChRs-based treatment strategies for improving cognition in schizophrenia. Current Pharmaceutical Design 2014, 20: 5077-92. PMID: 24345265, PMCID: PMC4442779, DOI: 10.2174/1381612819666131216121019.Peer-Reviewed Original ResearchMeSH KeywordsBrainCognition DisordersEvoked PotentialsHumansNicotineNicotinic AgonistsNootropic AgentsReceptors, NicotinicSchizophreniaSchizophrenic PsychologySelf MedicationSmokingConceptsCognitive impairmentStandardized cognitive test batteryCognitive test batteryInformation processing impairmentsNicotinic medicationsProcessing impairmentsCore deficitAttentional deficitsTest batteryCognitive deficitsProximal measuresBrain functionCognitionSchizophreniaDeficitsImpairmentNumber of medicationsNicotinic acetylcholine receptorsCertain symptomsConsistent improvementClinical evidenceTreatment strategiesClinical studiesNicotinic receptorsClinical utilityDifferences in Treatment Effect Among Clinical Subgroups in a Randomized Clinical Trial of Long-Acting Injectable Risperidone and Oral Antipsychotics in Unstable Chronic Schizophrenia
Leatherman SM, Liang MH, Krystal JH, Lew RA, Valley D, Thwin SS, Rosenheck RA. Differences in Treatment Effect Among Clinical Subgroups in a Randomized Clinical Trial of Long-Acting Injectable Risperidone and Oral Antipsychotics in Unstable Chronic Schizophrenia. The Journal Of Nervous And Mental Disease 2014, 202: 13-17. PMID: 24375206, DOI: 10.1097/nmd.0000000000000069.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAntipsychotic AgentsChronic DiseaseDrug Administration ScheduleFemaleHospitalizationHumansInjections, IntramuscularMaleMiddle AgedProportional Hazards ModelsPsychotic DisordersQuality of LifeRisk AssessmentRisperidoneSchizophreniaSchizophrenic PsychologySeverity of Illness IndexSubstance-Related DisordersTreatment OutcomeConceptsQuality of lifeOral antipsychoticsOral treatmentInjectable risperidoneCox regressionTreatment effectsLong-Acting Injectable RisperidoneBody mass indexPsychiatric service useSubstance abuse outcomesSubstance use outcomesLAI risperidonePrimary endpointStudy entryWhite patientsClinical outcomesMass indexUnstable patientsMedication compliancePsychiatric rehospitalizationChronic schizophreniaClinical trialsClinical subgroupsPsychiatric hospitalizationPsychiatric symptoms
2012
A broken filter: Prefrontal functional connectivity abnormalities in schizophrenia during working memory interference
Anticevic A, Repovs G, Krystal JH, Barch DM. A broken filter: Prefrontal functional connectivity abnormalities in schizophrenia during working memory interference. Schizophrenia Research 2012, 141: 8-14. PMID: 22863548, PMCID: PMC3879404, DOI: 10.1016/j.schres.2012.07.007.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnalysis of VarianceBrain MappingFemaleFunctional LateralityHumansImage Processing, Computer-AssistedMagnetic Resonance ImagingMaleMemory DisordersMemory, Short-TermMiddle AgedNerve NetNeural PathwaysNeuropsychological TestsOxygenPrefrontal CortexSchizophreniaSchizophrenic PsychologyConceptsFunctional connectivity abnormalitiesConnectivity abnormalitiesMedio-dorsal thalamusTask-based functional connectivityFinal common pathwayMaintenance phasePrefrontal cortical regionsDorsolateral prefrontal cortex activationPrefrontal cortex activationFunctional deficitsHealthy controlsSub-cortical regionsExtended amygdalaPatientsCortex activationCognitive deficitsCortical regionsFunctional connectivityLife outcomesAbnormalitiesDLPFC networkCommon pathwaySchizophrenia researchSchizophreniaMemory abnormalities
2010
Clinical significance of neurological soft signs in schizophrenia: Factor analysis of the Neurological Evaluation Scale
Sewell RA, Perry EB, Karper LP, Bell MD, Lysaker P, Goulet JL, Brenner L, Erdos J, d'Souza DC, Seibyl JP, Krystal JH. Clinical significance of neurological soft signs in schizophrenia: Factor analysis of the Neurological Evaluation Scale. Schizophrenia Research 2010, 124: 1-12. PMID: 20855185, DOI: 10.1016/j.schres.2010.08.036.Peer-Reviewed Original ResearchConceptsNeurological Evaluation ScaleAbnormal Involuntary Movement ScaleDigit Symbol Substitution TaskWisconsin Card Sorting TestNeurologic deficitsClinical significanceExtrapyramidal Symptom Rating ScaleMore extrapyramidal symptomsBarnes Akathisia ScaleDetailed clinical assessmentNeurological soft signsSymptom Rating ScaleNegative Syndrome ScaleHigher AIMS scoresEvaluation ScaleNeurological deficitsExtrapyramidal symptomsClinical correlatesDeficit syndrome schizophreniaClinical evaluationClinical assessmentAIMS scoresLower PANSSMovement ScaleSoft signs
2008
Identifying Cognitive Mechanisms Targeted for Treatment Development in Schizophrenia: An Overview of the First Meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia Initiative
Carter CS, Barch DM, Buchanan RW, Bullmore E, Krystal JH, Cohen J, Geyer M, Green M, Nuechterlein KH, Robbins T, Silverstein S, Smith EE, Strauss M, Wykes T, Heinssen R. Identifying Cognitive Mechanisms Targeted for Treatment Development in Schizophrenia: An Overview of the First Meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia Initiative. Biological Psychiatry 2008, 64: 4-10. PMID: 18466880, PMCID: PMC2577821, DOI: 10.1016/j.biopsych.2008.03.020.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntipsychotic AgentsBiomedical ResearchBrainCognition DisordersCooperative BehaviorDrug IndustryHumansNational Institute of Mental Health (U.S.)Neuropsychological TestsResearch Support as TopicSchizophreniaSchizophrenic PsychologyUnited StatesUnited States Food and Drug AdministrationConceptsCognitive Neuroscience Treatment ResearchSchizophrenia (MATRICS) initiativeTreatment researchCognitive neuroscience fieldCNTRICS initiativeCognitive mechanismsCognitive constructsTreatment developmentNeuroscience fieldCognitive impairmentCognitionBasic animalSchizophreniaResearchFirst meetingImpairmentConstructsParadigmTranslational researchTranslation effortsNovel treatmentsOrganization
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 responsesThe vulnerability to alcohol and substance abuse in individuals diagnosed with schizophrenia
Krystal JH, D’Souza D, Gallinat J, Driesen N, Abi-Dargham A, Petrakis I, Heinz A, Pearlson G. The vulnerability to alcohol and substance abuse in individuals diagnosed with schizophrenia. Neurotoxicity Research 2006, 10: 235-252. PMID: 17197373, DOI: 10.1007/bf03033360.Peer-Reviewed Original ResearchMeSH KeywordsAlcoholismComorbidityDiagnosis, Dual (Psychiatry)HumansMotivationRiskSchizophreniaSchizophrenic PsychologySubstance-Related DisordersConceptsSubstance abuse riskSubstance abuseSubstance abuse disordersAbuse riskSubstances of abuseNicotinic cholinergicPatient groupDopaminergic inputAbused substancesAbuse disordersSchizophrenic patientsDysphoric effectsAbuse liabilityHigh dosesLow dosesNegative symptomsReceptor functionAltered responseSchizophreniaSchizophrenic individualsRiskReward processingSubjective distressImpulsive behaviorDoses
2005
Temporoparietal Transcranial Magnetic Stimulation for Auditory Hallucinations: Safety, Efficacy and Moderators in a Fifty Patient Sample
Hoffman RE, Gueorguieva R, Hawkins KA, Varanko M, Boutros NN, Wu YT, Carroll K, Krystal JH. Temporoparietal Transcranial Magnetic Stimulation for Auditory Hallucinations: Safety, Efficacy and Moderators in a Fifty Patient Sample. Biological Psychiatry 2005, 58: 97-104. PMID: 15936729, DOI: 10.1016/j.biopsych.2005.03.041.Peer-Reviewed Original ResearchConceptsRepetitive transcranial magnetic stimulationTranscranial magnetic stimulationAuditory hallucinationsSham stimulationMagnetic stimulationTemporoparietal repetitive transcranial magnetic stimulationClinical Global Impression ScaleGlobal Impression ScaleRight-handed patientsMotor thresholdImpression ScaleRTMS effectsNew patientsNeurocognitive impairmentHallucination frequencySchizoaffective disorderPatient samplesSignificant distressPatientsChange scoresHallucinationsPreliminary reportStimulationNeurobiological factorsIntervention
2003
Transcranial Magnetic Stimulation of Left Temporoparietal Cortex and Medication-Resistant Auditory Hallucinations
Hoffman RE, Hawkins KA, Gueorguieva R, Boutros NN, Rachid F, Carroll K, Krystal JH. Transcranial Magnetic Stimulation of Left Temporoparietal Cortex and Medication-Resistant Auditory Hallucinations. JAMA Psychiatry 2003, 60: 49-56. PMID: 12511172, DOI: 10.1001/archpsyc.60.1.49.Peer-Reviewed Original ResearchConceptsRepetitive transcranial magnetic stimulationMedication-resistant auditory hallucinationsTranscranial magnetic stimulationLeft temporoparietal cortexAuditory hallucinationsSham stimulationMagnetic stimulationTemporoparietal cortexOpen-label trialMotor thresholdAntipsychotic medicationSustained reductionBrain areasSchizoaffective disorderCortical activationPossible treatmentNeuropsychological impairmentNeuropsychological assessmentPatientsAdditional studiesCortexStimulationTrialsHallucinationsTreatment effectsTreatment Models and Designs for Intervention Research During the Psychotic Prodrome
Kane JM, Krystal J, Correll CU. Treatment Models and Designs for Intervention Research During the Psychotic Prodrome. Schizophrenia Bulletin 2003, 29: 747-756. PMID: 14989412, DOI: 10.1093/oxfordjournals.schbul.a007044.Peer-Reviewed Original ResearchConceptsPsychotic prodromePsychotic disordersEarly interventionSubsequent symptom severityTreatment modelOngoing intervention trialsSpecific symptom clustersTreatment refractorinessFunctional disabilityPatient selectionIntervention trialsFunctional outcomeProdromal symptomsDisease progressionNatural courseTarget symptomsSubsyndromal symptomsDifferent treatment modelsOutcome measuresProdromal populationTreatment responseProdromal stateTrial designSymptom clustersSymptom severity
2001
A neurobiological basis for substance abuse comorbidity in schizophrenia
Chambers R, Krystal J, Self D. A neurobiological basis for substance abuse comorbidity in schizophrenia. Biological Psychiatry 2001, 50: 71-83. PMID: 11526998, PMCID: PMC2913410, DOI: 10.1016/s0006-3223(01)01134-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDisease SusceptibilityDopamineFrontal LobeHippocampusHumansNeurobiologyNucleus AccumbensSchizophreniaSchizophrenic PsychologySubstance-Related DisordersConceptsDrug rewardLong-term substance abuseMedication side effectsPrior drug exposureSubstance abuse comorbidityNeuropathology of schizophreniaPrimary disease symptomsAddictive behaviorsDrug-seeking behaviorHippocampal dysfunctionDrug exposureFrontal cortexNucleus accumbensHippocampal formationSchizophrenic patientsSide effectsCognitive impairmentNegative symptomsSubstance abuseAltered integrationNeural circuitrySymptomsSchizophreniaMotivational changesComorbidities
2000
Attenuation of the Neuropsychiatric Effects of Ketamine With Lamotrigine: Support for Hyperglutamatergic Effects of N-methyl-D-aspartate Receptor Antagonists
Anand A, Charney DS, Oren DA, Berman RM, Hu XS, Cappiello A, Krystal JH. Attenuation of the Neuropsychiatric Effects of Ketamine With Lamotrigine: Support for Hyperglutamatergic Effects of N-methyl-D-aspartate Receptor Antagonists. JAMA Psychiatry 2000, 57: 270-276. PMID: 10711913, DOI: 10.1001/archpsyc.57.3.270.Peer-Reviewed Original ResearchMeSH KeywordsAdultAffectBrief Psychiatric Rating ScaleCognition DisordersDouble-Blind MethodExcitatory Amino Acid AntagonistsFemaleGlutamatesHumansKetamineLamotrigineMaleMental DisordersPerceptual DisordersPlacebosPsychiatric Status Rating ScalesReceptors, N-Methyl-D-AspartateSchizophreniaSchizophrenic PsychologyTriazinesVerbal LearningConceptsN-methyl-D-aspartate receptor antagonistNMDA receptor dysfunctionReceptor antagonistNeuropsychiatric effectsGlutamate releaseReceptor dysfunctionSymptom subscalesPlacebo 2 hoursClinician-Administered Dissociative States ScaleAdministration of lamotrigineAdministration of ketamineDouble-blind conditionsNMDA receptor antagonistMood-elevating effectsPositive symptom subscaleBrief Psychiatric RatingNovel therapeutic agentsNegative symptom subscaleHopkins Verbal Learning TestVerbal Learning TestKetamine effectsPsychiatric illnessHealthy subjectsPathophysiologic processesPreclinical studies