2022
Sublingual Dexmedetomidine for the Treatment of Acute Agitation in Adults With Schizophrenia or Schizoaffective Disorder: A Randomized Placebo-Controlled Trial.
Citrome L, Preskorn SH, Lauriello J, Krystal JH, Kakar R, Finman J, De Vivo M, Yocca FD, Risinger R, Rajachandran L. Sublingual Dexmedetomidine for the Treatment of Acute Agitation in Adults With Schizophrenia or Schizoaffective Disorder: A Randomized Placebo-Controlled Trial. The Journal Of Clinical Psychiatry 2022, 83 PMID: 36198061, DOI: 10.4088/jcp.22m14447.Peer-Reviewed Original ResearchConceptsAcute agitationHours postdoseSchizoaffective disorderTotal scorePrimary efficacy endpointPlacebo-controlled studyAdrenergic receptor agonistFifth Edition criteriaNegative Syndrome ScaleDexmedetomidine groupOral hypoesthesiaStudy medicationDry mouthEfficacy endpointOrthostatic hypotensionRandomized PlaceboAdverse eventsReceptor agonistEdition criteriaDexmedetomidineMean changePEC scoresPlaceboSyndrome ScaleUS sites
2020
Predictive Processing in Mental Illness: Hierarchical Circuitry for Perception and Trauma
Kaye AP, Krystal JH. Predictive Processing in Mental Illness: Hierarchical Circuitry for Perception and Trauma. Journal Of Psychopathology And Clinical Science 2020, 129: 629-632. PMID: 32757606, DOI: 10.1037/abn0000628.Peer-Reviewed Original ResearchConceptsTrauma-related disordersPredictive processingDisorders of perceptionNeural circuitsHigher-order predictionsAbnormal psychologyPrediction errorSensory stimuliPredictive codingHierarchical circuitryPrior beliefsNew sensory dataPerceptionBayesian processPsychiatric disordersPsychotic disordersHierarchical viewHierarchical organizationMental illnessSensory dataBeliefsDisordersFuture directionsComputational layerProcessing
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
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 ResearchConceptsSZ 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 usersUtility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders: A Randomized Clinical Trial
Javitt DC, Carter CS, Krystal JH, Kantrowitz JT, Girgis RR, Kegeles LS, Ragland JD, Maddock RJ, Lesh TA, Tanase C, Corlett PR, Rothman DL, Mason G, Qiu M, Robinson J, Potter WZ, Carlson M, Wall MM, Choo TH, Grinband J, Lieberman JA. Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders: A Randomized Clinical Trial. JAMA Psychiatry 2018, 75: 11-19. PMID: 29167877, PMCID: PMC5833531, DOI: 10.1001/jamapsychiatry.2017.3572.Peer-Reviewed Original ResearchConceptsTarget engagement biomarkerKetamine infusionClinical trialsClinical studiesEarly-stage clinical studiesEarly phase clinical studiesTarget engagementFunctional target engagementRecent pivotal trialsFMRI responsesBlood oxygen level-dependent (BOLD) responseUtility of imagingProton magnetic resonance spectroscopySufficient effect sizeLevel-dependent responsesPlacebo infusionPivotal trialsPreclinical evidenceEngagement biomarkersKetamine effectsMean ageBrain glutamateHealthy volunteersMAIN OUTCOMEPsychiatric history
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 Research
2015
Role of GABA Deficit in Sensitivity to the Psychotomimetic Effects of Amphetamine
Ahn KH, Sewell A, Elander J, Pittman B, Ranganathan M, Gunduz-Bruce H, Krystal J, D'Souza DC. Role of GABA Deficit in Sensitivity to the Psychotomimetic Effects of Amphetamine. Neuropsychopharmacology 2015, 40: 2822-2831. PMID: 25953357, PMCID: PMC4864658, DOI: 10.1038/npp.2015.132.Peer-Reviewed Original ResearchConceptsGABA deficitHealthy subjectsPsychotomimetic effectsIntravenous infusionSchizophrenia patientsPANSS positive symptoms subscaleDouble-blind crossover designStriatal dopamine releasePositive symptom subscaleAdministration of drugsDose of AMPHPartial inverse agonistSubclinical responsePharmacokinetic interactionsSubthreshold doseDopamine releaseBenzodiazepine receptorsSymptom subscalesCrossover designCADSS scoresPositive symptomsAMPHInverse agonistSubjective effectsTest day
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 analysisVentral 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 cortexDifferences 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
Glycine treatment of the risk syndrome for psychosis: Report of two pilot studies
Woods SW, Walsh BC, Hawkins KA, Miller TJ, Saksa JR, D'Souza DC, Pearlson GD, Javitt DC, McGlashan TH, Krystal JH. Glycine treatment of the risk syndrome for psychosis: Report of two pilot studies. European Neuropsychopharmacology 2012, 23: 931-940. PMID: 23089076, PMCID: PMC4028140, DOI: 10.1016/j.euroneuro.2012.09.008.Peer-Reviewed Original ResearchConceptsPilot studyRisk syndromeSyndrome patientsNegative symptomsShort-term pilot studyEffect sizeAdjunctive antipsychotic medicationOpen-label studyPatients meeting criteriaNMDA receptor functionDurability of effectPsychosis risk symptomsGlycine site agonistsGroup effect sizesWeeks of evaluationAntipsychotic medicationSyndrome subjectsPromising effect sizesTreatment needsLarge effect sizesMeeting criteriaCognitive impairmentReduced symptomsReceptor functionSymptomsGlobal Prefrontal and Fronto-Amygdala Dysconnectivity in Bipolar I Disorder with Psychosis History
Anticevic A, Brumbaugh MS, Winkler AM, Lombardo LE, Barrett J, Corlett PR, Kober H, Gruber J, Repovs G, Cole MW, Krystal JH, Pearlson GD, Glahn DC. Global Prefrontal and Fronto-Amygdala Dysconnectivity in Bipolar I Disorder with Psychosis History. Biological Psychiatry 2012, 73: 565-573. PMID: 22980587, PMCID: PMC3549314, DOI: 10.1016/j.biopsych.2012.07.031.Peer-Reviewed Original ResearchConceptsPsychosis historyRisk factorsBipolar patientsSymptom severityResting-state functional magnetic resonanceAmygdala-mPFC connectivityFronto-limbic dysfunctionSevere clinical courseBipolar I patientsEmotion regulation regionsPsychotic symptom severityFunctional magnetic resonanceClinical courseI patientsLimbic structuresBipolar illnessConnectivity deficitsAmygdala findingsConnectivity abnormalitiesPathophysiological modelBipolar IPatientsBipolar disorderDysconnectivityAbnormal inhibitionCost and cost-effectiveness in a randomized trial of long-acting risperidone for schizophrenia.
Barnett PG, Scott JY, Krystal JH, Rosenheck RA. Cost and cost-effectiveness in a randomized trial of long-acting risperidone for schizophrenia. The Journal Of Clinical Psychiatry 2012, 73: 696-702. PMID: 22697193, DOI: 10.4088/jcp.11m07070.Peer-Reviewed Original ResearchMeSH KeywordsAntipsychotic AgentsComparative Effectiveness ResearchCost-Benefit AnalysisDelayed-Action PreparationsDouble-Blind MethodDrug CostsFemaleHealth Care CostsHospitalizationHumansInjectionsKaplan-Meier EstimateMaleMiddle AgedModels, EconometricPsychotic DisordersRisperidoneSchizophreniaUnited StatesVeteransConceptsTotal health care costsHealth care costsLAI risperidoneMedication costsControl groupCare costsVeterans Health Administration patientsHealth care utilizationHealth Related QualityStructured Clinical InterviewUS Medicaid programCase report formsMultisite clinical trialQuality of WellExperimental groupOral antipsychoticsAdverse eventsCare utilizationInjectable risperidoneOutpatient costsHospitalization costsClinical trialsRelated qualityLAI groupPhysician's choice
2010
Glutamatergic Model Psychoses: Prediction Error, Learning, and Inference
Corlett PR, Honey GD, Krystal JH, Fletcher PC. Glutamatergic Model Psychoses: Prediction Error, Learning, and Inference. Neuropsychopharmacology 2010, 36: 294-315. PMID: 20861831, PMCID: PMC3055519, DOI: 10.1038/npp.2010.163.Peer-Reviewed Original ResearchClinical 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
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 factorsInterventionDelta-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 alterationsDeficitsCannabisSubjectsAkathisiaExacerbation
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 effects
1996
Preliminary evidence of an association between sensorimotor gating and distractibility in psychosis
Karper LP, Freeman GK, Grillon C, Morgan CA, Charney DS, Krystal JH. Preliminary evidence of an association between sensorimotor gating and distractibility in psychosis. Journal Of Neuropsychiatry 1996, 8: 60-66. PMID: 8845703, DOI: 10.1176/jnp.8.1.60.Peer-Reviewed Original ResearchConceptsSensory gatingChronic psychotic patientsAcoustic startle reflexLateralized attentionImpaired sensory gatingPosner testSensorimotor gatingPsychotic patientsContinuous Performance TestStartle reflexInformation-processing deficitsDistractibility tasksPreliminary evidenceDistractibilityTask scores