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
2020
Proof of mechanism and target engagement of glutamatergic drugs for the treatment of schizophrenia: RCTs of pomaglumetad and TS-134 on ketamine-induced psychotic symptoms and pharmacoBOLD in healthy volunteers
Kantrowitz JT, Grinband J, Goff DC, Lahti AC, Marder SR, Kegeles LS, Girgis RR, Sobeih T, Wall MM, Choo TH, Green MF, Yang YS, Lee J, Horga G, Krystal JH, Potter WZ, Javitt DC, Lieberman JA. Proof of mechanism and target engagement of glutamatergic drugs for the treatment of schizophrenia: RCTs of pomaglumetad and TS-134 on ketamine-induced psychotic symptoms and pharmacoBOLD in healthy volunteers. Neuropsychopharmacology 2020, 45: 1842-1850. PMID: 32403118, PMCID: PMC7608251, DOI: 10.1038/s41386-020-0706-z.Peer-Reviewed Original ResearchConceptsDorsal anterior cingulate cortexBrief Psychiatric Rating ScaleTS-134Target engagementHealthy volunteersMetabotropic glutamate receptor 2/3 agonistKetamine-induced psychotic symptomsBPRS positive symptomsDouble-blind conditionsProof of mechanismKetamine-induced changesAntipsychotic drug developmentTreatment of schizophreniaPsychiatric Rating ScaleAnterior cingulate cortexPrimary outcomeClinical symptomsGlutamatergic drugsGlutamate neurotransmissionTotal symptomsClinical assessmentLow dosePsychotic symptomsHigh dosePlacebo dataDopamine and glutamate in schizophrenia: biology, symptoms and treatment
McCutcheon RA, Krystal JH, Howes OD. Dopamine and glutamate in schizophrenia: biology, symptoms and treatment. World Psychiatry 2020, 19: 15-33. PMID: 31922684, PMCID: PMC6953551, DOI: 10.1002/wps.20693.Peer-Reviewed Original ResearchDopamine systemAberrant dopamine signallingStriatal dopamine synthesisNovel pharmacological therapiesPathophysiology of schizophreniaEnvironmental risk factorsPharmacological therapyGlutamatergic dysfunctionDopaminergic functionRisk factorsGlutamate systemDopamine synthesisGenetic risk variantsPreclinical studiesPsychotic symptomsDopamine functionNew treatmentsNeural circuitsDopamine signalingNeuronal signalingSchizophreniaConsistent findingRisk variantsSymptomsGlutamate
2014
Ventral 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 cortex
2008
Relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy—a [123I]CNS-1261 SPET study
Stone JM, Erlandsson K, Arstad E, Squassante L, Teneggi V, Bressan RA, Krystal JH, Ell PJ, Pilowsky LS. Relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy—a [123I]CNS-1261 SPET study. Psychopharmacology 2008, 197: 401-408. PMID: 18176855, DOI: 10.1007/s00213-007-1047-x.Peer-Reviewed Original ResearchMeSH KeywordsAdultBrief Psychiatric Rating ScaleDose-Response Relationship, DrugGuanidinesHumansInfusions, IntravenousIodine RadioisotopesKetamineMalePrefrontal CortexPsychoses, Substance-InducedReceptors, N-Methyl-D-AspartateSchizophreniaSingle-Blind MethodTomography, Emission-Computed, Single-PhotonConceptsBrief Psychiatric Rating ScaleVolume of distributionNMDA receptorsPsychotic symptomsN-methyl-D-aspartate receptorsKetamine-induced psychotic symptomsSingle photon emission tomographyNMDA receptor bindingEffects of ketamineNegative subscaleHealthy human controlsPsychiatric Rating ScaleNegative psychotic symptomsInferior frontal cortexKetamine administrationBolus infusionHealthy controls
2007
Lamotrigine as Add-On Therapy in Schizophrenia
Goff DC, Keefe R, Citrome L, Davy K, Krystal JH, Large C, Thompson TR, Volavka J, Webster EL. Lamotrigine as Add-On Therapy in Schizophrenia. Journal Of Clinical Psychopharmacology 2007, 27: 582-589. PMID: 18004124, DOI: 10.1097/jcp.0b013e31815abf34.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnticonvulsantsAntipsychotic AgentsClozapineDiagnostic and Statistical Manual of Mental DisordersDose-Response Relationship, DrugDouble-Blind MethodDrug Administration ScheduleDrug ResistanceDrug Therapy, CombinationFemaleHumansLamotrigineMaleMiddle AgedPatient CompliancePatient DropoutsPsychiatric Status Rating ScalesSchizophreniaSeverity of Illness IndexSuicide, AttemptedTreatment OutcomeTriazinesConceptsNegative Syndrome Scale total scoreScale total scoreAntipsychotic medicationTotal scoreTreatment groupsSchizophrenia patientsPlacebo-controlled trialPrimary end pointParallel-group trialUse of lamotrigineClinical Global ImpressionAtypical antipsychotic medicationsResidual psychotic symptomsSymptom total scoreNegative Symptoms total scoreLamotrigine augmentationLamotrigine trialsRefractory psychosisAtypical antipsychoticsCognitive composite scoreWeek 12Global ImpressionTreat samplePsychotic symptomsLamotrigine
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 responses
2004
Cannabinoid ‘model’ psychosis, dopamine–cannabinoid interactions and implications for schizophrenia
D'souza D, Cho H, Perry E, Krystal J. Cannabinoid ‘model’ psychosis, dopamine–cannabinoid interactions and implications for schizophrenia. 2004, 142-165. DOI: 10.1017/cbo9780511543630.012.Peer-Reviewed Original ResearchReceptor dysfunctionCannabinoid compoundsCannabis consumptionPathophysiology of psychosisPathophysiology of schizophreniaRecent pharmacological studiesPrincipal psychoactive constituentEffects of exposurePostmortem studiesNormal controlsPsychotic symptomsPsychotic disordersPharmacological studiesPsychosisPsychoactive constituentPathophysiologyΔ9-tetrahydrocannabinolSchizophreniaCannabisDysfunctionAssociationPossible mechanismPatientsSymptomsPharmacological
2000
Similarities in the Disturbances in Cortical Information Processing in Alcoholism and Aging: A Pilot Evoked Potential Study
Boutros N, Reid M, Petrakis I, Campbell D, Torello M, Krystal J. Similarities in the Disturbances in Cortical Information Processing in Alcoholism and Aging: A Pilot Evoked Potential Study. International Psychogeriatrics 2000, 12: 513-525. PMID: 11263717, DOI: 10.1017/s1041610200006621.Peer-Reviewed Original ResearchConceptsInformation processingCortical information processingSensory gatingPaired-click paradigmOlder healthy subjectsAlcohol dependenceSensory gating deficitsStimulus classificationNovel stimuliOddball paradigmHealthy individualsYoung healthy groupEvoked potential studiesDSM-IV criteriaPotential studiesHealthy subjectsGender-matched groupAged healthy individualsGender-matched healthy individualsGating deficitsMiddle-aged individualsPsychotic symptomsOlder groupProcessingAlcoholic patients
1999
No Evidence of Altered In Vivo Benzodiazepine Receptor Binding in Schizophrenia
Abi-Dargham A, Laruelle M, Krystal J, D'Souza C, Zoghbi S, Baldwin R, Seibyl J, Mawlawi O, de Erasquin G, Charney D, Innis R. No Evidence of Altered In Vivo Benzodiazepine Receptor Binding in Schizophrenia. Neuropsychopharmacology 1999, 20: 650-661. PMID: 10327433, DOI: 10.1016/s0893-133x(98)00107-9.Peer-Reviewed Original ResearchConceptsReceptor densitySchizophrenic patientsVivo benzodiazepine receptor bindingBDZ receptor densityMale schizophrenic patientsBenzodiazepine receptor densityPathophysiology of schizophreniaBenzodiazepine receptor bindingSingle photon emissionRegional distribution volumesPrevious postmortemGABA transmissionBDZ antagonistBDZ receptorsReceptor expressionNeurotransmitter systemsHealthy volunteersPsychotic symptomsBrain regionsDistribution volumeReceptor bindingSchizophreniaVivo studiesPatientsPossible alterations
1996
Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects.
Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D'Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 9235-9240. PMID: 8799184, PMCID: PMC38625, DOI: 10.1073/pnas.93.17.9235.Peer-Reviewed Original ResearchConceptsAmphetamine-induced dopamine releaseDopamine releaseDopaminergic transmissionPsychotic symptomsSchizophrenic groupDopamine D2 receptor availabilityAmphetamine-induced decreaseAmphetamine-induced reductionD2 receptor availabilityD2 receptor radiotracerPositive psychotic symptomsSingle photon emissionExaggerated stimulationAbnormal responsivenessDopaminergic neuronsHealthy controlsReceptor radiotracerSchizophrenic patientsDopamine hypothesisDopamine functionReceptor availabilityAmphetamine effectsControl groupSchizophrenic subjectsSchizophrenia