2020
Impaired Potentiation of Theta Oscillations During a Visual Cortical Plasticity Paradigm in Individuals With Schizophrenia
Hamilton HK, Roach BJ, Cavus I, Teyler TJ, Clapp WC, Ford JM, Tarakci E, Krystal JH, Mathalon DH. Impaired Potentiation of Theta Oscillations During a Visual Cortical Plasticity Paradigm in Individuals With Schizophrenia. Frontiers In Psychiatry 2020, 11: 590567. PMID: 33391054, PMCID: PMC7772351, DOI: 10.3389/fpsyt.2020.590567.Peer-Reviewed Original ResearchLong-term potentiationN-methyl-D-aspartate receptorsHealthy controlsNeuroplastic changesPlasticity paradigmsHigh-frequency electrical stimulationExperience-dependent synaptic plasticityVisual cortical plasticityPathophysiology of schizophreniaHigh-frequency stimulationNMDA receptor dysfunctionFrequency electrical stimulationTheta oscillationsVisual stimuliImpaired potentiationGlutamatergic transmissionReceptor dysfunctionImpaired neuroplasticityEvent-related EEG oscillationsNMDAR hypofunctionCortical plasticityVEP amplitudeAnimal modelsElectrical stimulationWhite checkerboard stimuliDopamine 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
2018
2. 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
Impaired Tuning of Neural Ensembles and the Pathophysiology of Schizophrenia: A Translational and Computational Neuroscience Perspective
Krystal JH, Anticevic A, Yang GJ, Dragoi G, Driesen NR, Wang XJ, Murray JD. Impaired Tuning of Neural Ensembles and the Pathophysiology of Schizophrenia: A Translational and Computational Neuroscience Perspective. Biological Psychiatry 2017, 81: 874-885. PMID: 28434616, PMCID: PMC5407407, DOI: 10.1016/j.biopsych.2017.01.004.Peer-Reviewed Original ResearchConceptsNeural activityNeural ensemblesComputational neuroscience perspectiveHigher cognitive functionsNeuroscience perspectiveDevelopmental perspectiveDevelopmental correlatesCognitive functionNegative functional consequencesCortical networksComputational neuroscienceNeural codeCortical activityCognitive impairmentNeural dysfunctionAspartate glutamate receptor antagonistTemporal tuningSpatial tuningGlutamate receptor antagonistsPathophysiology of schizophreniaNeural network functionSchizophreniaPsychiatric disordersBalance of excitationInput-output curves
2015
Deconstructing N-Methyl-D-Aspartate Glutamate Receptor Contributions to Cortical Circuit Functions to Construct Better Hypotheses About the Pathophysiology of Schizophrenia
Krystal JH. Deconstructing N-Methyl-D-Aspartate Glutamate Receptor Contributions to Cortical Circuit Functions to Construct Better Hypotheses About the Pathophysiology of Schizophrenia. Biological Psychiatry 2015, 77: 508-510. PMID: 25687430, DOI: 10.1016/j.biopsych.2014.10.010.Peer-Reviewed Original ResearchConceptsCortical circuit functionPathophysiology of schizophreniaReceptor contributionCircuit functionPathophysiologySchizophrenia
2012
Capturing the Angel in “Angel Dust”: Twenty Years of Translational Neuroscience Studies of NMDA Receptor Antagonists in Animals and Humans
Moghaddam B, Krystal JH. Capturing the Angel in “Angel Dust”: Twenty Years of Translational Neuroscience Studies of NMDA Receptor Antagonists in Animals and Humans. Schizophrenia Bulletin 2012, 38: 942-949. PMID: 22899397, PMCID: PMC3446228, DOI: 10.1093/schbul/sbs075.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAnimalsAntipsychotic AgentsBrief Psychiatric Rating ScaleCerebral CortexDisease Models, AnimalDopamineEmotionsGlutamic AcidHumansKetamineNeurosciencesPhencyclidinePsychoses, Substance-InducedReceptor, Metabotropic Glutamate 5Receptors, Dopamine D2Receptors, Metabotropic GlutamateReceptors, N-Methyl-D-AspartateSchizophreniaSynapsesTranslational Research, BiomedicalConceptsNMDA receptor antagonistReceptor antagonistDopamine hypothesisN-methyl-D-aspartate receptor antagonistGlutamate synaptic functionTranslational neuroscience studiesTreatment of schizophreniaPathophysiology of schizophreniaPotential treatment targetPotential new targetsDopamine antagonistsCortical functionAnimal studiesTreatment targetsClinical testingSynaptic functionAntagonistTranslational toolSchizophreniaTranslational research fundingTranslational researchPotential mechanismsNew targetsAngel dustSystems neuroscience
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
2001
CURRENT PERSPECTIVES ON THE PATHOPHYSIOLOGY OF SCHIZOPHRENIA, DEPRESSION, AND ANXIETY DISORDERS
Krystal J, D'Souza D, Sanacora G, Goddard A, Charney D. CURRENT PERSPECTIVES ON THE PATHOPHYSIOLOGY OF SCHIZOPHRENIA, DEPRESSION, AND ANXIETY DISORDERS. Medical Clinics Of North America 2001, 85: 559-577. PMID: 11349473, DOI: 10.1016/s0025-7125(05)70329-1.Peer-Reviewed Original ResearchConceptsPathophysiology of schizophreniaMajor psychiatric disordersPsychiatric disordersPathophysiologyCurrent perspectivesPsychiatric researchDisordersCurrent eraSource of hopePatientsSchizophrenia
1999
Therapeutic Implications of the Hyperglutamatergic Effects of NMDA Antagonists
Krystal J, Belger A, D'Souza D, Anand A, Charney D, Aghajanian G, Moghaddam B. Therapeutic Implications of the Hyperglutamatergic Effects of NMDA Antagonists. Neuropsychopharmacology 1999, 21: s143-s157. DOI: 10.1016/s0893-133x(99)00102-5.Peer-Reviewed Original ResearchHealthy human subjectsNMDA antagonist effectsNMDA antagonistsClinical studiesMetabotropic glutamate receptor agonistN-methyl-D-aspartate (NMDA) subtypeD2 receptor blockadeGlutamate receptor agonistsD2 receptor stimulationDopamine 2 receptorNovel pharmacologic strategiesEffects of ketaminePathophysiology of schizophreniaCourse of schizophreniaNovel pharmacotherapeutic strategiesHuman subjectsHyperglutamatergic stateSerotonin 2AGlutamate neuronsGlutamate releaseCerebral cortexPharmacologic strategiesCurrent antipsychoticsPharmacotherapeutic strategiesSubanesthetic dosesComparison of four components of sensory gating in schizophrenia and normal subjects: a preliminary report
Boutros N, Belger A, Campbell D, D’Souza C, Krystal J. Comparison of four components of sensory gating in schizophrenia and normal subjects: a preliminary report. Psychiatry Research 1999, 88: 119-130. PMID: 10622348, DOI: 10.1016/s0165-1781(99)00074-8.Peer-Reviewed Original ResearchConceptsNormal control subjectsSchizophrenia patientsSensory gatingControl subjectsNormal subjectsSex-matched normal control subjectsPathophysiology of schizophreniaStimulus repetitionStable schizophrenia patientsSchizophrenia subjectsSimilar abnormalitiesPatientsPreliminary reportDysfunctionDegree of attenuationSchizophreniaLate phaseSubjectsDeviant stimuliStimulus changeIrrelevant stimuliPathophysiologyStimuliPotential paradigmAbnormalities[123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia
Verhoeff N, Soares J, D’Souza C, Gil R, Degen K, Abi-Dargham A, Zoghbi S, Fujita M, Rajeevan N, Seibyl J, Krystal J, van Dyck C, Charney D, Innis R. [123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia. Psychiatry Research 1999, 91: 163-173. PMID: 10641580, DOI: 10.1016/s0925-4927(99)00027-x.Peer-Reviewed Original ResearchConceptsDuration of illnessHealthy control subjectsControl subjectsGamma-aminobutyric acidLeft precentral gyrusSuperior occipital gyrusPANSS scoresPrecentral gyrusOccipital gyrusSignificant differencesTotal brain uptakeNon-smoking patientsGray matter atrophyConstant infusion paradigmPathophysiology of schizophreniaCortical brain regionsSingle photon emissionTypical antipsychoticsAtypical antipsychoticsCigarette smokingInhibitory neurotransmissionBrain uptakeInfusion paradigmMatter atrophyPostmortem studiesNo 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