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
2022
Validation of ketamine as a pharmacological model of thalamic dysconnectivity across the illness course of schizophrenia
Abram SV, Roach BJ, Fryer SL, Calhoun VD, Preda A, van Erp TGM, Bustillo JR, Lim KO, Loewy RL, Stuart BK, Krystal JH, Ford JM, Mathalon DH. Validation of ketamine as a pharmacological model of thalamic dysconnectivity across the illness course of schizophrenia. Molecular Psychiatry 2022, 27: 2448-2456. PMID: 35422467, PMCID: PMC9135621, DOI: 10.1038/s41380-022-01502-0.Peer-Reviewed Original ResearchConceptsThalamic dysconnectivityHealthy controlsDysconnectivity patternsIllness courseHealthy volunteersN-methyl-D-aspartate (NMDA) receptor hypofunctionResting-state functional magnetic resonance imaging studyHallucination severityEarly illness schizophreniaExcess glutamate releaseGlutamate release inhibitorNMDAR antagonist ketaminePlacebo-controlled studyMagnetic resonance imaging studySub-anesthetic dosesSchizophrenia-like symptomsResonance imaging studyFunctional magnetic resonance imaging studyKetamine infusionGlutamate releaseNMDAR hypofunctionReceptor hypofunctionKetamine effectsThalamic connectivityRelease inhibitor
2021
Effects of Altered Excitation-Inhibition Balance on Decision Making in a Cortical Circuit Model
Lam NH, Borduqui T, Hallak J, Roque A, Anticevic A, Krystal JH, Wang XJ, Murray JD. Effects of Altered Excitation-Inhibition Balance on Decision Making in a Cortical Circuit Model. Journal Of Neuroscience 2021, 42: 1035-1053. PMID: 34887320, PMCID: PMC8824494, DOI: 10.1523/jneurosci.1371-20.2021.Peer-Reviewed Original ResearchConceptsCortical circuitsCognitive deficitsCortical circuit modelAltered excitation-inhibition balanceExcitatory pyramidal neuronsNMDA receptor hypofunctionCerebral cortical circuitsExcitation-inhibition balancePyramidal neuronsReceptor hypofunctionDistinct time coursesSynaptic excitationInhibitory interneuronsMultiple neuropsychiatric disordersBehavioral deficitsSynaptic balanceSynaptic levelLatest evidenceNeuropsychiatric disordersCognitive functionCircuit mechanismsBehavioral effectsPsychometric performanceBehavioral levelTask paradigm
2001
NMDA receptor regulation of memory and behavior in humans
Newcomer J, Krystal J. NMDA receptor regulation of memory and behavior in humans. Hippocampus 2001, 11: 529-542. PMID: 11732706, DOI: 10.1002/hipo.1069.Peer-Reviewed Original ResearchConceptsNMDA receptor hypofunctionReceptor hypofunctionN-methyl-D-aspartate (NMDA) receptor hypofunctionNMDA receptor antagonist drugsNMDA receptor systemAge-related decreaseNMDA receptor regulationReceptor antagonist drugsClinical syndromeNeuropathological featuresNMDA antagonistsNMDA receptorsNeurotoxic processesAntagonist drugsAdult brainHypofunctionBehavioral dysfunctionHuman studiesRange of effectsReceptor regulationReceptor systemBrain functionBrain ageAdverse effectsDisease conditions