2022
Reward and loss incentives improve spatial working memory by shaping trial-by-trial posterior frontoparietal signals
Cho YT, Moujaes F, Schleifer CH, Starc M, Ji JL, Santamauro N, Adkinson B, Kolobaric A, Flynn M, Krystal JH, Murray JD, Repovs G, Anticevic A. Reward and loss incentives improve spatial working memory by shaping trial-by-trial posterior frontoparietal signals. NeuroImage 2022, 254: 119139. PMID: 35346841, PMCID: PMC9264479, DOI: 10.1016/j.neuroimage.2022.119139.Peer-Reviewed Original ResearchConceptsMemory precisionSpatial working memoryIntraparietal sulcusPrecentral sulcusWorking memoryMotivational signalsBOLD signalParietal cortexReward/lossVisual association regionsDorsolateral prefrontal cortexGoal-directed activityMemory paradigmMemory performanceMemory processesAnterior parietal cortexExecutive networkNeural changesSensory processesPrefrontal cortexLoss incentivesVentral striatumNon-human primate studiesTranslational neuroscienceMemoryImaging the effect of ketamine on synaptic density (SV2A) in the living brain
Holmes SE, Finnema SJ, Naganawa M, DellaGioia N, Holden D, Fowles K, Davis M, Ropchan J, Emory P, Ye Y, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Imaging the effect of ketamine on synaptic density (SV2A) in the living brain. Molecular Psychiatry 2022, 27: 2273-2281. PMID: 35165397, PMCID: PMC9133063, DOI: 10.1038/s41380-022-01465-2.Peer-Reviewed Original ResearchConceptsKetamine's therapeutic effectsMajor depressive disorderTherapeutic effectPositron emission tomographyPosttraumatic stress disorderHealthy controlsSynaptic connectionsSynaptic vesicle protein 2APost-synaptic mechanismsEffects of ketamineDiscovery of ketamineNon-human primatesAntidepressant effectsDepressive disorderSingle administrationSynaptic densityPsychiatric disordersDepression severityKetamineEmission tomographyTerminal densityLiving brainStress disorderRobust reductionDissociative symptoms
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
2020
Ketamine and rapid acting antidepressants: Are we ready to cure, rather than treat depression?
Abdallah CG, Krystal JH. Ketamine and rapid acting antidepressants: Are we ready to cure, rather than treat depression? Behavioural Brain Research 2020, 390: 112628. PMID: 32407817, PMCID: PMC7316409, DOI: 10.1016/j.bbr.2020.112628.Peer-Reviewed Original ResearchConceptsChronic stress pathologyRapid acting antidepressantsHigh treatment resistanceActing antidepressantsChronic courseClinical evidenceLeading causeTreatment resistancePsychiatric disordersStress pathologyDepressionLarge proportionAntidepressantsPatientsReviewKetamineIllnessPathologyComprehensive reviewImaging the glutamate synapse
Krystal JH. Imaging the glutamate synapse. Nature Medicine 2020, 26: 165-167. PMID: 32015559, DOI: 10.1038/s41591-020-0760-4.Peer-Reviewed Original Research
2019
Enhancing the Utility of Preclinical Research in Neuropsychiatry Drug Development
Kaffman A, White JD, Wei L, Johnson FK, Krystal JH. Enhancing the Utility of Preclinical Research in Neuropsychiatry Drug Development. Methods In Molecular Biology 2019, 2011: 3-22. PMID: 31273690, PMCID: PMC6895673, DOI: 10.1007/978-1-4939-9554-7_1.Peer-Reviewed Original ResearchConceptsPreclinical researchAnimal modelsPsychiatric conditionsLower clinical success ratesClinical success rateCommon psychiatric conditionsPsychiatric clinical trialsClinical trialsNew pharmacotherapiesMore effective interventionsPreclinical workPsychiatric disordersPsychiatric pathophysiologyMental illnessSystematic reviewEffective interventionsAnimal experimentsDrug development processSuccess rateDrug developmentHuman psychopathologyPharmaceutical companiesPredictive validityLarge pharmaceutical companiesAnimalsAltered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments
Duman RS, Sanacora G, Krystal JH. Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments. Neuron 2019, 102: 75-90. PMID: 30946828, PMCID: PMC6450409, DOI: 10.1016/j.neuron.2019.03.013.Peer-Reviewed Original ResearchConceptsAltered connectivityDepressed patientsExcitatory glutamate neuronsMajor neuronal typesRapid-acting agentsAtrophy of neuronsTreatment of depressionLimbic brain regionsChronic stress exposureStress-related disordersBrain imaging studiesImportant sex differencesNeurotransmitter deficitsGABA interneuronsImmunologic mechanismsGlutamate neuronsCurrent antidepressantsExcitotoxic effectsNeurochemical deficitsGlutamate dysfunctionPathophysiological mechanismsGABA systemInflammatory cytokinesAdrenal glucocorticoidsHippocampal regionKetamine: A Paradigm Shift for Depression Research and Treatment
Krystal JH, Abdallah CG, Sanacora G, Charney DS, Duman RS. Ketamine: A Paradigm Shift for Depression Research and Treatment. Neuron 2019, 101: 774-778. PMID: 30844397, PMCID: PMC6560624, DOI: 10.1016/j.neuron.2019.02.005.Peer-Reviewed Original Research
2018
The Neurobiology and Pharmacotherapy of Posttraumatic Stress Disorder
Abdallah CG, Averill LA, Akiki TJ, Raza M, Averill CL, Gomaa H, Adikey A, Krystal JH. The Neurobiology and Pharmacotherapy of Posttraumatic Stress Disorder. The Annual Review Of Pharmacology And Toxicology 2018, 59: 171-189. PMID: 30216745, PMCID: PMC6326888, DOI: 10.1146/annurev-pharmtox-010818-021701.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderStress disorderTreatment of PTSDBiology of PTSDExert complex effectsBrain functionNeurobiologySynaptic gainPathology modelRapid-acting antidepressantsBroader frameworkDisordersWordsPutative mechanismsDysconnectivitySynaptic lossPharmacotherapeutic optionsClinical efficacyCompelling efficacyPerspectiveAntidepressantsDrug developmentComplex effectsPathologyEfficacyThe neurobiology of depression, ketamine and rapid-acting antidepressants: Is it glutamate inhibition or activation?
Abdallah CG, Sanacora G, Duman RS, Krystal JH. The neurobiology of depression, ketamine and rapid-acting antidepressants: Is it glutamate inhibition or activation? Pharmacology & Therapeutics 2018, 190: 148-158. PMID: 29803629, PMCID: PMC6165688, DOI: 10.1016/j.pharmthera.2018.05.010.Peer-Reviewed Original ResearchConceptsRapid-acting antidepressantsNeurobiology of depressionMechanism of actionChronic stress pathologyRole of glutamateAntidepressant effectsEfficacy findingsGlutamate activationBiomarker findingsNeurobiology of stressVivo pharmacodynamicsCurrent perspective paperKetamineChronic stressReproducible biomarkersBehavioral effectsGlutamate inhibitionDepressionStress pathologyAntidepressantsNeurobiologyInhibitionActivationPharmacodynamicsPharmacokinetics
2017
Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic
Krystal JH, Abdallah CG, Averill LA, Kelmendi B, Harpaz-Rotem I, Sanacora G, Southwick SM, Duman RS. Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic. Current Psychiatry Reports 2017, 19: 74. PMID: 28844076, PMCID: PMC5904792, DOI: 10.1007/s11920-017-0829-z.Peer-Reviewed Original ResearchConceptsSynaptic connectivityRapid-acting treatmentPathophysiology of PTSDPotential clinical importanceTreatment of PTSDSynaptic lossPurpose of ReviewStudiesDisconnection syndromeClinical importanceNovel pharmacotherapeuticsNovel therapeuticsPTSD symptomsRecent FindingsHerePTSDPathophysiologyKetamineTreatmentDisordersTherapeutic applicationsStress-related lossesSyndromeSymptomsPharmacotherapeuticsNeurobiology of posttraumatic stress disorder (PTSD): A path from novel pathophysiology to innovative therapeutics
Abdallah CG, Southwick SM, Krystal JH. Neurobiology of posttraumatic stress disorder (PTSD): A path from novel pathophysiology to innovative therapeutics. Neuroscience Letters 2017, 649: 130-132. PMID: 28478864, DOI: 10.1016/j.neulet.2017.04.046.Peer-Reviewed Original ResearchIt Is Time to Address the Crisis in the Pharmacotherapy of Posttraumatic Stress Disorder: A Consensus Statement of the PTSD Psychopharmacology Working Group
Krystal JH, Davis LL, Neylan TC, Raskind M, Schnurr PP, Stein MB, Vessicchio J, Shiner B, Gleason TD, Huang GD. It Is Time to Address the Crisis in the Pharmacotherapy of Posttraumatic Stress Disorder: A Consensus Statement of the PTSD Psychopharmacology Working Group. Biological Psychiatry 2017, 82: e51-e59. PMID: 28454621, DOI: 10.1016/j.biopsych.2017.03.007.Peer-Reviewed Original ResearchSearching for Cross-Diagnostic Convergence: Neural Mechanisms Governing Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders
Foss-Feig JH, Adkinson BD, Ji JL, Yang G, Srihari VH, McPartland JC, Krystal JH, Murray JD, Anticevic A. Searching for Cross-Diagnostic Convergence: Neural Mechanisms Governing Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders. Biological Psychiatry 2017, 81: 848-861. PMID: 28434615, PMCID: PMC5436134, DOI: 10.1016/j.biopsych.2017.03.005.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderSpectrum disorderFunctional magnetic resonance imagingRecent theoretical accountsEarly course schizophreniaNeurodevelopmental disordersPharmacological challenge studiesNeural correlatesNeuroscience literatureTheoretical accountsNeural circuitryTheoretical neuroscienceNoninvasive neuroimagingBehavioral dysfunctionFuture researchNeuropsychiatric conditionsComputational modelSchizophreniaProton magnetic resonance spectroscopyDisordersInhibition imbalanceMagnetic resonance imagingDistinct modalitiesPoint of convergenceInhibition balanceImpaired 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
2016
Implication of NOTCH1 gene in susceptibility to anxiety and depression among sexual abuse victims
Steine IM, Zayats T, Stansberg C, Pallesen S, Mrdalj J, Håvik B, Soulé J, Haavik J, Milde AM, Skrede S, Murison R, Krystal J, Grønli J. Implication of NOTCH1 gene in susceptibility to anxiety and depression among sexual abuse victims. Translational Psychiatry 2016, 6: e977-e977. PMID: 27959334, PMCID: PMC5290341, DOI: 10.1038/tp.2016.248.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsAnxiety DisordersBrainDepressive DisorderDisease Models, AnimalFemaleGene ExpressionGenetic Predisposition to DiseaseHumansLife Change EventsMaleNeurodevelopmental DisordersPolymorphism, Single NucleotideRats, WistarReceptor, Notch1Sex OffensesTranslational Research, BiomedicalConceptsSingle nucleotide polymorphismsDifferent early-life conditionsGene expressionEarly-life conditionsBrain gene expressionGenetic association studiesCandidate genesAssociation studiesNeural developmentDifferential expressionTag single nucleotide polymorphismsBrain of rodentsGenesHuman samplesFalse discovery rateNotch1 geneSymptoms of anxietyExpressionSignificance analysisDiscovery ratePotential importanceEarly life stressMeans of correspondencePotential relevancePlk5The Role of GluN2C-Containing NMDA Receptors in Ketamine's Psychotogenic Action and in Schizophrenia Models
Khlestova E, Johnson JW, Krystal JH, Lisman J. The Role of GluN2C-Containing NMDA Receptors in Ketamine's Psychotogenic Action and in Schizophrenia Models. Journal Of Neuroscience 2016, 36: 11151-11157. PMID: 27807157, PMCID: PMC5148234, DOI: 10.1523/jneurosci.1203-16.2016.Peer-Reviewed Original ResearchConceptsNMDAR antagonistsNMDA receptor hypofunction hypothesisDifferent NMDAR subtypesHealthy human subjectsSymptoms of schizophreniaPsychotogenic effectsNMDA receptorsNMDAR subtypesSchizophrenia modelKetamine's abilityNegative symptomsKetamineMultiple subtypesPsychotic statesPreferential involvementSchizophreniaAntagonistGluN2CSubtypesReceptorsEEG powerHuman subjectsNMDARSymptomsΔ oscillationsKETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS
Abdallah CG, Adams TG, Kelmendi B, Esterlis I, Sanacora G, Krystal JH. KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS. Depression And Anxiety 2016, 33: 689-697. PMID: 27062302, PMCID: PMC4961540, DOI: 10.1002/da.22501.Peer-Reviewed Original ResearchConceptsMajor depressive disorderAntidepressant effectsKetamine's mechanismN-methyl-D-aspartate receptor antagonistRapid-acting antidepressant effectsPrefrontal cortexSingle subanesthetic doseRapid antidepressant effectsTreatment-resistant depressionFull therapeutic effectEfficacy of ketamineKetamine's antidepressant effectsRapid acting antidepressantsFuture clinical prospectsGlutamate surgeTraditional antidepressantsAntidepressant medicationCascade of eventsReceptor antagonistSubanesthetic doseDepressive disorderClinical dataTherapeutic effectTreatment responseLimited efficacy
2015
Decreased SGK1 Expression and Function Contributes to Behavioral Deficits Induced by Traumatic Stress
Licznerski P, Duric V, Banasr M, Alavian KN, Ota KT, Kang HJ, Jonas EA, Ursano R, Krystal JH, Duman RS, . Decreased SGK1 Expression and Function Contributes to Behavioral Deficits Induced by Traumatic Stress. PLOS Biology 2015, 13: e1002282. PMID: 26506154, PMCID: PMC4623974, DOI: 10.1371/journal.pbio.1002282.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsBehavior, AnimalCohort StudiesDendritic SpinesDepressive Disorder, MajorEnzyme RepressionFemaleGene Transfer TechniquesHippocampusHumansImmediate-Early ProteinsMaleMiddle AgedNerve Tissue ProteinsNeuronsPrefrontal CortexProtein Serine-Threonine KinasesRats, Sprague-DawleySignal TransductionStress Disorders, Post-TraumaticSynaptic TransmissionTissue BanksConceptsMajor depressive disorderPost-traumatic stress disorderPrefrontal cortexAbnormal dendritic spine morphologyCorticolimbic brain regionsAnhedonic-like behaviorInhibition of SGK1Dendritic spine morphologyKinase 1 expressionAmygdala of individualsTraumatic stressPostmortem prefrontal cortexSynaptic dysfunctionDepressive disorderBehavioral deficitsRodent modelsPTSD subjectsFunctional alterationsBrain regionsSGK1 expressionSpine morphologyStress disorderFunction contributesBehavioral changesDisordersA New Genomewide Association Meta‐Analysis of Alcohol Dependence
Zuo L, Tan Y, Zhang X, Wang X, Krystal J, Tabakoff B, Zhong C, Luo X. A New Genomewide Association Meta‐Analysis of Alcohol Dependence. Alcohol Clinical And Experimental Research 2015, 39: 1388-1395. PMID: 26173551, PMCID: PMC5587504, DOI: 10.1111/acer.12786.Peer-Reviewed Original ResearchConceptsAfrican American cohortAmerican cohortAlcohol dependenceSingle nucleotide polymorphismsAustralian cohortRisk genesEuropean American cohortRisk single nucleotide polymorphismsRat brainIndependent cohortMeta-AnalysisCohortMouse brainRisk variantsP-valueRNA expression analysisGenomewide association studiesBrainHuman tissuesNucleotide polymorphismsAssociation studiesGenomewide association analysis