2020
Mapping Lithium in the Brain: New 3-Dimensional Methodology Reveals Regional Distribution in Euthymic Patients With Bipolar Disorder
Mason GF, Krystal JH. Mapping Lithium in the Brain: New 3-Dimensional Methodology Reveals Regional Distribution in Euthymic Patients With Bipolar Disorder. Biological Psychiatry 2020, 88: 367-368. PMID: 32792052, DOI: 10.1016/j.biopsych.2020.05.023.Peer-Reviewed Original Research
2019
Altered 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 regionNeural computations of threat in the aftermath of combat trauma
Homan P, Levy I, Feltham E, Gordon C, Hu J, Li J, Pietrzak RH, Southwick S, Krystal JH, Harpaz-Rotem I, Schiller D. Neural computations of threat in the aftermath of combat trauma. Nature Neuroscience 2019, 22: 470-476. PMID: 30664770, PMCID: PMC6829910, DOI: 10.1038/s41593-018-0315-x.Peer-Reviewed Original ResearchConceptsPTSD symptomsPost-traumatic stress disorder symptomsHigher PTSD symptom severityThreat-predictive cuesPTSD symptom severityAssociative threatPredictive cuesNeural trackingDisorder symptomsPrediction errorCombat veteransDynamic learning rateNegative outcomesCombat traumaSmaller amygdala volumesNeural computationLatent markersSymptomatic veteransSymptom severityAmygdala volumeAssociabilityCuesLearning rateVeteransSymptoms
2017
Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia
Logue MW, van Rooij SJH, Dennis EL, Davis SL, Hayes JP, Stevens JS, Densmore M, Haswell CC, Ipser J, Koch SBJ, Korgaonkar M, Lebois LAM, Peverill M, Baker JT, Boedhoe PSW, Frijling JL, Gruber SA, Harpaz-Rotem I, Jahanshad N, Koopowitz S, Levy I, Nawijn L, O’Connor L, Olff M, Salat DH, Sheridan MA, Spielberg JM, van Zuiden M, Winternitz SR, Wolff JD, Wolf EJ, Wang X, Wrocklage K, Abdallah CG, Bryant RA, Geuze E, Jovanovic T, Kaufman ML, King AP, Krystal JH, Lagopoulos J, Bennett M, Lanius R, Liberzon I, McGlinchey RE, McLaughlin KA, Milberg WP, Miller MW, Ressler KJ, Veltman DJ, Stein DJ, Thomaes K, Thompson PM, Morey RA. Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia. Biological Psychiatry 2017, 83: 244-253. PMID: 29217296, PMCID: PMC5951719, DOI: 10.1016/j.biopsych.2017.09.006.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderStress disorderTrauma-exposed control subjectsCurrent posttraumatic stress disorderSmaller hippocampal volumesControl subjectsSmaller hippocampiHippocampal volumeClinical dataAmygdala volumeAmygdala findingsSmaller amygdalaConsortium studySubcortical structuresNeuroimaging studiesLargest neuroimaging studyENIGMA consortiumBrain responsesNeurobiological underpinningsPsychiatric Genomics ConsortiumDisordersSubjectsWorking GroupSignificance levelHippocampusAnterior hippocampal dysconnectivity in posttraumatic stress disorder: a dimensional and multimodal approach
Abdallah CG, Wrocklage KM, Averill CL, Akiki T, Schweinsburg B, Roy A, Martini B, Southwick SM, Krystal JH, Scott JC. Anterior hippocampal dysconnectivity in posttraumatic stress disorder: a dimensional and multimodal approach. Translational Psychiatry 2017, 7: e1045-e1045. PMID: 28244983, PMCID: PMC5545643, DOI: 10.1038/tp.2017.12.Peer-Reviewed Original ResearchConceptsGlobal brain connectivityPosttraumatic stress disorderAnterior hippocampusStress disorderPTSD severityTraumatic brain injuryMultimodal approachOverall PTSD severityAnxiety-related behaviorDorsolateral prefrontal connectivityDorsolateral prefrontal cortexElevated PTSD symptomsAnatomical dysconnectivityHippocampal dysconnectivityUS veteransBrain injuryHippocampal volumePTSD subgroupBrain biomarkersClinical valueMedication statusPrefrontal connectivitySignificant associationPrefrontal cortexBrain connectivity
2016
Amygdala volume is reduced in early course schizophrenia
Rich AM, Cho YT, Tang Y, Savic A, Krystal JH, Wang F, Xu K, Anticevic A. Amygdala volume is reduced in early course schizophrenia. Psychiatry Research Neuroimaging 2016, 250: 50-60. PMID: 27035063, PMCID: PMC4904038, DOI: 10.1016/j.pscychresns.2016.02.006.Peer-Reviewed Original ResearchConceptsMagnetic resonance imagingAmygdala volumeSchizophrenia patientsSubcortical structuresEarly course schizophrenia patientsEarly illness courseChronic schizophrenia patientsNeuropathology of schizophreniaMajor subcortical structuresSmaller amygdala volumesEarly course schizophreniaHealthy comparison subjectsBonferroni correctionGray matter volumeAcute stress responseMedication useIllness coursePathophysiologic changesGlobus pallidusIllness phaseNucleus accumbensHigh riskComparison subjectsMatter volumeHR subjects50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate
Cavus I, Widi GA, Duckrow RB, Zaveri H, Kennard JT, Krystal J, Spencer DD. 50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate. Epilepsia 2016, 57: 288-297. PMID: 26749134, DOI: 10.1111/epi.13269.Peer-Reviewed Original ResearchConceptsBasal glutamate levelsRefractory epilepsyGlutamate effluxBasal glutamateGlutamate levelsElectrical stimulationEpileptic hippocampusGlutamate releaseSeizure groupHz stimulationBrain glutamate releaseHippocampus of patientsStimulation-induced increaseEpilepsy monitoring unitStimulation-induced changesEpileptogenic hippocampusInduced seizuresSeizure inductionSpontaneous seizuresInterictal levelsGlutamate increaseAtrophic hippocampusElectroencephalography evaluationHippocampal stimulationHippocampal electrodes
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 changesDisordersAmygdala-Hippocampal Volume and the Phenotypic Heterogeneity of Posttraumatic Stress Disorder: A Cross-Sectional Study
Pietrzak RH, Averill LA, Abdallah CG, Neumeister A, Krystal JH, Levy I, Harpaz-Rotem I. Amygdala-Hippocampal Volume and the Phenotypic Heterogeneity of Posttraumatic Stress Disorder: A Cross-Sectional Study. JAMA Psychiatry 2015, 72: 396-398. PMID: 25692480, PMCID: PMC5134909, DOI: 10.1001/jamapsychiatry.2014.2470.Peer-Reviewed Original Research
2008
Decreased hippocampal volume on MRI is associated with increased extracellular glutamate in epilepsy patients
Cavus I, Pan JW, Hetherington HP, Abi‐Saab W, Zaveri HP, Vives KP, Krystal JH, Spencer SS, Spencer DD. Decreased hippocampal volume on MRI is associated with increased extracellular glutamate in epilepsy patients. Epilepsia 2008, 49: 1358-1366. PMID: 18410365, DOI: 10.1111/j.1528-1167.2008.01603.x.Peer-Reviewed Original ResearchConceptsTemporal lobe epilepsyHippocampal volumeClinical factorsHippocampal atrophyEpileptogenic hippocampusGABA levelsNeurochemical levelsElevated extracellular glutamate levelsContralateral hippocampal volumeIntracranial EEG evaluationMedication-resistant epilepsyRefractory TLE patientsHigh seizure frequencyRelevant clinical factorsSmaller hippocampal volumesExtracellular glutamate levelsFebrile seizure historyTreatment of epilepsySeizure frequencyLobe epilepsySeizure historyTLE patientsAtrophic hippocampusGlutamate levelsExtracellular glutamate
2005
Untangling depression and anxiety: clinical challenges.
Keller MB, Krystal JH, Hen R, Neumeister A, Simon NM. Untangling depression and anxiety: clinical challenges. The Journal Of Clinical Psychiatry 2005, 66: 1477-84. PMID: 16420087, DOI: 10.4088/jcp.v66n1119.Peer-Reviewed Original ResearchFirst in vivo evidence of an NMDA receptor deficit in medication-free schizophrenic patients
Pilowsky LS, Bressan RA, Stone JM, Erlandsson K, Mulligan RS, Krystal JH, Ell PJ. First in vivo evidence of an NMDA receptor deficit in medication-free schizophrenic patients. Molecular Psychiatry 2005, 11: 118-119. PMID: 16189506, DOI: 10.1038/sj.mp.4001751.Peer-Reviewed Original ResearchExtracellular metabolites in the cortex and hippocampus of epileptic patients
Cavus I, Kasoff WS, Cassaday MP, Jacob R, Gueorguieva R, Sherwin RS, Krystal JH, Spencer DD, Abi‐Saab W. Extracellular metabolites in the cortex and hippocampus of epileptic patients. Annals Of Neurology 2005, 57: 226-235. PMID: 15668975, DOI: 10.1002/ana.20380.Peer-Reviewed Original ResearchConceptsGlutamate-glutamine cyclingEpileptogenic hippocampusGlutamate levelsEpileptic patientsImpaired glutamate reuptakeBasal glutamate levelsBrain energy metabolismHigher lactate levelsGlutamine/glutamate ratioPoor glucose utilizationEnergy metabolismNeurometabolic processesNonepileptogenic cortexEpileptogenic cortexGlutamate reuptakeNeocortical epilepsyExtracellular glutamateSeizure generationInterictal periodLactate levelsMicrodialysis methodExtracellular levelsNeuronal toxicityGlucose utilizationDepth electrodes
2003
Amygdala and Hippocampal Volumes in Adolescents and Adults With Bipolar Disorder
Blumberg HP, Kaufman J, Martin A, Whiteman R, Zhang JH, Gore JC, Charney DS, Krystal JH, Peterson BS. Amygdala and Hippocampal Volumes in Adolescents and Adults With Bipolar Disorder. JAMA Psychiatry 2003, 60: 1201-1208. PMID: 14662552, DOI: 10.1001/archpsyc.60.12.1201.Peer-Reviewed Original ResearchConceptsHippocampal volumeMedial temporal lobe structuresTemporal lobe structuresBipolar disorderIllness featuresVeterans Affairs Medical CenterLobe structuresRepeated-measures statistical analysisCourse of illnessTotal brain volumeAmygdala volume reductionsBD type IAnatomic magnetic resonanceHealthy comparison subjectsPaucity of dataVolume reductionSignificant volume reductionVolumetric abnormalitiesNeurodegenerative changesIllness durationOutpatient treatmentUniversity HospitalGreater effect sizeMedical CenterHippocampal regionPreliminary evidence of hippocampal dysfunction in adolescent MDMA (“ecstasy”) users: possible relationship to neurotoxic effects
Jacobsen LK, Mencl WE, Pugh KR, Skudlarski P, Krystal JH. Preliminary evidence of hippocampal dysfunction in adolescent MDMA (“ecstasy”) users: possible relationship to neurotoxic effects. Psychopharmacology 2003, 173: 383-390. PMID: 14647960, DOI: 10.1007/s00213-003-1679-4.Peer-Reviewed Original ResearchConceptsFunctional magnetic resonance imagingMDMA usersCognitive deficitsMDMA useBrain functionDivided attentionMemory taskMemory loadResultsMDMA usersLeft hippocampusHippocampal dysfunctionSubstance useCognitive impairmentAdolescencePreliminary evidenceReaction timeDevelopmental impactPilot sampleDeficitsMDMAMagnetic resonance imagingIQAttentionMemoryHippocampus
2001
A neurobiological basis for substance abuse comorbidity in schizophrenia
Chambers R, Krystal J, Self D. A neurobiological basis for substance abuse comorbidity in schizophrenia. Biological Psychiatry 2001, 50: 71-83. PMID: 11526998, PMCID: PMC2913410, DOI: 10.1016/s0006-3223(01)01134-9.Peer-Reviewed Original ResearchConceptsDrug rewardLong-term substance abuseMedication side effectsPrior drug exposureSubstance abuse comorbidityNeuropathology of schizophreniaPrimary disease symptomsAddictive behaviorsDrug-seeking behaviorHippocampal dysfunctionDrug exposureFrontal cortexNucleus accumbensHippocampal formationSchizophrenic patientsSide effectsCognitive impairmentNegative symptomsSubstance abuseAltered integrationNeural circuitrySymptomsSchizophreniaMotivational changesComorbidities
1995
Functional neuroanatomical correlates of the effects of stress on memory
Bremner J, Krystal J, Southwick S, Charney D. Functional neuroanatomical correlates of the effects of stress on memory. Journal Of Traumatic Stress 1995, 8: 527-553. PMID: 8564272, DOI: 10.1002/jts.2490080403.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderEffects of stressBrain regionsTraumatic stressNeural mechanismsSymptoms of PTSDFalse memory syndromeFunctional neuroanatomical correlatesFear conditioningNeurobiological approachStress disorderDissociative amnesiaMemory syndromeStress sensitizationNeuroanatomical correlatesMemory functionChildhood memoriesMemoryStress-induced alterationsImplicationsAmnesiaPsychotherapyCorrelatesConditioningSymptoms