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 ResearchMeSH KeywordsAnimalsAntidepressive AgentsDepressive DisorderKetamineNeuronal PlasticitySecondary PreventionStress, PsychologicalConceptsChronic stress pathologyRapid acting antidepressantsHigh treatment resistanceActing antidepressantsChronic courseClinical evidenceLeading causeTreatment resistancePsychiatric disordersStress pathologyDepressionLarge proportionAntidepressantsPatientsReviewKetamineIllnessPathologyComprehensive review
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 region
2018
Predicting Barriers to Treatment for Depression in a U.S. National Sample: A Cross-Sectional, Proof-of-Concept Study
Chekroud AM, Foster D, Zheutlin AB, Gerhard DM, Roy B, Koutsouleris N, Chandra A, Esposti MD, Subramanyan G, Gueorguieva R, Paulus M, Krystal JH. Predicting Barriers to Treatment for Depression in a U.S. National Sample: A Cross-Sectional, Proof-of-Concept Study. Psychiatric Services 2018, 69: 927-934. PMID: 29962307, PMCID: PMC7232987, DOI: 10.1176/appi.ps.201800094.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overCross-Sectional StudiesDepressive DisorderFemaleHealth Services AccessibilityHumansLogistic ModelsMaleMiddle AgedPatient Acceptance of Health CarePrimary Health CareProof of Concept StudyPsychotherapySampling StudiesSelf-AssessmentSurveys and QuestionnairesTreatment RefusalUnited StatesYoung AdultConceptsDiagnosis of depressionHealth care providersSelf-report survey itemsImplementation of interventionsDerivation cohortUntreated depressionCare providersEffective treatmentU.S. national sampleDrug useDepressionDiagnosisTreatmentU.S. National SurveyPatientsCohortNational surveyNational sampleConcept studySurvey itemsBalanced accuracyIndividualsRetention rateIndependent responsesPrevalenceThe effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects
Abdallah CG, De Feyter HM, Averill LA, Jiang L, Averill CL, Chowdhury GMI, Purohit P, de Graaf RA, Esterlis I, Juchem C, Pittman BP, Krystal JH, Rothman DL, Sanacora G, Mason GF. The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects. Neuropsychopharmacology 2018, 43: 2154-2160. PMID: 29977074, PMCID: PMC6098048, DOI: 10.1038/s41386-018-0136-3.Peer-Reviewed Original ResearchConceptsGlutamate-glutamine cyclingGlutamate neurotransmissionAntidepressant effectsKetamine effectsRodent studiesN-methyl-D-aspartate receptor antagonistRapid antidepressant effectsClinician-Administered Dissociative States ScaleEffects of ketamineGlutamine enrichmentKetamine infusionGlutamate releaseKetamine administrationSubanesthetic dosesPsychotomimetic effectsReceptor antagonistNormal salineSchizophrenia pathophysiologyFrontal cortexMRS scansDepressed subjectsKetamineNeurotransmissionPrefrontal cortexPilot study
2017
Cumulative childhood maltreatment and its dose-response relation with adult symptomatology: Findings in a sample of adult survivors of sexual abuse
Steine IM, Winje D, Krystal JH, Bjorvatn B, Milde AM, Grønli J, Nordhus IH, Pallesen S. Cumulative childhood maltreatment and its dose-response relation with adult symptomatology: Findings in a sample of adult survivors of sexual abuse. Child Abuse & Neglect 2017, 65: 99-111. PMID: 28131947, DOI: 10.1016/j.chiabu.2017.01.008.Peer-Reviewed Original ResearchConceptsCumulative childhood maltreatmentChildhood maltreatmentPosttraumatic stressSexual abuseSocial supportChildhood adversityAdult survivorsRule-governed wayHierarchical regression analysisChildhood maltreatment experiencesSelf-harm behaviorsDose-response relationCumulative childhood adversityAdult symptomatologyDisorder symptomsSelf-reported symptomsPsychological distressRelational problemsSymptom complexityMaltreatment experiencesWork functioningEmotional painRelated distressMaltreatment scoresAdversity
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 relevancePlk5Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants
Duman RS, Aghajanian GK, Sanacora G, Krystal JH. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nature Medicine 2016, 22: 238-249. PMID: 26937618, PMCID: PMC5405628, DOI: 10.1038/nm.4050.Peer-Reviewed Original ResearchMeSH KeywordsAntidepressive AgentsBrain-Derived Neurotrophic FactorCytokinesDepressive DisorderDiabetes MellitusExcitatory Amino Acid AntagonistsFemaleGlucocorticoidsHumansHypothalamo-Hypophyseal SystemInflammationKetamineMaleNeuronal PlasticityPituitary-Adrenal SystemSelective Serotonin Reuptake InhibitorsSex FactorsSignal TransductionStress, PsychologicalTime Factors
2010
A Prospective Cohort Study Investigating Factors Associated With Depression During Medical Internship
Sen S, Kranzler HR, Krystal JH, Speller H, Chan G, Gelernter J, Guille C. A Prospective Cohort Study Investigating Factors Associated With Depression During Medical Internship. JAMA Psychiatry 2010, 67: 557-565. PMID: 20368500, PMCID: PMC4036806, DOI: 10.1001/archgenpsychiatry.2010.41.Peer-Reviewed Original ResearchMeSH KeywordsAdultCohort StudiesDepressionDepressive DisorderDepressive Disorder, MajorFemaleGenotypeHealth StatusHumansInternship and ResidencyLife Change EventsMaleMedicinePolymorphism, Single NucleotidePrevalenceProspective StudiesRisk FactorsSerotonin Plasma Membrane Transport ProteinsStress, PsychologicalStudents, MedicalSurveys and QuestionnairesConceptsDepressive symptomsPHQ-9 depression scoresProspective cohort studyPrevalence of depressionPatient Health QuestionnaireProportion of participantsMedical internsMedical internshipGreater increasePHQ-9 criteriaCohort studyHealth QuestionnaireMood symptomsGeneral populationDepression scoresUS hospitalsSymptomsSerotonin transporter protein geneGenetic polymorphismsDepressionGenetic factorsLife stressMarked increaseRecent reportsResidency programs
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 ResearchGABA and glutamate systems as therapeutic targets in depression and mood disorders
Kendell SF, Krystal JH, Sanacora G. GABA and glutamate systems as therapeutic targets in depression and mood disorders. Expert Opinion On Therapeutic Targets 2005, 9: 153-168. PMID: 15757488, DOI: 10.1517/14728222.9.1.153.Peer-Reviewed Original Research
2004
Subtype-Specific Alterations of γ-Aminobutyric Acid and Glutamatein Patients With Major Depression
Sanacora G, Gueorguieva R, Epperson CN, Wu YT, Appel M, Rothman DL, Krystal JH, Mason GF. Subtype-Specific Alterations of γ-Aminobutyric Acid and Glutamatein Patients With Major Depression. JAMA Psychiatry 2004, 61: 705-713. PMID: 15237082, DOI: 10.1001/archpsyc.61.7.705.Peer-Reviewed Original ResearchConceptsMajor depressive disorderGamma-aminobutyric acidOccipital cortex GABA concentrationsProton magnetic resonance spectroscopyDepressed subjectsGABA concentrationHealthy controlsSubtypes of MDDCortical gamma-aminobutyric acidHealthy control subjectsMetabolite levelsCholine-containing compoundsHealthy comparison subjectsClinical research programSubtype-specific alterationsΓ-aminobutyric acidClinical correlatesMDD patientsControl subjectsDepressive disorderNeurotransmitter levelsGlutamate levelsMajor depressionMDD subtypesOccipital cortex
2003
Mutation screen of the glutamate decarboxylase‐67 gene and haplotype association to unipolar depression
Lappalainen J, Sanacora G, Kranzler HR, Malison R, Hibbard ES, Price LH, Krystal J, Gelernter J. Mutation screen of the glutamate decarboxylase‐67 gene and haplotype association to unipolar depression. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2003, 124B: 81-86. PMID: 14681921, DOI: 10.1002/ajmg.b.20055.Peer-Reviewed Original ResearchA Functional Magnetic Resonance Imaging Study of Bipolar Disorder: State- and Trait-Related Dysfunction in Ventral Prefrontal Cortices
Blumberg HP, Leung HC, Skudlarski P, Lacadie CM, Fredericks CA, Harris BC, Charney DS, Gore JC, Krystal JH, Peterson BS. A Functional Magnetic Resonance Imaging Study of Bipolar Disorder: State- and Trait-Related Dysfunction in Ventral Prefrontal Cortices. JAMA Psychiatry 2003, 60: 601-609. PMID: 12796223, DOI: 10.1001/archpsyc.60.6.601.Peer-Reviewed Original ResearchConceptsVentral prefrontal cortexBipolar disorderPrefrontal cortexMood statesMagnetic resonance imaging studyHealthy control subjectsAcute mood statesLeft ventral prefrontal cortexResonance imaging studySignal changesDisturbances of attentionFunctional magnetic resonance imaging studyAnterior cingulate cortexBipolar disorder IDorsal anterior cingulateEvent-related functional magnetic resonanceFunctional magnetic resonanceAcute episodeControl subjectsExaggerated increaseFunctional impairmentBlunted activationMood episodesSpecific mood statesPrefrontal abnormalitiesIncreased Cortical GABA Concentrations in Depressed Patients Receiving ECT
Sanacora G, Mason GF, Rothman DL, Hyder F, Ciarcia JJ, Ostroff RB, Berman RM, Krystal JH. Increased Cortical GABA Concentrations in Depressed Patients Receiving ECT. American Journal Of Psychiatry 2003, 160: 577-579. PMID: 12611844, DOI: 10.1176/appi.ajp.160.3.577.Peer-Reviewed Original ResearchConceptsOccipital cortex GABA concentrationsCortical GABA concentrationsCourse of ECTGABA concentrationDepressed patientsConsiderable anticonvulsant effectsSevere refractory depressionGamma-aminobutyric acid concentrationProton magnetic resonance spectroscopyRefractory depressionAnticonvulsant effectsAntidepressant actionGABAergic transmissionECT treatmentGABAergic involvementEffective treatmentECT mechanismsDepressed subjectsPatientsSignificant increaseDepressionTreatmentECTMagnetic resonance spectroscopyAcid concentration
2002
A Functional Neuropeptide Y Leu7Pro Polymorphism Associated With Alcohol Dependence in a Large Population Sample From the United States
Lappalainen J, Kranzler HR, Malison R, Price LH, Van Dyck C, Rosenheck RA, Cramer J, Southwick S, Charney D, Krystal J, Gelernter J. A Functional Neuropeptide Y Leu7Pro Polymorphism Associated With Alcohol Dependence in a Large Population Sample From the United States. JAMA Psychiatry 2002, 59: 825-831. PMID: 12215082, DOI: 10.1001/archpsyc.59.9.825.Peer-Reviewed Original ResearchMeSH KeywordsAlcohol DrinkingAlcoholismBlack PeopleCase-Control StudiesComorbidityDepressive DisorderEthnicityEuropeFemaleGene FrequencyGenetic Predisposition to DiseaseGenetics, PopulationGenotypeHumansMaleNeuropeptide YPolymorphism, GeneticRacial GroupsSchizophreniaStress Disorders, Post-TraumaticUnited StatesConceptsAlcohol-dependent subjectsPro7 alleleAlcohol dependencePopulation sampleComorbid psychiatric disordersMain outcome measuresPopulation studiesEA controlsNeuropeptide Y geneRecent population studiesPosttraumatic stress disorderNPY polymorphismsRisk factorsAttributable fractionMajor depressionOutcome measuresLarge population samplePsychiatric disordersAlcohol consumptionPolymorphism AssociatedAlzheimer's diseaseAllele frequenciesStress disorderModulate riskEuropean Americans
2001
Attenuation of Ketamine Effects by Nimodipine Pretreatment in Recovering Ethanol Dependent Men: Psychopharmacologic Implications of the Interaction of NMDA and L-Type Calcium Channel Antagonists
Krupitsky E, Burakov A, Romanova T, Grinenko N, Grinenko A, Fletcher J, Petrakis I, Krystal J. Attenuation of Ketamine Effects by Nimodipine Pretreatment in Recovering Ethanol Dependent Men: Psychopharmacologic Implications of the Interaction of NMDA and L-Type Calcium Channel Antagonists. Neuropsychopharmacology 2001, 25: 936-947. PMID: 11750186, DOI: 10.1016/s0893-133x(01)00346-3.Peer-Reviewed Original ResearchConceptsVoltage-sensitive calcium channelsL-type voltage-sensitive calcium channelsKetamine effectsStimulant effectsCalcium channelsDouble-blind placebo-controlled studyN-methyl-D-aspartate (NMDA) glutamate receptorsL-type calcium channel antagonistL-type VSCC antagonistBehavioral effectsTransient behavioral effectsPlacebo-controlled studyCalcium channel antagonistsImproved memory functionInteraction of NMDAAspects of schizophreniaNimodipine pretreatmentVSCC antagonistsVerbal fluency impairmentPatient groupKetamine responseChannel antagonistsNMDA antagonistsNMDA receptorsEthanol intoxicationCURRENT 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 Research
2000
Impairment of GABAergic Transmission in Depression: New Insights from Neuroimaging Studies
Sanacora G, Mason G, Krystal J. Impairment of GABAergic Transmission in Depression: New Insights from Neuroimaging Studies. Critical Reviews In Neurobiology 2000, 14: 23. PMID: 11253954, DOI: 10.1615/critrevneurobiol.v14.i1.20.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsNeurobiology of depressionGABAergic functionTechnique of PETCSF GABA concentrationsGABA-mimetic agentsNovel neuroimaging techniquesNondepressed comparison subjectsMood stabilizingChronic administrationGABAergic transmissionGABAergic neurotransmissionAntidepressant propertiesGABAergic abnormalitiesDepressed patientsAntidepressant drugsDisorder pathophysiologyLower plasmaComparison subjectsAnimal studiesGABAergic contributionGABA concentrationNovel imaging techniqueNeuroimaging studiesNeuroimaging techniquesDepression
1999
Reduced Cortical γ-Aminobutyric Acid Levels in Depressed Patients Determined by Proton Magnetic Resonance Spectroscopy
Sanacora G, Mason GF, Rothman DL, Behar KL, Hyder F, Petroff OA, Berman RM, Charney DS, Krystal JH. Reduced Cortical γ-Aminobutyric Acid Levels in Depressed Patients Determined by Proton Magnetic Resonance Spectroscopy. JAMA Psychiatry 1999, 56: 1043-1047. PMID: 10565505, DOI: 10.1001/archpsyc.56.11.1043.Peer-Reviewed Original ResearchConceptsProton magnetic resonance spectroscopyDepressed patientsGABA levelsMedication-free depressed patientsOccipital cortex GABA levelsVivo proton magnetic resonance spectroscopyCortical GABA concentrationsGamma-aminobutyric acid (GABA) systemΓ-aminobutyric acid (GABA) levelsBrain GABA levelsMagnetic resonance spectroscopy protocolHealthy control subjectsDSM-IV criteriaGABA neurotransmitter systemEffect of depressionInteraction of diagnosisControl subjectsMajor depressionNeurotransmitter systemsHealthy subjectsOccipital cortexNeurobiologic processesAnalysis of covarianceGABA concentrationMental illness
1997
Elevated CSF corticotropin-releasing factor concentrations in posttraumatic stress disorder
Bremner JD, Licinio J, Darnell A, Krystal JH, Owens MJ, Southwick SM, Nemeroff CB, Charney DS. Elevated CSF corticotropin-releasing factor concentrations in posttraumatic stress disorder. American Journal Of Psychiatry 1997, 154: 624-629. PMID: 9137116, PMCID: PMC3233756, DOI: 10.1176/ajp.154.5.624.Peer-Reviewed Original ResearchConceptsCorticotropin-releasing factorPost-traumatic stress disorderCSF CRF concentrationsCSF concentrationsComparison subjectsCRF concentrationsPTSD patientsCorticotropin-releasing factor concentrationsStress disorderCSF somatostatin concentrationsChronic combat-related post-traumatic stress disorderCollection of CSFCombat-related post-traumatic stress disorderPosttraumatic stress disorderLumbar punctureSomatostatin concentrationsNeurotransmitter systemsPatientsVietnam combat veteransChronic stressFactor concentrationsLevel of significanceGroup differencesCombat veteransSomatostatin