2021
Imaging brain cortisol regulation in PTSD with a target for 11β-hydroxysteroid dehydrogenase type 1
Bhatt S, Hillmer AT, Rusowicz A, Nabulsi N, Matuskey D, Angarita GA, Najafzadeh S, Kapinos M, Southwick SM, Krystal JH, Carson RE, Huang Y, Cosgrove KP. Imaging brain cortisol regulation in PTSD with a target for 11β-hydroxysteroid dehydrogenase type 1. Journal Of Clinical Investigation 2021, 131: e150452. PMID: 34651587, PMCID: PMC8516462, DOI: 10.1172/jci150452.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderPositron emission tomographyVolume of distributionDehydrogenase type 1Trauma-exposed controlsPTSD groupTranslocator proteinType 1Veterans Affairs (VA) National CenterOverall PTSD severityBrain glucocorticoidBrain immuneMethodsSixteen individualsPeripheral cortisolMicroglial markersImmune suppressionTranslational Science AwardsCortisol levelsNIH National CenterTC groupCortisol regulationEmission tomographyStress disorderLower PTSD symptomsPTSD symptoms
2020
A Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia
Koblan KS, Kent J, Hopkins SC, Krystal JH, Cheng H, Goldman R, Loebel A. A Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia. New England Journal Of Medicine 2020, 382: 1497-1506. PMID: 32294346, DOI: 10.1056/nejmoa1911772.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdministration, OralAdultAntipsychotic AgentsDouble-Blind MethodDrug Administration ScheduleFemaleHumansLeast-Squares AnalysisMaleReceptors, Dopamine D2Receptors, G-Protein-CoupledSchizophreniaSchizophrenic PsychologySerotonin 5-HT1 Receptor AgonistsSeverity of Illness IndexTreatment OutcomeConceptsTrace amine-associated receptor 1Week 4Negative Symptom ScaleAcute exacerbationPlacebo groupBrief Negative Symptom ScaleTotal scoreSymptom ScaleClinical Global Impression-Severity ScaleEnd pointPrimary end pointSecondary end pointsSudden cardiac deathPANSS total scoreTreatment of schizophreniaDopamine D2 receptorsTreatment of psychosisType 1A receptorMean total scoreLevels of lipidsGastrointestinal symptomsAdverse eventsCardiac deathExtrapyramidal symptomsPrimary outcome
2018
BDNF Val66Met polymorphism and posttraumatic stress symptoms in U.S. military veterans: Protective effect of physical exercise
Pitts BL, Whealin JM, Harpaz-Rotem I, Duman RS, Krystal JH, Southwick SM, Pietrzak RH. BDNF Val66Met polymorphism and posttraumatic stress symptoms in U.S. military veterans: Protective effect of physical exercise. Psychoneuroendocrinology 2018, 100: 198-202. PMID: 30388593, DOI: 10.1016/j.psyneuen.2018.10.011.Peer-Reviewed Original ResearchMeSH KeywordsAgedAmino Acid SubstitutionBrain-Derived Neurotrophic FactorCase-Control StudiesExerciseFemaleHumansMaleMethionineMiddle AgedMilitary PersonnelPolymorphism, Single NucleotideProtective FactorsResilience, PsychologicalSeverity of Illness IndexStress Disorders, Post-TraumaticUnited StatesValineVeteransConceptsMet allele carriersBDNF Val66Met polymorphismAllele carriersVal66Met polymorphismPhysical exerciseGreater severityPTSD symptomsU.S. military veteransTrauma burdenBrain-derived neurotrophic factor (BDNF) Val66Met polymorphismPast-month PTSD symptomsNeurotrophic factor Val66Met polymorphismMilitary veteransLifetime trauma burdenHigh trauma burdenVal/ValAdrenal (HPA) axis reactivityPosttraumatic stress disorder (PTSD) symptomsBDNF releaseCurrent PTSD symptomsProtective effectRe-experiencing symptomsAxis reactivityPosttraumatic stress symptomsSymptoms
2017
Correlates of Nonimprovement to Pharmacotherapy for Chronic, Antidepressant-Resistant, Military Service–Related Posttraumatic Stress Disorder
Byrne SP, Krystal JH, Rosenheck RA, Vessicchio J, Pietrzak RH. Correlates of Nonimprovement to Pharmacotherapy for Chronic, Antidepressant-Resistant, Military Service–Related Posttraumatic Stress Disorder. Journal Of Clinical Psychopharmacology 2017, 37: 717-721. PMID: 28945664, DOI: 10.1097/jcp.0000000000000777.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntidepressive AgentsAntipsychotic AgentsDrug Therapy, CombinationFemaleHumansMaleMiddle AgedOutcome Assessment, Health CareRandomized Controlled Trials as TopicRisperidoneSeverity of Illness IndexStress Disorders, Post-TraumaticUnited StatesUnited States Department of Veterans AffairsVeteransConceptsPosttraumatic stress disorderAdjunctive risperidoneTreatment-resistant posttraumatic stress disorderClinician-Administered PTSD Scale scoresSymptom clustersStress disorderOriginal treatment regimenFirst-line pharmacotherapySpecific symptom clustersSpecific PTSD symptom clustersVeterans RANDTreatment regimenPharmacotherapeutic effectsHealth SurveyRole functioningPTSD symptom clustersTreat conditionScale scoreGreater severityVariable improvementRisperidoneTargeted pharmacotherapyPlaceboNonimprovementPharmacotherapyTrajectories of relapse in randomised, placebo-controlled trials of treatment discontinuation in major depressive disorder: an individual patient-level data meta-analysis
Gueorguieva R, Chekroud AM, Krystal JH. Trajectories of relapse in randomised, placebo-controlled trials of treatment discontinuation in major depressive disorder: an individual patient-level data meta-analysis. The Lancet Psychiatry 2017, 4: 230-237. PMID: 28189575, PMCID: PMC5340978, DOI: 10.1016/s2215-0366(17)30038-x.Peer-Reviewed Original ResearchConceptsActive medicationActive treatmentClinical trialsDepression severityHamilton Depression Rating Scale scoresDepression Rating Scale scoresClinical Global Impression scoresIndividual patient-level dataDouble-blind treatmentPlacebo-controlled trialPatterns of relapseGlobal Impression scoresIndividual patient dataPrevention of relapseTrajectory class membershipTreatment of depressionMajor depressive disorderRating Scale scoresPatient-level dataPost-traumatic stress disorderTreatment discontinuationAntidepressant treatmentClinical responseAlcohol Research CenterAntidepressant medication
2014
Differences in Treatment Effect Among Clinical Subgroups in a Randomized Clinical Trial of Long-Acting Injectable Risperidone and Oral Antipsychotics in Unstable Chronic Schizophrenia
Leatherman SM, Liang MH, Krystal JH, Lew RA, Valley D, Thwin SS, Rosenheck RA. Differences in Treatment Effect Among Clinical Subgroups in a Randomized Clinical Trial of Long-Acting Injectable Risperidone and Oral Antipsychotics in Unstable Chronic Schizophrenia. The Journal Of Nervous And Mental Disease 2014, 202: 13-17. PMID: 24375206, DOI: 10.1097/nmd.0000000000000069.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAntipsychotic AgentsChronic DiseaseDrug Administration ScheduleFemaleHospitalizationHumansInjections, IntramuscularMaleMiddle AgedProportional Hazards ModelsPsychotic DisordersQuality of LifeRisk AssessmentRisperidoneSchizophreniaSchizophrenic PsychologySeverity of Illness IndexSubstance-Related DisordersTreatment OutcomeConceptsQuality of lifeOral antipsychoticsOral treatmentInjectable risperidoneCox regressionTreatment effectsLong-Acting Injectable RisperidoneBody mass indexPsychiatric service useSubstance abuse outcomesSubstance use outcomesLAI risperidonePrimary endpointStudy entryWhite patientsClinical outcomesMass indexUnstable patientsMedication compliancePsychiatric rehospitalizationChronic schizophreniaClinical trialsClinical subgroupsPsychiatric hospitalizationPsychiatric symptoms
2013
Association of Posttraumatic Stress Disorder With Reduced In Vivo Norepinephrine Transporter Availability in the Locus Coeruleus
Pietrzak RH, Gallezot JD, Ding YS, Henry S, Potenza MN, Southwick SM, Krystal JH, Carson RE, Neumeister A. Association of Posttraumatic Stress Disorder With Reduced In Vivo Norepinephrine Transporter Availability in the Locus Coeruleus. JAMA Psychiatry 2013, 70: 1199-1205. PMID: 24048210, PMCID: PMC4026855, DOI: 10.1001/jamapsychiatry.2013.399.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderNorepinephrine transporter availabilityLocus coeruleusPTSD groupTransporter availabilityHC groupVeterans Affairs Medical CenterStress disorderPTSD symptomsClinician-Administered PTSD ScalePositron emission tomography studyEmission tomography studiesPositron emission tomographyAnxious arousal symptomsNoradrenergic dysfunctionMedical CenterStudy groupMAIN OUTCOMEPTSD symptom clustersPTSD ScaleHealthy adultsCoeruleusBrain regionsChronic stressEmission tomography
2012
Global Prefrontal and Fronto-Amygdala Dysconnectivity in Bipolar I Disorder with Psychosis History
Anticevic A, Brumbaugh MS, Winkler AM, Lombardo LE, Barrett J, Corlett PR, Kober H, Gruber J, Repovs G, Cole MW, Krystal JH, Pearlson GD, Glahn DC. Global Prefrontal and Fronto-Amygdala Dysconnectivity in Bipolar I Disorder with Psychosis History. Biological Psychiatry 2012, 73: 565-573. PMID: 22980587, PMCID: PMC3549314, DOI: 10.1016/j.biopsych.2012.07.031.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmygdalaBipolar DisorderCase-Control StudiesFemaleFunctional NeuroimagingHumansMaleNeural PathwaysPrefrontal CortexPsychotic DisordersSeverity of Illness IndexConceptsPsychosis historyRisk factorsBipolar patientsSymptom severityResting-state functional magnetic resonanceAmygdala-mPFC connectivityFronto-limbic dysfunctionSevere clinical courseBipolar I patientsEmotion regulation regionsPsychotic symptom severityFunctional magnetic resonanceClinical courseI patientsLimbic structuresBipolar illnessConnectivity deficitsAmygdala findingsConnectivity abnormalitiesPathophysiological modelBipolar IPatientsBipolar disorderDysconnectivityAbnormal inhibition
2011
Trajectories of Depression Severity in Clinical Trials of Duloxetine: Insights Into Antidepressant and Placebo Responses
Gueorguieva R, Mallinckrodt C, Krystal JH. Trajectories of Depression Severity in Clinical Trials of Duloxetine: Insights Into Antidepressant and Placebo Responses. JAMA Psychiatry 2011, 68: 1227-1237. PMID: 22147842, PMCID: PMC3339151, DOI: 10.1001/archgenpsychiatry.2011.132.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntidepressive AgentsData Interpretation, StatisticalDepressive Disorder, MajorDouble-Blind MethodDuloxetine HydrochlorideFemaleHumansLinear ModelsMalePatient DropoutsPlacebo EffectPsychiatric Status Rating ScalesRandomized Controlled Trials as TopicSelective Serotonin Reuptake InhibitorsSeverity of Illness IndexThiophenesTreatment OutcomeConceptsSelective serotonin reuptake inhibitorsPlacebo-treated patientsComparator selective serotonin reuptake inhibitorsHAM-D scoresClinical trialsAntidepressant treatmentPlacebo responseMajor depressionDouble-blind clinical trialHigh placebo response rateSerotonergic antidepressant treatmentPlacebo response ratesSerotonin reuptake inhibitorsAntidepressant nonrespondersPlacebo armMost patientsAntidepressant respondersMedication risksReuptake inhibitorsSerotonergic antidepressantsResponder statusTreatment responseClinical trajectoriesDepression scoresDepression severityAdjunctive Risperidone Treatment for Antidepressant-Resistant Symptoms of Chronic Military Service–Related PTSD: A Randomized Trial
Krystal JH, Rosenheck RA, Cramer JA, Vessicchio JC, Jones KM, Vertrees JE, Horney RA, Huang GD, Stock C, Group F. Adjunctive Risperidone Treatment for Antidepressant-Resistant Symptoms of Chronic Military Service–Related PTSD: A Randomized Trial. JAMA 2011, 306: 493-502. PMID: 21813427, DOI: 10.1001/jama.2011.1080.Peer-Reviewed Original ResearchConceptsMilitary-related posttraumatic stress disorderMontgomery-Asberg Depression Rating ScalePosttraumatic stress disorderClinical Global Impression ScaleClinician-Administered PTSD ScaleHamilton Anxiety ScalePlacebo-controlled multicenter trialCAPS scoresSelf-reported weight gainSecond-generation antipsychotic risperidoneAdjunctive risperidone treatmentAntidepressant-resistant symptomsPrimary outcome measureChronic military-related posttraumatic stress disorderGlobal Impression ScaleOutpatient medical centerDepression Rating ScaleSymptoms of depressionQuality of lifePlacebo groupRisperidone groupVeterans RANDAdverse eventsOngoing symptomsMulticenter trial
2010
Characterization of the Interactive Effects of Glycine and D-Cycloserine in Men: Further Evidence for Enhanced NMDA Receptor Function Associated with Human Alcohol Dependence
Krystal JH, Petrakis IL, Limoncelli D, Nappi SK, Trevisan L, Pittman B, D'Souza DC. Characterization of the Interactive Effects of Glycine and D-Cycloserine in Men: Further Evidence for Enhanced NMDA Receptor Function Associated with Human Alcohol Dependence. Neuropsychopharmacology 2010, 36: 701-710. PMID: 21124304, PMCID: PMC3055693, DOI: 10.1038/npp.2010.203.Peer-Reviewed Original ResearchConceptsNMDA receptor functionAlcohol-dependent patientsHuman alcohol dependenceAntagonist-like effectsReceptor functionReceptor antagonistDCS effectsD-cycloserineAlcohol-like effectsAlcohol dependenceNMDA glutamate receptor functionN-methyl-D-aspartate (NMDA) glutamate receptor antagonistStandard alcohol drinksGlutamate receptor antagonistsChronic alcohol consumptionDouble-blind conditionsNMDA receptor antagonistAlcohol-dependent menGlutamate receptor functionAlcohol-dependent animalsPlasma levelsGlycine administrationGlycine levelsNMDA receptorsCoagonist site
2009
Efficacy of D-Cycloserine for Enhancing Response to Cognitive-Behavior Therapy for Panic Disorder
Otto MW, Tolin DF, Simon NM, Pearlson GD, Basden S, Meunier SA, Hofmann SG, Eisenmenger K, Krystal JH, Pollack MH. Efficacy of D-Cycloserine for Enhancing Response to Cognitive-Behavior Therapy for Panic Disorder. Biological Psychiatry 2009, 67: 365-370. PMID: 19811776, DOI: 10.1016/j.biopsych.2009.07.036.Peer-Reviewed Original ResearchConceptsCognitive behavior therapyExposure-based cognitive behavior therapyD-cycloserinePanic disorderTherapeutic learningPanic Disorder Severity ScaleInternal sensationsManualized cognitive behavior therapyPlacebo-controlled augmentation trialD-cycloserine augmentationLarge effect sizesExposure interventionDCS administrationPill placeboAnxiety disordersDSM-IV criteriaSession 3Global ImpressionEffect sizePrimary outcome measureClinician Global ImpressionDisordersParticipantsLearningSignificant adverse effects
2008
Positron Emission Tomography Imaging of the Serotonin Transporter and 5-HT1A Receptor in Alcohol Dependence
Martinez D, Slifstein M, Gil R, Hwang DR, Huang Y, Perez A, Frankle WG, Laruelle M, Krystal J, Abi-Dargham A. Positron Emission Tomography Imaging of the Serotonin Transporter and 5-HT1A Receptor in Alcohol Dependence. Biological Psychiatry 2008, 65: 175-180. PMID: 18962444, PMCID: PMC2621104, DOI: 10.1016/j.biopsych.2008.08.034.Peer-Reviewed Original ResearchConceptsType II alcoholismSerotonergic transmissionControl subjectsTransporter levelsAlcohol-dependent subjectsNonspecific partition coefficientEmission Tomography ImagingPositron emission tomography (PET) imagingSeverity of alcoholismDifferent brain regionsTwo-tissue compartment modelSerotonin innervationTransporter availabilityAlcoholic subjectsRodent modelsAlcohol dependenceDisease severitySignificant negative correlationBrain regionsSerotonin transporterSubjects SubjectsAlcoholismTomography imagingSignificant differencesPatientsDecreased 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
2007
Lamotrigine as Add-On Therapy in Schizophrenia
Goff DC, Keefe R, Citrome L, Davy K, Krystal JH, Large C, Thompson TR, Volavka J, Webster EL. Lamotrigine as Add-On Therapy in Schizophrenia. Journal Of Clinical Psychopharmacology 2007, 27: 582-589. PMID: 18004124, DOI: 10.1097/jcp.0b013e31815abf34.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnticonvulsantsAntipsychotic AgentsClozapineDiagnostic and Statistical Manual of Mental DisordersDose-Response Relationship, DrugDouble-Blind MethodDrug Administration ScheduleDrug ResistanceDrug Therapy, CombinationFemaleHumansLamotrigineMaleMiddle AgedPatient CompliancePatient DropoutsPsychiatric Status Rating ScalesSchizophreniaSeverity of Illness IndexSuicide, AttemptedTreatment OutcomeTriazinesConceptsNegative Syndrome Scale total scoreScale total scoreAntipsychotic medicationTotal scoreTreatment groupsSchizophrenia patientsPlacebo-controlled trialPrimary end pointParallel-group trialUse of lamotrigineClinical Global ImpressionAtypical antipsychotic medicationsResidual psychotic symptomsSymptom total scoreNegative Symptoms total scoreLamotrigine augmentationLamotrigine trialsRefractory psychosisAtypical antipsychoticsCognitive composite scoreWeek 12Global ImpressionTreat samplePsychotic symptomsLamotrigine
2006
Brain-Derived Neurotrophic Factor–5-HTTLPR Gene Interactions and Environmental Modifiers of Depression in Children
Kaufman J, Yang BZ, Douglas-Palumberi H, Grasso D, Lipschitz D, Houshyar S, Krystal JH, Gelernter J. Brain-Derived Neurotrophic Factor–5-HTTLPR Gene Interactions and Environmental Modifiers of Depression in Children. Biological Psychiatry 2006, 59: 673-680. PMID: 16458264, DOI: 10.1016/j.biopsych.2005.10.026.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentBrain-Derived Neurotrophic FactorCase-Control StudiesChildChild AbuseChild, PreschoolChi-Square DistributionDepressionDNA Mutational AnalysisEnvironmentFemaleGene FrequencyGenetic VariationGenotypeHumansMaleMethioninePredictive Value of TestsPsychiatric Status Rating ScalesRisk FactorsSerotonin Plasma Membrane Transport ProteinsSeverity of Illness IndexSocial SupportSurveys and QuestionnairesValineConceptsBrain-derived neurotrophic factor (BDNF) genotypeNeurotrophic factor genotypeSocial supportHigher depression scoresBDNF genotypeProportion scoreBDNF geneProtective effectDepression scoresComparison subjectsPsychiatric symptomatologyModerate riskEnvironmental modifiersDepressionFactor genotypeChildrenDNA specimensStandard research instrumentsShort alleleRiskMaltreatment historyCurrent dataScoresAncestry informative markersChild abuse
2004
Social supports and serotonin transporter gene moderate depression in maltreated children
Kaufman J, Yang BZ, Douglas-Palumberi H, Houshyar S, Lipschitz D, Krystal JH, Gelernter J. Social supports and serotonin transporter gene moderate depression in maltreated children. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 17316-17321. PMID: 15563601, PMCID: PMC534414, DOI: 10.1073/pnas.0404376101.Peer-Reviewed Original ResearchConceptsSocial supportDevelopment of depressionGene promoter polymorphismTransporter gene promoter polymorphismSerotonin transporter gene promoter polymorphismHigher depression ratingsDepression ratingsClinical dataModerate depressionPsychiatric disordersDepression scoresPromoter polymorphismNegative sequelaeModerate riskDepressionEarly stressChildrenS genotypeHistory of maltreatmentRiskShort alleleSubtype-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
Naltrexone augmentation of neuroleptic treatment in alcohol abusing patients with schizophrenia
Petrakis IL, O’Malley S, Rounsaville B, Poling J, McHugh-Strong C, Krystal JH, VA Naltrexone Study Collaboration Group. Naltrexone augmentation of neuroleptic treatment in alcohol abusing patients with schizophrenia. Psychopharmacology 2003, 172: 291-297. PMID: 14634716, DOI: 10.1007/s00213-003-1658-9.Peer-Reviewed Original ResearchMeSH KeywordsAlcoholismComorbidityDouble-Blind MethodHumansMaleMiddle AgedNaltrexoneNarcotic AntagonistsNew EnglandSchizophreniaSeverity of Illness IndexTreatment OutcomeConceptsFederal Drug AdministrationSide effectsDrinking daysAlcohol dependenceDouble-blind fashionEfficacy of naltrexoneAbnormal involuntary movementsComorbid alcohol dependenceHeavy drinking daysTreatment of alcoholismSymptoms of schizophreniaRelapse prevention strategiesNegative Symptom ScaleNaltrexone augmentationTime-line follow-back methodNeuroleptic medicationNeuroleptic treatmentEffective medicationsMedication complianceComorbid schizophreniaOutpatient studyWeekly therapyEffective pharmacotherapyConclusionsThese dataInvoluntary movements
2000
Antidepressant effects of ketamine in depressed patients
Berman R, Cappiello A, Anand A, Oren D, Heninger G, Charney D, Krystal J. Antidepressant effects of ketamine in depressed patients. Biological Psychiatry 2000, 47: 351-354. PMID: 10686270, DOI: 10.1016/s0006-3223(99)00230-9.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntidepressive AgentsDepressive Disorder, MajorDose-Response Relationship, DrugDouble-Blind MethodExcitatory Amino Acid AntagonistsFemaleGlutamic AcidHumansInjections, IntravenousKetamineMaleMiddle AgedPsychiatric Status Rating ScalesReceptors, N-Methyl-D-AspartateSeverity of Illness IndexConceptsMajor depressionN-methyl-D-aspartate receptor antagonistBrain glutamate systemDouble-blind trialDouble-blind conditionsTreatment of depressionMechanism of actionPlacebo infusionAntidepressant effectsIntravenous treatmentSingle doseReceptor antagonistDepressed patientsGlutamate systemDepressive symptomsPreclinical researchKetamine hydrochlorideDepressionPotential roleTest dayTreatment effectsPatientsKetamineSaline solutionTreatment