2023
A pilot randomized controlled trial of ketamine in Borderline Personality Disorder
Fineberg S, Choi E, Shapiro-Thompson R, Dhaliwal K, Neustadter E, Sakheim M, Null K, Trujillo-Diaz D, Rondeau J, Pittaro G, Peters J, Corlett P, Krystal J. A pilot randomized controlled trial of ketamine in Borderline Personality Disorder. Neuropsychopharmacology 2023, 48: 991-999. PMID: 36804489, PMCID: PMC10209175, DOI: 10.1038/s41386-023-01540-4.Peer-Reviewed Original ResearchConceptsBorderline personality disorderSecondary outcome measuresOutcome measuresSocio-occupational functioningSuicidal ideationPilot studyTrial of ketaminePersonality disorderInfusion of ketaminePrimary outcome measureEffects of ketamineMidazolam groupAdverse eventsKetamine groupClinical benefitMood symptomsKetamineFDA approvalDrug midazolamInfusionBPD symptomsLarger studyDepressed moodSymptomsChronic mood
2022
Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial
Abdallah CG, Roache JD, Gueorguieva R, Averill LA, Young-McCaughan S, Shiroma PR, Purohit P, Brundige A, Murff W, Ahn KH, Sherif MA, Baltutis EJ, Ranganathan M, D’Souza D, Martini B, Southwick SM, Petrakis IL, Burson RR, Guthmiller KB, López-Roca AL, Lautenschlager KA, McCallin JP, Hoch MB, Timchenko A, Souza SE, Bryant CE, Mintz J, Litz BT, Williamson DE, Keane TM, Peterson AL, Krystal JH. Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial. Neuropsychopharmacology 2022, 47: 1574-1581. PMID: 35046508, PMCID: PMC8767037, DOI: 10.1038/s41386-022-01266-9.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderClinical trialsOutcome measuresMontgomery-Åsberg Depression Rating ScaleSelf-report PTSD ChecklistÅsberg Depression Rating ScaleStress disorderPTSD symptomsAntidepressant-resistant symptomsPrevious antidepressant treatmentClinician-Administered PTSD ScaleMulti-center clinical trialRapid antidepressant effectsSecondary outcome measuresPrimary outcome measureSignificant dose-related effectsRole of ketamineDepression Rating ScaleDose-related effectsEffects of ketamineDSM-5Intravenous placeboDose ketamineTreatment discontinuationActive duty military
2021
Design of the national adaptive trial for PTSD-related insomnia (NAP study), VA cooperative study program (CSP) #2016
Krystal JH, Chow B, Vessicchio J, Henrie AM, Neylan TC, Krystal AD, Marx BP, Xu K, Jindal RD, Davis LL, Schnurr PP, Stein MB, Thase ME, Ventura B, Huang GD, Shih MC, Team T. Design of the national adaptive trial for PTSD-related insomnia (NAP study), VA cooperative study program (CSP) #2016. Contemporary Clinical Trials 2021, 109: 106540. PMID: 34416369, DOI: 10.1016/j.cct.2021.106540.Peer-Reviewed Original ResearchConceptsCooperative Studies ProgramInsomnia medicationsMedical CenterRandomized placebo-controlled clinical trialPlacebo-controlled clinical trialVeterans Affairs Medical CenterVA Cooperative Studies ProgramPrimary outcome measureVA Medical CenterInsomnia Severity IndexAdaptive trialsPosttraumatic stress disorderFuture biomarker developmentStudy armsBiochemical predictorsEffective pharmacotherapyClinical trialsOutcome measuresTreatment responseInterim analysisRecruitment targetInsomniaPhone contactStress disorderBiomarker development
2019
Measuring the effects of ketamine on mGluR5 using [18F]FPEB and PET
Holmes SE, Gallezot JD, Davis MT, DellaGioia N, Matuskey D, Nabulsi N, Krystal JH, Javitch JA, DeLorenzo C, Carson RE, Esterlis I. Measuring the effects of ketamine on mGluR5 using [18F]FPEB and PET. Cerebrovascular And Brain Metabolism Reviews 2019, 40: 2254-2264. PMID: 31744389, PMCID: PMC7585925, DOI: 10.1177/0271678x19886316.Peer-Reviewed Original ResearchConceptsEffects of ketamineKetamine infusionGlutamate transmissionMetabotropic glutamate receptor 5Ketamine-induced effectsKetamine-induced changesGlutamate receptor 5Promising treatment targetDrug challenge studiesTwo-tissue compartment modelMGluR5 radioligandBlood pressureMGluR5 availabilityBaseline scanOutcome measuresHealthy subjectsHeart ratePsychiatric disordersReceptor 5Modulatory effectsMGluR5Treatment targetsChallenge studiesArterial input functionChallenge paradigm
2011
Noradrenergic vs Serotonergic Antidepressant with or without Naltrexone for Veterans with PTSD and Comorbid Alcohol Dependence
Petrakis IL, Ralevski E, Desai N, Trevisan L, Gueorguieva R, Rounsaville B, Krystal JH. Noradrenergic vs Serotonergic Antidepressant with or without Naltrexone for Veterans with PTSD and Comorbid Alcohol Dependence. Neuropsychopharmacology 2011, 37: 996-1004. PMID: 22089316, PMCID: PMC3280636, DOI: 10.1038/npp.2011.283.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderSerotonin uptake inhibitorNorepinephrine uptake inhibitorUptake inhibitorAlcohol dependenceMale veteransTreatment of PTSDUse outcomesSymptoms of PTSDDouble-blind conditionsMain outcome measuresEvidence of efficacyComorbid alcohol dependenceCurrent diagnostic criteriaAlcohol use disorderAlcohol use outcomesComorbid conditionsAdjunctive efficacyOutcome measuresOnly FDADiagnostic criteriaUse disordersClinical advantagesAlcohol consumptionDrug AdministrationThe Effect of Early Trauma Exposure on Serotonin Type 1B Receptor Expression Revealed by Reduced Selective Radioligand Binding
Murrough JW, Czermak C, Henry S, Nabulsi N, Gallezot JD, Gueorguieva R, Planeta-Wilson B, Krystal JH, Neumaier JF, Huang Y, Ding YS, Carson RE, Neumeister A. The Effect of Early Trauma Exposure on Serotonin Type 1B Receptor Expression Revealed by Reduced Selective Radioligand Binding. JAMA Psychiatry 2011, 68: 892-900. PMID: 21893657, PMCID: PMC3244836, DOI: 10.1001/archgenpsychiatry.2011.91.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsBrainCarbon RadioisotopesCross-Sectional StudiesDepressive Disorder, MajorFemaleHumansMaleMiddle AgedPiperazinesPositron-Emission TomographyPsychiatric Status Rating ScalesPyrrolidinonesRadioligand AssayReceptor, Serotonin, 5-HT1BSerotonin 5-HT1 Receptor AntagonistsStress Disorders, Post-TraumaticTrauma Severity IndicesWounds and InjuriesConceptsPosttraumatic stress disorderHealthy control participantsEarly trauma exposureTrauma exposureReceptor expressionCause of PTSDVeterans Affairs Medical CenterMajor depression comorbidityPositron emission tomography studyControl participantsMain outcome measuresRecent animal modelsTrauma-exposed control participantsSevere trauma exposureEmission tomography studiesFirst trauma exposureLimbic corticostriatal circuitsAnterior cingulate cortexPositron emission tomographyPTSD symptom severityDepression comorbiditySerotonergic dysfunctionMedical CenterOutcome measuresStudy group
2005
Absence of behavioral sensitization in healthy human subjects following repeated exposure to ketamine
Cho HS, D’Souza D, Gueorguieva R, Perry EB, Madonick S, Karper LP, Abi-Dargham A, Belger A, Abi-Saab W, Lipschitz D, Bennet A, Seibyl JP, Krystal JH. Absence of behavioral sensitization in healthy human subjects following repeated exposure to ketamine. Psychopharmacology 2005, 179: 136-143. PMID: 15682309, DOI: 10.1007/s00213-004-2066-5.Peer-Reviewed Original ResearchConceptsHealthy human subjectsBehavioral sensitizationReceptor antagonistN-methyl-D-aspartate (NMDA) glutamate receptor antagonistBehavioral effectsHuman subjectsGlutamate receptor antagonistsNMDA receptor antagonistConclusionsThe current dataEvidence of sensitizationRetrospective studyKetamine administrationOutcome measuresNegative symptomsObjectivesThe purposePrevious exposureFirst exposureKetamineSensitizationAntagonistExposurePerceptual alterationsCurrent dataSeparate studiesSubjects
2003
Treatment Models and Designs for Intervention Research During the Psychotic Prodrome
Kane JM, Krystal J, Correll CU. Treatment Models and Designs for Intervention Research During the Psychotic Prodrome. Schizophrenia Bulletin 2003, 29: 747-756. PMID: 14989412, DOI: 10.1093/oxfordjournals.schbul.a007044.Peer-Reviewed Original ResearchConceptsPsychotic prodromePsychotic disordersEarly interventionSubsequent symptom severityTreatment modelOngoing intervention trialsSpecific symptom clustersTreatment refractorinessFunctional disabilityPatient selectionIntervention trialsFunctional outcomeProdromal symptomsDisease progressionNatural courseTarget symptomsSubsyndromal symptomsDifferent treatment modelsOutcome measuresProdromal populationTreatment responseProdromal stateTrial designSymptom clustersSymptom severity
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