2020
Continuous Ketamine Infusion for Pain as an Opportunity for Psychotherapy for PTSD: A Case Series of Ketamine-Enhanced Psychotherapy for PTSD and Pain (KEP-P2)
Keizer BM, Roache JD, Jones JR, Kalpinski RJ, Porcerelli JH, Krystal JH. Continuous Ketamine Infusion for Pain as an Opportunity for Psychotherapy for PTSD: A Case Series of Ketamine-Enhanced Psychotherapy for PTSD and Pain (KEP-P2). Psychotherapy And Psychosomatics 2020, 89: 326-329. PMID: 32248200, DOI: 10.1159/000507095.Peer-Reviewed Original Research
2017
Minimal Clinically Important Differences (MCID) in Assessing Outcomes of Post-Traumatic Stress Disorder
Stefanovics EA, Rosenheck RA, Jones KM, Huang G, Krystal JH. Minimal Clinically Important Differences (MCID) in Assessing Outcomes of Post-Traumatic Stress Disorder. Psychiatric Quarterly 2017, 89: 141-155. PMID: 28634644, DOI: 10.1007/s11126-017-9522-y.Peer-Reviewed Original ResearchDose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression
Su TP, Chen MH, Li CT, Lin WC, Hong CJ, Gueorguieva R, Tu PC, Bai YM, Cheng CM, Krystal JH. Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression. Neuropsychopharmacology 2017, 42: 2482-2492. PMID: 28492279, PMCID: PMC5686503, DOI: 10.1038/npp.2017.94.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntidepressive AgentsAsian PeopleBlood PressureBrain-Derived Neurotrophic FactorDepressive Disorder, MajorDepressive Disorder, Treatment-ResistantDose-Response Relationship, DrugDouble-Blind MethodFemaleHeart RateHumansKetamineMaleMiddle AgedPolymorphism, GeneticPsychiatric Status Rating ScalesTaiwanTreatment OutcomeConceptsTreatment-resistant depressionHamilton Depression Rating ScaleAntidepressant effectsKetamine effectsBDNF genotypeBrain-derived neurotrophic factor (BDNF) genotypeChinese populationDose-related efficacyPlacebo-controlled trialSignificant dose-related effectsDepression Rating ScaleNeurotrophic factor genotypeDose-related effectsSingle ketamine infusionMost patientsKetamine infusionTaiwanese patientsAdjunctive ketamineResponder analysisBDNF geneS-ketamineKetamine levelsPatientsMet alleleRating ScaleSex differences in the interacting roles of impulsivity and positive alcohol expectancy in problem drinking: A structural brain imaging study
Ide JS, Zhornitsky S, Hu S, Zhang S, Krystal JH, Li CR. Sex differences in the interacting roles of impulsivity and positive alcohol expectancy in problem drinking: A structural brain imaging study. NeuroImage Clinical 2017, 14: 750-759. PMID: 28413777, PMCID: PMC5385596, DOI: 10.1016/j.nicl.2017.03.015.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcohol DrinkingAlcoholismBrainBrain MappingFemaleHumansImpulsive BehaviorLinear ModelsMagnetic Resonance ImagingMalePsychiatric Status Rating ScalesSex CharacteristicsSurveys and QuestionnairesYoung AdultConceptsPositive alcohol expectanciesGray matter volumeAlcohol expectanciesAlcohol Use Disorders Identification TestSocial drinkersNon-dependent social drinkersProblem drinkingRole of impulsivityBrain imaging studiesRight posterior insulaSex differencesStructural brain imagingStructural brain imaging studiesNeural basisDisorders Identification TestBarratt impulsivityPsychological factorsImpulsivityMediation analysisPosterior insulaDependent individualsRisk factorsAlcohol misuseLinear modelingGeneral linear modelingCortical thickness reduction in combat exposed U.S. veterans with and without PTSD
Wrocklage KM, Averill LA, Scott J, Averill CL, Schweinsburg B, Trejo M, Roy A, Weisser V, Kelly C, Martini B, Harpaz-Rotem I, Southwick SM, Krystal JH, Abdallah CG. Cortical thickness reduction in combat exposed U.S. veterans with and without PTSD. European Neuropsychopharmacology 2017, 27: 515-525. PMID: 28279623, PMCID: PMC5429865, DOI: 10.1016/j.euroneuro.2017.02.010.Peer-Reviewed Original ResearchConceptsClinician-Administered PTSD ScalePTSD symptom dimensionsPTSD diagnosisCombat exposureCortical thicknessSymptom dimensionsMagnetic resonance imagingPosttraumatic stress disorder (PTSD) symptomsU.S. veteransCortical thinningUnique brain regionsLeft lateral prefrontalAnxious arousalPTSD dimensionsNeural correlatesHigh-resolution magnetic resonance imagingCortical thickness reductionsLateral prefrontalPTSD symptomsDisorder symptomsCombat severityCurrent PTSDPTSD ScalePrefrontal cortexPotential confounds
2016
Shall we really say goodbye to first rank symptoms?
Heinz A, Voss M, Lawrie SM, Mishara A, Bauer M, Gallinat J, Juckel G, Lang U, Rapp M, Falkai P, Strik W, Krystal J, Abi-Dargham A, Galderisi S. Shall we really say goodbye to first rank symptoms? European Psychiatry 2016, 37: 8-13. PMID: 27429167, DOI: 10.1016/j.eurpsy.2016.04.010.Peer-Reviewed Original Research
2015
Role of GABA Deficit in Sensitivity to the Psychotomimetic Effects of Amphetamine
Ahn KH, Sewell A, Elander J, Pittman B, Ranganathan M, Gunduz-Bruce H, Krystal J, D'Souza DC. Role of GABA Deficit in Sensitivity to the Psychotomimetic Effects of Amphetamine. Neuropsychopharmacology 2015, 40: 2822-2831. PMID: 25953357, PMCID: PMC4864658, DOI: 10.1038/npp.2015.132.Peer-Reviewed Original ResearchConceptsGABA deficitHealthy subjectsPsychotomimetic effectsIntravenous infusionSchizophrenia patientsPANSS positive symptoms subscaleDouble-blind crossover designStriatal dopamine releasePositive symptom subscaleAdministration of drugsDose of AMPHPartial inverse agonistSubclinical responsePharmacokinetic interactionsSubthreshold doseDopamine releaseBenzodiazepine receptorsSymptom subscalesCrossover designCADSS scoresPositive symptomsAMPHInverse agonistSubjective effectsTest day
2014
Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia
Xu K, Krystal JH, Ning Y, Chen da C, He H, Wang D, Ke X, Zhang X, Ding Y, Liu Y, Gueorguieva R, Wang Z, Limoncelli D, Pietrzak RH, Petrakis IL, Zhang X, Fan N. Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia. Journal Of Psychiatric Research 2014, 61: 64-72. PMID: 25560772, PMCID: PMC4445679, DOI: 10.1016/j.jpsychires.2014.12.012.Peer-Reviewed Original ResearchConceptsKetamine groupNegative Syndrome ScaleSchizophrenia groupSyndrome ScaleN-methyl-D-aspartate (NMDA) glutamate receptor antagonistGlutamate receptor antagonistsPotential confounding factorsEarly course schizophreniaSymptom dimensionsSymptoms of schizophreniaReceptor antagonistChronic schizophreniaHealthy subjectsKetamine abuseSchizophrenia psychosisSchizophrenia patientsConfounding factorsSymptom severitySymptomsInpatientsSchizophreniaPsychosisKetamine usersDissociation symptomsPrincipal component factor analysisSymptom structure and severity: A comparison of responses to the positive and negative syndrome scale (PANSS) between patients with PTSD or schizophrenia
Stefanovics EA, Krystal JH, Rosenheck RA. Symptom structure and severity: A comparison of responses to the positive and negative syndrome scale (PANSS) between patients with PTSD or schizophrenia. Comprehensive Psychiatry 2014, 55: 887-895. PMID: 24602497, DOI: 10.1016/j.comppsych.2014.01.014.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntipsychotic AgentsChronic DiseaseCombat DisordersDiagnosis, DifferentialDouble-Blind MethodFemaleHumansMaleMiddle AgedPsychiatric Status Rating ScalesPsychometricsRisperidoneSchizophreniaSchizophrenic PsychologyStress Disorders, Post-TraumaticVeteransYoung AdultConceptsPost-traumatic stress disorderNegative Syndrome ScaleSyndrome ScalePTSD samplePlacebo-controlled trialPsychosis-related factorsClinical trial patientsClinical Antipsychotic TrialsT-testSchizophrenia sampleExploratory factor analysisSymptoms of schizophreniaMilitary-related post-traumatic stress disorderSymptom structureAdjunctive risperidoneTrial patientsTraumatic Stress DisorderAntipsychotic TrialsSecondary data analysisSevere symptomsIndependent factorsDepressive factorsPatientsSymptom ratingsStress disorder
2013
Characterizing Thalamo-Cortical Disturbances in Schizophrenia and Bipolar Illness
Anticevic A, Cole MW, Repovs G, Murray JD, Brumbaugh MS, Winkler AM, Savic A, Krystal JH, Pearlson GD, Glahn DC. Characterizing Thalamo-Cortical Disturbances in Schizophrenia and Bipolar Illness. Cerebral Cortex 2013, 24: 3116-3130. PMID: 23825317, PMCID: PMC4224238, DOI: 10.1093/cercor/bht165.Peer-Reviewed Original ResearchConceptsThalamo-cortical systemThalamic connectivityBipolar illnessResting-state functional magnetic resonance imagingSensory-motor cortexSevere mental illnessFunctional magnetic resonance imagingMagnetic resonance imagingThalamic dysconnectivityThalamic seedsClinical presentationNeuropsychiatric syndromeBrain dysconnectivityThalamic nucleiBipolar patientsSchizophrenia patientsSensory gatingMental illnessResonance imagingDysconnectivityCerebellar regionsDiagnostic membershipPrefrontal cortexSchizophreniaIllness
2012
Differential brain response to alcohol cue distractors across stages of alcohol dependence
Fryer SL, Jorgensen KW, Yetter EJ, Daurignac EC, Watson TD, Shanbhag H, Krystal JH, Mathalon DH. Differential brain response to alcohol cue distractors across stages of alcohol dependence. Biological Psychology 2012, 92: 282-291. PMID: 23131612, PMCID: PMC3947923, DOI: 10.1016/j.biopsycho.2012.10.004.Peer-Reviewed Original ResearchConceptsAnterior cingulate cortexAlcohol cuesBrain responsesLong-term abstainersAlcohol dependenceDorsal anterior cingulate cortexRecruitment of attentionVentral anterior cingulate cortexCognitive control regionsAlcohol-related cuesCue-reactivity studiesCue-related activationsNon-alcohol cuesAttention-demanding taskDifferential brain responsesTarget detection taskInferior parietal lobuleMedial prefrontal cortexAlcohol-dependent individualsCue exposureAltered attentionDistractor effectNeural responsesParietal lobulePrefrontal cortexGlycine treatment of the risk syndrome for psychosis: Report of two pilot studies
Woods SW, Walsh BC, Hawkins KA, Miller TJ, Saksa JR, D'Souza DC, Pearlson GD, Javitt DC, McGlashan TH, Krystal JH. Glycine treatment of the risk syndrome for psychosis: Report of two pilot studies. European Neuropsychopharmacology 2012, 23: 931-940. PMID: 23089076, PMCID: PMC4028140, DOI: 10.1016/j.euroneuro.2012.09.008.Peer-Reviewed Original ResearchConceptsPilot studyRisk syndromeSyndrome patientsNegative symptomsShort-term pilot studyEffect sizeAdjunctive antipsychotic medicationOpen-label studyPatients meeting criteriaNMDA receptor functionDurability of effectPsychosis risk symptomsGlycine site agonistsGroup effect sizesWeeks of evaluationAntipsychotic medicationSyndrome subjectsPromising effect sizesTreatment needsLarge effect sizesMeeting criteriaCognitive impairmentReduced symptomsReceptor functionSymptomsEffects of Ketamine in Treatment-Refractory Obsessive-Compulsive Disorder
Bloch MH, Wasylink S, Landeros-Weisenberger A, Panza KE, Billingslea E, Leckman JF, Krystal JH, Bhagwagar Z, Sanacora G, Pittenger C. Effects of Ketamine in Treatment-Refractory Obsessive-Compulsive Disorder. Biological Psychiatry 2012, 72: 964-970. PMID: 22784486, PMCID: PMC3667652, DOI: 10.1016/j.biopsych.2012.05.028.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntidepressive AgentsDepressionExcitatory Amino Acid AntagonistsFemaleHumansKetamineMaleMiddle AgedObsessive-Compulsive DisorderPatient SelectionPsychiatric Status Rating ScalesTreatment OutcomeConceptsObsessive-compulsive disorderKetamine infusionDepression symptomsLow-dose ketamine infusionTreatment-refractory obsessive-compulsive disorderOCD symptomsPathogenesis of OCDIncomplete symptom reliefTreatment-Refractory ObsessiveOpen-label trialRapid antidepressant effectsAspartate glutamate receptorsEffects of ketaminePotent noncompetitive antagonistGlutamate abnormalitiesAntidepressant effectsAntidepressant responseSymptom reliefKetamine effectsComorbid depressionAcute effectsGlutamate receptorsDepressive symptomsNoncompetitive antagonistInfusionKetamine effects on brain GABA and glutamate levels with 1H-MRS: relationship to ketamine-induced psychopathology
Stone JM, Dietrich C, Edden R, Mehta MA, De Simoni S, Reed LJ, Krystal JH, Nutt D, Barker GJ. Ketamine effects on brain GABA and glutamate levels with 1H-MRS: relationship to ketamine-induced psychopathology. Molecular Psychiatry 2012, 17: 664-665. PMID: 22212598, PMCID: PMC3883303, DOI: 10.1038/mp.2011.171.Peer-Reviewed Original ResearchMeSH KeywordsBrainExcitatory Amino Acid AntagonistsGamma-Aminobutyric AcidGlutamic AcidHumansKetamineMagnetic Resonance SpectroscopyMaleProtonsPsychiatric Status Rating ScalesPsychopathology
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 severityThe 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 groupThe antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [1H]-MRS
Valentine GW, Mason GF, Gomez R, Fasula M, Watzl J, Pittman B, Krystal JH, Sanacora G. The antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [1H]-MRS. Psychiatry Research 2011, 191: 122-127. PMID: 21232924, PMCID: PMC3061550, DOI: 10.1016/j.pscychresns.2010.10.009.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntidepressive AgentsBlood PressureDepressive Disorder, MajorDissociative DisordersFemaleGamma-Aminobutyric AcidGlutamic AcidHeart RateHumansKetamineMagnetic Resonance SpectroscopyMaleMiddle AgedOccipital LobeProtonsPsychiatric Status Rating ScalesPsychometricsRetrospective StudiesSingle-Blind MethodStatistics as TopicTime FactorsYoung AdultConceptsMajor depressive disorderAntidepressant effectsAntidepressant actionNeurotransmitter contentNMDA receptor antagonist ketamineProton magnetic resonance spectroscopy methodConventional antidepressant treatmentKetamine's antidepressant actionSingle intravenous doseSingle-blind conditionsAntidepressant treatmentChronic treatmentKetamine infusionIntravenous dosePharmacodynamic basisDepressive disorderAcute actionsMRS scansOccipital cortexDepressive symptomsDepression scoresRating ScaleBaseline measuresInfusionKetamine
2010
The interplay of cannabinoid and NMDA glutamate receptor systems in humans: Preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects
Hallak JE, Dursun SM, Bosi DC, de Macedo LR, Machado-de-Sousa JP, Abrão J, Crippa JA, McGuire P, Krystal JH, Baker GB, Zuardi AW. The interplay of cannabinoid and NMDA glutamate receptor systems in humans: Preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects. Progress In Neuro-Psychopharmacology And Biological Psychiatry 2010, 35: 198-202. PMID: 21062637, DOI: 10.1016/j.pnpbp.2010.11.002.Peer-Reviewed Original ResearchConceptsBrief Psychiatric Rating ScaleHealthy human subjectsGlutamate receptor systemMale healthy volunteersNMDA receptor antagonistEffects of ketamineTreatment of schizophreniaPsychiatric Rating ScaleHuman subjectsWeak partial agonistNon-significant trendKetamine administrationReceptor antagonistEndocannabinoid systemHealthy volunteersPartial agonistActivation subscalePsychiatric conditionsKetamineRandomized orderReceptor systemBehavioral effectsRating ScaleCannabidiolPreliminary evidenceClinical significance of neurological soft signs in schizophrenia: Factor analysis of the Neurological Evaluation Scale
Sewell RA, Perry EB, Karper LP, Bell MD, Lysaker P, Goulet JL, Brenner L, Erdos J, d'Souza DC, Seibyl JP, Krystal JH. Clinical significance of neurological soft signs in schizophrenia: Factor analysis of the Neurological Evaluation Scale. Schizophrenia Research 2010, 124: 1-12. PMID: 20855185, DOI: 10.1016/j.schres.2010.08.036.Peer-Reviewed Original ResearchConceptsNeurological Evaluation ScaleAbnormal Involuntary Movement ScaleDigit Symbol Substitution TaskWisconsin Card Sorting TestNeurologic deficitsClinical significanceExtrapyramidal Symptom Rating ScaleMore extrapyramidal symptomsBarnes Akathisia ScaleDetailed clinical assessmentNeurological soft signsSymptom Rating ScaleNegative Syndrome ScaleHigher AIMS scoresEvaluation ScaleNeurological deficitsExtrapyramidal symptomsClinical correlatesDeficit syndrome schizophreniaClinical evaluationClinical assessmentAIMS scoresLower PANSSMovement ScaleSoft signsSPECT imaging of nicotinic acetylcholine receptors in nonsmoking heavy alcohol drinking individuals
Esterlis I, Cosgrove KP, Petrakis IL, McKee SA, Bois F, Krantzler E, Stiklus SM, Perry EB, Tamagnan GD, Seibyl JP, Krystal JH, Staley JK. SPECT imaging of nicotinic acetylcholine receptors in nonsmoking heavy alcohol drinking individuals. Drug And Alcohol Dependence 2010, 108: 146-150. PMID: 20074869, PMCID: PMC2871672, DOI: 10.1016/j.drugalcdep.2009.12.006.Peer-Reviewed Original ResearchConceptsDrinks/occasionNicotinic acetylcholine receptorsControl nonsmokersAcetylcholine receptorsHeavy drinkersHeavy drinkingLast alcoholic beverageHeavy alcohol drinkersHeavy alcoholSingle photon emissionSeverity of drinkingEffect of ageTobacco smokingAlcohol drinkersAlcohol drinkingCommon neural substrateNonsmokersAlcohol consumptionReceptor availabilityLarger studyAlcohol drinksAlcohol use behaviorsAddictive disordersDrinkersNeural substrates