2021
The effect of ketamine on psychopathology and implications for understanding schizophrenia and its therapeutic use: a meta-analysis
Beck K, Hindley G, Borgan F, Ginestet C, McCutcheon R, Brugger S, Driesen N, Ranganathan M, D'Souza D, Taylor M, Krystal J, Howes O. The effect of ketamine on psychopathology and implications for understanding schizophrenia and its therapeutic use: a meta-analysis. BJPsych Open 2021, 7: s237-s237. PMCID: PMC8771247, DOI: 10.1192/bjo.2021.634.Peer-Reviewed Original ResearchBrief Psychiatric Rating ScaleEffects of ketaminePlacebo conditionPositive symptomsKetamine administrationKetamine effectsHealthy participantsHealthy volunteersNegative symptomsTherapeutic useAcute ketamine administrationAcute ketamine challengeMagnitude of symptomsStudy-level dataSub-group analysisPsychiatric Rating ScaleSchizophrenia-like symptomatologySchizophrenia-like symptomsMean change scoresNegative Syndrome ScalePositive psychotic symptomsSignificant increaseEffect sizeBolus dosesKetamine challenge
2020
Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia
Beck K, Hindley G, Borgan F, Ginestet C, McCutcheon R, Brugger S, Driesen N, Ranganathan M, D’Souza D, Taylor M, Krystal JH, Howes OD. Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia. JAMA Network Open 2020, 3: e204693. PMID: 32437573, PMCID: PMC7243091, DOI: 10.1001/jamanetworkopen.2020.4693.Peer-Reviewed Original ResearchConceptsBrief Psychiatric Rating ScalePlacebo conditionPositive symptomsNegative symptomsHealthy participantsMean differenceKetamine administrationPANSS scoresHealthy volunteersPsychotomimetic symptomsTherapeutic useAcute ketamine administrationAcute ketamine challengePlacebo-controlled studyEffect sizeMagnitude of symptomsStudy-level dataPsychiatric Rating ScaleMeta-Analyses (PRISMA) guidelinesPreferred Reporting ItemsAssociation of ketamineNegative Syndrome ScaleSignificant increaseAcute administrationBolus doses
2019
A multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms
Fleming LM, Javitt DC, Carter CS, Kantrowitz JT, Girgis RR, Kegeles LS, Ragland JD, Maddock RJ, Lesh TA, Tanase C, Robinson J, Potter WZ, Carlson M, Wall MM, Choo TH, Grinband J, Lieberman J, Krystal JH, Corlett PR. A multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms. NeuroImage Clinical 2019, 22: 101739. PMID: 30852397, PMCID: PMC6411494, DOI: 10.1016/j.nicl.2019.101739.Peer-Reviewed Original ResearchConceptsDorsolateral prefrontal cortexN-methyl-D-aspartate (NMDA) glutamate receptor antagonistFunctional connectivityKetamine-induced alterationsGlutamate receptor antagonistsAltered brain functionState functional connectivityRsfMRI connectivityRisk patientsMulticenter studyKetamine effectsReceptor antagonistDLPFC connectivityMimic symptomsHealthy individualsKetamine usePositive symptomsCertain biomarkersBrain functionPrefrontal cortexPatientsConnectivity signaturesSeed-based measuresSchizophreniaKetamine
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
2011
Glutamatergic Modulation of Auditory Information Processing in the Human Brain
Gunduz-Bruce H, Reinhart RM, Roach BJ, Gueorguieva R, Oliver S, D'Souza DC, Ford JM, Krystal JH, Mathalon DH. Glutamatergic Modulation of Auditory Information Processing in the Human Brain. Biological Psychiatry 2011, 71: 969-977. PMID: 22036036, PMCID: PMC3290754, DOI: 10.1016/j.biopsych.2011.09.031.Peer-Reviewed Original ResearchConceptsN-acetylcysteineAuditory mismatch negativityReceptor antagonistN-methyl-D-aspartate receptor antagonistAspartate glutamate receptor antagonistOral N-acetylcysteinePlacebo-controlled studyGlutamate receptor antagonistsEffects of ketamineInfusion of salineMismatch negativityTest dayMMN amplitudeCystine-glutamate exchangerAuditory information processingP300 event-related potentialGlutamatergic modulationCognitive enhancing agentsEvent-related potentialsKetamine effectsHealthy volunteersHealthy humansSchizophrenia patientsPositive symptomsKetamine
2005
Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine: Implications for Glutamatergic and Dopaminergic Model Psychoses and Cognitive Function
Krystal JH, Perry EB, Gueorguieva R, Belger A, Madonick SH, Abi-Dargham A, Cooper TB, MacDougall L, Abi-Saab W, D’Souza D. Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine: Implications for Glutamatergic and Dopaminergic Model Psychoses and Cognitive Function. JAMA Psychiatry 2005, 62: 985-995. PMID: 16143730, DOI: 10.1001/archpsyc.62.9.985.Peer-Reviewed Original Research
2002
Ritanserin antagonism of m-chlorophenylpiperazine effects in neuroleptic-free schizophrenics patients: support for serotonin-2 receptor modulation of schizophrenia symptoms
Abi-Saab W, Seibyl JP, D'Souza C, Karper LP, Gueorgueva R, Abi-Dargham A, Wong ML, Rajhans S, Erdos JP, Heninger GR, Charney DS, Krystal JH. Ritanserin antagonism of m-chlorophenylpiperazine effects in neuroleptic-free schizophrenics patients: support for serotonin-2 receptor modulation of schizophrenia symptoms. Psychopharmacology 2002, 162: 55-62. PMID: 12107618, DOI: 10.1007/s00213-002-1057-7.Peer-Reviewed Original ResearchConceptsReceptor antagonismSchizophrenic patientsNeuroleptic-free schizophrenic patientsBrief Psychiatric Rating ScaleDouble-blind conditionsPsychiatric Rating ScaleTest dayRitanserin pretreatmentIntravenous infusionReceptor modulationAntipsychotic activityMale inpatientsReceptor stimulationPlasma prolactinCortisol levelsSchizoaffective disorderSchizophrenia symptomsPositive symptomsNegative symptomsRandomized orderPatientsRating ScaleBehavioral activationSymptomsRitanserin
1998
Increased Striatal Dopamine Transmission in Schizophrenia: Confirmation in a Second Cohort
Abi-Dargham A, Gil R, Krystal J, Baldwin RM, Seibyl JP, Bowers M, van Dyck CH, Charney DS, Innis RB, Laruelle M. Increased Striatal Dopamine Transmission in Schizophrenia: Confirmation in a Second Cohort. American Journal Of Psychiatry 1998, 155: 761-767. PMID: 9619147, DOI: 10.1176/ajp.155.6.761.Peer-Reviewed Original ResearchConceptsD2 receptor availabilityAcute amphetamine challengeStriatal dopamine transmissionAmphetamine challengeReceptor availabilityDopamine releaseHealthy subjectsDopamine transmissionDopamine D2 receptor availabilityExcess dopamine releaseStriatal dopamine releaseComparison groupD2 receptor radiotracerHistory of alcoholDSM-IV criteriaSingle photon emissionNew cohortUntreated patientsReceptor radiotracerSchizophrenic patientsPatientsSecond cohortParental socioeconomic statusPositive symptomsSubstance abuse
1993
m-Chlorophenylpiperazine Effects in Neuroleptic-Free Schizophrenic Patients: Evidence Implicating Serotonergic Systems in the Positive Symptoms of Schizophrenia
Krystal JH, Seibyl JP, Price LH, Woods SW, Heninger GR, Aghajanian GK, Charney DS. m-Chlorophenylpiperazine Effects in Neuroleptic-Free Schizophrenic Patients: Evidence Implicating Serotonergic Systems in the Positive Symptoms of Schizophrenia. JAMA Psychiatry 1993, 50: 624-635. PMID: 8102048, DOI: 10.1001/archpsyc.1993.01820200034004.Peer-Reviewed Original ResearchConceptsBrief Psychiatric Rating ScaleHealthy subjectsPsychiatric Rating ScalePositive symptomsSchizophrenic patientsPatient groupDouble-blind randomized comparisonVeterans Affairs Medical CenterRating ScaleNeuroleptic-free schizophrenic patientsFirst patient groupSerotonin partial agonistPrincipal outcome variableVisual analog scaleBaseline prolactin levelsHigher baseline levelsSymptoms of schizophreniaAnalog scaleRandomized comparisonAnxiogenic responseSum of scoresProlactin levelsSerotonergic systemSerotonin functionHormone levels