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
Tobacco smoking interferes with GABAA receptor neuroadaptations during prolonged alcohol withdrawal
Cosgrove KP, McKay R, Esterlis I, Kloczynski T, Perkins E, Bois F, Pittman B, Lancaster J, Glahn DC, O’Malley S, Carson RE, Krystal JH. Tobacco smoking interferes with GABAA receptor neuroadaptations during prolonged alcohol withdrawal. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 18031-18036. PMID: 25453062, PMCID: PMC4273348, DOI: 10.1073/pnas.1413947111.Peer-Reviewed Original ResearchConceptsGABAA receptor levelsAlcohol withdrawalTobacco smokingReceptor levelsGABAA receptorsAlcohol-dependent smokersGABAA receptor availabilityMo of abstinenceProlonged alcohol withdrawalGABAA receptor systemCombination of alcoholNicotine blocksComorbid alcoholSustained elevationAlcohol abstinenceNicotine dependenceRobust elevationReceptor availabilityNicotine consumptionSmokingReceptor systemFirst weekNonhuman primatesControl levelsWithdrawal
2005
γ-Aminobutyric Acid–Serotonin Interactions in Healthy Men: Implications for Network Models of Psychosis and Dissociation
D’Souza D, Gil RB, Zuzarte E, MacDougall LM, Donahue L, Ebersole JS, Boutros NN, Cooper T, Seibyl J, Krystal JH. γ-Aminobutyric Acid–Serotonin Interactions in Healthy Men: Implications for Network Models of Psychosis and Dissociation. Biological Psychiatry 2005, 59: 128-137. PMID: 16140281, DOI: 10.1016/j.biopsych.2005.06.020.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnxietyCross-Over StudiesDissociative DisordersDouble-Blind MethodDrug SynergismFlumazenilGABA ModulatorsGamma-Aminobutyric AcidHumansMaleModels, NeurologicalPerceptual DisordersPiperazinesPsychoses, Substance-InducedReceptors, GABA-AReceptors, Serotonin, 5-HT2Reference ValuesSerotoninSerotonin Receptor AgonistsCortical γ-Aminobutyric Acid Type A–Benzodiazepine Receptors in Recovery From Alcohol Dependence: Relationship to Features of Alcohol Dependence and Cigarette Smoking
Staley JK, Gottschalk C, Petrakis IL, Gueorguieva R, O’Malley S, Baldwin R, Jatlow P, Verhoeff NP, Perry E, Weinzimmer D, Frohlich E, Ruff E, van Dyck CH, Seibyl JP, Innis RB, Krystal JH. Cortical γ-Aminobutyric Acid Type A–Benzodiazepine Receptors in Recovery From Alcohol Dependence: Relationship to Features of Alcohol Dependence and Cigarette Smoking. JAMA Psychiatry 2005, 62: 877-888. PMID: 16061765, DOI: 10.1001/archpsyc.62.8.877.Peer-Reviewed Original ResearchConceptsWeeks of abstinenceIomazenil single-photon emissionSingle photon emissionDays of sobrietyAlcohol dependenceIomazenil uptakeTomographic scanBenzodiazepine receptorsVoxel-based statistical parametric mappingReceptor adaptationDistribution volumeReceptor functionGamma-aminobutyric acid type ABenzodiazepine receptor levelsIodine I 123Reduced receptor functionHuman alcohol dependenceLast alcoholic drinkHealthy comparison groupStatistical parametric mappingAlcohol withdrawalClinical featuresSmoking statusCigarette smokingAcute withdrawal
1999
[123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia
Verhoeff N, Soares J, D’Souza C, Gil R, Degen K, Abi-Dargham A, Zoghbi S, Fujita M, Rajeevan N, Seibyl J, Krystal J, van Dyck C, Charney D, Innis R. [123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia. Psychiatry Research 1999, 91: 163-173. PMID: 10641580, DOI: 10.1016/s0925-4927(99)00027-x.Peer-Reviewed Original ResearchConceptsDuration of illnessHealthy control subjectsControl subjectsGamma-aminobutyric acidLeft precentral gyrusSuperior occipital gyrusPANSS scoresPrecentral gyrusOccipital gyrusSignificant differencesTotal brain uptakeNon-smoking patientsGray matter atrophyConstant infusion paradigmPathophysiology of schizophreniaCortical brain regionsSingle photon emissionTypical antipsychoticsAtypical antipsychoticsCigarette smokingInhibitory neurotransmissionBrain uptakeInfusion paradigmMatter atrophyPostmortem studiesNo Evidence of Altered In Vivo Benzodiazepine Receptor Binding in Schizophrenia
Abi-Dargham A, Laruelle M, Krystal J, D'Souza C, Zoghbi S, Baldwin R, Seibyl J, Mawlawi O, de Erasquin G, Charney D, Innis R. No Evidence of Altered In Vivo Benzodiazepine Receptor Binding in Schizophrenia. Neuropsychopharmacology 1999, 20: 650-661. PMID: 10327433, DOI: 10.1016/s0893-133x(98)00107-9.Peer-Reviewed Original ResearchConceptsReceptor densitySchizophrenic patientsVivo benzodiazepine receptor bindingBDZ receptor densityMale schizophrenic patientsBenzodiazepine receptor densityPathophysiology of schizophreniaBenzodiazepine receptor bindingSingle photon emissionRegional distribution volumesPrevious postmortemGABA transmissionBDZ antagonistBDZ receptorsReceptor expressionNeurotransmitter systemsHealthy volunteersPsychotic symptomsBrain regionsDistribution volumeReceptor bindingSchizophreniaVivo studiesPatientsPossible alterationsChanges of benzodiazepine receptors during chronic benzodiazepine administration in humans
Fujita M, Woods S, Verhoeff N, Abi-Dargham A, Baldwin R, Zoghbi S, Soares J, Jatlow P, Krystal J, Rajeevan N, Charney D, Seibyl J, Innis R. Changes of benzodiazepine receptors during chronic benzodiazepine administration in humans. European Journal Of Pharmacology 1999, 368: 161-172. PMID: 10193652, DOI: 10.1016/s0014-2999(99)00013-8.Peer-Reviewed Original ResearchConceptsClinical effectsReceptor levelsReceptor densityReceptor occupancyChronic benzodiazepine administrationBenzodiazepine receptor densityHealthy human subjectsComparison of baselineSingle photon emissionHopkins Verbal Learning TestInduced sedationVerbal Learning TestBenzodiazepine administrationOral administrationBaseline valuesBenzodiazepine receptorsTolerance developmentDay 3Day 17Day 4Day 10Central typeLearning TestReceptorsHuman subjects
1998
Alterations of Benzodiazepine Receptors in Type II Alcoholic Subjects Measured With SPECT and 123IIomazenil
Abi-Dargham A, Krystal JH, Anjilvel S, Scanley BE, Zoghbi S, Baldwin RM, Rajeevan N, Ellis S, Petrakis IL, Seibyl JP, Charney DS, Laruelle M, Innis RB. Alterations of Benzodiazepine Receptors in Type II Alcoholic Subjects Measured With SPECT and 123IIomazenil. American Journal Of Psychiatry 1998, 155: 1550-1555. PMID: 9812116, DOI: 10.1176/ajp.155.11.1550.Peer-Reviewed Original ResearchConceptsHealthy comparison subjectsBenzodiazepine receptorsComparison subjectsAlcoholic subjectsDistribution volumeAlcoholic patientsAnterior cingulateBenzodiazepine receptor densityRight middle frontal gyrusLeft occipital cortexType II alcoholismSingle photon emissionMiddle frontal gyrusStatistical parametric mappingContinuous infusionReceptor radiotracerReceptor densityOccipital cortexCerebellar cortexCortical regionsPatientsFrontal gyrusInterest analysisVivo studiesParametric mapping
1995
Effects of the benzodiazepine antagonist flumazenil in PTSD
Randall P, Bremner J, Krystal J, Nagy L, Heninger G, Nicolaou A, Charney D. Effects of the benzodiazepine antagonist flumazenil in PTSD. Biological Psychiatry 1995, 38: 319-324. PMID: 7495926, DOI: 10.1016/0006-3223(94)00306-n.Peer-Reviewed Original ResearchConceptsVisual analogue rating scaleAdministration of flumazenilAnxiety symptomsCrossover study designBenzodiazepine antagonist flumazenilGABAA receptor complexBenzodiazepine/GABAA receptor complexPanic disorder patientsAnalogue rating scalesFlumazenil administrationPTSD Symptom ScaleIntravenous infusionAntagonist flumazenilGABAA antagonistHealthy controlsClinical studiesDisorder patientsSymptom ScaleFlumazenilPanic disorderPanic attacksVietnam combat veteransStudy designRating ScalePTSD symptoms
1991
Behavioral, biochemical, and cardiovascular responses to the benzodiazepine receptor antagonist flumazenil in panic disorder
Woods S, Charney D, Silver J, Krystal J, Heninger G. Behavioral, biochemical, and cardiovascular responses to the benzodiazepine receptor antagonist flumazenil in panic disorder. Psychiatry Research 1991, 36: 115-127. PMID: 1850142, DOI: 10.1016/0165-1781(91)90124-8.Peer-Reviewed Original ResearchConceptsAntagonist flumazenilAnxiolytic effectsBenzodiazepine receptor antagonist flumazenilReceptor antagonist flumazenilDose of flumazenilVisual analog scaleBenzodiazepine receptor functionBZR inverse agonistsSignificant anxiolytic effectSeparate test daysPlacebo capsulesBlood pressureAnalog scaleCardiovascular responsesDisorder patientsHeart rateFlumazenilCrossover designPanic patientsPanic disorderPlasma cortisolBaseline levelsPanic attacksPlaceboReceptor function