2018
Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders: A Randomized Clinical Trial
Javitt DC, Carter CS, Krystal JH, Kantrowitz JT, Girgis RR, Kegeles LS, Ragland JD, Maddock RJ, Lesh TA, Tanase C, Corlett PR, Rothman DL, Mason G, Qiu M, Robinson J, Potter WZ, Carlson M, Wall MM, Choo TH, Grinband J, Lieberman JA. Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders: A Randomized Clinical Trial. JAMA Psychiatry 2018, 75: 11-19. PMID: 29167877, PMCID: PMC5833531, DOI: 10.1001/jamapsychiatry.2017.3572.Peer-Reviewed Original ResearchConceptsTarget engagement biomarkerKetamine infusionClinical trialsClinical studiesEarly-stage clinical studiesEarly phase clinical studiesTarget engagementFunctional target engagementRecent pivotal trialsFMRI responsesBlood oxygen level-dependent (BOLD) responseUtility of imagingProton magnetic resonance spectroscopySufficient effect sizeLevel-dependent responsesPlacebo infusionPivotal trialsPreclinical evidenceEngagement biomarkersKetamine effectsMean ageBrain glutamateHealthy volunteersMAIN OUTCOMEPsychiatric history
2011
Neuroimaging insights into the role of cortical GABA systems and the influence of nicotine on the recovery from alcohol dependence
Cosgrove KP, Esterlis I, Mason GF, Bois F, O’Malley S, Krystal JH. Neuroimaging insights into the role of cortical GABA systems and the influence of nicotine on the recovery from alcohol dependence. Neuropharmacology 2011, 60: 1318-1325. PMID: 21276806, PMCID: PMC3078950, DOI: 10.1016/j.neuropharm.2011.01.020.Peer-Reviewed Original ResearchConceptsAlcohol withdrawalTobacco smokingGABA levelsNeuronal functionNeuronal nicotinic acetylcholine receptorsAlcohol-dependent smokersCortical GABA systemGABA neuronal functionProlonged alcohol withdrawalInfluence of nicotineNicotinic acetylcholine receptorsAlcohol-dependent individualsEffects of alcoholPreclinical evidenceRole of alcoholGABA systemPreclinical modelsTobacco smokeErminio CostaBenzodiazepine receptorsAcetylcholine receptorsAlcohol dependenceSmokingPrimary actionClinical experiments
2001
Reductions in Occipital Cortex GABA Levels in Panic Disorder Detected With 1H-Magnetic Resonance Spectroscopy
Goddard AW, Mason GF, Almai A, Rothman DL, Behar KL, Petroff OA, Charney DS, Krystal JH. Reductions in Occipital Cortex GABA Levels in Panic Disorder Detected With 1H-Magnetic Resonance Spectroscopy. JAMA Psychiatry 2001, 58: 556-561. PMID: 11386984, DOI: 10.1001/archpsyc.58.6.556.Peer-Reviewed Original ResearchConceptsOccipital cortex GABA levelsCortical GABA levelsGABA levelsGamma-aminobutyric acidPanic disorderOccipital cortex GABA concentrationsSex-matched control subjectsGABA neuronal functionHuman panic disorderMeasures of illnessPatient-control pairsBrain GABA levelsDSM-IV criteriaPreclinical evidenceMedication historyControl subjectsUnmedicated patientsGABA functionMajor depressionCurrent diagnosisNeuronal functionGABA concentrationPatientsReference limitsDisorders
1996
Noradrenergic mechanisms in stress and anxiety: I. preclinical studies
Bremner J, Krystal J, Southwick S, Charney D. Noradrenergic mechanisms in stress and anxiety: I. preclinical studies. Synapse 1996, 23: 28-38. PMID: 8723133, DOI: 10.1002/(sici)1098-2396(199605)23:1<28::aid-syn4>3.0.co;2-j.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderBrain regionsNoradrenergic brain systemsMultiple subcortical areasConsiderable preclinical evidenceLocus coeruleusBrain systemsNeural mechanismsStress disorderTarget brain regionsBehavioral manifestationsBrain functionPanic disorderStress exposureChronic stress resultsTurnover of norepinephrineSubcortical areasAnxietyPsychiatric disordersNoradrenergic systemLong-term alterationsNoradrenergic mechanismsNoradrenergic neuronsNorepinephrine releasePreclinical evidence
1990
Noradrenergic function in panic disorder.
Charney DS, Woods SW, Nagy LM, Southwick SM, Krystal JH, Heninger GR. Noradrenergic function in panic disorder. The Journal Of Clinical Psychiatry 1990, 51 Suppl A: 5-11. PMID: 2258377.Peer-Reviewed Original ResearchConceptsLocus ceruleusNoradrenergic functionPanic disorderBrain noradrenergic functionNoradrenergic neuronal activityPanic disorder patientsNoradrenergic neuronsPreclinical evidenceNatural courseNoradrenergic nucleusDevelopment of anxietyAnxiogenic effectsClinical investigationDisorder patientsNeuronal activityUncontrollable stressNeuron firingNonhuman primatesNeurodevelopmental perspectiveLaboratory animalsSystem regulationFear responsesDisordersAnxietyElectrical activation