2020
Imaging the glutamate synapse
Krystal JH. Imaging the glutamate synapse. Nature Medicine 2020, 26: 165-167. PMID: 32015559, DOI: 10.1038/s41591-020-0760-4.Peer-Reviewed Original Research
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
2013
Increased brain uptake and oxidation of acetate in heavy drinkers
Jiang L, Gulanski BI, De Feyter HM, Weinzimer SA, Pittman B, Guidone E, Koretski J, Harman S, Petrakis IL, Krystal JH, Mason GF. Increased brain uptake and oxidation of acetate in heavy drinkers. Journal Of Clinical Investigation 2013, 123: 1605-1614. PMID: 23478412, PMCID: PMC3613911, DOI: 10.1172/jci65153.Peer-Reviewed Original ResearchConceptsHeavy drinkersBrain uptakeN-acetylaspartateLight drinkersChronic heavy drinkingNew therapeutic approachesGreater brain uptakeAlcohol detoxificationConsequences of drinkingTherapeutic approachesMagnetic resonance spectroscopyMore brainHeavy drinkingDrinkersBrainWeeksBloodDrinksGlutamateDrinkingResonance spectroscopy
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 ResearchExtracellular metabolites in the cortex and hippocampus of epileptic patients
Cavus I, Kasoff WS, Cassaday MP, Jacob R, Gueorguieva R, Sherwin RS, Krystal JH, Spencer DD, Abi‐Saab W. Extracellular metabolites in the cortex and hippocampus of epileptic patients. Annals Of Neurology 2005, 57: 226-235. PMID: 15668975, DOI: 10.1002/ana.20380.Peer-Reviewed Original ResearchConceptsGlutamate-glutamine cyclingEpileptogenic hippocampusGlutamate levelsEpileptic patientsImpaired glutamate reuptakeBasal glutamate levelsBrain energy metabolismHigher lactate levelsGlutamine/glutamate ratioPoor glucose utilizationEnergy metabolismNeurometabolic processesNonepileptogenic cortexEpileptogenic cortexGlutamate reuptakeNeocortical epilepsyExtracellular glutamateSeizure generationInterictal periodLactate levelsMicrodialysis methodExtracellular levelsNeuronal toxicityGlucose utilizationDepth electrodes
2004
Subtype-Specific Alterations of γ-Aminobutyric Acid and Glutamatein Patients With Major Depression
Sanacora G, Gueorguieva R, Epperson CN, Wu YT, Appel M, Rothman DL, Krystal JH, Mason GF. Subtype-Specific Alterations of γ-Aminobutyric Acid and Glutamatein Patients With Major Depression. JAMA Psychiatry 2004, 61: 705-713. PMID: 15237082, DOI: 10.1001/archpsyc.61.7.705.Peer-Reviewed Original ResearchConceptsMajor depressive disorderGamma-aminobutyric acidOccipital cortex GABA concentrationsProton magnetic resonance spectroscopyDepressed subjectsGABA concentrationHealthy controlsSubtypes of MDDCortical gamma-aminobutyric acidHealthy control subjectsMetabolite levelsCholine-containing compoundsHealthy comparison subjectsClinical research programSubtype-specific alterationsΓ-aminobutyric acidClinical correlatesMDD patientsControl subjectsDepressive disorderNeurotransmitter levelsGlutamate levelsMajor depressionMDD subtypesOccipital cortex