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
2017
Searching for Cross-Diagnostic Convergence: Neural Mechanisms Governing Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders
Foss-Feig JH, Adkinson BD, Ji JL, Yang G, Srihari VH, McPartland JC, Krystal JH, Murray JD, Anticevic A. Searching for Cross-Diagnostic Convergence: Neural Mechanisms Governing Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders. Biological Psychiatry 2017, 81: 848-861. PMID: 28434615, PMCID: PMC5436134, DOI: 10.1016/j.biopsych.2017.03.005.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderSpectrum disorderFunctional magnetic resonance imagingRecent theoretical accountsEarly course schizophreniaNeurodevelopmental disordersPharmacological challenge studiesNeural correlatesNeuroscience literatureTheoretical accountsNeural circuitryTheoretical neuroscienceNoninvasive neuroimagingBehavioral dysfunctionFuture researchNeuropsychiatric conditionsComputational modelSchizophreniaProton magnetic resonance spectroscopyDisordersInhibition imbalanceMagnetic resonance imagingDistinct modalitiesPoint of convergenceInhibition balance
2011
Intravenous Ethanol Infusion Decreases Human Cortical γ-Aminobutyric Acid and N-Acetylaspartate as Measured with Proton Magnetic Resonance Spectroscopy at 4 Tesla
Gomez R, Behar KL, Watzl J, Weinzimer SA, Gulanski B, Sanacora G, Koretski J, Guidone E, Jiang L, Petrakis IL, Pittman B, Krystal JH, Mason GF. Intravenous Ethanol Infusion Decreases Human Cortical γ-Aminobutyric Acid and N-Acetylaspartate as Measured with Proton Magnetic Resonance Spectroscopy at 4 Tesla. Biological Psychiatry 2011, 71: 239-246. PMID: 21855054, PMCID: PMC3227760, DOI: 10.1016/j.biopsych.2011.06.026.Peer-Reviewed Original ResearchConceptsIntravenous ethanol infusionProton magnetic resonance spectroscopyEthanol infusionNAA levelsN-acetylaspartateCortical γ-aminobutyric acidAcute pharmacologic effectsLevels of GABAHealthy social drinkersBreath alcohol levelsN-acetylaspartyl-glutamateCortical GABAEthanol modulatesFirst infusionΓ-aminobutyric acidGABA levelsPharmacologic effectsBrain ethanolOccipital GABAInfusionAlcohol levelsMagnetic resonance spectroscopyReceptor functionBreath ethanolHuman cortex
2006
The interaction of neuroactive steroids and GABA in the development of neuropsychiatric disorders in women
Amin Z, Mason GF, Cavus I, Krystal JH, Rothman DL, Epperson CN. The interaction of neuroactive steroids and GABA in the development of neuropsychiatric disorders in women. Pharmacology Biochemistry And Behavior 2006, 84: 635-643. PMID: 16860856, DOI: 10.1016/j.pbb.2006.06.007.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidNeuroactive steroidsMajor inhibitory neurotransmitterCentral nervous system responseProgesterone derivative allopregnanoloneMultiple neurotransmitter systemsProton magnetic resonance spectroscopySubstance use disordersNervous system responsesInhibitory neurotransmitterMenstrual cycleMenopausal transitionNeurotransmitter systemsHormonal fluctuationsPsychiatric disordersUse disordersAffective disordersPsychiatric syndromesNeuropsychiatric disordersNeuroendocrine systemSteroidsPreclinical researchDisordersAllopregnanoloneAminobutyric acid
2005
Cortical Gamma-Aminobutyric Acid Levels and the Recovery from Ethanol Dependence: Preliminary Evidence of Modification by Cigarette Smoking
Mason GF, Petrakis IL, de Graaf RA, Gueorguieva R, Guidone E, Coric V, Epperson CN, Rothman DL, Krystal JH. Cortical Gamma-Aminobutyric Acid Levels and the Recovery from Ethanol Dependence: Preliminary Evidence of Modification by Cigarette Smoking. Biological Psychiatry 2005, 59: 85-93. PMID: 16289397, DOI: 10.1016/j.biopsych.2005.06.009.Peer-Reviewed Original ResearchConceptsEthanol-dependent patientsTobacco smokingEthanol dependenceHealthy subjectsN-acetylaspartateCortical gamma-aminobutyric acid (GABA) levelsGamma-aminobutyric acid (GABA) levelsCortical GABA levelsCortical GABA systemAlcohol withdrawal symptomsAcute ethanol withdrawalComorbidity of alcoholismProton magnetic resonance spectroscopyGamma-aminobutyric acidCortical GABASmoking patientsEthanol withdrawalCigarette smokingGABA systemHealthy menWithdrawal symptomsGABA levelsClinical dataNAA levelsWithdrawal severityCortical γ-Aminobutyric Acid Concentrations in Depressed Patients Receiving Cognitive Behavioral Therapy
Sanacora G, Fenton LR, Fasula MK, Rothman DL, Levin Y, Krystal JH, Mason GF. Cortical γ-Aminobutyric Acid Concentrations in Depressed Patients Receiving Cognitive Behavioral Therapy. Biological Psychiatry 2005, 59: 284-286. PMID: 16139814, DOI: 10.1016/j.biopsych.2005.07.015.Peer-Reviewed Original ResearchMeSH KeywordsAdultCognitive Behavioral TherapyDepressive Disorder, MajorElectroconvulsive TherapyFemaleFollow-Up StudiesGamma-Aminobutyric AcidHumansImage Processing, Computer-AssistedMagnetic Resonance SpectroscopyMaleOccipital LobeOutcome and Process Assessment, Health CareSelective Serotonin Reuptake InhibitorsStatistics as TopicConceptsOccipital cortex GABA concentrationsSelective serotonin reuptake inhibitorsCognitive behavioral therapyElectroconvulsive therapyGABA concentrationDepressed patientsBehavioral therapyCortical GABA concentrationsEffects of CBTGamma-aminobutyric acid concentrationSerotonin reuptake inhibitorsΓ-aminobutyric acid (GABA) concentrationMajor depressive disorderProton magnetic resonance spectroscopyGABA contentAntidepressant actionSSRI treatmentCourse of CBTReuptake inhibitorsMedication treatmentDepressive disorderMajor depressionCerebrospinal fluidDepressed subjectsTherapySex, GABA, and nicotine: The impact of smoking on cortical GABA levels across the menstrual cycle as measured with proton magnetic resonance spectroscopy
Epperson CN, O’Malley S, Czarkowski KA, Gueorguieva R, Jatlow P, Sanacora G, Rothman DL, Krystal JH, Mason GF. Sex, GABA, and nicotine: The impact of smoking on cortical GABA levels across the menstrual cycle as measured with proton magnetic resonance spectroscopy. Biological Psychiatry 2005, 57: 44-48. PMID: 15607299, PMCID: PMC4097033, DOI: 10.1016/j.biopsych.2004.09.021.Peer-Reviewed Original ResearchConceptsCortical GABA levelsOccipital cortex GABA concentrationsGABA levelsProton magnetic resonance spectroscopyImpact of nicotineMenstrual cycleGABA concentrationFemale smokersCortical gamma-aminobutyric acid (GABA) levelsUnderwent proton magnetic resonance spectroscopyGamma-aminobutyric acid (GABA) levelsCentral GABAergic functionCortical GABA concentrationsNicotine-dependent menAmino acid neurotransmissionImpact of smokingPotential risk factorsMenstrual cycle phaseShort-term abstinenceGABAergic functionNicotine modulationSmoking menSmoking cessationFollicular phaseSmoking abstinence
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
2003
Increased Cortical GABA Concentrations in Depressed Patients Receiving ECT
Sanacora G, Mason GF, Rothman DL, Hyder F, Ciarcia JJ, Ostroff RB, Berman RM, Krystal JH. Increased Cortical GABA Concentrations in Depressed Patients Receiving ECT. American Journal Of Psychiatry 2003, 160: 577-579. PMID: 12611844, DOI: 10.1176/appi.ajp.160.3.577.Peer-Reviewed Original ResearchConceptsOccipital cortex GABA concentrationsCortical GABA concentrationsCourse of ECTGABA concentrationDepressed patientsConsiderable anticonvulsant effectsSevere refractory depressionGamma-aminobutyric acid concentrationProton magnetic resonance spectroscopyRefractory depressionAnticonvulsant effectsAntidepressant actionGABAergic transmissionECT treatmentGABAergic involvementEffective treatmentECT mechanismsDepressed subjectsPatientsSignificant increaseDepressionTreatmentECTMagnetic resonance spectroscopyAcid concentration
2002
Increased Occipital Cortex GABA Concentrations in Depressed Patients After Therapy With Selective Serotonin Reuptake Inhibitors
Sanacora G, Mason GF, Rothman DL, Krystal JH. Increased Occipital Cortex GABA Concentrations in Depressed Patients After Therapy With Selective Serotonin Reuptake Inhibitors. American Journal Of Psychiatry 2002, 159: 663-665. PMID: 11925309, DOI: 10.1176/appi.ajp.159.4.663.Peer-Reviewed Original ResearchConceptsOccipital cortex GABA concentrationsSelective serotonin reuptake inhibitorsSerotonin reuptake inhibitorsGamma-aminobutyric acidGABA concentrationReuptake inhibitorsDepressed patientsMajor depressionMedication-free depressed patientsMonths of treatmentInitiation of treatmentTreatment of depressionCSF of individualsProton magnetic resonance spectroscopyLow GABA concentrationsSSRI medicationAntidepressant actionSSRI treatmentOccipital cortexDepressed subjectsTreatmentDepressionPatientsSignificant increaseCommon mechanism
1999
Reduced Cortical γ-Aminobutyric Acid Levels in Depressed Patients Determined by Proton Magnetic Resonance Spectroscopy
Sanacora G, Mason GF, Rothman DL, Behar KL, Hyder F, Petroff OA, Berman RM, Charney DS, Krystal JH. Reduced Cortical γ-Aminobutyric Acid Levels in Depressed Patients Determined by Proton Magnetic Resonance Spectroscopy. JAMA Psychiatry 1999, 56: 1043-1047. PMID: 10565505, DOI: 10.1001/archpsyc.56.11.1043.Peer-Reviewed Original ResearchConceptsProton magnetic resonance spectroscopyDepressed patientsGABA levelsMedication-free depressed patientsOccipital cortex GABA levelsVivo proton magnetic resonance spectroscopyCortical GABA concentrationsGamma-aminobutyric acid (GABA) systemΓ-aminobutyric acid (GABA) levelsBrain GABA levelsMagnetic resonance spectroscopy protocolHealthy control subjectsDSM-IV criteriaGABA neurotransmitter systemEffect of depressionInteraction of diagnosisControl subjectsMajor depressionNeurotransmitter systemsHealthy subjectsOccipital cortexNeurobiologic processesAnalysis of covarianceGABA concentrationMental illness