2019
Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments
Duman RS, Sanacora G, Krystal JH. Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments. Neuron 2019, 102: 75-90. PMID: 30946828, PMCID: PMC6450409, DOI: 10.1016/j.neuron.2019.03.013.Peer-Reviewed Original ResearchConceptsAltered connectivityDepressed patientsExcitatory glutamate neuronsMajor neuronal typesRapid-acting agentsAtrophy of neuronsTreatment of depressionLimbic brain regionsChronic stress exposureStress-related disordersBrain imaging studiesImportant sex differencesNeurotransmitter deficitsGABA interneuronsImmunologic mechanismsGlutamate neuronsCurrent antidepressantsExcitotoxic effectsNeurochemical deficitsGlutamate dysfunctionPathophysiological mechanismsGABA systemInflammatory cytokinesAdrenal glucocorticoidsHippocampal region
2016
Glutamate dysregulation and glutamatergic therapeutics for PTSD: Evidence from human studies
Averill LA, Purohit P, Averill CL, Boesl MA, Krystal JH, Abdallah CG. Glutamate dysregulation and glutamatergic therapeutics for PTSD: Evidence from human studies. Neuroscience Letters 2016, 649: 147-155. PMID: 27916636, PMCID: PMC5482215, DOI: 10.1016/j.neulet.2016.11.064.Peer-Reviewed Original ResearchMeSH KeywordsBrainGamma-Aminobutyric AcidGlutamic AcidHumansReceptors, GlutamateStress Disorders, Post-TraumaticStress, PsychologicalSynaptic TransmissionConceptsPosttraumatic stress disorderPsychiatric disordersStress-related psychiatric disordersAlternative pharmacologic treatmentsPutative neurobiological underpinningsGlutamate-modulating agentsTrauma-related disordersGlutamatergic abnormalitiesGlutamate dysregulationPharmacologic treatmentPharmacologic interventionsGlutamatergic functionGlutamate neurotransmissionMillions of individualsHuman studiesCardinal featuresStress disorderDisordersNeurobiological underpinningsRelated future directionsEvidenceChronicDysfunctionNeurotransmissionSubject data
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
Glutamate Metabolism in Major Depressive Disorder
Abdallah CG, Jiang L, De Feyter HM, Fasula M, Krystal JH, Rothman DL, Mason GF, Sanacora G. Glutamate Metabolism in Major Depressive Disorder. American Journal Of Psychiatry 2014, 171: 1320-1327. PMID: 25073688, PMCID: PMC4472484, DOI: 10.1176/appi.ajp.2014.14010067.Peer-Reviewed Original Research
2012
Ketamine effects on brain GABA and glutamate levels with 1H-MRS: relationship to ketamine-induced psychopathology
Stone JM, Dietrich C, Edden R, Mehta MA, De Simoni S, Reed LJ, Krystal JH, Nutt D, Barker GJ. Ketamine effects on brain GABA and glutamate levels with 1H-MRS: relationship to ketamine-induced psychopathology. Molecular Psychiatry 2012, 17: 664-665. PMID: 22212598, PMCID: PMC3883303, DOI: 10.1038/mp.2011.171.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsAdultAspartic AcidBreath TestsCerebral CortexDipeptidesEthanolFemaleGamma-Aminobutyric AcidHumansInfusions, IntravenousMagnetic Resonance SpectroscopyMaleConceptsIntravenous 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 cortexNeuroimaging 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 ResearchMeSH KeywordsAlcoholismBrainClinical Trials as TopicDrug Evaluation, PreclinicalGamma-Aminobutyric AcidHumansNicotineNicotinic AgonistsRadionuclide ImagingReceptors, GABA-ASmokingConceptsAlcohol 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 experimentsThe antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [1H]-MRS
Valentine GW, Mason GF, Gomez R, Fasula M, Watzl J, Pittman B, Krystal JH, Sanacora G. The antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [1H]-MRS. Psychiatry Research 2011, 191: 122-127. PMID: 21232924, PMCID: PMC3061550, DOI: 10.1016/j.pscychresns.2010.10.009.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntidepressive AgentsBlood PressureDepressive Disorder, MajorDissociative DisordersFemaleGamma-Aminobutyric AcidGlutamic AcidHeart RateHumansKetamineMagnetic Resonance SpectroscopyMaleMiddle AgedOccipital LobeProtonsPsychiatric Status Rating ScalesPsychometricsRetrospective StudiesSingle-Blind MethodStatistics as TopicTime FactorsYoung AdultConceptsMajor depressive disorderAntidepressant effectsAntidepressant actionNeurotransmitter contentNMDA receptor antagonist ketamineProton magnetic resonance spectroscopy methodConventional antidepressant treatmentKetamine's antidepressant actionSingle intravenous doseSingle-blind conditionsAntidepressant treatmentChronic treatmentKetamine infusionIntravenous dosePharmacodynamic basisDepressive disorderAcute actionsMRS scansOccipital cortexDepressive symptomsDepression scoresRating ScaleBaseline measuresInfusionKetamine
2008
Decreased hippocampal volume on MRI is associated with increased extracellular glutamate in epilepsy patients
Cavus I, Pan JW, Hetherington HP, Abi‐Saab W, Zaveri HP, Vives KP, Krystal JH, Spencer SS, Spencer DD. Decreased hippocampal volume on MRI is associated with increased extracellular glutamate in epilepsy patients. Epilepsia 2008, 49: 1358-1366. PMID: 18410365, DOI: 10.1111/j.1528-1167.2008.01603.x.Peer-Reviewed Original ResearchConceptsTemporal lobe epilepsyHippocampal volumeClinical factorsHippocampal atrophyEpileptogenic hippocampusGABA levelsNeurochemical levelsElevated extracellular glutamate levelsContralateral hippocampal volumeIntracranial EEG evaluationMedication-resistant epilepsyRefractory TLE patientsHigh seizure frequencyRelevant clinical factorsSmaller hippocampal volumesExtracellular glutamate levelsFebrile seizure historyTreatment of epilepsySeizure frequencyLobe epilepsySeizure historyTLE patientsAtrophic hippocampusGlutamate levelsExtracellular glutamate
2006
γ-Aminobutyric Acid Type A Receptors and Alcoholism: Intoxication, Dependence, Vulnerability, and Treatment
Krystal JH, Staley J, Mason G, Petrakis IL, Kaufman J, Harris RA, Gelernter J, Lappalainen J. γ-Aminobutyric Acid Type A Receptors and Alcoholism: Intoxication, Dependence, Vulnerability, and Treatment. JAMA Psychiatry 2006, 63: 957-968. PMID: 16952998, DOI: 10.1001/archpsyc.63.9.957.Peer-Reviewed Original ResearchConceptsBrain GABA systemsGABA systemAlcohol dependenceWithdrawal symptomsGABA functionGamma-aminobutyric acid (GABA) functionCortical GABA levelsAlcohol withdrawal symptomsΓ-Aminobutyric Acid Type A ReceptorsEnvironmental risk factorsLong-term alcohol effectsType A ReceptorsAlcohol-dependent individualsLong-term sobrietyGABA releaseNeurosteroid levelsAcute withdrawalAlcoholism vulnerabilityGABA neurotransmissionRisk factorsGABA levelsExtrasynaptic locationsLow chloride conductanceReceptor densityTonic componentThe 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 acidPreliminary evidence of reduced occipital GABA concentrations in puerperal women: a 1H-MRS study
Epperson CN, Gueorguieva R, Czarkowski KA, Stiklus S, Sellers E, Krystal JH, Rothman DL, Mason GF. Preliminary evidence of reduced occipital GABA concentrations in puerperal women: a 1H-MRS study. Psychopharmacology 2006, 186: 425. PMID: 16724188, DOI: 10.1007/s00213-006-0313-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultDepression, PostpartumEstradiolFemaleGamma-Aminobutyric AcidHumansMagnetic Resonance SpectroscopyOccipital LobePostpartum PeriodPregnanesConceptsPostpartum major depressionCortical GABA concentrationsGABA concentrationPostpartum womenOccipital cortex GABA concentrationsOccipital cortex GABA levelsProton magnetic resonance spectroscopy studyFollicular phase femalesGamma-aminobutyric acid concentrationResumption of menstruationFollicular phase womenMonths of deliveryMid-follicular phaseOvarian hormone levelsSubgroup of womenMagnetic resonance spectroscopy studyAllopregnanolone concentrationsPuerperal womenALLO levelsBlood levelsPostpartum periodHealthy controlsMajor depressionGABA levelsHormone levels
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 ResearchMeSH KeywordsAdultAlcoholismAspartic AcidCholineCreatineGamma-Aminobutyric AcidHumansMagnetic Resonance SpectroscopyMaleMiddle AgedOccipital LobeSmokingConceptsEthanol-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 severityγ-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 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 subjectsTherapyGABA and glutamate systems as therapeutic targets in depression and mood disorders
Kendell SF, Krystal JH, Sanacora G. GABA and glutamate systems as therapeutic targets in depression and mood disorders. Expert Opinion On Therapeutic Targets 2005, 9: 153-168. PMID: 15757488, DOI: 10.1517/14728222.9.1.153.Peer-Reviewed Original ResearchSex, 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
Impaired GABA Neuronal Response to Acute Benzodiazepine Administration in Panic Disorder
Goddard AW, Mason GF, Appel M, Rothman DL, Gueorguieva R, Behar KL, Krystal JH. Impaired GABA Neuronal Response to Acute Benzodiazepine Administration in Panic Disorder. American Journal Of Psychiatry 2004, 161: 2186-2193. PMID: 15569888, DOI: 10.1176/appi.ajp.161.12.2186.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidPanic disorder patientsAcute benzodiazepine administrationCortical GABA levelsBenzodiazepine administrationGABA levelsPanic disorderDisorder patientsNeuronal responsesOccipital cortex GABA levelsTransmitter gamma-aminobutyric acidChronic benzodiazepine treatmentGABA neuronal functionHuman panic disorderTrait-like abnormalitiesGABA synthetic enzymeHealthy comparison subjectsStress-induced releaseCerebral cortexBenzodiazepine treatmentMedication administrationGABA responsesHealthy subjectsPathogenic factorsHuman anxiety disordersSubtype-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 cortexFamily Psychopathology and Magnitude of Reductions in Occipital Cortex GABA Levels in Panic Disorder
Goddard AW, Mason GF, Rothman DL, Behar KL, Petroff O, Krystal JH. Family Psychopathology and Magnitude of Reductions in Occipital Cortex GABA Levels in Panic Disorder. Neuropsychopharmacology 2004, 29: 639-640. PMID: 14973435, DOI: 10.1038/sj.npp.1300374.Peer-Reviewed Original Research