2020
Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin
Abdallah CG, Averill LA, Gueorguieva R, Goktas S, Purohit P, Ranganathan M, Sherif M, Ahn KH, D’Souza D, Formica R, Southwick SM, Duman RS, Sanacora G, Krystal JH. Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin. Neuropsychopharmacology 2020, 45: 990-997. PMID: 32092760, PMCID: PMC7162891, DOI: 10.1038/s41386-020-0644-9.Peer-Reviewed Original ResearchConceptsAntidepressant effectsKetamine administrationRapamycin pretreatmentMontgomery-Åsberg Depression Rating ScaleDouble-blind cross-over designBenefits of ketamineRobust antidepressant effectsKetamine's antidepressant effectsMajor depressive episodeDepression Rating ScaleCross-over designKetamine exertsOral rapamycinRemission rateDepressive episodePlacebo 2Ketamine 0.5Local blockadeDepressed patientsIntravenous administrationTreatment daysDepression relapseDepression severityKetamineRating Scale
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
2007
Neurobiology and Treatment of Depression
Neumeister A, Charney D, Sanacora G, Krystal J. Neurobiology and Treatment of Depression. 2007 DOI: 10.1002/9780470101001.hcn018.Peer-Reviewed Original ResearchNeurobiology of depressionTreatment of depressionPotential novel treatment approachesNovel treatment approachesEtiology of depressionAvailable treatmentsDepressed patientsNeuroanatomical disruptionsTreatment approachesNeural circuitsAbstract DepressionNovel targetCurrent conceptsDepressionTreatmentNeurobiological systemsNeurobiologyPatientsPathogenesisEtiologyEnvironmental factors
2005
Cortical 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 subjectsTherapy
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
2000
Antidepressant effects of ketamine in depressed patients
Berman R, Cappiello A, Anand A, Oren D, Heninger G, Charney D, Krystal J. Antidepressant effects of ketamine in depressed patients. Biological Psychiatry 2000, 47: 351-354. PMID: 10686270, DOI: 10.1016/s0006-3223(99)00230-9.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntidepressive AgentsDepressive Disorder, MajorDose-Response Relationship, DrugDouble-Blind MethodExcitatory Amino Acid AntagonistsFemaleGlutamic AcidHumansInjections, IntravenousKetamineMaleMiddle AgedPsychiatric Status Rating ScalesReceptors, N-Methyl-D-AspartateSeverity of Illness IndexConceptsMajor depressionN-methyl-D-aspartate receptor antagonistBrain glutamate systemDouble-blind trialDouble-blind conditionsTreatment of depressionMechanism of actionPlacebo infusionAntidepressant effectsIntravenous treatmentSingle doseReceptor antagonistDepressed patientsGlutamate systemDepressive symptomsPreclinical researchKetamine hydrochlorideDepressionPotential roleTest dayTreatment effectsPatientsKetamineSaline solutionTreatmentImpairment of GABAergic Transmission in Depression: New Insights from Neuroimaging Studies
Sanacora G, Mason G, Krystal J. Impairment of GABAergic Transmission in Depression: New Insights from Neuroimaging Studies. Critical Reviews In Neurobiology 2000, 14: 23. PMID: 11253954, DOI: 10.1615/critrevneurobiol.v14.i1.20.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsNeurobiology of depressionGABAergic functionTechnique of PETCSF GABA concentrationsGABA-mimetic agentsNovel neuroimaging techniquesNondepressed comparison subjectsMood stabilizingChronic administrationGABAergic transmissionGABAergic neurotransmissionAntidepressant propertiesGABAergic abnormalitiesDepressed patientsAntidepressant drugsDisorder pathophysiologyLower plasmaComparison subjectsAnimal studiesGABAergic contributionGABA concentrationNovel imaging techniqueNeuroimaging studiesNeuroimaging techniquesDepression
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 illnessTryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine: implications for the role of serotonin in the mechanism of antidepressant action
Delgado P, Miller H, Salomon R, Licinio J, Krystal J, Moreno F, Heninger G, Charney D. Tryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine: implications for the role of serotonin in the mechanism of antidepressant action. Biological Psychiatry 1999, 46: 212-220. PMID: 10418696, DOI: 10.1016/s0006-3223(99)00014-1.Peer-Reviewed Original ResearchConceptsTRP depletionAntidepressant responseDepressed patientsSuccessful antidepressant treatmentBrain serotonin contentSignificant depressive symptomsAmino acid drinkRole of serotoninMonoamine oxidase inhibitorsRelationship of relapseAntidepressant actionAntidepressant treatmentReuptake inhibitorsPlasma tryptophanPlasma levelsAntidepressant typeTherapeutic responseDepressive relapseSerotonin contentTherapeutic effectTRP levelsDepressive symptomsTreatment phasePatientsAcid drink
1996
Clinical and Biochemical Effects of Catecholamine Depletion on Antidepressant-Induced Remission of Depression
Miller HL, Delgado PL, Salomon RM, Berman R, Krystal JH, Heninger GR, Charney DS. Clinical and Biochemical Effects of Catecholamine Depletion on Antidepressant-Induced Remission of Depression. JAMA Psychiatry 1996, 53: 117-128. PMID: 8629887, DOI: 10.1001/archpsyc.1996.01830020031005.Peer-Reviewed Original ResearchConceptsNorepinephrine reuptake inhibitorsReuptake inhibitorsCatecholamine depletionAlpha-methylparatyrosineTreatment groupsHamilton Depression Rating ScaleHomovanillic acid levelsSerotonin reuptake inhibitorsDepression Rating ScaleSimilar significant decreaseAntihistamine diphenhydramine hydrochlorideSeparate test sessionsFeelings of worthlessnessConsiderable sedationLoss of interestDepressed patientsDepressive relapseAntidepressant drugsInactive placeboTherapeutic effectTherapeutic mechanismDepressive symptomsCatecholamine metabolitesPlasma 3Remission
1994
Effects of sleep deprivation on serotonin function in depression
Salomon R, Delgado P, Licinio J, Krystal J, Heninger G, Charney D. Effects of sleep deprivation on serotonin function in depression. Biological Psychiatry 1994, 36: 840-846. PMID: 7893848, DOI: 10.1016/0006-3223(94)90595-9.Peer-Reviewed Original ResearchConceptsUndisturbed sleepSleep deprivationPRL riseDepressed patientsSerotonin functionFemale depressed patientsSD-induced changesIntravenous tryptophanAntidepressant treatmentPRL responseDepressed menTRP infusionScore changeMood changesPatientsMood ratingsMenProlactinConsiderable evidenceWomenLow sensitivitySignificant relationshipDeprivationInfusionSleep
1991
Rapid serotonin depletion as a provocative challenge test for patients with major depression: relevance to antidepressant action and the neurobiology of depression.
Delgado PL, Price LH, Miller HL, Salomon RM, Licinio J, Krystal JH, Heninger GR, Charney DS. Rapid serotonin depletion as a provocative challenge test for patients with major depression: relevance to antidepressant action and the neurobiology of depression. Psychopharmacology Bulletin 1991, 27: 321-30. PMID: 1775606.Peer-Reviewed Original ResearchConceptsDepressed patientsTRP depletionDesipramine-treated patientsFluvoxamine-treated patientsProvocative challenge testsBrain serotonin contentNeurobiology of depressionMonoamine oxidase inhibitorsMechanism of actionAntidepressant medicationCrossover fashionSerotonin depletionPlasma levelsDepressive relapseSerotonin contentMajor depressionPsychiatric patientsPatientsChallenge testOxidase inhibitorsEssential amino acidsDepressionPercentDaysMedications
1990
Clinical studies of 5-HT function using I.V. l-Tryptophan
Price L, Charney D, Delgado P, Goodman W, Krystal J, Woods S, Heninger G. Clinical studies of 5-HT function using I.V. l-Tryptophan. Progress In Neuro-Psychopharmacology And Biological Psychiatry 1990, 14: 459-472. PMID: 2236580, DOI: 10.1016/0278-5846(90)90002-x.Peer-Reviewed Original ResearchConceptsPRL responseClinical studiesDrug actionAntidepressant drug actionLong-term treatmentSuch clinical studiesThymoleptic drugsTime-dependent fashionPlasma TrpObsessive-compulsive disorderSerum prolactinElectrophysiological findingsDepressed patientsHealthy controlsAntidepressant drugsTherapeutic effectPreclinical studiesReceptor sensitivityPanic disorderChallenge agentNeuropsychiatric diseasesNeuropsychopharmacological studiesClinical levelCompulsive disorderL-Trp