2024
Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression
Jha M, Wilkinson S, Krishnan K, Collins K, Sanacora G, Murrough J, Goes F, Altinay M, Aloysi A, Asghar-Ali A, Barnett B, Chang L, Costi S, Malone D, Nikayin S, Nissen S, Ostroff R, Reti I, Wolski K, Wang D, Hu B, Mathew S, Anand A. Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression. JAMA Network Open 2024, 7: e2417786. PMID: 38916891, PMCID: PMC11200139, DOI: 10.1001/jamanetworkopen.2024.17786.Peer-Reviewed Original ResearchConceptsTreatment-resistant depressionQIDS-SR16 scoresElectroconvulsive therapy groupElectroconvulsive therapyQIDS-SR16Measure of premorbid intelligencePosttraumatic stress disorder diagnosisTrial of electroconvulsive therapyNonpsychotic depressive episodeImpaired memory recallAssociated with differential improvementStress disorder diagnosisIntravenous ketamineEnd-of-treatment visitInfusion of ketamineMADRS scorePremorbid intelligenceResistant depressionDepressive episodeMeasures mixed-effects modelsFalse discovery rate adjustmentDisorder diagnosisMemory recallSevere depressionDifferential improvement
2023
Single-Dose Psilocybin Treatment for Major Depressive Disorder
Raison C, Sanacora G, Woolley J, Heinzerling K, Dunlop B, Brown R, Kakar R, Hassman M, Trivedi R, Robison R, Gukasyan N, Nayak S, Hu X, O’Donnell K, Kelmendi B, Sloshower J, Penn A, Bradley E, Kelly D, Mletzko T, Nicholas C, Hutson P, Tarpley G, Utzinger M, Lenoch K, Warchol K, Gapasin T, Davis M, Nelson-Douthit C, Wilson S, Brown C, Linton W, Johnson M, Ross S, Griffiths R. Single-Dose Psilocybin Treatment for Major Depressive Disorder. JAMA 2023, 330: 843-853. PMID: 37651119, PMCID: PMC10472268, DOI: 10.1001/jama.2023.14530.Peer-Reviewed Original ResearchConceptsMajor depressive disorderSheehan Disability Scale scoresAdverse eventsDisability scale scorePsilocybin treatmentDay 43Scale scoreSecondary outcomesSingle doseDepressive disorderExclusion criteriaPsychological supportMontgomery-Asberg Depression Rating Scale scoreSerious treatment-emergent adverse eventsDay 8Key secondary outcome measuresTreatment-emergent adverse eventsDepression Rating Scale scoresActive substance use disorderFifth Edition diagnosisIdentical-appearing capsulesOverall adverse eventsPhase 2 trialSerious adverse eventsSevere adverse events
2021
Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions
Levey DF, Stein MB, Wendt FR, Pathak GA, Zhou H, Aslan M, Quaden R, Harrington KM, Nuñez YZ, Overstreet C, Radhakrishnan K, Sanacora G, McIntosh AM, Shi J, Shringarpure SS, Concato J, Polimanti R, Gelernter J. Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nature Neuroscience 2021, 24: 954-963. PMID: 34045744, PMCID: PMC8404304, DOI: 10.1038/s41593-021-00860-2.Peer-Reviewed Original ResearchConceptsTranscriptome-wide association studyMillion Veteran ProgramTranscriptome-wide association study (TWAS) analysisGenomic risk lociComplex psychiatric traitsGenetic architectureRisk lociGene expressionAssociation studiesLikely pathogenicityPsychiatric traitsVeteran ProgramNew therapeutic directionEuropean ancestryNew insightsAncestryUK BiobankAfrican ancestrySubstantial replicationExpressionLarge independent cohortsGWASTherapeutic directionsGenesLoci
2012
Rapid Antidepressant Effect of Ketamine in the Electroconvulsive Therapy Setting
Abdallah CG, Fasula M, Kelmendi B, Sanacora G, Ostroff R. Rapid Antidepressant Effect of Ketamine in the Electroconvulsive Therapy Setting. Journal Of Ect 2012, 28: 157-161. PMID: 22847373, PMCID: PMC3426617, DOI: 10.1097/yct.0b013e31824f8296.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAnesthesiaAnesthetics, DissociativeAntidepressive AgentsBipolar DisorderCombined Modality TherapyDepressionDepressive Disorder, MajorElectroconvulsive TherapyElectroencephalographyFemaleHumansHypnotics and SedativesKetamineMaleMiddle AgedPsychiatric Status Rating ScalesSeizuresThiopentalTreatment OutcomeYoung AdultConceptsHamilton Depression Rating ScaleAntidepressant effectsElectroconvulsive therapyECT sessionsDepressive episodeN-methyl-D-aspartate receptor antagonist ketamineN-methyl-D-aspartate antagonistsCoadministration of ketamineFirst ECT sessionRapid antidepressant effectsSevere depressive episodeSignificant antidepressant effectMajor depressive episodeDepression Rating ScaleMajor depressive disorderSixth ECT sessionSignificant group effectImmediate antidepressant effectECT treatmentAntidepressant propertiesHDRS scoresDepressive disorderLow doseBipolar disorderKetamineBrain-Derived Neurotrophic Factor Val66Met Polymorphism and Antidepressant Efficacy of Ketamine in Depressed Patients
Laje G, Lally N, Mathews D, Brutsche N, Chemerinski A, Akula N, Kelmendi B, Simen A, McMahon FJ, Sanacora G, Zarate C. Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Antidepressant Efficacy of Ketamine in Depressed Patients. Biological Psychiatry 2012, 72: e27-e28. PMID: 22771240, PMCID: PMC3786174, DOI: 10.1016/j.biopsych.2012.05.031.Peer-Reviewed Original ResearchCortical GABA Levels in Primary Insomnia
Morgan PT, Pace-Schott EF, Mason GF, Forselius E, Fasula M, Valentine GW, Sanacora G. Cortical GABA Levels in Primary Insomnia. Sleep 2012, 35: 807-814. PMID: 22654200, PMCID: PMC3353043, DOI: 10.5665/sleep.1880.Peer-Reviewed Original ResearchConceptsGABA levelsSleep complaintsPrimary insomniaSleep onsetCortical GABA levelsGABA/creatine ratiosOccipital GABA levelsPolysomnographic sleep measuresBrain GABA levelsBody mass indexMain outcome measuresUniversity research clinicPrimary insomnia groupAllostatic responseProton magnetic resonance spectroscopyMaintenance of sleepGABA contentUse of cigarettesUse of caffeineMass indexOutpatient studyCreatine ratioOutcome measuresResearch clinicTwo-group comparison study
2011
1H-[13C]-Nuclear Magnetic Resonance Spectroscopy Measures of Ketamine's Effect on Amino Acid Neurotransmitter Metabolism
Chowdhury GM, Behar KL, Cho W, Thomas MA, Rothman DL, Sanacora G. 1H-[13C]-Nuclear Magnetic Resonance Spectroscopy Measures of Ketamine's Effect on Amino Acid Neurotransmitter Metabolism. Biological Psychiatry 2011, 71: 1022-1025. PMID: 22169441, PMCID: PMC3660962, DOI: 10.1016/j.biopsych.2011.11.006.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexSubanesthetic dosesAcute effectsNeurotransmitter cyclingMagnetic resonance spectroscopy measuresMPFC of ratsPotential physiological processesAntidepressant-like propertiesSaline-treated animalsAmino acid neurotransmittersHippocampus of ratsDose of ketamineEffects of ketamineGlial energy metabolismMPFC levelsGlutamate releaseKetamine effectsΓ-aminobutyric acidGlial metabolismKetaminePrefrontal cortexEnrichment of glutamateVivo studiesEnergy metabolismRatsThe 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
Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole
Banasr M, Chowdhury GM, Terwilliger R, Newton SS, Duman RS, Behar KL, Sanacora G. Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole. Molecular Psychiatry 2008, 15: 501-511. PMID: 18825147, PMCID: PMC3347761, DOI: 10.1038/mp.2008.106.Peer-Reviewed Original ResearchMeSH KeywordsAcetatesAnimalsAvoidance LearningBehavioral SymptomsDepressionDisease Models, AnimalFood PreferencesGene Expression RegulationGlial Fibrillary Acidic ProteinGlutamic AcidIsotopesMagnetic Resonance SpectroscopyMaleNeurogliaNeuroprotective AgentsPrefrontal CortexRadionuclide ImagingRatsRats, Sprague-DawleyRiluzoleRNA, MessengerStatistics, NonparametricStress, PsychologicalSucroseSweetening AgentsConceptsChronic unpredictable stressPrefrontal cortexGlial dysfunctionGlial functionBehavioral deficitsDrug riluzoleOpen-label clinical trialMRNA expressionAmino acid neurotransmissionAntidepressant drug developmentDepressive-like behaviorPathophysiology of depressionEffects of riluzoleGlial cell metabolismMajor depressive disorderRat prefrontal cortexGFAP mRNA expressionProtein mRNA expressionNeurotransmitter system abnormalitiesGlia pathologyGlial pathologyRiluzole treatmentAntidepressant actionChronic treatmentGlutamate release
2001
ECS-Induced Mossy Fiber Sprouting and BDNF Expression Are Attenuated By Ketamine Pretreatment
Chen A, Shin K, Duman R, Sanacora G. ECS-Induced Mossy Fiber Sprouting and BDNF Expression Are Attenuated By Ketamine Pretreatment. Journal Of Ect 2001, 17: 27-32. PMID: 11281511, DOI: 10.1097/00124509-200103000-00006.Peer-Reviewed Original ResearchConceptsNeurotrophic factor expressionMossy fiber sproutingBDNF expressionElectroconvulsive seizuresKetamine pretreatmentSeizure durationFiber sproutingDentate gyrusBrain-derived neurotrophic factor (BDNF) expressionFactor expressionChronic electroconvulsive seizureSpecific anesthetic agentsTreatment of depressionNMDA receptor activationMossy fiber pathwayUse of ECTMedial prefrontal cortexTimm histochemistryCortical atrophySeizure intensitySeizure activityMajor depressionNMDA antagonistsNMDA receptorsAnesthetic agents
2000
A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression
Berman R, Narasimhan M, Sanacora G, Miano A, Hoffman R, Hu X, Charney D, Boutros N. A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression. Biological Psychiatry 2000, 47: 332-337. PMID: 10686268, DOI: 10.1016/s0006-3223(99)00243-7.Peer-Reviewed Original ResearchConceptsRepetitive transcranial magnetic stimulationTranscranial magnetic stimulationMajor depressionHDRS scoresMagnetic stimulationEfficacy of rTMSHamilton Depression Rating Scale scoresActive repetitive transcranial magnetic stimulationRandomized double-blind mannerTreatment-resistant major depressionDepression Rating Scale scoresDouble-blind mannerTreatment-resistant patientsRandomized clinical trialsRating Scale scoresMotor threshold determinationActive treatmentSham treatmentTreatment trialsClinical trialsTreatment resistanceMean decreaseDepressive symptomsControl groupScale score
1998
Reduced brain serotonin transporter availability in major depression as measured by [123I]-2β-carbomethoxy-3β-(4-iodophenyl)tropane and single photon emission computed tomography
Malison R, Price L, Berman R, van Dyck C, Pelton G, Carpenter L, Sanacora G, Owens M, Nemeroff C, Rajeevan N, Baldwin R, Seibyl J, Innis R, Charney D. Reduced brain serotonin transporter availability in major depression as measured by [123I]-2β-carbomethoxy-3β-(4-iodophenyl)tropane and single photon emission computed tomography. Biological Psychiatry 1998, 44: 1090-1098. PMID: 9836013, DOI: 10.1016/s0006-3223(98)00272-8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntidepressive AgentsBrainBrain StemCarrier ProteinsCocaineDepressive DisorderFemaleHumansMaleMembrane GlycoproteinsMembrane Transport ProteinsMiddle AgedNerve Tissue ProteinsParoxetinePsychiatric Status Rating ScalesSerotoninSerotonin Plasma Membrane Transport ProteinsTomography, Emission-Computed, Single-PhotonConceptsDepressed patientsMajor depressionHealthy subjectsBrain serotonin transporter availabilitySerotonin transporterBeta-CIT SPECTDensity of brainPost-mortem brain tissuePathophysiology of depressionSerotonin transporter availabilityUnipolar major depressionBeta-CIT bindingSingle photon emissionSerotonergic neuronsBrain uptakeSERT availabilityTransporter availabilityBeta-CITBrain tissueCarbomethoxy-3βPatientsBlood plateletsDepressionPhoton emissionSignificant reduction