2023
Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments
Krystal J, Kaye A, Jefferson S, Girgenti M, Wilkinson S, Sanacora G, Esterlis I. Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2305772120. PMID: 38011560, PMCID: PMC10710048, DOI: 10.1073/pnas.2305772120.Peer-Reviewed Original Research
2020
Ketamine and rapid acting antidepressants: Are we ready to cure, rather than treat depression?
Abdallah CG, Krystal JH. Ketamine and rapid acting antidepressants: Are we ready to cure, rather than treat depression? Behavioural Brain Research 2020, 390: 112628. PMID: 32407817, PMCID: PMC7316409, DOI: 10.1016/j.bbr.2020.112628.Peer-Reviewed Original ResearchConceptsChronic stress pathologyRapid acting antidepressantsHigh treatment resistanceActing antidepressantsChronic courseClinical evidenceLeading causeTreatment resistancePsychiatric disordersStress pathologyDepressionLarge proportionAntidepressantsPatientsReviewKetamineIllnessPathologyComprehensive reviewA New Rapid-Acting Antidepressant
Krystal JH, Charney DS, Duman RS. A New Rapid-Acting Antidepressant. Cell 2020, 181: 7. PMID: 32243798, DOI: 10.1016/j.cell.2020.02.033.Peer-Reviewed Original Research
2019
A Unique Brain Connectome Fingerprint Predates and Predicts Response to Antidepressants
Nemati S, Akiki TJ, Roscoe J, Ju Y, Averill CL, Fouda S, Dutta A, McKie S, Krystal JH, Deakin JFW, Averill LA, Abdallah CG. A Unique Brain Connectome Fingerprint Predates and Predicts Response to Antidepressants. IScience 2019, 23: 100800. PMID: 31918047, PMCID: PMC6992944, DOI: 10.1016/j.isci.2019.100800.Peer-Reviewed Original ResearchMonoaminergic antidepressantsAcute neurochemical effectsMechanism of actionMonoaminergic actionsBrain functional connectomeNeurochemical effectsTherapeutic effectAntidepressantsConnectomics signaturesEarly changesBrain functionConnectome fingerprintFunctional connectomeConnectivity architectureDiseaseWeeksMonthsResponse
2018
The Neurobiology and Pharmacotherapy of Posttraumatic Stress Disorder
Abdallah CG, Averill LA, Akiki TJ, Raza M, Averill CL, Gomaa H, Adikey A, Krystal JH. The Neurobiology and Pharmacotherapy of Posttraumatic Stress Disorder. The Annual Review Of Pharmacology And Toxicology 2018, 59: 171-189. PMID: 30216745, PMCID: PMC6326888, DOI: 10.1146/annurev-pharmtox-010818-021701.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderStress disorderTreatment of PTSDBiology of PTSDExert complex effectsBrain functionNeurobiologySynaptic gainPathology modelRapid-acting antidepressantsBroader frameworkDisordersWordsPutative mechanismsDysconnectivitySynaptic lossPharmacotherapeutic optionsClinical efficacyCompelling efficacyPerspectiveAntidepressantsDrug developmentComplex effectsPathologyEfficacyThe neurobiology of depression, ketamine and rapid-acting antidepressants: Is it glutamate inhibition or activation?
Abdallah CG, Sanacora G, Duman RS, Krystal JH. The neurobiology of depression, ketamine and rapid-acting antidepressants: Is it glutamate inhibition or activation? Pharmacology & Therapeutics 2018, 190: 148-158. PMID: 29803629, PMCID: PMC6165688, DOI: 10.1016/j.pharmthera.2018.05.010.Peer-Reviewed Original ResearchConceptsRapid-acting antidepressantsNeurobiology of depressionMechanism of actionChronic stress pathologyRole of glutamateAntidepressant effectsEfficacy findingsGlutamate activationBiomarker findingsNeurobiology of stressVivo pharmacodynamicsCurrent perspective paperKetamineChronic stressReproducible biomarkersBehavioral effectsGlutamate inhibitionDepressionStress pathologyAntidepressantsNeurobiologyInhibitionActivationPharmacodynamicsPharmacokinetics
2016
Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants
Duman RS, Aghajanian GK, Sanacora G, Krystal JH. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nature Medicine 2016, 22: 238-249. PMID: 26937618, PMCID: PMC5405628, DOI: 10.1038/nm.4050.Peer-Reviewed Original ResearchMeSH KeywordsAntidepressive AgentsBrain-Derived Neurotrophic FactorCytokinesDepressive DisorderDiabetes MellitusExcitatory Amino Acid AntagonistsFemaleGlucocorticoidsHumansHypothalamo-Hypophyseal SystemInflammationKetamineMaleNeuronal PlasticityPituitary-Adrenal SystemSelective Serotonin Reuptake InhibitorsSex FactorsSignal TransductionStress, PsychologicalTime FactorsCross-trial prediction of treatment outcome in depression: a machine learning approach
Chekroud AM, Zotti RJ, Shehzad Z, Gueorguieva R, Johnson MK, Trivedi MH, Cannon TD, Krystal JH, Corlett PR. Cross-trial prediction of treatment outcome in depression: a machine learning approach. The Lancet Psychiatry 2016, 3: 243-250. PMID: 26803397, DOI: 10.1016/s2215-0366(15)00471-x.Peer-Reviewed Original ResearchConceptsTreatment outcomesTreatment groupsEscitalopram treatment groupSpecific antidepressantsPatient-reported dataSequenced Treatment AlternativesClinical trial dataIndependent clinical trialsClinical remissionSymptomatic remissionClinical trialsTreatment efficacyPatientsProspective identificationTreatment alternativesTrial dataDepressionRemissionAntidepressantsOutcomesGroupLevel 1CitalopramCohortClinicians
2015
Ketamine as a promising prototype for a new generation of rapid‐acting antidepressants
Abdallah CG, Averill LA, Krystal JH. Ketamine as a promising prototype for a new generation of rapid‐acting antidepressants. Annals Of The New York Academy Of Sciences 2015, 1344: 66-77. PMID: 25727103, PMCID: PMC4412785, DOI: 10.1111/nyas.12718.Peer-Reviewed Original ResearchConceptsOpen-label studyRobust antidepressant effectsRapid-acting antidepressantsNeurobiology of depressionRoute of administrationModerate adverse effectsMechanism of actionTrauma-related disordersTraditional antidepressantsAntidepressant effectsTransient mildChronic treatmentControlled TrialsClinical effectsOptimal dosingPsychopharmacologic interventionsPatient groupPatient populationTreatment targetsKetamineAntidepressantsRelevant biomarkersAdverse effectsNeurobiological underpinningsInfusion
2014
Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics
Abdallah CG, Sanacora G, Duman RS, Krystal JH. Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics. Annual Review Of Medicine 2014, 66: 1-15. PMID: 25341010, PMCID: PMC4428310, DOI: 10.1146/annurev-med-053013-062946.Peer-Reviewed Original ResearchConceptsRapid antidepressant effectsAntidepressant effectsGlutamate-based antidepressantsTolerability of ketamineRapid-acting antidepressantsTreatment-resistant depressionNeurobiology of depressionPotent antidepressant effectsRapid acting antidepressantsBiology of depressionPotential treatment targetHours of treatmentTreatment targetsKetamineAntidepressantsBiomarker studiesDepressionNeurobiologyTolerability
2013
Rapid-Acting Glutamatergic Antidepressants: The Path to Ketamine and Beyond
Krystal JH, Sanacora G, Duman RS. Rapid-Acting Glutamatergic Antidepressants: The Path to Ketamine and Beyond. Biological Psychiatry 2013, 73: 1133-1141. PMID: 23726151, PMCID: PMC3671489, DOI: 10.1016/j.biopsych.2013.03.026.Peer-Reviewed Original ResearchConceptsAspartate glutamate receptor antagonist ketamineNovel antidepressant mechanismNovel treatment mechanismsSingle subanesthetic doseRapid-acting antidepressantsMeaningful clinical improvementGlutamatergic antidepressantsTraditional antidepressantsAntidepressant mechanismClinical improvementAntidepressant responseAntidepressant researchSubanesthetic doseKetamine studiesTherapeutic effectAntidepressantsKetamineTreatment mechanismsN-methylDose
2002
Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments
Krystal JH, Sanacora G, Blumberg H, Anand A, Charney DS, Marek G, Epperson CN, Goddard A, Mason GF. Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Molecular Psychiatry 2002, 7: s71-s80. PMID: 11986998, DOI: 10.1038/sj.mp.4001021.Peer-Reviewed Original ResearchConceptsCortical GABA levelsMood-stabilizing treatmentMood disordersGABA levelsΓ-amino-butyric acid (GABA) systemMood-stabilizing agentsGlutamate receptor functionDevelopment of medicationsGABA deficitAvailable antidepressantsGABAergic modulationAntimanic effectsGlutamatergic activityClinical evidenceNovel antidepressantsGABA systemAntidepressant drugsNew agentsReceptor functionAvailable evidenceReceptor targetsAntidepressantsDisordersGlutamateTreatment
1990
Clinical data on the role of serotonin in the mechanism(s) of action of antidepressant drugs.
Price LH, Charney DS, Delgado PL, Goodman WK, Krystal JH, Woods SW, Heninger GR. Clinical data on the role of serotonin in the mechanism(s) of action of antidepressant drugs. The Journal Of Clinical Psychiatry 1990, 51 Suppl: 44-50; discussion 51-2. PMID: 2182616.Peer-Reviewed Original ResearchConceptsIntravenous L-tryptophanBrain serotonin functionAntidepressant drug actionRole of serotoninL-tryptophanThymoleptic drugsPlasma TrpView of evidencePRL responseNeuroendocrine effectsSerum prolactinSerotonin functionAntidepressant drugsClinical dataTherapeutic effectPreclinical studiesReceptor sensitivityClinical settingChallenge paradigmDrug actionRecent evidenceAntidepressantsProlactinDrugsDepression