2022
Imaging the effect of ketamine on synaptic density (SV2A) in the living brain
Holmes SE, Finnema SJ, Naganawa M, DellaGioia N, Holden D, Fowles K, Davis M, Ropchan J, Emory P, Ye Y, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Imaging the effect of ketamine on synaptic density (SV2A) in the living brain. Molecular Psychiatry 2022, 27: 2273-2281. PMID: 35165397, PMCID: PMC9133063, DOI: 10.1038/s41380-022-01465-2.Peer-Reviewed Original ResearchConceptsKetamine's therapeutic effectsMajor depressive disorderTherapeutic effectPositron emission tomographyPosttraumatic stress disorderHealthy controlsSynaptic connectionsSynaptic vesicle protein 2APost-synaptic mechanismsEffects of ketamineDiscovery of ketamineNon-human primatesAntidepressant effectsDepressive disorderSingle administrationSynaptic densityPsychiatric disordersDepression severityKetamineEmission tomographyTerminal densityLiving brainStress disorderRobust reductionDissociative symptoms
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 architectureDiseaseWeeksMonthsResponseRepeated ketamine infusions for antidepressant-resistant PTSD: Methods of a multicenter, randomized, placebo-controlled clinical trial
Abdallah CG, Roache JD, Averill LA, Young-McCaughan S, Martini B, Gueorguieva R, Amoroso T, Southwick SM, Guthmiller K, López-Roca AL, Lautenschlager K, Mintz J, Litz BT, Williamson DE, Keane TM, Peterson AL, Krystal JH, PTSD F. Repeated ketamine infusions for antidepressant-resistant PTSD: Methods of a multicenter, randomized, placebo-controlled clinical trial. Contemporary Clinical Trials 2019, 81: 11-18. PMID: 30999057, DOI: 10.1016/j.cct.2019.04.009.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderStudy drugClinical trialsTherapeutic effectPharmacotherapy of PTSDFirst placebo-controlled trialPlacebo-controlled clinical trialActive duty military populationDose-related efficacyMedication treatment optionsPlacebo-controlled trialDose-related effectsNovel neural mechanismActive duty militaryKetamine infusionSerotonergic antidepressantsEligible participantsTreatment optionsCase reportNew drug developmentOnly trialSustained reductionVeteran populationDrug AdministrationPilot evidence
2016
PTSD: from neurobiology to pharmacological treatments
Kelmendi B, Adams TG, Yarnell S, Southwick S, Abdallah CG, Krystal JH. PTSD: from neurobiology to pharmacological treatments. European Journal Of Psychotraumatology 2016, 7: 31858. PMID: 27837583, PMCID: PMC5106865, DOI: 10.3402/ejpt.v7.31858.Peer-Reviewed Original ResearchPosttraumatic stress disorderPharmacological treatmentPathophysiology of PTSDFirst-line pharmacotherapyMultiple neurobiological systemsEtiology of PTSDFull remissionTherapeutic effectPsychiatric disordersPharmacologic targetStress disorderNeurobiological systemsPathophysiologyFuture targetsTreatmentTraumatic eventsDisordersRemissionPharmacotherapyEtiologyInjurySymptomsYearsWeeksKETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS
Abdallah CG, Adams TG, Kelmendi B, Esterlis I, Sanacora G, Krystal JH. KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS. Depression And Anxiety 2016, 33: 689-697. PMID: 27062302, PMCID: PMC4961540, DOI: 10.1002/da.22501.Peer-Reviewed Original ResearchConceptsMajor depressive disorderAntidepressant effectsKetamine's mechanismN-methyl-D-aspartate receptor antagonistRapid-acting antidepressant effectsPrefrontal cortexSingle subanesthetic doseRapid antidepressant effectsTreatment-resistant depressionFull therapeutic effectEfficacy of ketamineKetamine's antidepressant effectsRapid acting antidepressantsFuture clinical prospectsGlutamate surgeTraditional antidepressantsAntidepressant medicationCascade of eventsReceptor antagonistSubanesthetic doseDepressive disorderClinical dataTherapeutic effectTreatment responseLimited efficacy
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
1999
Tryptophan-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 3RemissionEffects of Rapid Tryptophan Depletion in Patients With Seasonal Affective Disorder in Remission After Light Therapy
Lam RW, Zis AP, Grewal A, Delgado PL, Charney DS, Krystal JH. Effects of Rapid Tryptophan Depletion in Patients With Seasonal Affective Disorder in Remission After Light Therapy. JAMA Psychiatry 1996, 53: 41-44. PMID: 8540776, DOI: 10.1001/archpsyc.1996.01830010043007.Peer-Reviewed Original ResearchConceptsRapid tryptophan depletionSeasonal affective disorderTryptophan depletionLight therapyClinical remissionAffective disordersTryptophan levelsDouble-blind crossover studyRecurrent major depressive episodesMajor depressive episodeBright light therapyEffect of therapyFree tryptophan levelsAntidepressant effectsCrossover studySerotonergic mechanismsDepressive episodeAntidepressant drugsTherapeutic effectSignificant relapseDepression scoresPatientsTherapyRemissionNonseasonal depression
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 evidenceAntidepressantsProlactinDrugsDepressionClinical 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