2024
Medial prefrontal cortex neurotransmitter abnormalities in posttraumatic stress disorder with and without comorbidity to major depression
Swanberg K, Prinsen H, Averill C, Campos L, Kurada A, Krystal J, Petrakis I, Averill L, Rothman D, Abdallah C, Juchem C. Medial prefrontal cortex neurotransmitter abnormalities in posttraumatic stress disorder with and without comorbidity to major depression. NMR In Biomedicine 2024, 37: e5220. PMID: 39054694, DOI: 10.1002/nbm.5220.Peer-Reviewed Original ResearchPosttraumatic stress disorderMedial prefrontal cortexStress disorderPosttraumatic stress disorder patientsPosttraumatic stress disorder diagnosisChronic psychiatric conditionImpact of psychiatric comorbiditiesComorbid MDDPrefrontal cortexDepressive disorderTraumatic stressorsPsychiatric conditionsMDDPsychiatric comorbiditiesNeurotransmitter abnormalitiesConcentrations of glutamateMetabolite abnormalitiesHealthy controlsDisordersPattern of abnormalitiesParticipantsGlutamateIn vivo protonMetabolic abnormalitiesDepressionRecent Advances in the Treatment of Treatment-Resistant Depression: A Narrative Review of Literature Published from 2018 to 2023
Havlik J, Wahid S, Teopiz K, McIntyre R, Krystal J, Rhee T. Recent Advances in the Treatment of Treatment-Resistant Depression: A Narrative Review of Literature Published from 2018 to 2023. Current Psychiatry Reports 2024, 26: 176-213. PMID: 38386251, DOI: 10.1007/s11920-024-01494-4.Peer-Reviewed Original ResearchTreatment of treatment-resistant depressionTreatment-resistant depressionMedication discontinuation ratesTranscranial magnetic stimulationElectroconvulsive therapyPsychiatric approachApproach to treatmentAdjunctive pharmacotherapyIntervention approachesAdjunctive treatmentDiscontinuation ratesMagnetic stimulationGeneralizability resultsDepressionPharmacotherapyInclusion criteriaAntipsychoticsPsychotherapyNarrative reviewKetamine/esketamineSide effectsStudy inclusion criteriaRecent FindingsRecent evidenceDisordersBuprenorphine
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
2022
Polygenic scores for empathy associate with posttraumatic stress severity in response to certain traumatic events
Wendt FR, Warrier V, Pathak GA, Koenen KC, Stein MB, Krystal JH, Pietrzak RH, Gelernter J, Goldfarb EV, Baron-Cohen S, Polimanti R. Polygenic scores for empathy associate with posttraumatic stress severity in response to certain traumatic events. Neurobiology Of Stress 2022, 17: 100439. PMID: 35242894, PMCID: PMC8881478, DOI: 10.1016/j.ynstr.2022.100439.Peer-Reviewed Original ResearchPosttraumatic stress disorderTraumatic eventsPolygenic scoringGreater emotional sensitivityChildhood neglect/abusePTSD symptom severityCertain traumatic eventsSevere PTSD symptomsPosttraumatic stress severityContext of traumaNeglect/abuseEarly life adversityHigher empathyPTSD symptomsEmotional sensitivityHigh empathizersStress disorderLife eventsEmpathyPotential traumaSymptom severityPolygenic scoresAutismStress severityDepression
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
Lower synaptic density is associated with depression severity and network alterations
Holmes SE, Scheinost D, Finnema SJ, Naganawa M, Davis MT, DellaGioia N, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Lower synaptic density is associated with depression severity and network alterations. Nature Communications 2019, 10: 1529. PMID: 30948709, PMCID: PMC6449365, DOI: 10.1038/s41467-019-09562-7.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPost-traumatic stress disorderLower synaptic densitySynaptic densityPositron emission tomographyFunctional connectivityNetwork alterationsSynaptic vesicle glycoprotein 2ASymptoms of depressionSynaptic lossDepressive disorderHealthy controlsNerve terminalsDepressive symptomsDepression severityUnmedicated individualsSynaptic connectionsEmission tomographyStress disorderVivo evidenceSymptomsDepressionSeverityDisordersAlterations
2018
Predicting Barriers to Treatment for Depression in a U.S. National Sample: A Cross-Sectional, Proof-of-Concept Study
Chekroud AM, Foster D, Zheutlin AB, Gerhard DM, Roy B, Koutsouleris N, Chandra A, Esposti MD, Subramanyan G, Gueorguieva R, Paulus M, Krystal JH. Predicting Barriers to Treatment for Depression in a U.S. National Sample: A Cross-Sectional, Proof-of-Concept Study. Psychiatric Services 2018, 69: 927-934. PMID: 29962307, PMCID: PMC7232987, DOI: 10.1176/appi.ps.201800094.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overCross-Sectional StudiesDepressive DisorderFemaleHealth Services AccessibilityHumansLogistic ModelsMaleMiddle AgedPatient Acceptance of Health CarePrimary Health CareProof of Concept StudyPsychotherapySampling StudiesSelf-AssessmentSurveys and QuestionnairesTreatment RefusalUnited StatesYoung AdultConceptsDiagnosis of depressionHealth care providersSelf-report survey itemsImplementation of interventionsDerivation cohortUntreated depressionCare providersEffective treatmentU.S. national sampleDrug useDepressionDiagnosisTreatmentU.S. National SurveyPatientsCohortNational surveyNational sampleConcept studySurvey itemsBalanced accuracyIndividualsRetention rateIndependent responsesPrevalenceThe 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
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
2010
A Prospective Cohort Study Investigating Factors Associated With Depression During Medical Internship
Sen S, Kranzler HR, Krystal JH, Speller H, Chan G, Gelernter J, Guille C. A Prospective Cohort Study Investigating Factors Associated With Depression During Medical Internship. JAMA Psychiatry 2010, 67: 557-565. PMID: 20368500, PMCID: PMC4036806, DOI: 10.1001/archgenpsychiatry.2010.41.Peer-Reviewed Original ResearchMeSH KeywordsAdultCohort StudiesDepressionDepressive DisorderDepressive Disorder, MajorFemaleGenotypeHealth StatusHumansInternship and ResidencyLife Change EventsMaleMedicinePolymorphism, Single NucleotidePrevalenceProspective StudiesRisk FactorsSerotonin Plasma Membrane Transport ProteinsStress, PsychologicalStudents, MedicalSurveys and QuestionnairesConceptsDepressive symptomsPHQ-9 depression scoresProspective cohort studyPrevalence of depressionPatient Health QuestionnaireProportion of participantsMedical internsMedical internshipGreater increasePHQ-9 criteriaCohort studyHealth QuestionnaireMood symptomsGeneral populationDepression scoresUS hospitalsSymptomsSerotonin transporter protein geneGenetic polymorphismsDepressionGenetic factorsLife stressMarked increaseRecent reportsResidency programs
2007
The NMDA receptor as a therapeutic target in major depressive disorder.
Pittenger C, Sanacora G, Krystal JH. The NMDA receptor as a therapeutic target in major depressive disorder. CNS & Neurological Disorders - Drug Targets 2007, 6: 101-15. PMID: 17430148, DOI: 10.2174/187152707780363267.Peer-Reviewed Original ResearchConceptsMajor depressive disorderNMDA receptorsDepressive disorderNovel antidepressant medicationsCognitive side effectsPotential of drugsAntidepressant medicationAntidepressant propertiesSuch medicationsGlutamatergic neurotransmissionGlutamate receptorsPreclinical studiesPsychotomimetic propertiesSide effectsTherapeutic targetAnimal modelsUseful agentNeurotransmissionReceptorsLines of evidenceMedicationsDisordersDrugsCurrent knowledgeDepressionNeurobiology 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
2006
Brain-Derived Neurotrophic Factor–5-HTTLPR Gene Interactions and Environmental Modifiers of Depression in Children
Kaufman J, Yang BZ, Douglas-Palumberi H, Grasso D, Lipschitz D, Houshyar S, Krystal JH, Gelernter J. Brain-Derived Neurotrophic Factor–5-HTTLPR Gene Interactions and Environmental Modifiers of Depression in Children. Biological Psychiatry 2006, 59: 673-680. PMID: 16458264, DOI: 10.1016/j.biopsych.2005.10.026.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentBrain-Derived Neurotrophic FactorCase-Control StudiesChildChild AbuseChild, PreschoolChi-Square DistributionDepressionDNA Mutational AnalysisEnvironmentFemaleGene FrequencyGenetic VariationGenotypeHumansMaleMethioninePredictive Value of TestsPsychiatric Status Rating ScalesRisk FactorsSerotonin Plasma Membrane Transport ProteinsSeverity of Illness IndexSocial SupportSurveys and QuestionnairesValineConceptsBrain-derived neurotrophic factor (BDNF) genotypeNeurotrophic factor genotypeSocial supportHigher depression scoresBDNF genotypeProportion scoreBDNF geneProtective effectDepression scoresComparison subjectsPsychiatric symptomatologyModerate riskEnvironmental modifiersDepressionFactor genotypeChildrenDNA specimensStandard research instrumentsShort alleleRiskMaltreatment historyCurrent dataScoresAncestry informative markersChild abuse
2004
Social supports and serotonin transporter gene moderate depression in maltreated children
Kaufman J, Yang BZ, Douglas-Palumberi H, Houshyar S, Lipschitz D, Krystal JH, Gelernter J. Social supports and serotonin transporter gene moderate depression in maltreated children. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 17316-17321. PMID: 15563601, PMCID: PMC534414, DOI: 10.1073/pnas.0404376101.Peer-Reviewed Original ResearchConceptsSocial supportDevelopment of depressionGene promoter polymorphismTransporter gene promoter polymorphismSerotonin transporter gene promoter polymorphismHigher depression ratingsDepression ratingsClinical dataModerate depressionPsychiatric disordersDepression scoresPromoter polymorphismNegative sequelaeModerate riskDepressionEarly stressChildrenS genotypeHistory of maltreatmentRiskShort allele
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
Frontotemporal neural systems in bipolar disorder.
Blumberg HP, Charney DS, Krystal JH. Frontotemporal neural systems in bipolar disorder. Seminars In Clinical Neuropsychiatry 2002, 7: 243-54. PMID: 12382207, DOI: 10.1053/scnp.2002.35220.Peer-Reviewed Original ResearchConceptsBipolar disorderBD symptomsNeural system abnormalitiesRegional brain abnormalitiesLocalization of lesionsAmygdalar abnormalitiesNeural systemsFrontotemporal neural systemBrain abnormalitiesBrain lesionsSystem abnormalitiesManic stateMood symptomsTrait abnormalityUnipolar depressionAbnormalitiesMood changesVivo evidenceSymptomsPotential targetNeuroanatomic modelLesionsDisordersDepressionInvolvementIncreased 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