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 evidenceSymptomsDepressionSeverityDisordersAlterationsAssociation of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder
Yoon G, Petrakis IL, Krystal JH. Association of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder. JAMA Psychiatry 2019, 76: 337-338. PMID: 30624551, PMCID: PMC6439824, DOI: 10.1001/jamapsychiatry.2018.3990.Peer-Reviewed Original Research
2017
Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder
Scheinost D, Holmes SE, DellaGioia N, Schleifer C, Matuskey D, Abdallah CG, Hampson M, Krystal JH, Anticevic A, Esterlis I. Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder. Neuropsychopharmacology 2017, 43: 1119-1127. PMID: 28944772, PMCID: PMC5854800, DOI: 10.1038/npp.2017.229.Peer-Reviewed Original ResearchConceptsMajor depressive disorderAnterior cingulate cortexIntrinsic functional connectivityMedial prefrontal cortexFunctional connectivityLarge-scale brain networksDepressive disorderMDD groupAnatomical covarianceBrain networksUnmedicated major depressive disorderWhole-brain intrinsic functional connectivitySystem-level disorderIntrinsic connectivity distributionRegional brain structureMultiple brain networksAltered connectivityCommon findingHealthy comparison participantsDepressive symptomsAltered volumeUnmedicated individualsLocal circuitryCingulate cortexDepressive symptomatology
2012
Effects of Ketamine in Treatment-Refractory Obsessive-Compulsive Disorder
Bloch MH, Wasylink S, Landeros-Weisenberger A, Panza KE, Billingslea E, Leckman JF, Krystal JH, Bhagwagar Z, Sanacora G, Pittenger C. Effects of Ketamine in Treatment-Refractory Obsessive-Compulsive Disorder. Biological Psychiatry 2012, 72: 964-970. PMID: 22784486, PMCID: PMC3667652, DOI: 10.1016/j.biopsych.2012.05.028.Peer-Reviewed Original ResearchConceptsObsessive-compulsive disorderKetamine infusionDepression symptomsLow-dose ketamine infusionTreatment-refractory obsessive-compulsive disorderOCD symptomsPathogenesis of OCDIncomplete symptom reliefTreatment-Refractory ObsessiveOpen-label trialRapid antidepressant effectsAspartate glutamate receptorsEffects of ketaminePotent noncompetitive antagonistGlutamate abnormalitiesAntidepressant effectsAntidepressant responseSymptom reliefKetamine effectsComorbid depressionAcute effectsGlutamate receptorsDepressive symptomsNoncompetitive antagonistInfusionMild Worry Symptoms Predict Decline in Learning and Memory in Healthy Older Adults: A 2-Year Prospective Cohort Study
Pietrzak RH, Maruff P, Woodward M, Fredrickson J, Fredrickson A, Krystal JH, Southwick SM, Darby D. Mild Worry Symptoms Predict Decline in Learning and Memory in Healthy Older Adults: A 2-Year Prospective Cohort Study. American Journal Of Geriatric Psychiatry 2012, 20: 266-275. PMID: 22354117, PMCID: PMC3285262, DOI: 10.1097/jgp.0b013e3182107e24.Peer-Reviewed Original ResearchConceptsWorry symptomsOlder adultsCommunity-dwelling older adultsCognitive functionAge-related cognitive changesHealthy Older AdultsImportance of anxietyEarly cognitive declineDepressive symptomsAssociate learningCognitive agingVisual learningCognitive changesProspective cohort studyCognitive declineDepression symptomsEarly dementiaCohort studyObservational prospective cohort studyMemoryMild levelsLearningWorryAdultsTheoretical model
2011
The 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
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
2006
Preliminary Evidence of Riluzole Efficacy in Antidepressant-Treated Patients with Residual Depressive Symptoms
Sanacora G, Kendell SF, Levin Y, Simen AA, Fenton LR, Coric V, Krystal JH. Preliminary Evidence of Riluzole Efficacy in Antidepressant-Treated Patients with Residual Depressive Symptoms. Biological Psychiatry 2006, 61: 822-825. PMID: 17141740, PMCID: PMC2754299, DOI: 10.1016/j.biopsych.2006.08.037.Peer-Reviewed Original ResearchConceptsHamilton Depression Rating ScaleHamilton Anxiety Rating ScaleTreatment-resistant depressionMajor depressive disorderHARS scoresRating ScaleExcessive glutamatergic neurotransmissionEffects of riluzoleDepression Rating ScaleResidual depressive symptomsAnxiety Rating ScaleRiluzole efficacyMedication regimenAugmentation therapyContinuation phaseAntidepressant activityGlutamate neurotransmissionGlutamatergic neurotransmissionDepressive disorderAnxiolytic effectsDepressive symptomsRiluzolePatientsFirst weekLinear mixed modelsDecreased Cerebrospinal Fluid Allopregnanolone Levels in Women with Posttraumatic Stress Disorder
Rasmusson AM, Pinna G, Paliwal P, Weisman D, Gottschalk C, Charney D, Krystal J, Guidotti A. Decreased Cerebrospinal Fluid Allopregnanolone Levels in Women with Posttraumatic Stress Disorder. Biological Psychiatry 2006, 60: 704-713. PMID: 16934764, DOI: 10.1016/j.biopsych.2006.03.026.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderPremenopausal womenALLO levelsStress disorderCerebrospinal fluid levelsPTSD re-experiencing symptomsAllopregnanolone levelsOral contraceptivesGABAergic neurotransmissionDHEAS levelsPsychotropic medicationsFollicular phaseMenstrual cycleDHEA ratioExcitatory neurotransmissionNeurotransmitter systemsRe-experiencing symptomsDepressive symptomsPTSD subjectsFluid levelsGroup differencesIllicit drugsWomenNeurotransmissionProgesterone
2003
Frontostriatal Abnormalities in Adolescents With Bipolar Disorder: Preliminary Observations From Functional MRI
Blumberg HP, Martin A, Kaufman J, Leung HC, Skudlarski P, Lacadie C, Fulbright RK, Gore JC, Charney DS, Krystal JH, Peterson BS. Frontostriatal Abnormalities in Adolescents With Bipolar Disorder: Preliminary Observations From Functional MRI. American Journal Of Psychiatry 2003, 160: 1345-1347. PMID: 12832254, DOI: 10.1176/appi.ajp.160.7.1345.Peer-Reviewed Original ResearchConceptsBipolar disorder groupBipolar disorderHealthy groupComparison subjectsDisorder groupNormal comparison subjectsAdult bipolar disorderHealthy comparison subjectsPresence of dysfunctionFunctional magnetic resonance imagingMagnetic resonance imagingBipolar disorder subjectsAge-related increaseEvent-related functional magnetic resonance imagingFrontostriatal abnormalitiesLeft putamenFunctional abnormalitiesPrefrontal abnormalitiesDepressive symptomsResonance imagingVentral striatumFrontostriatal circuitsDisorder subjectsFunctional MRIDevelopmental disturbances
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 solutionTreatment
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
1997
Positron Emission Tomography Measurement of Cerebral Metabolic Correlates of Tryptophan Depletion—Induced Depressive Relapse
Bremner JD, Innis RB, Salomon RM, Staib LH, Ng CK, Miller HL, Bronen RA, Krystal JH, Duncan J, Rich D, Price LH, Malison R, Dey H, Soufer R, Charney DS. Positron Emission Tomography Measurement of Cerebral Metabolic Correlates of Tryptophan Depletion—Induced Depressive Relapse. JAMA Psychiatry 1997, 54: 364-374. PMID: 9107153, DOI: 10.1001/archpsyc.1997.01830160092012.Peer-Reviewed Original ResearchConceptsCerebral metabolic correlatesDepressive relapseBrain metabolismMajor depressionMiddle frontal gyrusOrbitofrontal cortexTryptophan depletionMetabolic correlatesPositron emission tomography scanningFrontal gyrusRelapse-prone patientsPathogenesis of depressionPositron emission tomography (PET) measurementsSerotonin reuptake inhibitorsSymptoms of patientsPositron emission tomographySingle photon emissionSpecific brain regionsDorsolateral prefrontal cortexReuptake inhibitorsPlasma tryptophanLimbic regionsCaudate nucleusDepressive symptomsPatients
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
1990
Specificity of Serotonin Reuptake Inhibitors in the Treatment of Obsessive-Compulsive Disorder: Comparison of Fluvoxamine and Desipramine
Goodman WK, Price LH, Delgado PL, Palumbo J, Krystal JH, Nagy LM, Rasmussen SA, Heninger GR, Charney DS. Specificity of Serotonin Reuptake Inhibitors in the Treatment of Obsessive-Compulsive Disorder: Comparison of Fluvoxamine and Desipramine. JAMA Psychiatry 1990, 47: 577-585. PMID: 2112374, DOI: 10.1001/archpsyc.1990.01810180077011.Peer-Reviewed Original ResearchConceptsSerotonin reuptake inhibitorsObsessive-compulsive disorderReuptake inhibitorsComparison of fluvoxamineSerotonin receptor functionDouble-blind fashionGlobal response rateWeeks of treatmentBaseline depressive symptomsYale-Brown Obsessive Compulsive ScaleMechanism of actionObsessive Compulsive ScaleReuptake inhibitionDopaminergic functionPrincipal diagnosisDepressive symptomsResponse rateFluvoxamineDesipramineReceptor functionObsessive-compulsive symptomsDesipramine hydrochlorideCompulsive ScaleSymptomsFluvoxamine maleate