2022
Abnormal glutamate metabolism in prefrontal cortex of post-traumatic stress disorder linked to comorbidity with major depression
Swanberg K, Prinsen H, Averill C, Campos L, Kurada A, Krystal J, Petrakis I, Averill L, Abdallah C, Juchem C. Abnormal glutamate metabolism in prefrontal cortex of post-traumatic stress disorder linked to comorbidity with major depression. Proceedings Of The International Society For Magnetic Resonance In Medicine ... Scientific Meeting And Exhibition. 2022 DOI: 10.58530/2022/3344.Peer-Reviewed Original Research
2020
Multivariate genome-wide analysis of education, socioeconomic status and brain phenome
Wendt FR, Pathak GA, Lencz T, Krystal JH, Gelernter J, Polimanti R. Multivariate genome-wide analysis of education, socioeconomic status and brain phenome. Nature Human Behaviour 2020, 5: 482-496. PMID: 33349686, PMCID: PMC8068566, DOI: 10.1038/s41562-020-00980-y.Peer-Reviewed Original ResearchConceptsPsychosocial factorsSocioeconomic statusPsychiatric disordersBipolar disorderGenetic riskNeuronal cell typesMajor depressionTourette syndromeBrain morphologyDisordersImaging phenotypesCell typesRisky behaviorsPsychopathologyGenetic overlapRiskGenetic discoveriesPsychiatric traitsStatusSyndrome
2011
Trajectories of Depression Severity in Clinical Trials of Duloxetine: Insights Into Antidepressant and Placebo Responses
Gueorguieva R, Mallinckrodt C, Krystal JH. Trajectories of Depression Severity in Clinical Trials of Duloxetine: Insights Into Antidepressant and Placebo Responses. JAMA Psychiatry 2011, 68: 1227-1237. PMID: 22147842, PMCID: PMC3339151, DOI: 10.1001/archgenpsychiatry.2011.132.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntidepressive AgentsData Interpretation, StatisticalDepressive Disorder, MajorDouble-Blind MethodDuloxetine HydrochlorideFemaleHumansLinear ModelsMalePatient DropoutsPlacebo EffectPsychiatric Status Rating ScalesRandomized Controlled Trials as TopicSelective Serotonin Reuptake InhibitorsSeverity of Illness IndexThiophenesTreatment OutcomeConceptsSelective serotonin reuptake inhibitorsPlacebo-treated patientsComparator selective serotonin reuptake inhibitorsHAM-D scoresClinical trialsAntidepressant treatmentPlacebo responseMajor depressionDouble-blind clinical trialHigh placebo response rateSerotonergic antidepressant treatmentPlacebo response ratesSerotonin reuptake inhibitorsAntidepressant nonrespondersPlacebo armMost patientsAntidepressant respondersMedication risksReuptake inhibitorsSerotonergic antidepressantsResponder statusTreatment responseClinical trajectoriesDepression scoresDepression severity
2006
The resistance to depressive relapse in menopausal women undergoing tryptophan depletion: preliminary findings
Epperson CN, Amin Z, Naftolin F, Cappiello A, Czarkowski KA, Stiklus S, Anderson GM, Krystal JH. The resistance to depressive relapse in menopausal women undergoing tryptophan depletion: preliminary findings. Journal Of Psychopharmacology 2006, 21: 414-420. PMID: 16891341, DOI: 10.1177/0269881106067330.Peer-Reviewed Original ResearchConceptsMenopausal womenTryptophan depletionSelective serotonin reuptake inhibitor fluoxetineAcute tryptophan depletion paradigmSerotonin reuptake inhibitor fluoxetineTryptophan depletion paradigmPathogenesis of depressionReuptake inhibitor fluoxetineMajor depressive episodeAcute tryptophan depletionRelapse of depressionWorsening of moodWeeks of recoveryActive tryptophan depletionWechsler Memory ScaleAssessment of moodDepressive episodeRisk factorsDepressive relapseMajor depressionSignificant worseningNeuroendocrine functionVerbal memorySerotonergic contributionMemory ScalePreliminary evidence of reduced occipital GABA concentrations in puerperal women: a 1H-MRS study
Epperson CN, Gueorguieva R, Czarkowski KA, Stiklus S, Sellers E, Krystal JH, Rothman DL, Mason GF. Preliminary evidence of reduced occipital GABA concentrations in puerperal women: a 1H-MRS study. Psychopharmacology 2006, 186: 425. PMID: 16724188, DOI: 10.1007/s00213-006-0313-7.Peer-Reviewed Original ResearchConceptsPostpartum major depressionCortical GABA concentrationsGABA concentrationPostpartum womenOccipital cortex GABA concentrationsOccipital cortex GABA levelsProton magnetic resonance spectroscopy studyFollicular phase femalesGamma-aminobutyric acid concentrationResumption of menstruationFollicular phase womenMonths of deliveryMid-follicular phaseOvarian hormone levelsSubgroup of womenMagnetic resonance spectroscopy studyAllopregnanolone concentrationsPuerperal womenALLO levelsBlood levelsPostpartum periodHealthy controlsMajor depressionGABA levelsHormone levels
2005
Cortical γ-Aminobutyric Acid Concentrations in Depressed Patients Receiving Cognitive Behavioral Therapy
Sanacora G, Fenton LR, Fasula MK, Rothman DL, Levin Y, Krystal JH, Mason GF. Cortical γ-Aminobutyric Acid Concentrations in Depressed Patients Receiving Cognitive Behavioral Therapy. Biological Psychiatry 2005, 59: 284-286. PMID: 16139814, DOI: 10.1016/j.biopsych.2005.07.015.Peer-Reviewed Original ResearchMeSH KeywordsAdultCognitive Behavioral TherapyDepressive Disorder, MajorElectroconvulsive TherapyFemaleFollow-Up StudiesGamma-Aminobutyric AcidHumansImage Processing, Computer-AssistedMagnetic Resonance SpectroscopyMaleOccipital LobeOutcome and Process Assessment, Health CareSelective Serotonin Reuptake InhibitorsStatistics as TopicConceptsOccipital cortex GABA concentrationsSelective serotonin reuptake inhibitorsCognitive behavioral therapyElectroconvulsive therapyGABA concentrationDepressed patientsBehavioral therapyCortical GABA concentrationsEffects of CBTGamma-aminobutyric acid concentrationSerotonin reuptake inhibitorsΓ-aminobutyric acid (GABA) concentrationMajor depressive disorderProton magnetic resonance spectroscopyGABA contentAntidepressant actionSSRI treatmentCourse of CBTReuptake inhibitorsMedication treatmentDepressive disorderMajor depressionCerebrospinal fluidDepressed subjectsTherapy
2004
Subtype-Specific Alterations of γ-Aminobutyric Acid and Glutamatein Patients With Major Depression
Sanacora G, Gueorguieva R, Epperson CN, Wu YT, Appel M, Rothman DL, Krystal JH, Mason GF. Subtype-Specific Alterations of γ-Aminobutyric Acid and Glutamatein Patients With Major Depression. JAMA Psychiatry 2004, 61: 705-713. PMID: 15237082, DOI: 10.1001/archpsyc.61.7.705.Peer-Reviewed Original ResearchConceptsMajor depressive disorderGamma-aminobutyric acidOccipital cortex GABA concentrationsProton magnetic resonance spectroscopyDepressed subjectsGABA concentrationHealthy controlsSubtypes of MDDCortical gamma-aminobutyric acidHealthy control subjectsMetabolite levelsCholine-containing compoundsHealthy comparison subjectsClinical research programSubtype-specific alterationsΓ-aminobutyric acidClinical correlatesMDD patientsControl subjectsDepressive disorderNeurotransmitter levelsGlutamate levelsMajor depressionMDD subtypesOccipital cortex
2002
A Functional Neuropeptide Y Leu7Pro Polymorphism Associated With Alcohol Dependence in a Large Population Sample From the United States
Lappalainen J, Kranzler HR, Malison R, Price LH, Van Dyck C, Rosenheck RA, Cramer J, Southwick S, Charney D, Krystal J, Gelernter J. A Functional Neuropeptide Y Leu7Pro Polymorphism Associated With Alcohol Dependence in a Large Population Sample From the United States. JAMA Psychiatry 2002, 59: 825-831. PMID: 12215082, DOI: 10.1001/archpsyc.59.9.825.Peer-Reviewed Original ResearchMeSH KeywordsAlcohol DrinkingAlcoholismBlack PeopleCase-Control StudiesComorbidityDepressive DisorderEthnicityEuropeFemaleGene FrequencyGenetic Predisposition to DiseaseGenetics, PopulationGenotypeHumansMaleNeuropeptide YPolymorphism, GeneticRacial GroupsSchizophreniaStress Disorders, Post-TraumaticUnited StatesConceptsAlcohol-dependent subjectsPro7 alleleAlcohol dependencePopulation sampleComorbid psychiatric disordersMain outcome measuresPopulation studiesEA controlsNeuropeptide Y geneRecent population studiesPosttraumatic stress disorderNPY polymorphismsRisk factorsAttributable fractionMajor depressionOutcome measuresLarge population samplePsychiatric disordersAlcohol consumptionPolymorphism AssociatedAlzheimer's diseaseAllele frequenciesStress disorderModulate riskEuropean AmericansIncreased 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
2001
Reductions in Occipital Cortex GABA Levels in Panic Disorder Detected With 1H-Magnetic Resonance Spectroscopy
Goddard AW, Mason GF, Almai A, Rothman DL, Behar KL, Petroff OA, Charney DS, Krystal JH. Reductions in Occipital Cortex GABA Levels in Panic Disorder Detected With 1H-Magnetic Resonance Spectroscopy. JAMA Psychiatry 2001, 58: 556-561. PMID: 11386984, DOI: 10.1001/archpsyc.58.6.556.Peer-Reviewed Original ResearchConceptsOccipital cortex GABA levelsCortical GABA levelsGABA levelsGamma-aminobutyric acidPanic disorderOccipital cortex GABA concentrationsSex-matched control subjectsGABA neuronal functionHuman panic disorderMeasures of illnessPatient-control pairsBrain GABA levelsDSM-IV criteriaPreclinical evidenceMedication historyControl subjectsUnmedicated patientsGABA functionMajor depressionCurrent diagnosisNeuronal functionGABA concentrationPatientsReference limitsDisorders
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
Reduced Cortical γ-Aminobutyric Acid Levels in Depressed Patients Determined by Proton Magnetic Resonance Spectroscopy
Sanacora G, Mason GF, Rothman DL, Behar KL, Hyder F, Petroff OA, Berman RM, Charney DS, Krystal JH. Reduced Cortical γ-Aminobutyric Acid Levels in Depressed Patients Determined by Proton Magnetic Resonance Spectroscopy. JAMA Psychiatry 1999, 56: 1043-1047. PMID: 10565505, DOI: 10.1001/archpsyc.56.11.1043.Peer-Reviewed Original ResearchConceptsProton magnetic resonance spectroscopyDepressed patientsGABA levelsMedication-free depressed patientsOccipital cortex GABA levelsVivo proton magnetic resonance spectroscopyCortical GABA concentrationsGamma-aminobutyric acid (GABA) systemΓ-aminobutyric acid (GABA) levelsBrain GABA levelsMagnetic resonance spectroscopy protocolHealthy control subjectsDSM-IV criteriaGABA neurotransmitter systemEffect of depressionInteraction of diagnosisControl subjectsMajor depressionNeurotransmitter systemsHealthy subjectsOccipital cortexNeurobiologic processesAnalysis of covarianceGABA concentrationMental illnessNMDA Agonists and Antagonists as Probes of Glutamatergic Dysfunction and Pharmacotherapies in Neuropsychiatric Disorders
Krystal J, D'Souza C, Petrakis I, Belger A, Berman R, Charney D, AbiSaab W, Madonick S. NMDA Agonists and Antagonists as Probes of Glutamatergic Dysfunction and Pharmacotherapies in Neuropsychiatric Disorders. Harvard Review Of Psychiatry 1999, 7: 125-143. PMID: 10483932, DOI: 10.3109/hrp.7.3.125.Peer-Reviewed Original ResearchConceptsN-methyl-D-aspartate (NMDA) subclassChronic pain syndromePain syndromeGlutamatergic dysfunctionNMDA agonistClinical studiesMajor depressionNMDA antagonistsGlutamate receptorsCoagonist siteParkinson's diseaseHuman psychopharmacological studiesPartial agonistAlzheimer's diseaseNeuropsychiatric conditionsNeuropsychiatric disordersDiseasePsychopharmacological studiesAnxiety disordersHuntington's diseaseAgonistsAntagonistTherapeutic hypothesesDisordersAddiction disorders
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
1994
Alcohol Dependence May Be the Missing Link Between Posttraumatic Stress Disorder and Panic-Reply
Krystal J, Southwick S, Charney D. Alcohol Dependence May Be the Missing Link Between Posttraumatic Stress Disorder and Panic-Reply. JAMA Psychiatry 1994, 51: 430-430. DOI: 10.1001/archpsyc.1994.03950050090014.Peer-Reviewed Original ResearchPanic disorderPTSD symptomsΑ2-adrenergic antagonistMajor psychiatric disordersPosttraumatic stress disorderAcute alcoholOpiate withdrawalMajor depressionNoradrenergic systemHealthy subjectsPsychiatric disordersClinical reportsAlcohol consumptionPatientsPanic attacksAlcohol dependenceSubstance abuseStress disorderNeurobiological significanceAnxiety disordersDisordersSymptomsPTSDWithdrawalLittle evidence
1993
Long-Term Outcome of Panic Disorder After Short-Term Imipramine and Behavioral Group Treatment
NAGY L, KRYSTAL J, CHARNEY D, MERIKANGAS K, WOODS S. Long-Term Outcome of Panic Disorder After Short-Term Imipramine and Behavioral Group Treatment. Journal Of Clinical Psychopharmacology 1993, 13: 16-24. PMID: 8098050, DOI: 10.1097/00004714-199302000-00003.Peer-Reviewed Original ResearchConceptsMonths of treatmentLong-term outcomesTime of admissionTime of dischargeEfficacy of treatmentPanic attack frequencyDSM-III diagnosesBehavioral treatment programBehavioral group treatmentNonpharmacological therapiesTerm outcomesMajor depressionAntipanic medicationSame doseLow doseLifetime diagnosisTreatment durationPatientsPanic disorderPanic attacksAttack frequencyImipramineTreatment programBehavioral therapyImpairment ratingsEnhanced suppression of cortisol following dexamethasone administration in posttraumatic stress disorder
Yehuda R, Southwick SM, Krystal JH, Bremner D, Charney DS, Mason JW. Enhanced suppression of cortisol following dexamethasone administration in posttraumatic stress disorder. American Journal Of Psychiatry 1993, 150: 83-86. PMID: 8417586, DOI: 10.1176/ajp.150.1.83.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderDexamethasone administrationDexamethasone levelsLow-dose dexamethasone suppression testEnhanced negative feedback sensitivityStress disorderBaseline blood samplesDexamethasone suppression testNegative feedback sensitivityMale patientsHPA abnormalitiesSuppression testMajor depressionBlood samplesLow doseDiagnostic criteriaNormal subjectsPTSD patientsPatientsDexamethasoneCortisolGreater suppressionFeedback sensitivityEnhanced suppressionAdministration
1991
Rapid serotonin depletion as a provocative challenge test for patients with major depression: relevance to antidepressant action and the neurobiology of depression.
Delgado PL, Price LH, Miller HL, Salomon RM, Licinio J, Krystal JH, Heninger GR, Charney DS. Rapid serotonin depletion as a provocative challenge test for patients with major depression: relevance to antidepressant action and the neurobiology of depression. Psychopharmacology Bulletin 1991, 27: 321-30. PMID: 1775606.Peer-Reviewed Original ResearchConceptsDepressed patientsTRP depletionDesipramine-treated patientsFluvoxamine-treated patientsProvocative challenge testsBrain serotonin contentNeurobiology of depressionMonoamine oxidase inhibitorsMechanism of actionAntidepressant medicationCrossover fashionSerotonin depletionPlasma levelsDepressive relapseSerotonin contentMajor depressionPsychiatric patientsPatientsChallenge testOxidase inhibitorsEssential amino acidsDepressionPercentDaysMedications
1989
Clinical and Medication Outcome After Short-term Alprazolam and Behavorial Group Treatment in Panic Disorder: 2.5-Year Naturalistic Follow-up Study
Nagy LM, Krystal JH, Woods SW, Charney DS. Clinical and Medication Outcome After Short-term Alprazolam and Behavorial Group Treatment in Panic Disorder: 2.5-Year Naturalistic Follow-up Study. JAMA Psychiatry 1989, 46: 993-999. PMID: 2818144, DOI: 10.1001/archpsyc.1989.01810110035005.Peer-Reviewed Original ResearchConceptsFU periodAlprazolam treatmentMajor depressionPanic disorderPanic attacksPanic attack frequencyBehavioral group treatment programGreater symptom severityAntipanic effectsNonpharmacologic therapiesMedication outcomesNaturalistic followGroup treatment programAlprazolam dosesSame doseLow doseLifetime diagnosisAttack frequencySymptom severityTreatment programBehavioral therapyPatientsAdmissionAlprazolamTreatment gains