2022
Dissecting the epigenomic differences between smoking and nicotine dependence in a veteran cohort
Nagamatsu S, Pietrzak R, Xu K, Krystal J, Gelernter J, Montalvo‐Ortiz J. Dissecting the epigenomic differences between smoking and nicotine dependence in a veteran cohort. Addiction Biology 2022, 28: e13259. PMID: 36577721, DOI: 10.1111/adb.13259.Peer-Reviewed Original ResearchConceptsSmoking statusNicotine dependenceVeteran cohortNon-current smokersSerious public health issueNovel treatment strategiesPublic health issueUS military veteransEpigenome-wide association studiesCurrent smokersTreatment strategiesFagerström TestNicotine addictionSmokingHealth issuesRole of epigeneticsMilitary veteransMethylationEPIC BeadChip arraySmokersContinuous variablesF2RL3 geneCohortBiomarkersBeadChip arrayPrevious findings
2020
DNA methylation signature on phosphatidylethanol, not on self-reported alcohol consumption, predicts hazardous alcohol consumption in two distinct populations
Liang X, Justice AC, So-Armah K, Krystal JH, Sinha R, Xu K. DNA methylation signature on phosphatidylethanol, not on self-reported alcohol consumption, predicts hazardous alcohol consumption in two distinct populations. Molecular Psychiatry 2020, 26: 2238-2253. PMID: 32034291, PMCID: PMC8440221, DOI: 10.1038/s41380-020-0668-x.Peer-Reviewed Original ResearchConceptsHazardous alcohol drinkingSelf-reported alcohol consumptionAlcohol consumptionCohort 2Cohort 1Epigenome-wide association studiesSelf-reported dataHazardous alcohol consumptionAlcohol use disorderDNAm signaturesObjective measuresAlcohol drinkingClinical assessmentUse disordersRobust biomarkersDNA methylation signaturesValidation setDistinct populationsCharacteristic curvePEthEpigenetic biomarkersMethylation signatures
2019
Enhancing the Utility of Preclinical Research in Neuropsychiatry Drug Development
Kaffman A, White JD, Wei L, Johnson FK, Krystal JH. Enhancing the Utility of Preclinical Research in Neuropsychiatry Drug Development. Methods In Molecular Biology 2019, 2011: 3-22. PMID: 31273690, PMCID: PMC6895673, DOI: 10.1007/978-1-4939-9554-7_1.Peer-Reviewed Original ResearchConceptsPreclinical researchAnimal modelsPsychiatric conditionsLower clinical success ratesClinical success rateCommon psychiatric conditionsPsychiatric clinical trialsClinical trialsNew pharmacotherapiesMore effective interventionsPreclinical workPsychiatric disordersPsychiatric pathophysiologyMental illnessSystematic reviewEffective interventionsAnimal experimentsDrug development processSuccess rateDrug developmentHuman psychopathologyPharmaceutical companiesPredictive validityLarge pharmaceutical companiesAnimalsIn vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation
Davis MT, Hillmer A, Holmes SE, Pietrzak RH, DellaGioia N, Nabulsi N, Matuskey D, Angarita G, Carson RE, Krystal JH, Esterlis I. In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 11490-11495. PMID: 31085640, PMCID: PMC6561298, DOI: 10.1073/pnas.1818871116.Peer-Reviewed Original ResearchConceptsMGluR5 availabilitySuicidal ideationHC individualsPathophysiology of PTSDLimbic brain regionsVolume of distributionHealthy comparison controlsSuicide risk managementPositron emission tomographyReceptor 5Venous input functionsBrain regionsPTSD individualsEmission tomographyMDD individualsVivo evidenceRecent evidencePotential roleMGluR5PTSDComparison controlsDysregulationMDDIdeationIndividuals
2018
The 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 pathologyAntidepressantsNeurobiologyInhibitionActivationPharmacodynamicsPharmacokineticsUtility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders: A Randomized Clinical Trial
Javitt DC, Carter CS, Krystal JH, Kantrowitz JT, Girgis RR, Kegeles LS, Ragland JD, Maddock RJ, Lesh TA, Tanase C, Corlett PR, Rothman DL, Mason G, Qiu M, Robinson J, Potter WZ, Carlson M, Wall MM, Choo TH, Grinband J, Lieberman JA. Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders: A Randomized Clinical Trial. JAMA Psychiatry 2018, 75: 11-19. PMID: 29167877, PMCID: PMC5833531, DOI: 10.1001/jamapsychiatry.2017.3572.Peer-Reviewed Original ResearchConceptsTarget engagement biomarkerKetamine infusionClinical trialsClinical studiesEarly-stage clinical studiesEarly phase clinical studiesTarget engagementFunctional target engagementRecent pivotal trialsFMRI responsesBlood oxygen level-dependent (BOLD) responseUtility of imagingProton magnetic resonance spectroscopySufficient effect sizeLevel-dependent responsesPlacebo infusionPivotal trialsPreclinical evidenceEngagement biomarkersKetamine effectsMean ageBrain glutamateHealthy volunteersMAIN OUTCOMEPsychiatric history
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
2011
Plasma proteomic alterations in non-human primates and humans after chronic alcohol self-administration
Freeman WM, VanGuilder HD, Guidone E, Krystal JH, Grant KA, Vrana KE. Plasma proteomic alterations in non-human primates and humans after chronic alcohol self-administration. The International Journal Of Neuropsychopharmacology 2011, 14: 899-911. PMID: 21303580, PMCID: PMC3107900, DOI: 10.1017/s1461145711000046.Peer-Reviewed Original ResearchConceptsSerum amyloid A4Excessive alcohol consumptionNon-human primatesAlcohol consumptionPotential biomarkersInter-alpha inhibitor H4Plasma proteinsAltered plasma levelsPlasma samplesExcessive alcohol useAlcohol use disorderNovel potential biomarkersLevels of fibronectinMonitoring of subjectsRetinol-binding proteinAlcohol intakeChronic alcoholWidespread clinical usagePlasma levelsAmyloid A4Lipoprotein metabolismImmune functionUse disordersSelf-administer high levelsBiomarker panel
2006
MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases
Mason GF, Krystal JH. MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases. NMR In Biomedicine 2006, 19: 690-701. PMID: 16986118, DOI: 10.1002/nbm.1080.Peer-Reviewed Original ResearchConceptsPsychiatric diseasesMagnetic resonance spectroscopyGlial abnormalitiesPsychiatric disordersBiochemical markersNon-invasive techniqueNeuropsychiatric disordersPotential roleDrug developmentDrug discoveryMRS techniquesDiseaseDisordersStudy of mechanismsTreatmentLines of investigationAbnormalitiesNeurochemistryDrug delivery
1999
CSF Monoamine Metabolite and Beta Endorphin Levels in Recently Detoxified Alcoholics and Healthy Controls: Prediction of Alcohol Cue‐Induced Craving?
Petrakis I, Trevisan L, D'Souza C, Gil R, Krasnicki S, Webb E, Heninger G, Cooney N, Krystal J. CSF Monoamine Metabolite and Beta Endorphin Levels in Recently Detoxified Alcoholics and Healthy Controls: Prediction of Alcohol Cue‐Induced Craving? Alcohol Clinical And Experimental Research 1999, 23: 1336-1341. PMID: 10470976, DOI: 10.1111/j.1530-0277.1999.tb04355.x.Peer-Reviewed Original ResearchConceptsAlcohol-dependent patientsHealthy controlsEndorphin levelsCSF levelsMonoamine metabolitesCSF measuresHealthy subjectsNorepinephrine metabolite MHPGLower CSF levelsBeta-endorphin levelsEarly-onset patientsCerebrospinal fluid levelsLate-onset patientsCentral neurotransmitter systemsCSF monoamine metabolitesDopamine metabolite HVAAlcohol cue exposureAlcohol-dependent individualsCue-Induced CravingAlcohol cue reactivityLumbar punctureMetabolite HVANeurotransmitter systemsMonoaminergic dysregulationMetabolite MHPG