2024
Human brain state dynamics are highly reproducible and associated with neural and behavioral features
Lee K, Ji J, Fonteneau C, Berkovitch L, Rahmati M, Pan L, Repovš G, Krystal J, Murray J, Anticevic A. Human brain state dynamics are highly reproducible and associated with neural and behavioral features. PLOS Biology 2024, 22: e3002808. PMID: 39316635, PMCID: PMC11421804, DOI: 10.1371/journal.pbio.3002808.Peer-Reviewed Original ResearchConceptsCo-activation patternsResting-state functional magnetic resonance imagingFunctional magnetic resonance imagingBehavioral featuresNeural variationsMoment-to-moment changesSingle-subject levelBrain state dynamicsEmotion regulationHealthy young adultsBehavioral phenotypesCognitive functionSubstance useNeural activityNeuroimaging markersNeural featuresYoung adultsMagnetic resonance imagingCo-activationResonance imagingCo-variationNeuroimagingIndividualsEmotionsFunctional outcomesMicroglia-mediated neuroimmune suppression in PTSD is associated with anhedonia
Bonomi R, Hillmer A, Woodcock E, Bhatt S, Rusowicz A, Angarita G, Carson R, Davis M, Esterlis I, Nabulsi N, Huang Y, Krystal J, Pietrzak R, Cosgrove K. Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2406005121. PMID: 39172786, PMCID: PMC11363315, DOI: 10.1073/pnas.2406005121.Peer-Reviewed Original ResearchConceptsPTSD groupPrefrontal-limbic circuitsNeuroimmune responseAssociated with anhedoniaPosttraumatic stress disorderPositron emission tomography brain imagingTranslocator protein availabilityBrain immune functionAnhedonic symptomsStress disorderPeripheral immune dysfunctionPTSDGroup differencesSeverity of symptomsPsychiatric diseasesTranslocator proteinBrain imagingAdministration of lipopolysaccharideSymptomsMicroglial markersLPS-induced increaseCompared to controlsImmune functionSickness symptomsAnhedoniaKetamine induces multiple individually distinct whole-brain functional connectivity signatures
Moujaes F, Ji J, Rahmati M, Burt J, Schleifer C, Adkinson B, Savic A, Santamauro N, Tamayo Z, Diehl C, Kolobaric A, Flynn M, Rieser N, Fonteneau C, Camarro T, Xu J, Cho Y, Repovs G, Fineberg S, Morgan P, Seifritz E, Vollenweider F, Krystal J, Murray J, Preller K, Anticevic A. Ketamine induces multiple individually distinct whole-brain functional connectivity signatures. ELife 2024, 13: e84173. PMID: 38629811, PMCID: PMC11023699, DOI: 10.7554/elife.84173.Peer-Reviewed Original ResearchConceptsResponse to ketamineAcute ketamineBehavioral effectsQuantified resting-state functional connectivityEffects of acute ketamineSymptom variationResting-state functional connectivityTreatment-resistant depressionFunctional connectivity signaturesGlobal brain connectivitySingle-subject levelInter-individual variabilityPlacebo-controlled studyFunctional connectivityConnectivity signaturesBrain connectivityHealthy participantsSingle-blind placebo-controlled studyNeural variationsTreatment conditionsKetamineGene expression targetsPharmacological biomarkersPilot awardParvalbuminIllusory generalizability of clinical prediction models
Chekroud A, Hawrilenko M, Loho H, Bondar J, Gueorguieva R, Hasan A, Kambeitz J, Corlett P, Koutsouleris N, Krumholz H, Krystal J, Paulus M. Illusory generalizability of clinical prediction models. Science 2024, 383: 164-167. PMID: 38207039, DOI: 10.1126/science.adg8538.Peer-Reviewed Original Research
2023
Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals
Zhou H, Kember R, Deak J, Xu H, Toikumo S, Yuan K, Lind P, Farajzadeh L, Wang L, Hatoum A, Johnson J, Lee H, Mallard T, Xu J, Johnston K, Johnson E, Nielsen T, Galimberti M, Dao C, Levey D, Overstreet C, Byrne E, Gillespie N, Gordon S, Hickie I, Whitfield J, Xu K, Zhao H, Huckins L, Davis L, Sanchez-Roige S, Madden P, Heath A, Medland S, Martin N, Ge T, Smoller J, Hougaard D, Børglum A, Demontis D, Krystal J, Gaziano J, Edenberg H, Agrawal A, Justice A, Stein M, Kranzler H, Gelernter J. Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals. Nature Medicine 2023, 29: 3184-3192. PMID: 38062264, PMCID: PMC10719093, DOI: 10.1038/s41591-023-02653-5.Peer-Reviewed Original ResearchNeural patterns differentiate traumatic from sad autobiographical memories in PTSD
Perl O, Duek O, Kulkarni K, Gordon C, Krystal J, Levy I, Harpaz-Rotem I, Schiller D. Neural patterns differentiate traumatic from sad autobiographical memories in PTSD. Nature Neuroscience 2023, 26: 2226-2236. PMID: 38036701, DOI: 10.1038/s41593-023-01483-5.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderTraumatic memoriesAutobiographical memoryNeural patternsIntersubject representational similarity analysisSimilar neural representationsRepresentational similarity analysisPosterior cingulate cortexTrauma memoriesMnemonic featuresNegative memoriesMultivoxel patternsNeural representationCognitive stateHippocampal representationsCognitive entitiesStress disorderCingulate cortexNeural activityTraumatic narrativesIndividual symptom severitySemantic representationMemory typesOwn memoryMemoryAssessing the impact of a comprehensive mental health program on frontline health service workers
Ward E, Fragala M, Birse C, Hawrilenko M, Smolka C, Ambwani G, Brown M, Krystal J, Corlett P, Chekroud A. Assessing the impact of a comprehensive mental health program on frontline health service workers. PLOS ONE 2023, 18: e0294414. PMID: 37988363, PMCID: PMC10662717, DOI: 10.1371/journal.pone.0294414.Peer-Reviewed Original ResearchConceptsMental health benefitsSheehan Disability ScaleHealth service workersMental health issuesHealth benefitsHealth issuesRetrospective cohort studyPHQ-9 scaleMental health screeningComprehensive mental health programGAD-7 scaleMental health programsCare navigationCohort studyHealth screeningDisability ScaleMedication managementTreatment appointmentsFunctional impairmentLeast moderate anxietyHealth services companyOutcome assessmentHealth programsModerate anxietyAnxiety symptomsNeuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium
Zhu X, Kim Y, Ravid O, He X, Suarez-Jimenez B, Zilcha-Mano S, Lazarov A, Lee S, Abdallah C, Angstadt M, Averill C, Baird C, Baugh L, Blackford J, Bomyea J, Bruce S, Bryant R, Cao Z, Choi K, Cisler J, Cotton A, Daniels J, Davenport N, Davidson R, DeBellis M, Dennis E, Densmore M, deRoon-Cassini T, Disner S, Hage W, Etkin A, Fani N, Fercho K, Fitzgerald J, Forster G, Frijling J, Geuze E, Gonenc A, Gordon E, Gruber S, Grupe D, Guenette J, Haswell C, Herringa R, Herzog J, Hofmann D, Hosseini B, Hudson A, Huggins A, Ipser J, Jahanshad N, Jia-Richards M, Jovanovic T, Kaufman M, Kennis M, King A, Kinzel P, Koch S, Koerte I, Koopowitz S, Korgaonkar M, Krystal J, Lanius R, Larson C, Lebois L, Li G, Liberzon I, Lu G, Luo Y, Magnotta V, Manthey A, Maron-Katz A, May G, McLaughlin K, Mueller S, Nawijn L, Nelson S, Neufeld R, Nitschke J, O'Leary E, Olatunji B, Olff M, Peverill M, Phan K, Qi R, Quidé Y, Rektor I, Ressler K, Riha P, Ross M, Rosso I, Salminen L, Sambrook K, Schmahl C, Shenton M, Sheridan M, Shih C, Sicorello M, Sierk A, Simmons A, Simons R, Simons J, Sponheim S, Stein M, Stein D, Stevens J, Straube T, Sun D, Théberge J, Thompson P, Thomopoulos S, van der Wee N, van der Werff S, van Erp T, van Rooij S, van Zuiden M, Varkevisser T, Veltman D, Vermeiren R, Walter H, Wang L, Wang X, Weis C, Winternitz S, Xie H, Zhu Y, Wall M, Neria Y, Morey R. Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium. NeuroImage 2023, 283: 120412. PMID: 37858907, PMCID: PMC10842116, DOI: 10.1016/j.neuroimage.2023.120412.Peer-Reviewed Original ResearchPositive personality traits moderate persistent high alcohol consumption, determined by polygenic risk in U.S. military veterans: results from a 10-year, population-based, observational cohort study
Na P, Zhou H, Montalvo-Ortiz J, Cabrera-Mendoza B, Petrakis I, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Positive personality traits moderate persistent high alcohol consumption, determined by polygenic risk in U.S. military veterans: results from a 10-year, population-based, observational cohort study. Psychological Medicine 2023, 53: 7893-7901. PMID: 37642191, DOI: 10.1017/s003329172300199x.Peer-Reviewed Original ResearchProfiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex
Rompala G, Nagamatsu S, Martínez-Magaña J, Nuñez-Ríos D, Wang J, Girgenti M, Krystal J, Gelernter J, Hurd Y, Montalvo-Ortiz J. Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex. Nature Communications 2023, 14: 4544. PMID: 37507366, PMCID: PMC10382503, DOI: 10.1038/s41467-023-40285-y.Peer-Reviewed Original ResearchConceptsOpioid use disorderMulti-omics findingsGene expression patternsCo-methylation analysisGene expression profilesMulti-omics profilingGene networksDNA methylationNeuronal methylomesDNA hydroxymethylationMethylomic analysisExpression patternsExpression profilesEpigenetic disturbancesUse disordersPsychiatric traitsOrbitofrontal cortexOpioid-related drugsPostmortem orbitofrontal cortexEnvironmental factorsDrug interaction analysisOUD treatmentHuman orbitofrontal cortexOpioid signalingInteraction analysisKetamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms
Krystal J, Kavalali E, Monteggia L. Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms. Neuropsychopharmacology 2023, 49: 41-50. PMID: 37488280, PMCID: PMC10700627, DOI: 10.1038/s41386-023-01629-w.Peer-Reviewed Original ResearchConceptsMood disordersEffective treatmentN-methyl-D-aspartate receptorsGlutamatergic N-methyl-D-aspartate receptorRapid antidepressant effectsTreatment-resistant depressionKey clinical aspectsRapid antidepressant actionsNovel effective treatmentsSynaptic signaling mechanismsMore effective treatmentsSynaptic plasticity mechanismsOpen channel blockerAntidepressant actionAntidepressant effectsKetamine effectsChannel blockersClinical aspectsClinical practiceNew treatmentsNeuropsychiatric disordersCircuit mechanismsDisordersTreatmentKetamineLong term structural and functional neural changes following a single infusion of Ketamine in PTSD
Duek O, Korem N, Li Y, Kelmendi B, Amen S, Gordon C, Milne M, Krystal J, Levy I, Harpaz-Rotem I. Long term structural and functional neural changes following a single infusion of Ketamine in PTSD. Neuropsychopharmacology 2023, 48: 1648-1658. PMID: 37270621, PMCID: PMC10517133, DOI: 10.1038/s41386-023-01606-3.Peer-Reviewed Original ResearchConceptsKetamine recipientsSingle infusionMain study outcomeTiming of administrationEnd of treatmentNMDA receptor antagonistFunctional neural changesFrequency of administrationSignificant clinical implicationsTrauma-focused psychotherapyBrief exposure therapyAmygdala-vmPFC connectivityPost-retrieval extinctionKetamine doseKetamine administrationReceptor antagonistTrauma scriptsNeural changesClinical implicationsDecreased connectivityExposure therapyKetamineTrauma memoriesStudy outcomesUncinate fasciculusLongitudinal Trends in Suicidal Thoughts and Behaviors Among US Military Veterans During the COVID-19 Pandemic
Fischer I, Nichter B, Na P, Norman S, Krystal J, Pietrzak R. Longitudinal Trends in Suicidal Thoughts and Behaviors Among US Military Veterans During the COVID-19 Pandemic. JAMA Psychiatry 2023, 80: 577-584. PMID: 37017978, PMCID: PMC10077136, DOI: 10.1001/jamapsychiatry.2023.0393.Peer-Reviewed Original ResearchConceptsNew-onset suicidal ideationUS military veteransLifetime substance use disorderPast-year suicidal ideationSubstance use disordersSuicidal ideationSuicide planningMilitary veteransUse disordersPsychiatric distressCOVID-19 pandemicSuicidal thoughtsPopulation-based longitudinal studyEvidence-based preventionLongitudinal studyLongitudinal trendsCohort studyNational HealthUS veteransMAIN OUTCOMEVeterans StudySuicide attemptsSuicide riskVulnerable populationsVeteransRandomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia
Surti T, Ranganathan M, Johannesen J, Gueorguieva R, Deaso E, Kenney J, Krystal J, D'Souza D. Randomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia. Schizophrenia Research 2023, 256: 36-43. PMID: 37141764, PMCID: PMC10257994, DOI: 10.1016/j.schres.2023.04.010.Peer-Reviewed Original ResearchConceptsGlycine transporter 1Cytochrome P450 2D6 extensive metabolizersGlyT1 inhibitorsWeeks of washoutWeeks of CTMedication adherenceReceptor hypofunctionImpaired neuroplasticityPharmacodynamic variabilityNMDAR functionExtensive metabolizersTreatment periodPsychotic symptomsStable outpatientsCognitive impairmentGlyT1 occupancyTransporter 1CTNeuroplasticityCognitive training strategiesSchizophreniaComputerized CTCognitive performanceAugmentation studiesGreater improvementStructural Racism in Psychiatric Research Careers: Eradicating Barriers to a More Diverse Workforce
Widge A, Jordan A, Kraguljac N, Sullivan C, Wilson S, Benton T, Alpert J, Carpenter L, Krystal J, Nemeroff C, Dzirasa K. Structural Racism in Psychiatric Research Careers: Eradicating Barriers to a More Diverse Workforce. American Journal Of Psychiatry 2023, 180: 645-659. PMID: 37073513, PMCID: PMC11227892, DOI: 10.1176/appi.ajp.20220685.Peer-Reviewed Original ResearchCharacteristics of Esketamine Prescribers Among Medicare Beneficiaries in the United States, 2019-2020
Havlik J, Murphy M, Gong N, Tang D, Krystal J. Characteristics of Esketamine Prescribers Among Medicare Beneficiaries in the United States, 2019-2020. JAMA Network Open 2023, 6: e2311250. PMID: 37103934, PMCID: PMC10140803, DOI: 10.1001/jamanetworkopen.2023.11250.Peer-Reviewed Original ResearchNeural valuation of rewards and punishments in posttraumatic stress disorder: a computational approach
Jia R, Ruderman L, Pietrzak R, Gordon C, Ehrlich D, Horvath M, Mirchandani S, DeFontes C, Southwick S, Krystal J, Harpaz-Rotem I, Levy I. Neural valuation of rewards and punishments in posttraumatic stress disorder: a computational approach. Translational Psychiatry 2023, 13: 101. PMID: 36977676, PMCID: PMC10050320, DOI: 10.1038/s41398-023-02388-4.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderValuation systemStress disorderCombat veteransMaintenance of PTSDSubjective valueBrain valuation systemNeural valuation systemVentromedial prefrontal cortexFunctional MRI studyFunction of symptomsMale combat veteransNeural valuationSeries of choicesFear learningPunishment processingPosttrauma symptomsPTSD symptomsNeural encodingNeural mechanismsUncertain optionsPrefrontal cortexSubjective valuationVentral striatumMonetary gainsTrajectories of alcohol consumption in U.S. military veterans: Results from a 10-year population-based longitudinal study
Na P, Montalvo-Ortiz J, Petrakis I, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Trajectories of alcohol consumption in U.S. military veterans: Results from a 10-year population-based longitudinal study. Drug And Alcohol Dependence 2023, 246: 109833. PMID: 36963160, PMCID: PMC10811960, DOI: 10.1016/j.drugalcdep.2023.109833.Peer-Reviewed Original ResearchConceptsAlcohol consumption groupCurrent mental health treatmentDysphoric arousal symptomsMental health treatmentUS veteransAlcohol consumptionHealth treatmentConsumption groupArousal symptomsYounger agePopulation-based longitudinal studyPublic health problemLongitudinal studyExcessive alcohol consumptionAlcohol use disorderPosttraumatic stress disorderU.S. military veteransMedical comorbiditiesChronic courseNational HealthClose monitoringUse disordersHealth problemsVeterans StudyStress disorderA pilot randomized controlled trial of ketamine in Borderline Personality Disorder
Fineberg S, Choi E, Shapiro-Thompson R, Dhaliwal K, Neustadter E, Sakheim M, Null K, Trujillo-Diaz D, Rondeau J, Pittaro G, Peters J, Corlett P, Krystal J. A pilot randomized controlled trial of ketamine in Borderline Personality Disorder. Neuropsychopharmacology 2023, 48: 991-999. PMID: 36804489, PMCID: PMC10209175, DOI: 10.1038/s41386-023-01540-4.Peer-Reviewed Original ResearchConceptsBorderline personality disorderSecondary outcome measuresOutcome measuresSocio-occupational functioningSuicidal ideationPilot studyTrial of ketaminePersonality disorderInfusion of ketaminePrimary outcome measureEffects of ketamineMidazolam groupAdverse eventsKetamine groupClinical benefitMood symptomsKetamineFDA approvalDrug midazolamInfusionBPD symptomsLarger studyDepressed moodSymptomsChronic moodCharacterization of Mental Health in US Veterans Before, During, and 2 Years After the Onset of the COVID-19 Pandemic
Fischer I, Na P, Harpaz-Rotem I, Krystal J, Pietrzak R. Characterization of Mental Health in US Veterans Before, During, and 2 Years After the Onset of the COVID-19 Pandemic. JAMA Network Open 2023, 6: e230463. PMID: 36821116, PMCID: PMC9951035, DOI: 10.1001/jamanetworkopen.2023.0463.Peer-Reviewed Original Research