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 symptomsAnhedonia
2023
Profiling 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 analysisLongitudinal 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 populationsVeteransNeural 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 gains
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 findingsGenetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden
Nichter B, Koller D, De Angelis F, Wang J, Girgenti M, Na P, Hill M, Norman S, Krystal J, Gelernter J, Polimanti R, Pietrzak R. Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden. Psychological Medicine 2022, 53: 6325-6333. PMID: 36444557, DOI: 10.1017/s0033291722003646.Peer-Reviewed Original ResearchConceptsPolygenic risk scoresUS military veteransLifetime suicide attemptsSuicide attemptsTrauma exposureTrauma burdenGenetic liabilityMilitary veteransDrug repurposing analysisPopulation-based sampleCumulative trauma exposureLifetime trauma exposureLow trauma exposureSuicide prediction modelsChronic inflammationInflammatory processNervous system developmentRisk scorePsychiatric characteristicsSuicidal behaviorExposure interactionsLarge genome-wide association studiesHigh levelsVeteransSuicidalitySublingual Dexmedetomidine for the Treatment of Acute Agitation in Adults With Schizophrenia or Schizoaffective Disorder: A Randomized Placebo-Controlled Trial.
Citrome L, Preskorn SH, Lauriello J, Krystal JH, Kakar R, Finman J, De Vivo M, Yocca FD, Risinger R, Rajachandran L. Sublingual Dexmedetomidine for the Treatment of Acute Agitation in Adults With Schizophrenia or Schizoaffective Disorder: A Randomized Placebo-Controlled Trial. The Journal Of Clinical Psychiatry 2022, 83 PMID: 36198061, DOI: 10.4088/jcp.22m14447.Peer-Reviewed Original ResearchConceptsAcute agitationHours postdoseSchizoaffective disorderTotal scorePrimary efficacy endpointPlacebo-controlled studyAdrenergic receptor agonistFifth Edition criteriaNegative Syndrome ScaleDexmedetomidine groupOral hypoesthesiaStudy medicationDry mouthEfficacy endpointOrthostatic hypotensionRandomized PlaceboAdverse eventsReceptor agonistEdition criteriaDexmedetomidineMean changePEC scoresPlaceboSyndrome ScaleUS sitesPsychosocial Factors Associated With Accelerated GrimAge in Male U.S. Military Veterans
Tamman AJF, Nagamatsu S, Krystal JH, Gelernter J, Montalvo-Ortiz JL, Pietrzak RH. Psychosocial Factors Associated With Accelerated GrimAge in Male U.S. Military Veterans. American Journal Of Geriatric Psychiatry 2022, 31: 97-109. PMID: 36210262, DOI: 10.1016/j.jagp.2022.09.002.Peer-Reviewed Original ResearchConceptsRisk factorsPremature mortalityU.S. veteransPsychosocial variablesNovel epigenetic clockLifetime substance use disorderRisk stratification modelMale U.S. veteransCross-sectional studyU.S. veteran populationWeekly physical exerciseSubstance use disordersMale U.S. military veteransBiological agingU.S. military veteransHealth morbidityModifiable correlatesMortality riskSleep qualityHigh riskGreater oddsUse disordersPhysical exercisePsychosocial factorsVeteran populationSex-Specific Genetic and Transcriptomic Liability to Neuroticism
Wendt FR, Pathak GA, Singh K, Stein MB, Koenen KC, Krystal JH, Gelernter J, Davis LK, Polimanti R. Sex-Specific Genetic and Transcriptomic Liability to Neuroticism. Biological Psychiatry 2022, 93: 243-252. PMID: 36244801, PMCID: PMC10508260, DOI: 10.1016/j.biopsych.2022.07.019.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesTranscriptomic profilesAssociation studiesSingle nucleotide polymorphism heritabilityGene expression variationGenome-wide significanceSex-specific geneticChromosomal variationTranscriptomic changesRisk lociExpression variationBiological processesMolecular pathwaysLociPolygenic associationSex-specific effectsGenetic correlatesPolygenic scoresUK BiobankGenetic riskNCOA6GeneticsHeritabilityPathwayFemalesA comparison of methods to harmonize cortical thickness measurements across scanners and sites
Sun D, Rakesh G, Haswell CC, Logue M, Baird CL, O'Leary EN, Cotton AS, Xie H, Tamburrino M, Chen T, Dennis EL, Jahanshad N, Salminen LE, Thomopoulos SI, Rashid F, Ching CRK, Koch SBJ, Frijling JL, Nawijn L, van Zuiden M, Zhu X, Suarez-Jimenez B, Sierk A, Walter H, Manthey A, Stevens JS, Fani N, van Rooij SJH, Stein M, Bomyea J, Koerte IK, Choi K, van der Werff SJA, Vermeiren RRJM, Herzog J, Lebois LAM, Baker JT, Olson EA, Straube T, Korgaonkar MS, Andrew E, Zhu Y, Li G, Ipser J, Hudson AR, Peverill M, Sambrook K, Gordon E, Baugh L, Forster G, Simons RM, Simons JS, Magnotta V, Maron-Katz A, du Plessis S, Disner SG, Davenport N, Grupe DW, Nitschke JB, deRoon-Cassini TA, Fitzgerald JM, Krystal JH, Levy I, Olff M, Veltman DJ, Wang L, Neria Y, De Bellis MD, Jovanovic T, Daniels JK, Shenton M, van de Wee NJA, Schmahl C, Kaufman ML, Rosso IM, Sponheim SR, Hofmann DB, Bryant RA, Fercho KA, Stein DJ, Mueller SC, Hosseini B, Phan KL, McLaughlin KA, Davidson RJ, Larson CL, May G, Nelson SM, Abdallah CG, Gomaa H, Etkin A, Seedat S, Harpaz-Rotem I, Liberzon I, van Erp TGM, Quidé Y, Wang X, Thompson PM, Morey RA. A comparison of methods to harmonize cortical thickness measurements across scanners and sites. NeuroImage 2022, 261: 119509. PMID: 35917919, PMCID: PMC9648725, DOI: 10.1016/j.neuroimage.2022.119509.Peer-Reviewed Original ResearchClinical and Financial Outcomes Associated With a Workplace Mental Health Program Before and During the COVID-19 Pandemic
Bondar J, Morrow C, Gueorguieva R, Brown M, Hawrilenko M, Krystal JH, Corlett PR, Chekroud AM. Clinical and Financial Outcomes Associated With a Workplace Mental Health Program Before and During the COVID-19 Pandemic. JAMA Network Open 2022, 5: e2216349. PMID: 35679044, PMCID: PMC9185188, DOI: 10.1001/jamanetworkopen.2022.16349.Peer-Reviewed Original ResearchConceptsMental health programsHealth programsCohort studyLarge clinical effect sizesPatient Health Questionnaire-9Common mental health conditionsSheehan Disability ScaleClinical effect sizeMental health conditionsMental health symptomsCost of treatmentGeneralized anxiety disorderMental health difficultiesMental health benefitsWorkplace wellness programsCare navigationClinical improvementPrimary outcomeClinical benefitQuestionnaire-9Disability ScaleMedication managementLeast moderate anxietyMixed-effects regressionPerson psychotherapyEpigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans
Montalvo-Ortiz JL, Gelernter J, Cheng Z, Girgenti MJ, Xu K, Zhang X, Gopalan S, Zhou H, Duman RS, Southwick SM, Krystal JH, Pietrzak R. Epigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans. Translational Psychiatry 2022, 12: 65. PMID: 35177594, PMCID: PMC8854688, DOI: 10.1038/s41398-022-01822-3.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesAssociation studiesTranscription regulationCpG sitesGenome-wide association studiesCell type proportionsPosttraumatic stress disorderPotential epigenetic biomarkersSignificant CpG sitesEpigenetic mechanismsDNA methylationNovel lociCell signalingEpigenetic biomarkersMethylation analysisAxonal guidanceNovel molecular biomarkersEPIC BeadChipLifetime posttraumatic stress disorderMilitary veteransPostmortem brain tissueMedial orbitofrontal cortexMolecular biomarkersRegulationU.S. military veterans
2021
Assessment of brain age in posttraumatic stress disorder: Findings from the ENIGMA PTSD and brain age working groups
Clausen AN, Fercho KA, Monsour M, Disner S, Salminen L, Haswell CC, Rubright EC, Watts AA, Buckley MN, Maron-Katz A, Sierk A, Manthey A, Suarez-Jimenez B, Olatunji BO, Averill CL, Hofmann D, Veltman DJ, Olson EA, Li G, Forster GL, Walter H, Fitzgerald J, Théberge J, Simons JS, Bomyea JA, Frijling JL, Krystal JH, Baker JT, Phan KL, Ressler K, Han LKM, Nawijn L, Lebois LAM, Schmaal L, Densmore M, Shenton ME, van Zuiden M, Stein M, Fani N, Simons RM, Neufeld RWJ, Lanius R, van Rooij S, Koch SBJ, Bonomo S, Jovanovic T, deRoon-Cassini T, Ely TD, Magnotta VA, He X, Abdallah CG, Etkin A, Schmahl C, Larson C, Rosso IM, Blackford JU, Stevens JS, Daniels JK, Herzog J, Kaufman ML, Olff M, Davidson RJ, Sponheim SR, Mueller SC, Straube T, Zhu X, Neria Y, Baugh LA, Cole JH, Thompson PM, Morey RA. Assessment of brain age in posttraumatic stress disorder: Findings from the ENIGMA PTSD and brain age working groups. Brain And Behavior 2021, 12: e2413. PMID: 34907666, PMCID: PMC8785613, DOI: 10.1002/brb3.2413.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderEffects of PTSDBrain-PADBrain ageMale controlsOld maleStress disorderAge-related brain changesStructural magnetic resonance imagingBrain structural magnetic resonance imagingOlder age groupsMagnetic resonance imagingChronological ageSubset of controlsContext of PTSDControl subjectsBrain changesBrain agingFuture longitudinal researchTreatment approachesLinear mixed effects modelsAdult subjectsResonance imagingAge groupsPTSD assessmentPrevalence and Trends in Suicidal Behavior Among US Military Veterans During the COVID-19 Pandemic
Nichter B, Hill ML, Na PJ, Kline AC, Norman SB, Krystal JH, Southwick SM, Pietrzak RH. Prevalence and Trends in Suicidal Behavior Among US Military Veterans During the COVID-19 Pandemic. JAMA Psychiatry 2021, 78: 1218-1227. PMID: 34431973, PMCID: PMC8387942, DOI: 10.1001/jamapsychiatry.2021.2332.Peer-Reviewed Original ResearchConceptsUS military veteransCOVID-19 infectionCohort studySuicidal behaviorPast-year suicide ideationRisk factorsMilitary veteransPopulation-based prospective cohort studyCOVID-19 pandemicSuicide ideationSuicide attemptsProspective cohort studyLifetime posttraumatic stress disorderStrong risk factorCOVID-19 public health emergencyLow social supportPosttraumatic stress disorderPublic health emergencyAlcohol use disorder severityUS veteransNational HealthMAIN OUTCOMESuicide attempt historyVeterans StudyCOVID-19-related variablesImaging brain cortisol regulation in PTSD with a target for 11β-hydroxysteroid dehydrogenase type 1
Bhatt S, Hillmer AT, Rusowicz A, Nabulsi N, Matuskey D, Angarita GA, Najafzadeh S, Kapinos M, Southwick SM, Krystal JH, Carson RE, Huang Y, Cosgrove KP. Imaging brain cortisol regulation in PTSD with a target for 11β-hydroxysteroid dehydrogenase type 1. Journal Of Clinical Investigation 2021, 131: e150452. PMID: 34651587, PMCID: PMC8516462, DOI: 10.1172/jci150452.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderPositron emission tomographyVolume of distributionDehydrogenase type 1Trauma-exposed controlsPTSD groupTranslocator proteinType 1Veterans Affairs (VA) National CenterOverall PTSD severityBrain glucocorticoidBrain immuneMethodsSixteen individualsPeripheral cortisolMicroglial markersImmune suppressionTranslational Science AwardsCortisol levelsNIH National CenterTC groupCortisol regulationEmission tomographyStress disorderLower PTSD symptomsPTSD symptomsIndividual Differences in the Associations Between Risk Factors for Alcohol Use Disorder and Alcohol Use-Related Outcomes
Haeny AM, Gueorguieva R, Jackson A, Morean ME, Krishnan-Sarin S, DeMartini KS, Pearlson GD, Anticevic A, Krystal JH, O’Malley S. Individual Differences in the Associations Between Risk Factors for Alcohol Use Disorder and Alcohol Use-Related Outcomes. Psychology Of Addictive Behaviors 2021, 35: 501-513. PMID: 34110841, PMCID: PMC9211405, DOI: 10.1037/adb0000733.Peer-Reviewed Original ResearchMapping data‐driven individualized neurobehavioral phenotypes in heavy alcohol drinkers
DeMartini KS, Gueorguieva R, Pearlson G, Krishnan‐Sarin S, Anticevic A, Ji LJ, Krystal JH, O’Malley S. Mapping data‐driven individualized neurobehavioral phenotypes in heavy alcohol drinkers. Alcohol Clinical And Experimental Research 2021, 45: 841-853. PMID: 33605439, DOI: 10.1111/acer.14580.Peer-Reviewed Original ResearchConceptsConfirmatory factor analysisIncentive salienceNeurofunctional domainsAlcohol use disorderExecutive functionLatent factorsPhysical neglectSelf-report measuresChildhood emotional abuseUse disordersChildhood physical neglectEarly life stressSignificant predictorsMultiple significant predictorsMultiple causes modelCurrent AUDNegative emotionalityAddiction developmentEmotional abuseChildhood neglectFactor structureDrinking frequencySalienceCause modelFactor analysis
2020
Transcriptomic organization of the human brain in post-traumatic stress disorder
Girgenti MJ, Wang J, Ji D, Cruz DA, Stein M, Gelernter J, Young K, Huber B, Williamson D, Friedman M, Krystal J, Zhao H, Duman R. Transcriptomic organization of the human brain in post-traumatic stress disorder. Nature Neuroscience 2020, 24: 24-33. PMID: 33349712, DOI: 10.1038/s41593-020-00748-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutopsyBrain ChemistryCohort StudiesDepressive Disorder, MajorFemaleGene Expression RegulationGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInterneuronsMaleMiddle AgedNerve Tissue ProteinsSex CharacteristicsStress Disorders, Post-TraumaticTranscriptomeYoung AdultConceptsGenome-wide association studiesSignificant gene networksDifferential gene expressionSystems-level evidenceSignificant genetic liabilityMajor depressive disorder cohortGene networksTranscriptomic organizationTranscriptomic landscapeDownregulated setsGenomic networksGene expressionAssociation studiesMolecular determinantsExtensive remodelingGenotype dataSexual dimorphismSignificant divergenceMolecular profileNetwork analysisELFN1TranscriptsDimorphismPostmortem tissueDivergenceTransdiagnostic, Connectome-Based Prediction of Memory Constructs Across Psychiatric Disorders
Barron DS, Gao S, Dadashkarimi J, Greene AS, Spann MN, Noble S, Lake EMR, Krystal JH, Constable RT, Scheinost D. Transdiagnostic, Connectome-Based Prediction of Memory Constructs Across Psychiatric Disorders. Cerebral Cortex 2020, 31: 2523-2533. PMID: 33345271, PMCID: PMC8023861, DOI: 10.1093/cercor/bhaa371.Peer-Reviewed Original ResearchConceptsMacroscale brain networksIndividual differencesBrain networksMemory deficitsFunctional connectivityAttention deficit hyper-activity disorderTask-based functional MRI dataLong-term memoryWhole-brain functional connectivityDiagnostic groupsWhole-brain patternsDefault mode networkFunctional MRI dataHuman Connectome ProjectPsychiatric disordersMemory constructsMemory performanceTransdiagnostic sampleBrain correlatesMode networkFunctional connectomeConnectome ProjectLimbic networkHealthy participantsMemory