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 populationsVeteransTrajectories 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 disorderCpH methylome analysis in human cortical neurons identifies novel gene pathways and drug targets for opioid use disorder
Nagamatsu S, Rompala G, Hurd Y, Núñez-Rios D, Montalvo-Ortiz J, Group T, Alvarez V, Benedek D, Che A, Cruz D, Davis D, Girgenti M, Hoffman E, Holtzheimer P, Huber B, Kaye A, Krystal J, Labadorf A, Keane T, Logue M, McKee A, Marx B, Mash D, Miller M, Noller C, JM-O, Scott W, Schnurr P, Stein T, Ursano R, Williamson D, Wolf E, Young K. CpH methylome analysis in human cortical neurons identifies novel gene pathways and drug targets for opioid use disorder. Frontiers In Psychiatry 2023, 13: 1078894. PMID: 36745154, PMCID: PMC9892724, DOI: 10.3389/fpsyt.2022.1078894.Peer-Reviewed Original ResearchOpioid use disorderOrbital frontal cortexDNA methylationKEGG enrichment analysisUse disordersMCPH lociTreatment of OUDGene OntologyEnrichment analysisOpioid-related drugsCpG sitesDrug targetsOxidative bisulfite sequencingImportant biological pathwaysDrug interaction analysisDrug-gene interaction databaseNervous system developmentSmoking statusBrain BankCortical neuronsFrontal cortexNeuronal nucleiHuman studiesGene regulationMethylome analysis
2022
Psychosocial 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 populationMultimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder
Smart K, Worhunsky PD, Scheinost D, Angarita GA, Esterlis I, Carson RE, Krystal JH, O'Malley SS, Cosgrove KP, Hillmer AT. Multimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder. Alcohol Clinical And Experimental Research 2022, 46: 770-782. PMID: 35342968, PMCID: PMC9117461, DOI: 10.1111/acer.14816.Peer-Reviewed Original ResearchConceptsMetabotropic glutamate 5 receptorsDefault mode networkFunctional magnetic resonance imagingReceptor availabilityPositron emission tomographyAUD groupFunctional connectivityReceptor positron emission tomographyResting-state functional magnetic resonance imagingNetwork-level functional connectivityBrain connectivityWeeks of abstinenceGlobal functional connectivityAlcohol use disorderMagnetic resonance imagingFMRI outcomesHealthy controlsSupervised abstinencePET resultsUse disordersSynaptic plasticityResonance imagingBrain regionsEmission tomographyOrbitofrontal cortex
2021
Mapping 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
Characteristics of Ongoing Clinical Trials for Alcohol Use Disorder Registered on ClinicalTrials.gov
Wallach JD, Krystal JH, Ross JS, O’Malley S. Characteristics of Ongoing Clinical Trials for Alcohol Use Disorder Registered on ClinicalTrials.gov. JAMA Psychiatry 2020, 77: 1081-1084. PMID: 32459295, PMCID: PMC7254444, DOI: 10.1001/jamapsychiatry.2020.1167.Peer-Reviewed Original ResearchLongitudinal imaging of metabotropic glutamate 5 receptors during early and extended alcohol abstinence
Hillmer AT, Angarita GA, Esterlis I, Anderson JM, Nabulsi N, Lim K, Ropchan J, Carson RE, Krystal JH, Malley S, Cosgrove KP. Longitudinal imaging of metabotropic glutamate 5 receptors during early and extended alcohol abstinence. Neuropsychopharmacology 2020, 46: 380-385. PMID: 32919411, PMCID: PMC7852514, DOI: 10.1038/s41386-020-00856-9.Peer-Reviewed Original ResearchConceptsMetabotropic glutamate 5 receptorsSmoking statusAlcohol abstinenceEarly abstinenceMGlu5 receptor negative allosteric modulatorReceptor negative allosteric modulatorChronic alcohol useCortical brain regionsAlcohol use disorderEmission Tomography ImagingPositron emission tomography (PET) imagingNegative allosteric modulatorsDSM-5 criteriaCue-induced reinstatementHealthy controlsPreclinical literatureGlutamate systemPreclinical modelsHuman evidenceReceptor drugsPET scansUse disordersHuman studiesReceptor availabilityStudy durationExamining the Relationship Between Self‐Reported Drinking and In‐Laboratory Drinking and Craving: Is There Concordance?
DeMartini KS, Pittman B, Krystal JH, O’Malley S, Krishnan‐Sarin S. Examining the Relationship Between Self‐Reported Drinking and In‐Laboratory Drinking and Craving: Is There Concordance? Alcohol Clinical And Experimental Research 2020, 44: 1151-1157. PMID: 32352581, PMCID: PMC10158572, DOI: 10.1111/acer.14329.Peer-Reviewed Original ResearchConceptsSelf-reported drinkingAlcohol cravingDrinking daysAlcohol consumptionDrinking paradigmHeavy drinking daysAlcohol use disorderSummary drinking measuresMaximum drinksPharmacotherapy studiesAdult heavy drinkersMedication administrationAverage drinksUse disordersHeavy drinkersAlcohol assessmentSignificant associationTotal drinksDrinking sessionDrinking indicesAdditional outcomesBehavioral interventionsLimited evidenceRisk classificationCravingSystematic review and meta‐analysis of the moderating effect of rs1799971 in OPRM1, the mu‐opioid receptor gene, on response to naltrexone treatment of alcohol use disorder
Hartwell EE, Feinn R, Morris PE, Gelernter J, Krystal J, Arias AJ, Hoffman M, Petrakis I, Gueorguieva R, Schacht JP, Oslin D, Anton RF, Kranzler HR. Systematic review and meta‐analysis of the moderating effect of rs1799971 in OPRM1, the mu‐opioid receptor gene, on response to naltrexone treatment of alcohol use disorder. Addiction 2020, 115: 1426-1437. PMID: 31961981, PMCID: PMC7340566, DOI: 10.1111/add.14975.Peer-Reviewed Original ResearchConceptsAsn40Asp single-nucleotide polymorphismRandomized clinical trialsAlcohol use disorderNaltrexone treatmentMu-opioid receptor geneUse disordersSingle nucleotide polymorphismsPlacebo-controlled randomized clinical trialsSystematic reviewPublication biasOpioid receptor antagonist naltrexoneWide inter-individual variabilityHeavy drinkingRisk of biasNaltrexone treatment responseReceptor geneRandom-effects modelAlcohol consumption outcomesAntagonist naltrexoneInter-individual variabilityStudy criteriaClinical trialsNucleotide polymorphismsTreatment responseMinor alleleDNA 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
Regulation of Craving and Negative Emotion in Alcohol Use Disorder
Suzuki S, Mell MM, O'Malley SS, Krystal JH, Anticevic A, Kober H. Regulation of Craving and Negative Emotion in Alcohol Use Disorder. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2019, 5: 239-250. PMID: 31892465, PMCID: PMC7010564, DOI: 10.1016/j.bpsc.2019.10.005.Peer-Reviewed Original ResearchConceptsAlcohol use disorderNegative emotionsNegative affectPrefrontal cortexIndividual differencesRegulation conditionsCognitive behavioral therapy treatmentEmotion regulation taskFunctional magnetic resonance imagingNegative affect conditionRegulation of cravingNegative alcohol expectanciesNotable individual differencesSelf-reported cravingBehavioral therapy treatmentUse disordersRegulation successCognitive strategiesAffect conditionRegulation strategiesAlcohol expectanciesPFC regionsNeural mechanismsRegulation taskAUD treatmentThe Association of Impulsivity and Family History of Alcohol Use Disorder on Alcohol Use and Consequences
Haeny AM, Gueorguieva R, Morean ME, Krishnan‐Sarin S, DeMartini KS, Pearlson GD, Anticevic A, Krystal JH, O'Malley SS. The Association of Impulsivity and Family History of Alcohol Use Disorder on Alcohol Use and Consequences. Alcohol Clinical And Experimental Research 2019, 44: 159-167. PMID: 31693193, PMCID: PMC6981005, DOI: 10.1111/acer.14230.Peer-Reviewed Original ResearchConceptsFacets of impulsivityBarratt Impulsiveness ScaleAlcohol-related problemsAlcohol use disorderProblem drinkingAssociation of impulsivityImpulsivity-related traitsAlcohol-related consequencesUse disordersFHP individualsAlcohol outcomesImpulsiveness ScaleImpulsivityProblematic drinkingFHN individualsDrinking quantityAlcohol quantityTranslational neuroscienceAlcohol misuseAlcohol useTransdisciplinary Tobacco Use Research CenterMain effectAnalysis of covariancePhenotypic riskStrong positive associationAssociation 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
2018
Thalamic Cortical Error–Related Responses in Adult Social Drinkers: Sex Differences and Problem Alcohol Use
Ide JS, Zhornitsky S, Chao HH, Zhang S, Hu S, Wang W, Krystal JH, Li CR. Thalamic Cortical Error–Related Responses in Adult Social Drinkers: Sex Differences and Problem Alcohol Use. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2018, 3: 868-877. PMID: 29859929, PMCID: PMC6177312, DOI: 10.1016/j.bpsc.2018.04.008.Peer-Reviewed Original ResearchConceptsWhole-brain linear regressionError-related activationSex differencesBilateral dorsal anterior cingulate cortexAlcohol Use Disorders Identification Test (AUDIT) scoresSocial drinkersDorsal anterior cingulate cortexSubstance use disordersAnterior cingulate cortexFunctional magnetic resonance imagingMagnetic resonance imagingSuperior temporal cortexStatistical parametric mappingProblem alcohol useBilateral thalamusAlcohol drinkersAdult social drinkersStop-signal taskMale social drinkersTemporal cortexUse disordersCerebral activationIndependent sample t-testCingulate cortexSubcortical regionsTrajectories of alcohol consumption in U.S. military veterans: Results from the National Health and Resilience in Veterans Study
Fuehrlein BS, Kachadourian LK, DeVylder EK, Trevisan LA, Potenza MN, Krystal JH, Southwick SM, Pietrzak RH. Trajectories of alcohol consumption in U.S. military veterans: Results from the National Health and Resilience in Veterans Study. American Journal On Addictions 2018, 27: 383-390. PMID: 29667712, DOI: 10.1111/ajad.12731.Peer-Reviewed Original ResearchMajor depressive disorderLifetime major depressive disorderAlcohol consumptionPredominant trajectoriesNational HealthVeterans StudyAlcohol Use Disorders Identification Test-ConsumptionBrief alcohol screensExcessive drinkingPopulation-based preventionSocial supportExcessive alcohol consumptionAlcohol use disorderLow social supportU.S. military veteransAlcohol screenBaseline determinantsDepressive disorderLatent growth mixture modelingMedical conditionsModerate drinkersRare drinkersModerate drinkingUse disordersGreater social support
2017
Mecamylamine treatment for alcohol dependence: a randomized controlled trial
Petrakis IL, Ralevski E, Gueorguieva R, O'Malley SS, Arias A, Sevarino KA, Jane JS, O'Brien E, Krystal JH. Mecamylamine treatment for alcohol dependence: a randomized controlled trial. Addiction 2017, 113: 6-14. PMID: 28710873, PMCID: PMC5725262, DOI: 10.1111/add.13943.Peer-Reviewed Original ResearchConceptsHeavy drinking daysDrinking daysAlcohol use disorderUse disordersAlcohol consumptionAlcohol dependenceDouble-blind clinical trialNicotinic acetylcholine receptor antagonistWeeks of treatmentAcetylcholine receptor antagonistCurrent alcohol dependenceSignificant differencesTreatment-seeking smokersMecamylamine treatmentPlacebo groupMonth 3Primary outcomeSmoking statusNicotine withdrawalReceptor antagonistNovel pharmacotherapiesClinical trialsManagement therapyMecamylamineTreatment groups
2016
The Connecticut Mental Health Center: Celebrating 50 Years of a Successful Partnership Between the State and Yale University
Steiner JL, Anez-Nava L, Baranoski M, Cole R, Davidson L, Delphin-Rittmon M, Dike C, DiLeo PJ, Duman RS, Kirk T, Krystal J, Malison RT, Rohrbaugh RM, Sernyak MJ, Srihari V, Styron T, Tebes JK, Woods S, Zonana H, Jacobs SC. The Connecticut Mental Health Center: Celebrating 50 Years of a Successful Partnership Between the State and Yale University. Psychiatric Services 2016, 67: 1286-1289. PMID: 27691379, DOI: 10.1176/appi.ps.201600373.Peer-Reviewed Original ResearchImproving Access to Effective Care for People Who Have Mental Health and Substance Use Disorders: A Vital Direction for Health and Health Care
Knickman J, Krishnan K, Pincus H, Blanco C, Blazer D, Coye M, Krystal J, Rauch S, Simon G, Vitiello B. Improving Access to Effective Care for People Who Have Mental Health and Substance Use Disorders: A Vital Direction for Health and Health Care. NAM Perspectives 2016, 6 DOI: 10.31478/201609v.Peer-Reviewed Original Research