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 ResearchTrajectories 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 ResearchMeSH KeywordsAlcohol DrinkingAlcoholismHumansLongitudinal StudiesStress Disorders, Post-TraumaticVeteransConceptsAlcohol 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 disorder
2022
Multimodal 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
Dynamic structural equation modeling of the relationship between alcohol habit and drinking variability
DeMartini KS, Gueorguieva R, Taylor JR, Krishnan-Sarin S, Pearlson G, Krystal JH, O'Malley SS. Dynamic structural equation modeling of the relationship between alcohol habit and drinking variability. Drug And Alcohol Dependence 2021, 233: 109202. PMID: 35151022, PMCID: PMC10046111, DOI: 10.1016/j.drugalcdep.2021.109202.Peer-Reviewed Original ResearchEffects of the Fyn kinase inhibitor saracatinib on ventral striatal activity during performance of an fMRI monetary incentive delay task in individuals family history positive or negative for alcohol use disorder. A pilot randomised trial
Patel KT, Stevens MC, Dunlap A, Gallagher A, O’Malley S, DeMartini K, Potenza MN, Krystal JH, Pearlson GD. Effects of the Fyn kinase inhibitor saracatinib on ventral striatal activity during performance of an fMRI monetary incentive delay task in individuals family history positive or negative for alcohol use disorder. A pilot randomised trial. Neuropsychopharmacology 2021, 47: 840-846. PMID: 34475522, PMCID: PMC8882177, DOI: 10.1038/s41386-021-01157-5.Peer-Reviewed Original ResearchConceptsProtein tyrosine kinasesSrc regulationSrc familyProtein kinaseTyrosine kinaseFyn kinaseSrc inhibitorSrc/FynDependent pathwayKinaseNMDAR upregulationNMDAR functionNMDA receptorsRegulationSaracatinibGluN2B subunitGlutamate receptorsFynInhibitorsReceptorsSubunitsN-methyl-D-aspartate (NMDA) glutamate receptorsPrevious evidenceIndividual 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 Research
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 ResearchExamining 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 allele
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 ResearchMeSH KeywordsAdultAlcohol DrinkingAlcoholismCravingEmotionsFemaleHumansMagnetic Resonance ImagingMaleConceptsAlcohol 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 associationEpigenome‐Wide DNA Methylation Association Analysis Identified Novel Loci in Peripheral Cells for Alcohol Consumption Among European American Male Veterans
Xu K, Montalvo‐Ortiz J, Zhang X, Southwick SM, Krystal JH, Pietrzak RH, Gelernter J. Epigenome‐Wide DNA Methylation Association Analysis Identified Novel Loci in Peripheral Cells for Alcohol Consumption Among European American Male Veterans. Alcohol Clinical And Experimental Research 2019, 43: 2111-2121. PMID: 31386212, PMCID: PMC9377208, DOI: 10.1111/acer.14168.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesDNA methylationCpG sitesSignificant CpG sitesHigh-density methylation arraysNovel DNA methylation sitesNew CpG sitesDNA methylation sitesEpigenome-wide DNA methylationAmino acid transportIndividual CpG sitesGene lengthPeripheral cellsNovel lociDNA sitesKEGG databaseMethylation sitesEnrichment analysisMethylation arraysAssociation studiesAssociation analysisGenesMethylationAcid transportFalse discovery rateRigorous Trial Design Is Essential to Understand the Role of Opioid Receptors in Ketamine’s Antidepressant Effect—Reply
Krystal JH, Yoon G, Petrakis IL. Rigorous Trial Design Is Essential to Understand the Role of Opioid Receptors in Ketamine’s Antidepressant Effect—Reply. JAMA Psychiatry 2019, 76: 658-659. PMID: 31042270, DOI: 10.1001/jamapsychiatry.2019.0763.Peer-Reviewed Original ResearchAssociation 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 regionsEnhanced Striatal Dopamine Release to Expectation of Alcohol: A Potential Risk Factor for Alcohol Use Disorder
Kegeles LS, Horga G, Ghazzaoui R, Rosengard R, Ojeil N, Xu X, Slifstein M, Petrakis I, O’Malley S, Krystal JH, Abi-Dargham A. Enhanced Striatal Dopamine Release to Expectation of Alcohol: A Potential Risk Factor for Alcohol Use Disorder. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2018, 3: 591-598. PMID: 29803635, PMCID: PMC6953614, DOI: 10.1016/j.bpsc.2018.03.018.Peer-Reviewed Original Research
2017
Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence
Andersen AM, Pietrzak RH, Kranzler HR, Ma L, Zhou H, Liu X, Kramer J, Kuperman S, Edenberg HJ, Nurnberger JI, Rice JP, Tischfield JA, Goate A, Foroud TM, Meyers JL, Porjesz B, Dick DM, Hesselbrock V, Boerwinkle E, Southwick SM, Krystal JH, Weissman MM, Levinson DF, Potash JB, Gelernter J, Han S. Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence. JAMA Psychiatry 2017, 74: 1153-1160. PMID: 28813562, PMCID: PMC5710224, DOI: 10.1001/jamapsychiatry.2017.2269.Peer-Reviewed Original ResearchConceptsMDD polygenic risk scoresMajor depressive disorderPolygenic risk scoresAlcohol dependenceDepressive disorderSignificant public health burdenPublic health burdenAD comorbidityNational HealthHealth burdenMAIN OUTCOMECase-control statusRisk scoreRisk of ADVeterans StudyYale-PennGenetic susceptibilityMDD statusCommon genetic factorsSubstance dependenceMDD casesAD samplesPolygenic riskGenetic factorsHeritable disorderMecamylamine 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 groupsSex differences in the interacting roles of impulsivity and positive alcohol expectancy in problem drinking: A structural brain imaging study
Ide JS, Zhornitsky S, Hu S, Zhang S, Krystal JH, Li CR. Sex differences in the interacting roles of impulsivity and positive alcohol expectancy in problem drinking: A structural brain imaging study. NeuroImage Clinical 2017, 14: 750-759. PMID: 28413777, PMCID: PMC5385596, DOI: 10.1016/j.nicl.2017.03.015.Peer-Reviewed Original ResearchConceptsPositive alcohol expectanciesGray matter volumeAlcohol expectanciesAlcohol Use Disorders Identification TestSocial drinkersNon-dependent social drinkersProblem drinkingRole of impulsivityBrain imaging studiesRight posterior insulaSex differencesStructural brain imagingStructural brain imaging studiesNeural basisDisorders Identification TestBarratt impulsivityPsychological factorsImpulsivityMediation analysisPosterior insulaDependent individualsRisk factorsAlcohol misuseLinear modelingGeneral linear modelingNMDA Glutamate Receptor Antagonism and the Heritable Risk for Alcoholism: New Insights from a Study of Nitrous Oxide
Krystal JH, Petrakis IL, O’Malley S, Krishnan-Sarin S, Pearlson G, Yoon G. NMDA Glutamate Receptor Antagonism and the Heritable Risk for Alcoholism: New Insights from a Study of Nitrous Oxide. The International Journal Of Neuropsychopharmacology 2017, 20: 351-353. PMID: 28158462, PMCID: PMC5409033, DOI: 10.1093/ijnp/pyw118.Peer-Reviewed Original Research