2024
Next‐generation biomarkers for alcohol consumption and alcohol use disorder diagnosis, prognosis, and treatment: A critical review
Clark S, Hartwell E, Choi D, Krystal J, Messing R, Ferguson L. Next‐generation biomarkers for alcohol consumption and alcohol use disorder diagnosis, prognosis, and treatment: A critical review. Alcohol Clinical And Experimental Research 2024 PMID: 39532676, DOI: 10.1111/acer.15476.Peer-Reviewed Original ResearchAlcohol use disorderRisk biomarkersAlcohol consumptionDiagnostic biomarkersAlcohol use disorder diagnosisAlcohol research fieldPredictive biomarkersAlcohol-related problemsMetabolomic informationUse disorderOmics-based biomarkersRegular drinkingClinical implicationsProblematic drinkingDisorder diagnosisBiomarkersNext-generation biomarkersRiskAcamprosateAlcoholPrognosisDiagnosisDrinking
2023
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
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 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 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 disorder
2021
Saracatinib Fails to Reduce Alcohol-Seeking and Consumption in Mice and Human Participants
Thompson SL, Gianessi CA, O'Malley SS, Cavallo DA, Shi JM, Tetrault JM, DeMartini KS, Gueorguieva R, Pittman B, Krystal JH, Taylor JR, Krishnan-Sarin S. Saracatinib Fails to Reduce Alcohol-Seeking and Consumption in Mice and Human Participants. Frontiers In Psychiatry 2021, 12: 709559. PMID: 34531767, PMCID: PMC8438169, DOI: 10.3389/fpsyt.2021.709559.Peer-Reviewed Original ResearchNMDA receptorsSrc/FynAlcohol consumptionEffect of saracatinibVehicle 2 hChronic alcohol useDays of treatmentDSM-IV criteriaMore effective treatmentsNumber of drinksGlutamatergic systemAdditional drinkAlcohol drinkingAdditional dosesEthanol exposureEffective treatmentNR2B subunitAlcohol abuseHuman studiesPriming drinkAlcohol cravingSaracatinibDrinking paradigmNovel pharmacotherapeuticsHuman participants
2020
The Moderate Alcohol and Cardiovascular Health Trial (MACH15): Design and methods for a randomized trial of moderate alcohol consumption and cardiometabolic risk
Spiegelman D, Lovato LC, Khudyakov P, Wilkens TL, Adebamowo CA, Adebamowo SN, Appel LJ, Beulens JW, Coughlin JW, Dragsted LO, Edenberg HJ, Eriksen JN, Estruch R, Grobbee DE, Gulayin PE, Irazola V, Krystal JH, Lazo M, Murray MM, Rimm EB, Schrieks IC, Williamson JD, Mukamal KJ. The Moderate Alcohol and Cardiovascular Health Trial (MACH15): Design and methods for a randomized trial of moderate alcohol consumption and cardiometabolic risk. European Journal Of Preventive Cardiology 2020, 27: 1967-1982. PMID: 32250171, PMCID: PMC7541556, DOI: 10.1177/2047487320912376.Peer-Reviewed Original ResearchConceptsModerate alcohol consumptionCardiovascular Health TrialAlcohol consumptionHealth trialsCardiovascular diseaseModerate alcoholNon-fatal ischemic strokeNon-fatal myocardial infarctionPrimary composite endpointCongestive heart failureCoronary heart diseaseModerate alcohol consumersAdults 50 yearsPublic health guidelinesAlcohol use disorderPreferred alcoholic beverageCardiometabolic effectsCardiometabolic riskCarotid revascularizationIschemic strokeSecondary outcomesComposite endpointHeart failurePrimary outcomeMyocardial infarctionExamining 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 classificationCravingDNA 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
2018
Trajectories 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
Moderate Alcohol Consumption and Chronic Disease: The Case for a Long‐Term Trial
Mukamal KJ, Clowry CM, Murray MM, Hendriks HF, Rimm EB, Sink KM, Adebamowo CA, Dragsted LO, Lapinski PS, Lazo M, Krystal JH. Moderate Alcohol Consumption and Chronic Disease: The Case for a Long‐Term Trial. Alcohol Clinical And Experimental Research 2016, 40: 2283-2291. PMID: 27688006, PMCID: PMC5073014, DOI: 10.1111/acer.13231.Peer-Reviewed Original ResearchConceptsModerate alcohol consumptionChronic diseasesAlcohol consumptionRandomized trialsLong-term clinical trialsCoronary heart diseaseMajor chronic diseasesStrong epidemiological associationLong-term trialsGold standard evidenceNutritional interventionHeart diseaseClinical trialsBreast cancerEpidemiological associationModerate drinkingYears durationClinical investigatorsBiological mediatorsAvailable evidenceDiseaseObserved associationsTrialsStandard evidenceVariety of settings
2013
Glutamatergic targets for new alcohol medications
Holmes A, Spanagel R, Krystal JH. Glutamatergic targets for new alcohol medications. Psychopharmacology 2013, 229: 539-554. PMID: 23995381, PMCID: PMC3811052, DOI: 10.1007/s00213-013-3226-2.Peer-Reviewed Original ResearchConceptsGlutamate systemGlycineB siteAlcohol-related behaviorsNMDA receptorsAlcohol abuseAlcohol consumptionN-methyl-D-aspartate receptorsChronic alcohol exposureElevated extracellular glutamatePathophysiology of alcoholismAMPA receptor subunitsAlcohol use disorderNovel pharmacotherapeutic approachesEffects of alcoholAlcohol medicationsBlocking NMDAHyperglutamatergic stateMetabotropic receptorsPharmacotherapeutic approachesAlcohol exposureExcess glutamateExtracellular glutamateGlutamate receptorsPreclinical studiesKainate receptors
2011
Noradrenergic vs Serotonergic Antidepressant with or without Naltrexone for Veterans with PTSD and Comorbid Alcohol Dependence
Petrakis IL, Ralevski E, Desai N, Trevisan L, Gueorguieva R, Rounsaville B, Krystal JH. Noradrenergic vs Serotonergic Antidepressant with or without Naltrexone for Veterans with PTSD and Comorbid Alcohol Dependence. Neuropsychopharmacology 2011, 37: 996-1004. PMID: 22089316, PMCID: PMC3280636, DOI: 10.1038/npp.2011.283.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderSerotonin uptake inhibitorNorepinephrine uptake inhibitorUptake inhibitorAlcohol dependenceMale veteransTreatment of PTSDUse outcomesSymptoms of PTSDDouble-blind conditionsMain outcome measuresEvidence of efficacyComorbid alcohol dependenceCurrent diagnostic criteriaAlcohol use disorderAlcohol use outcomesComorbid conditionsAdjunctive efficacyOutcome measuresOnly FDADiagnostic criteriaUse disordersClinical advantagesAlcohol consumptionDrug AdministrationPlasma 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
2010
Sex Differences in Striatal Dopamine Release in Young Adults After Oral Alcohol Challenge: A Positron Emission Tomography Imaging Study With [11C]Raclopride
Urban NB, Kegeles LS, Slifstein M, Xu X, Martinez D, Sakr E, Castillo F, Moadel T, O'Malley SS, Krystal JH, Abi-Dargham A. Sex Differences in Striatal Dopamine Release in Young Adults After Oral Alcohol Challenge: A Positron Emission Tomography Imaging Study With [11C]Raclopride. Biological Psychiatry 2010, 68: 689-696. PMID: 20678752, PMCID: PMC2949533, DOI: 10.1016/j.biopsych.2010.06.005.Peer-Reviewed Original ResearchConceptsDopamine releaseStriatal subregionsAlcohol-induced dopamine releasePositron emission tomography scanAlcohol challengeStriatal dopamine releaseEmission tomography scanMaximum alcohol consumptionOral alcohol challengePositron emission tomographySex differencesAlcohol administrationYoung social drinkersTomography scanAbility of alcoholOral alcoholRewarding effectsMixed model analysisAlcohol consumptionAbuse liabilitySeparate daysSignificant negative correlationEmission tomographyVentral striatumSignificant positive correlationDecreased Beta2*‐nicotinic acetylcholine receptor availability after chronic ethanol exposure in nonhuman primates
Cosgrove KP, Kloczynski T, Bois F, Pittman B, Tamagnan G, Seibyl JP, Krystal JH, Staley JK. Decreased Beta2*‐nicotinic acetylcholine receptor availability after chronic ethanol exposure in nonhuman primates. Synapse 2010, 64: 729-732. PMID: 20340174, PMCID: PMC2904861, DOI: 10.1002/syn.20795.Peer-Reviewed Original ResearchConceptsChronic ethanol consumptionEthanol consumptionAlcohol consumptionNicotinic acetylcholine receptor availabilityAverage daily ethanol consumptionChronic ethanol exposureDaily ethanol consumptionEthanol-induced changesNicotinic acetylcholine receptorsSelf-administer ethanolIA-85380H withdrawalEthanol exposureReceptor availabilityAcetylcholine receptorsParietal cortexMale animalsTotal gramsBaselinePercent decreasePersistent changesWithdrawalMidbrainCortexAnimalsSPECT imaging of nicotinic acetylcholine receptors in nonsmoking heavy alcohol drinking individuals
Esterlis I, Cosgrove KP, Petrakis IL, McKee SA, Bois F, Krantzler E, Stiklus SM, Perry EB, Tamagnan GD, Seibyl JP, Krystal JH, Staley JK. SPECT imaging of nicotinic acetylcholine receptors in nonsmoking heavy alcohol drinking individuals. Drug And Alcohol Dependence 2010, 108: 146-150. PMID: 20074869, PMCID: PMC2871672, DOI: 10.1016/j.drugalcdep.2009.12.006.Peer-Reviewed Original ResearchConceptsDrinks/occasionNicotinic acetylcholine receptorsControl nonsmokersAcetylcholine receptorsHeavy drinkersHeavy drinkingLast alcoholic beverageHeavy alcohol drinkersHeavy alcoholSingle photon emissionSeverity of drinkingEffect of ageTobacco smokingAlcohol drinkersAlcohol drinkingCommon neural substrateNonsmokersAlcohol consumptionReceptor availabilityLarger studyAlcohol drinksAlcohol use behaviorsAddictive disordersDrinkersNeural substrates
2002
A Functional Neuropeptide Y Leu7Pro Polymorphism Associated With Alcohol Dependence in a Large Population Sample From the United States
Lappalainen J, Kranzler HR, Malison R, Price LH, Van Dyck C, Rosenheck RA, Cramer J, Southwick S, Charney D, Krystal J, Gelernter J. A Functional Neuropeptide Y Leu7Pro Polymorphism Associated With Alcohol Dependence in a Large Population Sample From the United States. JAMA Psychiatry 2002, 59: 825-831. PMID: 12215082, DOI: 10.1001/archpsyc.59.9.825.Peer-Reviewed Original ResearchMeSH KeywordsAlcohol DrinkingAlcoholismBlack PeopleCase-Control StudiesComorbidityDepressive DisorderEthnicityEuropeFemaleGene FrequencyGenetic Predisposition to DiseaseGenetics, PopulationGenotypeHumansMaleNeuropeptide YPolymorphism, GeneticRacial GroupsSchizophreniaStress Disorders, Post-TraumaticUnited StatesConceptsAlcohol-dependent subjectsPro7 alleleAlcohol dependencePopulation sampleComorbid psychiatric disordersMain outcome measuresPopulation studiesEA controlsNeuropeptide Y geneRecent population studiesPosttraumatic stress disorderNPY polymorphismsRisk factorsAttributable fractionMajor depressionOutcome measuresLarge population samplePsychiatric disordersAlcohol consumptionPolymorphism AssociatedAlzheimer's diseaseAllele frequenciesStress disorderModulate riskEuropean Americans
1994
Alcohol Dependence May Be the Missing Link Between Posttraumatic Stress Disorder and Panic-Reply
Krystal J, Southwick S, Charney D. Alcohol Dependence May Be the Missing Link Between Posttraumatic Stress Disorder and Panic-Reply. JAMA Psychiatry 1994, 51: 430-430. DOI: 10.1001/archpsyc.1994.03950050090014.Peer-Reviewed Original ResearchPanic disorderPTSD symptomsΑ2-adrenergic antagonistMajor psychiatric disordersPosttraumatic stress disorderAcute alcoholOpiate withdrawalMajor depressionNoradrenergic systemHealthy subjectsPsychiatric disordersClinical reportsAlcohol consumptionPatientsPanic attacksAlcohol dependenceSubstance abuseStress disorderNeurobiological significanceAnxiety disordersDisordersSymptomsPTSDWithdrawalLittle evidence
1991
NO Association Between an Allele at the D2 Dopamine Receptor Gene (DRD2) and Alcoholism
Gelernter J, O'Malley S, Risch N, Kranzler HR, Krystal J, Merikangas K, Kennedy JL, Kidd KK. NO Association Between an Allele at the D2 Dopamine Receptor Gene (DRD2) and Alcoholism. JAMA 1991, 266: 1801-1807. PMID: 1832467, DOI: 10.1001/jama.1991.03470130081033.Peer-Reviewed Original ResearchConceptsControl groupA1 allelePopulation control groupPhysical withdrawal symptomsRandom population controlsSignificant differencesAge of onsetRecent alcohol consumptionAllele frequenciesD2 dopamine receptor geneAntisocial personality disorderWithdrawal symptomsFamily historyAlcoholic subjectsDirect structured interviewsGroup overallAllelic associationDopamine receptor geneAlcohol consumptionAlcohol dependenceControl populationPositive allelic associationAlcoholismPersonality disorderWhite individuals