2024
Application of polygenic scores to a deeply phenotyped sample enriched for substance use disorders reveals extensive pleiotropy with psychiatric and somatic traits
Hartwell E, Jinwala Z, Milone J, Ramirez S, Gelernter J, Kranzler H, Kember R. Application of polygenic scores to a deeply phenotyped sample enriched for substance use disorders reveals extensive pleiotropy with psychiatric and somatic traits. Neuropsychopharmacology 2024, 49: 1958-1967. PMID: 39043921, PMCID: PMC11480112, DOI: 10.1038/s41386-024-01922-2.Peer-Reviewed Original ResearchSubstance use disordersPost-traumatic stress disorderGeneralized anxiety disorderGenetic liabilityPolygenic scoresBipolar disorderSubstance use phenotypesSomatic traitsBody mass indexSubstance use categoriesEffect of genetic liabilityAnxiety disordersDepression-relatedDepressive disorderApplication of polygenic scoresStress disorderPsychiatric disordersPsychiatric phenotypesUse disorderPhenome-wide association studyGenetic influencesCross-sectional sampleMedical illnessPrecision medicine effortsPhenotyped samplePolygenic risk for suicide attempt is associated with lifetime suicide attempt in US soldiers independent of parental risk
Stein M, Jain S, Papini S, Campbell-Sills L, Choi K, Martis B, Sun X, He F, Ware E, Naifeh J, Aliaga P, Ge T, Consortium F, Workgroup F, Program F, Consortium F, Smoller J, Gelernter J, Kessler R, Ursano R. Polygenic risk for suicide attempt is associated with lifetime suicide attempt in US soldiers independent of parental risk. Journal Of Affective Disorders 2024, 351: 671-682. PMID: 38309480, PMCID: PMC11259154, DOI: 10.1016/j.jad.2024.01.254.Peer-Reviewed Original ResearchConceptsHistory of Major Depressive DisorderMajor depressive disorderNon-suicidal self-injuryLifetime non-suicidal self-injuryHistory of SAAssociated with lifetime SAParental historyMultivariate modelLifetime SASuicide attemptsParental major depressive disorderAssociated with non-suicidal self-injuryAssociated with lifetime suicide attemptsLifetime suicide attemptsClinical decision-makingDepressive disorderGWA studiesPolygenic risk scoresRisk scoreCohortEuropean ancestrySelf-injuryParental SAGenetic liabilityCombined analysis
2022
Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder
Oslin DW, Lynch KG, Shih MC, Ingram EP, Wray LO, Chapman SR, Kranzler HR, Gelernter J, Pyne JM, Stone A, DuVall SL, Lehmann LS, Thase ME, Aslam M, Batki S, Bjork J, Blow F, Brenner L, Chen P, Desai S, Dieperink E, Fears S, Fuller M, Goodman C, Graham D, Haas G, Hamner M, Helstrom A, Hurley R, Icardi M, Jurjus G, Kilbourne A, Kreyenbuhl J, Lache D, Lieske S, Lynch J, Meyer L, Montalvo C, Muralidhar S, Ostacher M, Paschall G, Pfeiffer P, Prieto S, Przygodzki R, Ranganathan M, Rodriguez-Suarez M, Roggenkamp H, Schichman S, Schneeweis J, Simonetti J, Steinhauer S, Suppes T, Umbert M, Vassy J, Voora D, Wiechers I, Wood A. Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder. JAMA 2022, 328: 151-161. PMID: 35819423, PMCID: PMC9277497, DOI: 10.1001/jama.2022.9805.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPatient Health Questionnaire-9Usual care groupUsual carePharmacogenomic testingDrug-gene interactionsRemission rateMedication selectionCare groupDepressive disorderVeterans Affairs Medical CenterActive substance use disorderCo-primary outcomesPrescription of medicationsBetter clinical outcomesProportion of prescriptionsRemission of symptomsSubstance use disordersEligible patientsWeek 24Effective antidepressantSingle antidepressantClinical outcomesInitial treatmentQuestionnaire-9Unique and joint associations of polygenic risk for major depression and opioid use disorder with endogenous opioid system function
Love T, Shabalin AA, Kember RL, Docherty AR, Zhou H, Koppelmans V, Gelernter J, Baker AK, Hartwell E, Dubroff J, Zubieta JK, Kranzler HR. Unique and joint associations of polygenic risk for major depression and opioid use disorder with endogenous opioid system function. Neuropsychopharmacology 2022, 47: 1784-1790. PMID: 35545664, PMCID: PMC9372136, DOI: 10.1038/s41386-022-01325-1.Peer-Reviewed Original ResearchConceptsOpioid use disorderMajor depressive disorderPolygenic risk scoresUse disordersEndogenous opioid system functionOpioid system functionOpioid system activityMDD polygenic risk scoresPolygenic riskAssociation of PRSEndogenous opioid responseOpioid system activationNon-displaceable bindingPathophysiologic linkOpioid responseMOR availabilityOpioid releaseDepressive disorderMajor depressionNeurotransmitter systemsVentral pallidumRisk scoreReceptor concentrationSystem activationRegion of interestAlcohol withdrawal in past‐year drinkers with unhealthy alcohol use: Prevalence, characteristics, and correlates in a national epidemiologic survey
Livne O, Feinn R, Knox J, Hartwell EE, Gelernter J, Hasin DS, Kranzler HR. Alcohol withdrawal in past‐year drinkers with unhealthy alcohol use: Prevalence, characteristics, and correlates in a national epidemiologic survey. Alcohol Clinical And Experimental Research 2022, 46: 422-433. PMID: 35275407, PMCID: PMC8928097, DOI: 10.1111/acer.14781.Peer-Reviewed Original ResearchConceptsAlcohol withdrawal syndromeUnhealthy alcohol useSerious adverse outcomesNational Epidemiologic SurveyAlcohol useHealthcare utilizationAdverse outcomesGeneral populationPsychiatric disordersEpidemiologic SurveyAlcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnairePast-year alcohol use disorderNausea/vomitingMajor depressive disorderImportant clinical populationAlcohol use disorderRelated Conditions-IIIBorderline personality disorderPast-year prevalenceAlcohol withdrawalWithdrawal syndromeWithdrawal symptomsDepressive disorderUnhealthy drinkersHigher odds
2021
Polygenic risk for major depression is associated with lifetime suicide attempt in US soldiers independent of personal and parental history of major depression
Stein MB, Jain S, Campbell‐Sills L, Ware EB, Choi KW, He F, Ge T, Gelernter J, Smoller JW, Kessler RC, Ursano RJ. Polygenic risk for major depression is associated with lifetime suicide attempt in US soldiers independent of personal and parental history of major depression. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2021, 186: 469-475. PMID: 34288400, PMCID: PMC8692314, DOI: 10.1002/ajmg.b.32868.Peer-Reviewed Original ResearchConceptsMajor depressive disorderLifetime suicide attemptsParental historySuicide attemptsMajor depressionMDD-PRSMultivariable modelLifetime historyMajor public health problemIncident suicide attemptsPolygenic riskPublic health problemUS Army soldiersRisk stratificationDepressive disorderPolygenic risk scoresRisk scoreSecond cohortHealth problemsCommon genetic variantsFirst cohortPersonal historyCohortGenetic variantsArmy soldiersPsychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder
Mundy J, Hübel C, Gelernter J, Levey D, Murray RM, Skelton M, Stein MB, Maihofer A, Nievergelt C, Baker D, Risborough V, Calabrese J, Galea S, Stein D, Koen N, Dalvie S, Aiello A, Roberts A, Koenen K, Solovieff N, Kranzler H, Zhao H, Gelernter J, Farrer L, Johnson E, Rice J, Bierut L, Saccone N, McFarlane A, Forbes D, Silove D, O'Donnell M, Bryant R, van Hooff M, Sponheim S, Disner S, Pietrzak R, Chen C, Smoller J, Stein M, Ursano R, Kessler R, Junglen A, Delahanty D, Amstadter A, Sheerin C, Ruggiero K, McLaughlin K, Peverill M, Caldas-de-Almeida J, Austin S, Gelaye B, Williams M, Sanchez S, Franz C, Panizzon M, Lyons M, Kremen W, Andreassen O, Dale A, Rutten B, Vinkers C, Schijven D, Geuze E, Vermetten E, Luykx J, Boks M, Ashley-Koch A, Beckham J, Garrett M, Hauser M, Dennis M, Kimbrel N, Qin X, Karstoft K, Andersen S, Borglum A, Hougaard D, Bybjerg-Grauholm J, Duncan L, Bµkvad-Hansen M, Nordentoft M, Mors O, Mortensen P, Werge T, Thompson W, Wang Y, Heath A, Nelson E, Martin N, Gordon S, Wolf E, Logue M, Miller M, McGlinchey R, Milberg W, Erbes C, Polusny M, Arbisi P, Peterson A, Williamson D, Young K, Maurer D, Rothbaum A, Zoellner L, Mavissakalian M, Feeny N, Roy-Byrne P, Rothbaum B, Maples-Keller J, Khan A, Wolff J, Lebois L, Teicher M, Kaufman M, Winternitz S, Bolger E, Seligowski A, Orcutt H, Evans A, Lugonja B, Lewis C, Jones I, Bisson J, McLean S, Linnstaedt S, Peters E, Rung A, Trapido E, Brashear M, Lori A, Smith A, Bradley B, Gillespie C, Guffanti G, Ressler K, Almli L, Jovanovic T, Bustamante A, Uddin M, van den Heuvel L, Seedat S, Hemmings S, Uka A, Kulenovic A, Wolf C, Babic D, Avdibegovic E, Deckert J, Domschke K, Jakovljevic M, Marmar C, Flory J, Jett M, Yehuda R, Hammamieh R, King A, Liberzon I, Seng J, Morris C, Mehta D, Voisey J, Lawford B, Young R, McLeay S, Daskalakis N, Norman S, Wang Z, Breen G, Coleman J, Klengel T, Torres K, Choi K, Levey D, Polimanti R, Atkinson E, Martin A, Neale B, Daly M, Ripke S, Ratanatharathorn A, Provost A, Haas M, Stevens J, Morey R, Harnal S, Mortensen P, Seedat S, Sumner J, Vassos E, Breen G, Coleman J. Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder. Psychological Medicine 2021, 52: 3975-3984. PMID: 34085609, PMCID: PMC8962503, DOI: 10.1017/s0033291721000830.Peer-Reviewed Original ResearchRecurrent major depressive disorderMajor depressive disorderPosttraumatic stress disorderSingle-episode major depressive disorderDepressive disorderTrauma exposureStress disorderPsychological trauma exposureLifetime major depressive disorderTrauma sensitivityGenetic loadingUK Biobank participantsKey risk factorsMental health consequencesRisk factorsMillion Veteran ProgramPolygenic risk scoresRisk scoreGenetic overlapHealth consequencesBiobank participantsTraumaDisordersVeteran ProgramPsychiatric Genomics ConsortiumDissecting the heterogeneity of posttraumatic stress disorder: differences in polygenic risk, stress exposures, and course of PTSD subtypes
Campbell-Sills L, Sun X, Choi KW, He F, Ursano RJ, Kessler RC, Levey DF, Smoller JW, Gelernter J, Jain S, Stein MB. Dissecting the heterogeneity of posttraumatic stress disorder: differences in polygenic risk, stress exposures, and course of PTSD subtypes. Psychological Medicine 2021, 52: 3646-3654. PMID: 33947479, PMCID: PMC9772910, DOI: 10.1017/s0033291721000428.Peer-Reviewed Original ResearchPosttraumatic stress disorderPersistence of PTSDMajor depressionPTSD subtypesStress disorderCo-occurring major depressionStress exposureMonths postdeploymentCourse of PTSDPolygenic riskProbable posttraumatic stress disorderU.S. Army Brigade Combat TeamHigh polygenic riskConcurrent mental disordersGenetic risk factorsTrauma-related factorsHigh symptom profileLeast comorbidityProspective studyRisk factorsDepressive disorderTreatment responsePolygenic risk scoresRisk scoreComorbiditiesPrevalence of predicted gene-drug interactions for antidepressants in the treatment of major depressive disorder in the Precision Medicine in Mental Health Care Study
Ramsey CM, Lynch KG, Thase ME, Gelernter J, Kranzler HR, Pyne JM, Shih MC, Stone A, Committee C, Oslin DW. Prevalence of predicted gene-drug interactions for antidepressants in the treatment of major depressive disorder in the Precision Medicine in Mental Health Care Study. Journal Of Affective Disorders 2021, 282: 1272-1277. PMID: 33601706, DOI: 10.1016/j.jad.2021.01.034.Peer-Reviewed Original ResearchConceptsMajor depressive disorderMental Health Care studyGene-drug interactionsDepressive disorderPGx testingAD treatmentCare studiesHealth care studiesPrecision medicineContext of pharmacotherapyPrevalence of antidepressantsUtility of PGxPrescribing practicesUS veteransPharmacogenetic testingAntidepressantsPatientsPrevious treatmentPrevalenceTreatmentDisordersPGxMedicineTest panelParticipants
2020
Study design and implementation of the PRecision Medicine In MEntal health Care (PRIME Care) Trial
Oslin DW, Chapman S, Duvall SL, Gelernter J, Ingram E, Kranzler HR, Lehmann LS, Lynch JA, Lynch KG, Pyne JM, Shih MC, Stone A, Thase ME, Wray LO. Study design and implementation of the PRecision Medicine In MEntal health Care (PRIME Care) Trial. Contemporary Clinical Trials 2020, 101: 106247. PMID: 33316457, DOI: 10.1016/j.cct.2020.106247.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPGx test resultsRandomized clinical trialsClinical trialsPGx testingHealth care cost implicationsUtility of PGxRoutine clinical carePragmatic randomized clinical trialsEpisode of careHealth care trialsPrecision medicineHealth care providersPrecision medicine approachPatient care costsImplementation science methodsCare trialsMedication selectionPsychotropic medicationsProvider educationDepressive disorderPatient outcomesPharmacogenetic testingCare providersClinical care
2018
Methylation in OTX2 and related genes, maltreatment, and depression in children
Kaufman J, Wymbs NF, Montalvo-Ortiz JL, Orr C, Albaugh MD, Althoff R, O’Loughlin K, Holbrook H, Garavan H, Kearney C, Yang BZ, Zhao H, Peña C, Nestler EJ, Lee RS, Mostofsky S, Gelernter J, Hudziak J. Methylation in OTX2 and related genes, maltreatment, and depression in children. Neuropsychopharmacology 2018, 43: 2204-2211. PMID: 30089883, PMCID: PMC6135753, DOI: 10.1038/s41386-018-0157-y.Peer-Reviewed Original ResearchConceptsMouse modelStress-related depressive disordersResting-state functional connectivity dataResting-state functional MRI dataDepressive-like behaviorEarly life stressSubset of childrenDNA specimensMedial frontal cortexPeripheral markersMeasures of depressionHomeobox 2 geneSubcallosal gyrusFunctional connectivity dataDepressive disorderFrontal cortexChild adversityMultiple molecular toolsFunctional MRI dataFrontal poleLarger studyFunctional connectivitySaliva samplesBilateral regionsUnbiased transcriptomics
2017
Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers
Polimanti R, Kaufman J, Zhao H, Kranzler HR, Ursano RJ, Kessler RC, Stein MB, Gelernter J. Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers. Acta Psychiatrica Scandinavica 2017, 137: 148-156. PMID: 29230810, PMCID: PMC6110087, DOI: 10.1111/acps.12843.Peer-Reviewed Original ResearchConceptsBD polygenic risk scorePolygenic risk scoresAlcohol misuseBipolar disorderTrauma exposurePsychiatric disordersGenetic riskMajor depressive disorderNicotine dependence symptomsSubstance use disordersSchizophrenia polygenic risk scoresVoltage-gated calcium channel activityCalcium channel activityUS Army soldiersBeta2-adrenergic receptorDepressive disorderRisk scoreUse disordersAdrenergic receptorsMental disordersSubstance abuseDisordersDependence symptomsChannel activityExposurePolygenic 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 disorder
2016
Genome-wide Association Study of Cannabis Dependence Severity, Novel Risk Variants, and Shared Genetic Risks
Sherva R, Wang Q, Kranzler H, Zhao H, Koesterer R, Herman A, Farrer LA, Gelernter J. Genome-wide Association Study of Cannabis Dependence Severity, Novel Risk Variants, and Shared Genetic Risks. JAMA Psychiatry 2016, 73: 472. PMID: 27028160, PMCID: PMC4974817, DOI: 10.1001/jamapsychiatry.2016.0036.Peer-Reviewed Original ResearchConceptsCannabis dependenceNeuronal calcium homeostasisGenetic factorsMajor depressive disorderSushi multiple domains-1 (CSMD1) geneSubstance abuse treatment centersSpecific genetic risk factorsGenetic risk factorsShared genetic riskPotential genetic factorsCentral nervous system developmentCriterion countsCannabis dependence severityDomain 1 geneCAD riskMean ageRisk factorsDepressive disorderNervous system developmentMajor depressionLarge cohortMAIN OUTCOMEGenome-wide association studiesTreatment centersCalcium homeostasis
2008
Association of psychiatric and substance use disorder comorbidity with cocaine dependence severity and treatment utilization in cocaine-dependent individuals
Ford JD, Gelernter J, DeVoe JS, Zhang W, Weiss RD, Brady K, Farrer L, Kranzler HR. Association of psychiatric and substance use disorder comorbidity with cocaine dependence severity and treatment utilization in cocaine-dependent individuals. Drug And Alcohol Dependence 2008, 99: 193-203. PMID: 18775607, PMCID: PMC2745327, DOI: 10.1016/j.drugalcdep.2008.07.004.Peer-Reviewed Original ResearchConceptsCocaine dependence severitySubstance use disordersTreatment utilizationSelf-help group participationDependence severityPsychiatric disordersUse disordersCo-occurring substance dependenceMajor depressive disorderSubstance dependence disordersAssociation of psychiatricLogistic regression analysisCocaine dependence treatmentPosttraumatic stress disorderSemi-Structured AssessmentAntisocial personality disorderHeavy cocaine useClinical managementDependence treatmentDepressive disorderDisorder comorbidityService utilizationCocaine-dependent individualsDependence disordersBipolar disorder