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 sampleGene × environment effects and mediation involving adverse childhood events, mood and anxiety disorders, and substance dependence
Kranzler H, Davis C, Feinn R, Jinwala Z, Khan Y, Oikonomou A, Silva-Lopez D, Burton I, Dixon M, Milone J, Ramirez S, Shifman N, Levey D, Gelernter J, Hartwell E, Kember R. Gene × environment effects and mediation involving adverse childhood events, mood and anxiety disorders, and substance dependence. Nature Human Behaviour 2024, 8: 1616-1627. PMID: 38834750, DOI: 10.1038/s41562-024-01885-w.Peer-Reviewed Original ResearchAdverse childhood eventsSubstance dependenceMood/anxiety disordersAnxiety disordersChildhood eventsIndirect associationsGenetic riskExposure to adverse childhood eventsDevelopment of moodSubstance use disordersAssociations of adverse childhood eventsUse disorderMediation modelMood/anxietyDisorder factorsPolygenic scoresIndirect pathsDisordersEuropean ancestry individualsMoodTreatment approachesAnxietySelf-medicationEuropean ancestryLatent variables
2023
Genome-wide association study of antisocial personality disorder diagnostic criteria provides evidence for shared risk factors across disorders
Li W, Zhou H, Thygesen J, Heydtmann M, Smith I, Degenhardt F, Nöthen M, Morgan M, Kranzler H, Gelernter J, Bass N, McQuillin A. Genome-wide association study of antisocial personality disorder diagnostic criteria provides evidence for shared risk factors across disorders. Psychiatric Genetics 2023, 33: 233-242. PMID: 37756443, PMCID: PMC10635348, DOI: 10.1097/ypg.0000000000000352.Peer-Reviewed Original ResearchConceptsAntisocial personality disorderAttention deficit hyperactivity disorderSubstance use disordersPosttraumatic stress disorderGenome-wide association studiesDeficit hyperactivity disorderDisorder diagnostic criteriaRisk factorsFrontal cortexDiagnostic criteriaUse disordersRisk score analysisAnterior cingulateAlcohol-dependent participantsPsychiatric conditionsSignificant associationBrain regionsPersonality disorder diagnostic criteriaStress disorderAnxiety disordersASPD criteriaHyperactivity disorderPolygenic risk score analysisPersonality disorderScore analysis
2015
RDoC and translational perspectives on the genetics of trauma‐related psychiatric disorders
Montalvo-Ortiz JL, Gelernter J, Hudziak J, Kaufman J. RDoC and translational perspectives on the genetics of trauma‐related psychiatric disorders. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2015, 171: 81-91. PMID: 26592203, PMCID: PMC4754782, DOI: 10.1002/ajmg.b.32395.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsStress-related psychiatric disordersPsychiatric disordersTrauma-related psychiatric disordersAdverse early life experiencesSubstance use disordersGenetic risk factorsKey brain structuresDistinct neural circuitsDistinct psychiatric disordersSubstance use problemsClinical syndromeRisk factorsHigh riskPsychiatric problemsUse disordersAdverse early experiencesTranslational studiesGenome-wide association studiesClinical phenotypeNeural circuitsBrain structuresResearch Domain Criteria frameworkCircuitry developmentEarly life experiencesAnxiety disordersInter-observer reliability of DSM-5 substance use disorders
Denis CM, Gelernter J, Hart AB, Kranzler HR. Inter-observer reliability of DSM-5 substance use disorders. Drug And Alcohol Dependence 2015, 153: 229-235. PMID: 26048641, PMCID: PMC4509850, DOI: 10.1016/j.drugalcdep.2015.05.019.Peer-Reviewed Original ResearchConceptsDSM-5 SUD diagnosesSUD diagnosisDSM-IV diagnosisLifetime moodInter-observer reliabilityDSM-5 substance use disordersDisorder diagnosisCo-occurring SUDSubstance use disorder diagnosisSubstance use disordersDSM-5 criteriaSemi-Structured AssessmentAnxiety disorder diagnosisLifetime SUDMild severityUse disordersDrug dependenceSevere disordersDSM-IVPercent agreementDiagnosisAnxiety disordersLifetime alcoholLimited evidenceDisorders
2014
The α-endomannosidase gene (MANEA) is associated with panic disorder and social anxiety disorder
Jensen KP, Stein MB, Kranzler HR, Yang BZ, Farrer LA, Gelernter J. The α-endomannosidase gene (MANEA) is associated with panic disorder and social anxiety disorder. Translational Psychiatry 2014, 4: e353-e353. PMID: 24473444, PMCID: PMC3905232, DOI: 10.1038/tp.2013.122.Peer-Reviewed Original ResearchConceptsPanic disorderAnxiety disordersCocaine-induced paranoiaAnxiety disorder casesWhole blood cellsPsychiatric disorder riskWarrants further investigationAfrican American subjectsComorbid drugPD casesPsychiatric disordersAlcohol dependenceBrain tissueCocaine useBehavioral effectsBlood cellsClinical potentialGene variantsDisordersDisorder casesSingle nucleotide polymorphismsDisorder riskIndependent samplesPsychiatric phenotypesFurther investigation
2013
Association of CRHR1 variants and posttraumatic stress symptoms in hurricane exposed adults
White S, Acierno R, Ruggiero KJ, Koenen KC, Kilpatrick DG, Galea S, Gelernter J, Williamson V, McMichael O, Vladimirov VI, Amstadter AB. Association of CRHR1 variants and posttraumatic stress symptoms in hurricane exposed adults. Journal Of Anxiety Disorders 2013, 27: 678-683. PMID: 24077033, PMCID: PMC4182958, DOI: 10.1016/j.janxdis.2013.08.003.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderPTSD symptomsHormone receptor 1 geneCorticotropin-releasing hormone receptor 1 (CRHR1) geneSingle nucleotide polymorphismsReceptor 1 geneCRHR1 variationEtiology of PTSDHPA axisAdrenal axisCRHR1 variantsPosttraumatic stress symptomsStress disorderAnxiety disordersFinal analysisSymptomsHeritable anxiety disordersEuropean-American subsampleAdultsStress symptomsCRHR1Genetic variantsMultiple testingDiagnosisDisorders
2010
The role of early life stress in development of the anterior limb of the internal capsule in nonhuman primates
Coplan JD, Abdallah CG, Tang CY, Mathew SJ, Martinez J, Hof PR, Smith EL, Dwork AJ, Perera TD, Pantol G, Carpenter D, Rosenblum LA, Shungu DC, Gelernter J, Kaffman A, Jackowski A, Kaufman J, Gorman JM. The role of early life stress in development of the anterior limb of the internal capsule in nonhuman primates. Neuroscience Letters 2010, 480: 93-96. PMID: 20541590, PMCID: PMC2951885, DOI: 10.1016/j.neulet.2010.06.012.Peer-Reviewed Original ResearchConceptsDeep brain stimulationInternal capsuleDiffusion tensor imagingWhite matterFractional anisotropyAnterior limbNonhuman primate modelWhite matter impairmentAdult male bonnet macaquesOccipital white matterEarly life stressWhite matter tract integrityWhite matter integrityParental verbal abuseMother-infant attachmentPrimate modelPosterior limbBrain stimulationTract integrityTensor imagingAnxiety disordersAnxiety scoresMale bonnet macaquesLife stressSignificant reduction
2009
NPY moderates the relation between hurricane exposure and generalized anxiety disorder in an epidemiologic sample of hurricane‐exposed adults
Amstadter AB, Koenen KC, Ruggiero KJ, Acierno R, Galea S, Kilpatrick DG, Gelernter J. NPY moderates the relation between hurricane exposure and generalized anxiety disorder in an epidemiologic sample of hurricane‐exposed adults. Depression And Anxiety 2009, 27: 270-275. PMID: 20037921, PMCID: PMC2879267, DOI: 10.1002/da.20648.Peer-Reviewed Original ResearchConceptsGeneralized anxiety disorderNeuropeptide YEpidemiologic sampleGAD diagnosisHurricane exposureAnxiety disordersRandom digit dial proceduresHigh hurricane exposureFlorida Hurricane StudyFunctional single nucleotide polymorphismsNPY rs16147NPY expressionOutcome measuresGene-environment interactionsStressor exposureBuccal DNA samplesSingle nucleotide polymorphismsGAD symptomsRs16147AdultsStructured interviewsExposureDiagnosisRiskDisordersSubtypes of major depression in substance dependence
Niciu MJ, Chan G, Gelernter J, Arias AJ, Douglas K, Weiss R, Anton RF, Farrer L, Cubells JF, Kranzler HR. Subtypes of major depression in substance dependence. Addiction 2009, 104: 1700-1709. PMID: 19681804, PMCID: PMC2980795, DOI: 10.1111/j.1360-0443.2009.02672.x.Peer-Reviewed Original ResearchMeSH KeywordsAcademic Medical CentersAdolescentAdultAge FactorsAnxiety DisordersBlack or African AmericanComorbidityData Interpretation, StatisticalDepressive Disorder, MajorFemaleHispanic or LatinoHumansInterview, PsychologicalLogistic ModelsMaleRecurrenceSocioeconomic FactorsSubstance-Related DisordersSuicide, AttemptedWhite PeopleYoung AdultConceptsMajor depressive episodeSubstance dependenceMDE subtypesDrug dependenceRelated clinical featuresPotential therapeutic implicationsSubstance use disordersAcademic medical centerGreater psychiatric severitySemi-Structured AssessmentClinical featuresDepressive episodeMajor depressionMedical CenterSecondary data analysisDepressive symptomsDiagnostic criteriaPsychiatric severityTherapeutic implicationsUse disordersSubtypesAnxiety disordersPsychiatric measuresCase-control genetic studyCommunity recruitmentAdverse childhood events as risk factors for substance dependence: Partial mediation by mood and anxiety disorders
Douglas KR, Chan G, Gelernter J, Arias AJ, Anton RF, Weiss RD, Brady K, Poling J, Farrer L, Kranzler HR. Adverse childhood events as risk factors for substance dependence: Partial mediation by mood and anxiety disorders. Addictive Behaviors 2009, 35: 7-13. PMID: 19720467, PMCID: PMC2763992, DOI: 10.1016/j.addbeh.2009.07.004.Peer-Reviewed Original ResearchConceptsAdverse childhood eventsSD riskSubstance dependenceAnxiety disordersRisk factorsNegative health outcomesSemi-Structured AssessmentChildhood eventsOpioid dependenceSD diagnosisLifetime moodEffective treatmentLifetime diagnosisFirst onsetHealth outcomesDrug dependenceEarly life experiencesDisordersChildhood abuseRiskMoodDiagnosisAlcoholismCocaineInteraction of Childhood Maltreatment with the Corticotropin-Releasing Hormone Receptor Gene: Effects on Hypothalamic-Pituitary-Adrenal Axis Reactivity
Tyrka AR, Price LH, Gelernter J, Schepker C, Anderson GM, Carpenter LL. Interaction of Childhood Maltreatment with the Corticotropin-Releasing Hormone Receptor Gene: Effects on Hypothalamic-Pituitary-Adrenal Axis Reactivity. Biological Psychiatry 2009, 66: 681-685. PMID: 19596121, PMCID: PMC2881567, DOI: 10.1016/j.biopsych.2009.05.012.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAdult Survivors of Child AbuseCorticotropin-Releasing HormoneDepressionDexamethasoneFemaleGenotypeHumansHydrocortisoneHypothalamo-Hypophyseal SystemLinear ModelsLinkage DisequilibriumMaleMiddle AgedPituitary-Adrenal SystemPolymorphism, GeneticReceptors, Corticotropin-Releasing HormoneStress, PsychologicalSurveys and QuestionnairesYoung AdultConceptsDEX/CRH testAdrenal (HPA) axis reactivityEarly life stressCortisol responseCRH testAxis reactivityDexamethasone/corticotropin-releasing hormone testCorticotropin-releasing hormone testChildhood maltreatmentCRHR1 polymorphismsHormone receptor geneHPA axis activationLife stressReceptor geneElevated cortisol responseDevelopment of moodChildhood Trauma QuestionnaireHormone testAxis activationHypothalamic-PituitaryNon-Hispanic adultsBlood samplesGG genotypeAdult depressionAnxiety disorders
2008
RGS2 and generalized anxiety disorder in an epidemiologic sample of hurricane‐exposed adults
Koenen KC, Amstadter AB, Ruggiero KJ, Acierno R, Galea S, Kilpatrick DG, Gelernter J. RGS2 and generalized anxiety disorder in an epidemiologic sample of hurricane‐exposed adults. Depression And Anxiety 2008, 26: 309-315. PMID: 18833580, PMCID: PMC2666784, DOI: 10.1002/da.20528.Peer-Reviewed Original ResearchConceptsEpidemiologic sampleC alleleAnxiety disordersRisk of GADRandom digit dial proceduresSingle nucleotide polymorphismsLogistic regression analysisPanic disorder patientsDSM-IV diagnosisGeneralized anxiety disorderHurricane exposureFlorida Hurricane StudyRGS2 geneSocial supportStressful life eventsHigh prevalenceOutcome measuresDisorder patientsPanic disorderBuccal DNA samplesRelevant polymorphismsDisordersGADAnxious behaviorGAD symptomsInfluence of RGS2 on Anxiety-Related Temperament, Personality, and Brain Function
Smoller JW, Paulus MP, Fagerness JA, Purcell S, Yamaki LH, Hirshfeld-Becker D, Biederman J, Rosenbaum JF, Gelernter J, Stein MB. Influence of RGS2 on Anxiety-Related Temperament, Personality, and Brain Function. JAMA Psychiatry 2008, 65: 298-308. PMID: 18316676, DOI: 10.1001/archgenpsychiatry.2007.48.Peer-Reviewed Original ResearchConceptsFunctional magnetic resonanceHuman anxiety disordersAnxiety disordersEmotional facesEmotion processingChildhood temperamentLaboratory-based behavioral measuresSocial anxiety disorderBrain functionChildhood behavioral inhibitionSelf-report measuresInsular cortex activationIndependent samplesLaboratory-based assessmentsTemperamental precursorsBehavioral inhibitionBehavioral measuresAdult personalityCortex activationLimbic activationAnxiety phenotypeTemperamentIntermediate phenotypesAnxietyAnxiety behavior
2001
Family‐based association study of serotonin transporter promoter in suicidal adolescents: No association with suicidality but possible role in violence traits
Zalsman G, Frisch A, Bromberg M, Gelernter J, Michaelovsky E, Campino A, Erlich Z, Tyano S, Apter A, Weizman A. Family‐based association study of serotonin transporter promoter in suicidal adolescents: No association with suicidality but possible role in violence traits. American Journal Of Medical Genetics 2001, 105: 239-245. PMID: 11353442, DOI: 10.1002/ajmg.1261.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnalysis of VarianceCarrier ProteinsFamily HealthFemaleGene FrequencyGenetic Predisposition to DiseaseGenotypeHumansIsraelMaleMembrane GlycoproteinsMembrane Transport ProteinsMental DisordersNerve Tissue ProteinsPhenotypePolymorphism, GeneticPromoter Regions, GeneticPsychology, AdolescentSerotonin Plasma Membrane Transport ProteinsSuicide, AttemptedViolenceConceptsSuicidal behaviorDetailed clinical historySerotonin transporter promoterSuicide-related behaviorsPromoter region polymorphismsSerotonin dysfunctionClinical parametersClinical historyBlood samplesHaplotype relative risk methodRelative risk methodSuicidal adolescentsSuicide riskLS genotypeAdolescent inpatientsAnxiety disordersSuicide intentSignificant allelic associationSuicidal adolescent inpatientsSignificant differencesFamily-based association studyPatientsRegion polymorphismsTransporter promoterPossible role