2025
Integrating HiTOP and RDoC frameworks part II: shared and distinct biological mechanisms of externalizing and internalizing psychopathology
Davis C, Khan Y, Toikumo S, Jinwala Z, Boomsma D, Levey D, Gelernter J, Kember R, Kranzler H. Integrating HiTOP and RDoC frameworks part II: shared and distinct biological mechanisms of externalizing and internalizing psychopathology. Psychological Medicine 2025, 55: e137. PMID: 40340892, PMCID: PMC12094665, DOI: 10.1017/s0033291725000819.Peer-Reviewed Original ResearchConceptsDrug repurposing analysisAssociated with reduced gray matter volumeHierarchical Taxonomy of PsychopathologyGenome-wide association studiesTaxonomy of PsychopathologyResearch Domain CriteriaTissue-specific expression patternsAspects of psychopathologyGray matter volumeSingle-cell RNA sequencing dataGene identification methodsMagnetic resonance imaging dataMulti-omics approachRNA sequencing dataBrain cell typesHiTOP frameworkInternalizing psychopathologyPhysical health conditionsPsychopathological spectrumSubcallosal cortexGene annotationMatter volumeGenomic insightsSequence dataGenetic liability
2024
A multi-ancestry genetic study of pain intensity in 598,339 veterans
Toikumo S, Vickers-Smith R, Jinwala Z, Xu H, Saini D, Hartwell E, Pavicic M, Sullivan K, Xu K, Jacobson D, Gelernter J, Rentsch C, Stahl E, Cheatle M, Zhou H, Waxman S, Justice A, Kember R, Kranzler H. A multi-ancestry genetic study of pain intensity in 598,339 veterans. Nature Medicine 2024, 30: 1075-1084. PMID: 38429522, PMCID: PMC12105102, DOI: 10.1038/s41591-024-02839-5.Peer-Reviewed Original ResearchPain intensityChronic painTreat chronic painCalcium channel blockersCross-ancestry meta-analysisGenome-wide association studiesExperience of painSamples of European ancestryPain phenotypesFunctional genomics dataGABAergic neuronsCalcium channelsAnalgesic effectB-blockersDrug groupMillion Veteran ProgramPainSubstance use disordersQuality of lifeDrug repurposing analysisOpioid crisisGenetic architectureCausal genesGenetic lociGenomic data
2023
9. THE GENETIC ARCHITECTURE OF PAIN INTENSITY IN THE MILLION VETERAN PROGRAM
Toikumo S, Vickers-Smith R, Jinwala Z, Xu H, Saini D, Hartwell E, Pavicic M, Sullivan K, Jacobson D, Cheatle M, Zhou H, Waxman S, Justice A, Kember R, Kranzler H. 9. THE GENETIC ARCHITECTURE OF PAIN INTENSITY IN THE MILLION VETERAN PROGRAM. European Neuropsychopharmacology 2023, 75: s60-s61. DOI: 10.1016/j.euroneuro.2023.08.120.Peer-Reviewed Original ResearchIndependent lociGenetic architectureMillion Veteran ProgramGenome-wide association testingIndependent genetic lociLinkage disequilibrium score regressionDrug-gene interaction databaseDisequilibrium score regressionNovel genetic variantsPotential drug targetsComplex traitsGWAS resultsCausal genesDruggable genomeDrug repurposing analysisGenetic lociDruggable genesInteraction databasesDrug targetsGenetic correlationsMolecular contributorsAssociation testingLociPsychiatric traitsScore regression
2022
Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden
Nichter B, Koller D, De Angelis F, Wang J, Girgenti M, Na P, Hill M, Norman S, Krystal J, Gelernter J, Polimanti R, Pietrzak R. Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden. Psychological Medicine 2022, 53: 6325-6333. PMID: 36444557, DOI: 10.1017/s0033291722003646.Peer-Reviewed Original ResearchConceptsPolygenic risk scoresUS military veteransLifetime suicide attemptsSuicide attemptsTrauma exposureTrauma burdenGenetic liabilityMilitary veteransDrug repurposing analysisPopulation-based sampleCumulative trauma exposureLifetime trauma exposureLow trauma exposureSuicide prediction modelsChronic inflammationInflammatory processNervous system developmentRisk scorePsychiatric characteristicsSuicidal behaviorExposure interactionsLarge genome-wide association studiesHigh levelsVeteransSuicidality
2019
Towards precision medicine for stress disorders: diagnostic biomarkers and targeted drugs
Le-Niculescu H, Roseberry K, Levey D, Rogers J, Kosary K, Prabha S, Jones T, Judd S, McCormick M, Wessel A, Williams A, Phalen P, Mamdani F, Sequeira A, Kurian S, Niculescu A. Towards precision medicine for stress disorders: diagnostic biomarkers and targeted drugs. Molecular Psychiatry 2019, 25: 918-938. PMID: 30862937, PMCID: PMC7192849, DOI: 10.1038/s41380-019-0370-z.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultbeta 2-MicroglobulinBiomarkersDEAD-box RNA HelicasesFemaleGene ExpressionHumansMaleMental DisordersMiddle AgedMolecular Targeted TherapyNogo ProteinsPrecision MedicinePredictive Value of TestsProto-Oncogene ProteinsReceptors, ImmunologicStress, PsychologicalTacrolimus Binding ProteinsTelomere HomeostasisConceptsPredictive biomarkersGene expression biomarkersTelomere lengthBlood gene expression biomarkersPossible new drug candidateStress disorderPsychological stressFuture psychiatric hospitalizationsVisual analog scaleHigh-risk groupSimple visual analog scaleDrug repurposing analysisExpression biomarkersGene expression signaturesAnalog scaleAdverse outcomesCalcium folinateCohort designHormonal changesPsychiatric hospitalizationDecreased qualityBiomarker findingsPsychiatric disordersPsychiatric patientsPatient stratificationTowards precision medicine for pain: diagnostic biomarkers and repurposed drugs
Niculescu A, Le-Niculescu H, Levey D, Roseberry K, Soe K, Rogers J, Khan F, Jones T, Judd S, McCormick M, Wessel A, Williams A, Kurian S, White F. Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs. Molecular Psychiatry 2019, 24: 501-522. PMID: 30755720, PMCID: PMC6477790, DOI: 10.1038/s41380-018-0345-5.Peer-Reviewed Original ResearchConceptsBlood gene expression biomarkersPossible new drug candidateFuture emergency department (ED) visitsEmergency department visitsHigh-risk groupDrug repurposing analysisCurrent opioid epidemicPerception of painSubjects longitudinal designGene expression signaturesPain statesDepartment visitsPain disordersTreatment dilemmaBlood biomarkersSC-560Opioid epidemicCohort designRisk groupsIndependent cohortPainGene expression biomarkersPsychiatric patientsDiagnostic biomarkersIndividual biomarkers
2017
Precision medicine for suicidality: from universality to subtypes and personalization
Niculescu A, Le-Niculescu H, Levey D, Phalen P, Dainton H, Roseberry K, Niculescu E, Niezer J, Williams A, Graham D, Jones T, Venugopal V, Ballew A, Yard M, Gelbart T, Kurian S, Shekhar A, Schork N, Sandusky G, Salomon D. Precision medicine for suicidality: from universality to subtypes and personalization. Molecular Psychiatry 2017, 22: 1250-1273. PMID: 28809398, PMCID: PMC5582166, DOI: 10.1038/mp.2017.128.Peer-Reviewed Original ResearchConceptsSuicidal ideationIndependent cohortPersonalized approachFuture hospitalizationPsychiatric diagnosisCandidate biomarkersUniversal biomarkerBlood gene expression biomarkersBiology of suicideTop biomarkersNovel predictive biomarkerHigh-risk groupNon-psychiatric disordersDrug repurposing analysisPublic health problemMonitoring of responseNovel potential therapeuticsHigher suicidal ideationPredictive biomarkersClinical trialsComprehensive stepwise approachRisk groupsLarge cohortMood disordersPreventive therapeutics
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