2024
Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder
Zillich E, Belschner H, Avetyan D, Andrade-Brito D, Martínez-Magaña J, Frank J, Mechawar N, Turecki G, Cabana-Domínguez J, Fernàndez-Castillo N, Cormand B, Montalvo-Ortiz J, Nöthen M, Hansson A, Rietschel M, Spanagel R, Witt S, Zillich L. Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder. Translational Psychiatry 2024, 14: 428. PMID: 39384764, PMCID: PMC11464785, DOI: 10.1038/s41398-024-03139-9.Peer-Reviewed Original ResearchConceptsCocaine use disorderUse disorderAlternative splicingHuman prefrontal cortexProfiling of DNA methylationBrodmann area 9Differential alternative splicingDeregulated biological processesPostmortem brain tissueMulti-omics approachCocaine intakeMulti-omics studiesPrefrontal cortexBrain alterationsMulti-omics profilingGene expression alterationsArea 9Fatty acid metabolismReceptor-targeting drugsSpliced transcriptsEpigenome-wideDNA methylationNeuronal morphogenesisAS changesDrug repositioning analysisA phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals
Jennings M, Martínez-Magaña J, Courchesne-Krak N, Cupertino R, Vilar-Ribó L, Bianchi S, Hatoum A, Atkinson E, Giusti-Rodriguez P, Montalvo-Ortiz J, Gelernter J, Artigas M, 23andMe I, Aslibekyan S, Auton A, Babalola E, Bell R, Bielenberg J, Bryc K, Bullis E, Coker D, Partida G, Dhamija D, Das S, Elson S, Eriksson N, Filshtein T, Fitch A, Fletez-Brant K, Fontanillas P, Freyman W, Granka J, Heilbron K, Hernandez A, Hicks B, Hinds D, Jewett E, Jiang Y, Kukar K, Kwong A, Lin K, Llamas B, Lowe M, McCreight J, McIntyre M, Micheletti S, Moreno M, Nandakumar P, Nguyen D, Noblin E, O'Connell J, Petrakovitz A, Poznik G, Reynoso A, Schumacher M, Shastri A, Shelton J, Shi J, Shringarpure S, Su Q, Tat S, Tchakouté C, Tran V, Tung J, Wang X, Wang W, Weldon C, Wilton P, Wong C, Elson S, Edenberg H, Fontanillas P, Palmer A, Sanchez-Roige S. A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals. EBioMedicine 2024, 103: 105086. PMID: 38580523, PMCID: PMC11121167, DOI: 10.1016/j.ebiom.2024.105086.Peer-Reviewed Original ResearchConceptsMultiple domains of healthDomains of healthEffects of alcohol consumptionAlcohol consumptionHealth outcomesPhenome-wide association studyAlcohol-related behaviorsCardio-metabolic healthPotential causal effectMendelian randomisation studiesGenome-wide association studiesPhenome-wide associationMR analysisPheWAS associationsMultiple domainsHypothesis-free approachPreventive medicineDiverse cohortPheWASAssociation studiesHealthReproductive healthAlcohol behaviorConsequences of drinkingEuropean cohort
2022
Psychosocial Factors Associated With Accelerated GrimAge in Male U.S. Military Veterans
Tamman AJF, Nagamatsu S, Krystal JH, Gelernter J, Montalvo-Ortiz JL, Pietrzak RH. Psychosocial Factors Associated With Accelerated GrimAge in Male U.S. Military Veterans. American Journal Of Geriatric Psychiatry 2022, 31: 97-109. PMID: 36210262, DOI: 10.1016/j.jagp.2022.09.002.Peer-Reviewed Original ResearchConceptsRisk factorsPremature mortalityU.S. veteransPsychosocial variablesNovel epigenetic clockLifetime substance use disorderRisk stratification modelMale U.S. veteransCross-sectional studyU.S. veteran populationWeekly physical exerciseSubstance use disordersMale U.S. military veteransBiological agingU.S. military veteransHealth morbidityModifiable correlatesMortality riskSleep qualityHigh riskGreater oddsUse disordersPhysical exercisePsychosocial factorsVeteran population
2021
DNA methylation changes in African American women with a history of preterm birth from the InterGEN study
Barcelona V, Montalvo-Ortiz JL, Wright ML, Nagamatsu ST, Dreisbach C, Crusto CA, Sun YV, Taylor JY. DNA methylation changes in African American women with a history of preterm birth from the InterGEN study. BMC Genomic Data 2021, 22: 30. PMID: 34482817, PMCID: PMC8418749, DOI: 10.1186/s12863-021-00988-x.Peer-Reviewed Original ResearchConceptsPreterm birthHealth disordersFull-term birthCentral nervous systemEpigenome-wide association studiesAfrican American womenInterGEN StudyBackgroundPreterm birthMaternal moodWomen 3Cardiovascular diseaseIndependent cohortPhysiologic mechanismsNervous systemAfrican American mothersSignificant CpG sitesEWAS approachWomenBirthSensory processingDNA methylationLong-term epigenetic effectsAmerican womenCommon outcomeFurther studies
2020
Tubulin Polymerization Promoting Protein (TPPP) gene methylation and corpus callosum measures in maltreated children
de Araújo CM, Hudziak J, Crocetti D, Wymbs NF, Montalvo-Ortiz JL, Orr C, Albaugh MD, Althoff RR, O'Loughlin K, Holbrook H, Garavan H, Yang BZ, Mostofsky S, Jackowski A, Lee RS, Gelernter J, Kaufman J. Tubulin Polymerization Promoting Protein (TPPP) gene methylation and corpus callosum measures in maltreated children. Psychiatry Research Neuroimaging 2020, 298: 111058. PMID: 32120304, PMCID: PMC11079625, DOI: 10.1016/j.pscychresns.2020.111058.Peer-Reviewed Original ResearchConceptsStress-related psychiatric disordersCorpus callosum measuresFractional anisotropyPsychiatric disordersTrauma experiencesWhite matter tractsChild trauma experiencesBrain changesLarger studyRelevant covariatesAtlas-based approachSplenium fractional anisotropyDNA specimensMultiple comparisonsGene methylationDisordersChildrenCurrent studySocial supports moderate the effects of child adversity on neural correlates of threat processing
Wymbs NF, Orr C, Albaugh MD, Althoff RR, O’Loughlin K, Holbrook H, Garavan H, Montalvo-Ortiz JL, Mostofsky S, Hudziak J, Kaufman J. Social supports moderate the effects of child adversity on neural correlates of threat processing. Child Abuse & Neglect 2020, 102: 104413. PMID: 32065988, PMCID: PMC8060780, DOI: 10.1016/j.chiabu.2020.104413.Peer-Reviewed Original ResearchConceptsFunctional magnetic resonance imagingThreat processingAnterior cingulate cortexSocial supportEmotion regulationNeural correlatesEmotional Go-Nogo taskGo-NoGo taskPositive social supportChildren ages 7Forms of adversityKey brain regionsAdverse experiencesFacial stimuliThreat stimuliNeural processingBrain systemsBrain activationModerate adversitySevere adversityAnterior insulaConjunction analysisLeft amygdalaOrbitofrontal cortexActivation foci
2019
Genomewide Study of Epigenetic Biomarkers of Opioid Dependence in European- American Women
Montalvo-Ortiz JL, Cheng Z, Kranzler HR, Zhang H, Gelernter J. Genomewide Study of Epigenetic Biomarkers of Opioid Dependence in European- American Women. Scientific Reports 2019, 9: 4660. PMID: 30874594, PMCID: PMC6420601, DOI: 10.1038/s41598-019-41110-7.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesEpigenetic mechanismsAssociation studiesAssociation analysisCpG sitesFirst epigenome-wide association studyGenome-wide association studiesPrevious genome-wide association studyCandidate gene approachChromatin remodelingDNA bindingGene approachGenomewide studiesDNA methylation ageCell survivalEpigenetic biomarkersRisk variantsPopulation stratificationMethylation ageGenesCell projectionsOpioid dependenceNovel peripheral biomarkersEuropean American womenCell proportion
2018
Adverse Childhood Experiences, Epigenetic Measures, and Obesity in Youth
Kaufman J, Montalvo-Ortiz JL, Holbrook H, O'Loughlin K, Orr C, Kearney C, Yang BZ, Wang T, Zhao H, Althoff R, Garavan H, Gelernter J, Hudziak J. Adverse Childhood Experiences, Epigenetic Measures, and Obesity in Youth. The Journal Of Pediatrics 2018, 202: 150-156.e3. PMID: 30177354, PMCID: PMC6513669, DOI: 10.1016/j.jpeds.2018.06.051.Peer-Reviewed Original ResearchConceptsBody mass indexAdverse childhood experiencesMass indexIndices of obesityAssessment of obesityChildhood experiencesFuture longitudinal studiesObesity riskHealth burdenPsychiatric outcomesSecond cohortObesityNovel interventionsCohortEarly adversityCross-sectional measuresEpigenetic predictorsLongitudinal studySaliva DNAEpigenetic measuresWhole genome testingDiscovery sampleReplication sampleChildrenRiskMethylation 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 transcriptomicsTranslational studies support a role for serotonin 2B receptor (HTR2B) gene in aggression-related cannabis response
Montalvo-Ortiz JL, Zhou H, D’Andrea I, Maroteaux L, Lori A, Smith A, Ressler KJ, Nuñez YZ, Farrer LA, Zhao H, Kranzler HR, Gelernter J. Translational studies support a role for serotonin 2B receptor (HTR2B) gene in aggression-related cannabis response. Molecular Psychiatry 2018, 23: 2277-2286. PMID: 29875475, PMCID: PMC6281782, DOI: 10.1038/s41380-018-0077-6.Peer-Reviewed Original ResearchConceptsGrady Trauma ProjectAfrican AmericansWild-type miceReceptor geneEffects of cannabisWide significant risk lociResident-intruder paradigmImpulsivity/aggressionConcordant findingsTHC administrationKnockout miceTranslational studiesAA subjectsCannabis useStudy designTrauma ProjectAdverse effectsMiceCannabisAggressive behaviorEuropean AmericansNominal associationAdverse consequencesGenome-wide association study (GWAS) designRisk lociCorticotrophin releasing factor receptor 1 antagonists prevent chronic stress-induced behavioral changes and synapse loss in aged rats
Dong H, Keegan JM, Hong E, Gallardo C, Montalvo-Ortiz J, Wang B, Rice KC, Csernansky J. Corticotrophin releasing factor receptor 1 antagonists prevent chronic stress-induced behavioral changes and synapse loss in aged rats. Psychoneuroendocrinology 2018, 90: 92-101. PMID: 29477954, PMCID: PMC5864558, DOI: 10.1016/j.psyneuen.2018.02.013.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsAnxietyBehaviorBehavior, AnimalCorticotropin-Releasing HormoneDepressionDisease Models, AnimalFemaleHypothalamo-Hypophyseal SystemMalePituitary-Adrenal SystemPyrimidinesPyrrolesRatsRats, Sprague-DawleyReceptors, Corticotropin-Releasing HormoneStress, PsychologicalSynapsesConceptsStress-induced behavioral changesStress-induced anxietyAnxiety-related behaviorMemory deficitsChronic stressSynapse lossCRF1 antagonistsFactor receptor 1 antagonistCortical dendritic spinesHPA axis dysfunctionBody weight lossReceptor 1 antagonistMonths of ageSubset of animalsBehavioral changesFactor receptor 1Axis dysfunctionAged brainAged ratsPotential therapyDendritic spinesAnimal modelsCorticosterone levelsAlzheimer's diseaseReceptor 1
2017
Genome-Wide DNA Methylation Changes Associated with Intermittent Explosive Disorder: A Gene-Based Functional Enrichment Analysis
Montalvo-Ortiz JL, Zhang H, Chen C, Liu C, Coccaro EF. Genome-Wide DNA Methylation Changes Associated with Intermittent Explosive Disorder: A Gene-Based Functional Enrichment Analysis. The International Journal Of Neuropsychopharmacology 2017, 21: 12-20. PMID: 29106553, PMCID: PMC5789263, DOI: 10.1093/ijnp/pyx087.Peer-Reviewed Original ResearchConceptsGenome-wide DNA methylation changesFunctional enrichment analysisDNA methylation changesEnrichment analysisCpG sitesMethylation changesGenome-wide significant thresholdIllumina Infinium HumanMethylation450 BeadChipBlood DNA methylomeNovel biological processesInfinium HumanMethylation450 BeadChipDNA methylomeEpigenetic mechanismsPathway analysisBiological processesGenetic studiesNeuronal differentiationHumanMethylation450 BeadChipGenesBehavioral genetic studiesR packageImportant mechanismGenetic influencesEndocrine systemMethylome
2008
Chronic underactivity of medial frontal cortical β2-containing nicotinic receptors increases clozapine-induced working memory impairment in female rats
Levin ED, Perkins A, Brotherton T, Qazi M, Berez C, Montalvo-Ortiz J, Davis K, Williams P, Christopher NC. Chronic underactivity of medial frontal cortical β2-containing nicotinic receptors increases clozapine-induced working memory impairment in female rats. Progress In Neuro-Psychopharmacology And Biological Psychiatry 2008, 33: 296-302. PMID: 19146909, PMCID: PMC2684503, DOI: 10.1016/j.pnpbp.2008.12.003.Peer-Reviewed Original ResearchMeSH KeywordsAconitineAlpha7 Nicotinic Acetylcholine ReceptorAnimalsAntipsychotic AgentsCerebral CortexChronic DiseaseClozapineDihydro-beta-ErythroidineFemaleMaze LearningMemory DisordersMemory, Short-TermMicroinjectionsNicotinic AntagonistsPrefrontal CortexRatsRats, Sprague-DawleyReceptors, NicotinicConceptsMedial frontal cortexMemory impairmentNicotinic receptor activityFrontal cortexCognitive functionHippocampal infusionsRadial arm mazeNicotinic receptor involvementNicotinic receptor lossProcognitive treatmentsBrain systemsCognitive effectsMemory functionAntipsychotic drug interactionsMLA infusionsMemoryNicotinic receptorsCognitive impairmentBrain functionFemale ratsAntipsychotic drugsReceptor lossAntispychotic drugsCurrent studyAlzheimer's disease