2024
Maternal Adverse Childhood Experiences and Biological Aging During Pregnancy and in Newborns
Dye C, Alschuler D, Wu H, Duarte C, Monk C, Belsky D, Lee S, O’Donnell K, Baccarelli A, Scorza P. Maternal Adverse Childhood Experiences and Biological Aging During Pregnancy and in Newborns. JAMA Network Open 2024, 7: e2427063. PMID: 39120899, PMCID: PMC11316241, DOI: 10.1001/jamanetworkopen.2024.27063.Peer-Reviewed Original ResearchConceptsMaternal adverse childhood experiencesAdverse childhood experiencesEdinburgh Postnatal Depression ScaleAccessible Resource for Integrated Epigenomics StudiesEpigenetic age accelerationGestational age accelerationAssociated with epigenetic agingAvon Longitudinal Study of ParentsLongitudinal Study of ParentsPostnatal Depression ScalePrimary outcomeChildhood experiencesAvon Longitudinal StudyEpigenetic ageStudy of ParentsAge accelerationHigher ACE scoresCross-sectional studyEpigenetic clocksMother-offspring dyadsDepression ScaleHealth districtMother-child dyadsDNA methylation–based epigenetic clocksInvestigate depression
2023
Maternal prenatal depression is associated with dysregulation over the first five years of life moderated by child polygenic risk for comorbid psychiatric problems
Babineau V, Jolicoeur‐Martineau A, Szekely E, Green C, Sassi R, Gaudreau H, Levitan R, Lydon J, Steiner M, O'Donnell K, Kennedy J, Burack J, Wazana A. Maternal prenatal depression is associated with dysregulation over the first five years of life moderated by child polygenic risk for comorbid psychiatric problems. Developmental Psychobiology 2023, 65: e22395. PMID: 37338256, DOI: 10.1002/dev.22395.Peer-Reviewed Original ResearchConceptsMaternal prenatal depressionPolygenic risk scoresPrenatal depressionPsychiatric problemsChild psychiatric problemsComorbid psychiatric problemsChildhood psychiatric problemsMajor depressive disorderHigher dysregulationYears of lifeAttention deficit hyperactivity disorderDeficit hyperactivity disorderWeeks' gestationPsychiatric comorbidityPrenatal cohortDepressive disorderPostnatal depressionRisk scorePrenatal stressDepression symptomsMaternal educationGreater riskHyperactivity disorderDysregulationPolygenic risk
2021
Maternal Prenatal Anxiety and the Fetal Origins of Epigenetic Aging
McGill MG, Pokhvisneva I, Clappison AS, McEwen LM, Beijers R, Tollenaar MS, Pham H, Kee MZL, Garg E, de Mendonça Filho EJ, Karnani N, Silveira PP, Kobor MS, de Weerth C, Meaney MJ, O'Donnell KJ. Maternal Prenatal Anxiety and the Fetal Origins of Epigenetic Aging. Biological Psychiatry 2021, 91: 303-312. PMID: 34756561, DOI: 10.1016/j.biopsych.2021.07.025.Peer-Reviewed Original ResearchConceptsPrenatal maternal anxietyFetal originEpigenetic age accelerationMaternal anxietyAge accelerationPrenatal anxietyMental healthPrenatal maternal mental healthMaternal mental healthYears of ageGenetic risk factorsMonths of ageMental health supportMaternal prenatal anxietyRisk factorsLongitudinal cohortPrenatal adversityPregnant individualsLarge effect sizesLongitudinal assessmentHealth supportEffective mental health supportCohortPrenatal environmentLate childhoodImpact of parental socioeconomic status on offspring’s mental health: protocol for a longitudinal community-based study
Li M, O'Donnell KJ, Caron J, D'Arcy C, Meng X. Impact of parental socioeconomic status on offspring’s mental health: protocol for a longitudinal community-based study. BMJ Open 2021, 11: e038409. PMID: 33593762, PMCID: PMC7888321, DOI: 10.1136/bmjopen-2020-038409.Peer-Reviewed Original ResearchConceptsOffspring's mental healthEpigenetic Age Acceleration and Risk for Posttraumatic Stress Disorder following Exposure to Substantiated Child Maltreatment
Shenk CE, O’Donnell K, Pokhvisneva I, Kobor MS, Meaney MJ, Bensman HE, Allen EK, Olson AE. Epigenetic Age Acceleration and Risk for Posttraumatic Stress Disorder following Exposure to Substantiated Child Maltreatment. Journal Of Clinical Child & Adolescent Psychology 2021, 51: 651-661. PMID: 33471576, PMCID: PMC8289945, DOI: 10.1080/15374416.2020.1864738.Peer-Reviewed Original ResearchDCC gene network in the prefrontal cortex is associated with total brain volume in childhood
Morgunova A, Pokhvisneva I, Nolvi S, Entringer S, Wadhwa P, Gilmore J, Styner M, Buss C, Sassi RB, Hall GBC, O'Donnell KJ, Meaney MJ, Silveira PP, Flores CA. DCC gene network in the prefrontal cortex is associated with total brain volume in childhood. Journal Of Psychiatry And Neuroscience 2021, 46: e154-e163. PMID: 33206040, PMCID: PMC7955849, DOI: 10.1503/jpn.200081.Peer-Reviewed Original ResearchConceptsTotal brain volumeExpression-based polygenic risk scoreBrain volumePrefrontal cortexSingle nucleotide polymorphismsHigher total brain volumeCommunity-based cohortChildren 1.5Polygenic risk scoresMaternal adversityRisk scoreIndependent cohortReplication cohortCohortCortexBrain developmentChildren 8Donor databaseSmall sample sizeEffect sizeReplication analysis
2020
Genetically predicted gene expression of prefrontal DRD4 gene and the differential susceptibility to childhood emotional eating in response to positive environment
Barth B, Bizarro L, Miguel PM, Dubé L, Levitan R, O'Donnell K, Meaney MJ, Silveira PP. Genetically predicted gene expression of prefrontal DRD4 gene and the differential susceptibility to childhood emotional eating in response to positive environment. Appetite 2020, 148: 104594. PMID: 31927071, DOI: 10.1016/j.appet.2020.104594.Peer-Reviewed Original ResearchMeSH KeywordsAdultChild BehaviorChild DevelopmentChild, PreschoolCohort StudiesEatingEmotionsFamily ConflictFeeding BehaviorFemaleGene ExpressionGenetic Predisposition to DiseaseHumansHyperphagiaInfantInfant, NewbornMachine LearningMaleMother-Child RelationsMothersObesityReceptors, Dopamine D4SingaporeSocial EnvironmentConceptsPositive environmentEmotional eatingEating Behavior QuestionnaireChildren's Eating Behaviour QuestionnaireGenetic differential susceptibilityDopamine D4 receptor geneD4 receptor geneBehavior QuestionnaireMonths of agePositive outcomesDRD4 genePositive settingEatingDifferential susceptibilityMAVANFurther evidenceOutcome measuresDRD4Susceptibility stateAdverse environmentsIndividualsQuestionnaireMeasuresDesireEvidence
2019
The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells
McEwen LM, O'Donnell KJ, McGill MG, Edgar RD, Jones MJ, MacIsaac JL, Lin DTS, Ramadori K, Morin A, Gladish N, Garg E, Unternaehrer E, Pokhvisneva I, Karnani N, Kee MZL, Klengel T, Adler NE, Barr RG, Letourneau N, Giesbrecht GF, Reynolds JN, Czamara D, Armstrong JM, Essex MJ, de Weerth C, Beijers R, Tollenaar MS, Bradley B, Jovanovic T, Ressler KJ, Steiner M, Entringer S, Wadhwa PD, Buss C, Bush NR, Binder EB, Boyce WT, Meaney MJ, Horvath S, Kobor MS. The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 117: 23329-23335. PMID: 31611402, PMCID: PMC7519312, DOI: 10.1073/pnas.1820843116.Peer-Reviewed Original ResearchIntegrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
Czamara D, Eraslan G, Page CM, Lahti J, Lahti-Pulkkinen M, Hämäläinen E, Kajantie E, Laivuori H, Villa PM, Reynolds RM, Nystad W, Håberg SE, London SJ, O’Donnell K, Garg E, Meaney MJ, Entringer S, Wadhwa PD, Buss C, Jones MJ, Lin DTS, MacIsaac JL, Kobor MS, Koen N, Zar HJ, Koenen KC, Dalvie S, Stein DJ, Kondofersky I, Müller NS, Theis FJ, Räikkönen K, Binder E. Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns. Nature Communications 2019, 10: 2548. PMID: 31186427, PMCID: PMC6559955, DOI: 10.1038/s41467-019-10461-0.Peer-Reviewed Original ResearchConceptsDNA methylationEnvironmental factorsCellular functionsEpigenetic processesCord blood DNA methylationBlood DNA methylationMethylationGenetic variantsGenetic contributionIntegrated analysisPrenatal environmental factorsComplex disorderGenetic influencesGxE modelsGenotypesGWASRelative contributionGxEIndependent cohortCpGDisease riskEnrichmentVariantsPrefrontal Cortex Dopamine Transporter Gene Network Moderates the Effect of Perinatal Hypoxic-Ischemic Conditions on Cognitive Flexibility and Brain Gray Matter Density in Children
Miguel PM, Pereira LO, Barth B, de Mendonça Filho EJ, Pokhvisneva I, Nguyen TTT, Garg E, Razzolini BR, Koh DXP, Gallant H, Sassi RB, Hall GBC, O'Donnell KJ, Meaney MJ, Silveira PP. Prefrontal Cortex Dopamine Transporter Gene Network Moderates the Effect of Perinatal Hypoxic-Ischemic Conditions on Cognitive Flexibility and Brain Gray Matter Density in Children. Biological Psychiatry 2019, 86: 621-630. PMID: 31142432, DOI: 10.1016/j.biopsych.2019.03.983.Peer-Reviewed Original ResearchConceptsExpression-based polygenic risk scoreGray matter densityBrain gray matter densityPrefrontal cortexHypoxic-ischemic conditionsHistory of exposurePrefrontal cortex expressionExecutive functionIdentification of childrenHypoxia-ischemiaPerinatal complicationsHealthy childrenRisk factorsPolygenic risk scoresHigh riskRisk scoreDopamine reuptakeBirth cohortCortex expressionPoor oxygenationImpaired executive functionBrain developmentGenetic polymorphismsA biologically-informed polygenic score identifies endophenotypes and clinical conditions associated with the insulin receptor function on specific brain regions
Dass S, McCracken K, Pokhvisneva I, Chen LM, Garg E, Nguyen TTT, Wang Z, Barth B, Yaqubi M, McEwen LM, MacIsaac JL, Diorio J, Kobor MS, O'Donnell KJ, Meaney MJ, Silveira PP. A biologically-informed polygenic score identifies endophenotypes and clinical conditions associated with the insulin receptor function on specific brain regions. EBioMedicine 2019, 42: 188-202. PMID: 30922963, PMCID: PMC6491717, DOI: 10.1016/j.ebiom.2019.03.051.Peer-Reviewed Original ResearchMeSH KeywordsBrainEndophenotypesFemaleGene Expression ProfilingGene Expression RegulationGene Regulatory NetworksGenetic Association StudiesGenetic Predisposition to DiseaseGenome-Wide Association StudyHippocampusHumansMalePhenotypePolymorphism, Single NucleotideReceptor, InsulinReproducibility of ResultsConceptsCognitive performancePolygenic scoresRelated mental disordersChild impulsivityIndividual differencesSpecific brain regionsInhibitory controlNeurobiological mechanismsCommunity sampleBrain regionsConventional GWASMesocorticolimbic systemImpulsivityMental disordersPsychopathologyAddictionNeural functionEndophenotypesAlzheimer's diseaseScoresADHDDisordersMemoryFunctioningGenetic scoreDynamic DNA methylation changes in the maternal oxytocin gene locus (OXT) during pregnancy predict postpartum maternal intrusiveness
Toepfer P, O'Donnell KJ, Entringer S, Garg E, Heim CM, Lin DTS, MacIsaac JL, Kobor MS, Meaney MJ, Provençal N, Binder EB, Wadhwa PD, Buss C. Dynamic DNA methylation changes in the maternal oxytocin gene locus (OXT) during pregnancy predict postpartum maternal intrusiveness. Psychoneuroendocrinology 2019, 103: 156-162. PMID: 30690225, PMCID: PMC6554513, DOI: 10.1016/j.psyneuen.2019.01.013.Peer-Reviewed Original ResearchConceptsLate pregnancyMaternal behaviorMonths postpartumEarly postnatal developmentNovel potential biomarkersRace/ethnicityPregnancy inducesPeripheral bloodPregnancyMother-child dyadsPostnatal maternal behaviourPostnatal developmentPotential biomarkersSteroid hormonesDNA methylationSocioeconomic statusWhole bloodPromoter DNA methylationMother-child interactionPostpartumBloodDNA methylation changesOxytocinDNAm trajectoriesMaternal intrusiveness
2018
Maternal antenatal mood and child development: an exploratory study of treatment effects on child outcomes up to 5 years
Milgrom J, Holt CJ, Bleker LS, Holt C, Ross J, Ericksen J, Glover V, O’Donnell K, de Rooij SR, Gemmill AW. Maternal antenatal mood and child development: an exploratory study of treatment effects on child outcomes up to 5 years. Journal Of Developmental Origins Of Health And Disease 2018, 10: 221-231. PMID: 30303063, DOI: 10.1017/s2040174418000739.Peer-Reviewed Original ResearchMeSH KeywordsAnxietyBehavior Rating ScaleChild BehaviorChild DevelopmentChild, PreschoolCognitive Behavioral TherapyDepressionFemaleFollow-Up StudiesHumansIntelligence TestsLongitudinal StudiesMaleMothersParent-Child RelationsPregnancyPregnancy ComplicationsPrenatal Exposure Delayed EffectsRandomized Controlled Trials as TopicSeverity of Illness IndexTreatment OutcomeConceptsChild Behavior ChecklistParenting Stress IndexNeurodevelopmental outcomesChild developmentHigher CBCLIntervention effectsAntenatal depression treatmentMaternal antenatal depressionAdverse neurodevelopmental outcomesInfant neurodevelopmental outcomesAge 2Age 5Cognitive behavioral therapyWPPSI-III scoresNon-significant trendPSI total scoreAntenatal moodAntenatal depressionRoutine careDepression treatmentOriginal cohortTreatment allocationIntervention groupLong-term effectsEffective treatmentPolygenic differential susceptibility to prenatal adversity
Belsky J, Pokhvisneva I, Rema ASS, Broekman BFP, Pluess M, O'Donnell KJ, Meaney MJ, Silveira PP. Polygenic differential susceptibility to prenatal adversity. Development And Psychopathology 2018, 31: 439-441. PMID: 30081968, DOI: 10.1017/s0954579418000378.Peer-Reviewed Original ResearchThe early care environment and DNA methylome variation in childhood
Garg E, Chen L, Nguyen TTT, Pokhvisneva I, Chen LM, Unternaehrer E, MacIsaac JL, McEwen LM, Mah SM, Gaudreau H, Levitan R, Moss E, Sokolowski MB, Kennedy JL, Steiner MS, Meaney MJ, Holbrook JD, Silveira PP, Karnani N, Kobor MS, O'Donnell KJ. The early care environment and DNA methylome variation in childhood. Development And Psychopathology 2018, 30: 891-903. PMID: 30068421, DOI: 10.1017/s0954579418000627.Peer-Reviewed Original ResearchConceptsGenome-wide DNA methylationDNA methylationGenetic variationGenetic dataEarly care environmentsMethylome variationInfant attachment styleInfant attachmentEpigenetic modificationsAttachment styleBuccal epithelial samplesMethylationMolecular signaturesPrenatal adversityGenetic contributionInfant developmentChild genetic variationInfant cognitive developmentDisorganized attachment styleLater mental health problemsNegative effectsEarly intervention programsChild mental healthMental health problemsCognitive developmentAssociations between maternal prenatal cortisol and fetal growth are specific to infant sex: findings from the Wirral Child Health and Development Study
Braithwaite EC, Hill J, Pickles A, Glover V, O’Donnell K, Sharp H. Associations between maternal prenatal cortisol and fetal growth are specific to infant sex: findings from the Wirral Child Health and Development Study. Journal Of Developmental Origins Of Health And Disease 2018, 9: 425-431. PMID: 29631648, PMCID: PMC6075696, DOI: 10.1017/s2040174418000181.Peer-Reviewed Original ResearchConceptsInfant birth weightBirth weightPrenatal cortisolMaternal prenatal cortisolWirral Child HealthFetal growthChild healthAffective disordersDevelopment Study cohortGeneral population estimatesSex-dependent mannerSex-specific mechanismsInverse probability weightsSex-specific effectsCurve cortisolWeeks' gestationGestational ageHospital recordsStudy cohortRisk stratifierFetal programmingGeneral populationGlucocorticoid mechanismsSignificant associationCortisolAgreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and time
Forest M, O'Donnell KJ, Voisin G, Gaudreau H, MacIsaac JL, McEwen LM, Silveira PP, Steiner M, Kobor MS, Meaney MJ, Greenwood CMT. Agreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and time. Epigenetics 2018, 13: 19-32. PMID: 29381404, PMCID: PMC5837078, DOI: 10.1080/15592294.2017.1411443.Peer-Reviewed Original ResearchBrain-Derived Neurotrophic FactorCanadaCatechol O-MethyltransferaseDNA MethylationDried Blood Spot TestingEpigenesis, GeneticFemaleHumansMaleMouth MucosaNetherlandsOligonucleotide Array Sequence AnalysisReceptors, Dopamine D2Receptors, Dopamine D4Receptors, OxytocinReproducibility of ResultsSerotonin Plasma Membrane Transport ProteinsTime Factors
2017
Cumulative prenatal exposure to adversity reveals associations with a broad range of neurodevelopmental outcomes that are moderated by a novel, biologically informed polygenetic score based on the serotonin transporter solute carrier family C6, member 4 (SLC6A4) gene expression
Silveira PP, Pokhvisneva I, Parent C, Cai S, Rema ASS, Broekman BFP, Rifkin-Graboi A, Pluess M, O'Donnell KJ, Meaney MJ. Cumulative prenatal exposure to adversity reveals associations with a broad range of neurodevelopmental outcomes that are moderated by a novel, biologically informed polygenetic score based on the serotonin transporter solute carrier family C6, member 4 (SLC6A4) gene expression. Development And Psychopathology 2017, 29: 1601-1617. PMID: 29162172, DOI: 10.1017/s0954579417001262.Peer-Reviewed Original ResearchConceptsEarly life adversityNeurodevelopmental outcomesPrenatal adversityChild Behavior ChecklistGenetic scoreAdversity scoreLife adversityCommunity birth cohortYears of agePervasive developmental problemsMaternal smokingGestational ageBirth weightLater riskPrenatal exposureAdverse exposuresBehavioral alterationsBirth cohortSerotonin transporter geneFetal periodPostnatal influencesPrefrontal cortexRelevant single nucleotide polymorphismsSerotonin transporterPrenatal lifeMaternal prenatal anxiety and child COMT genotype predict working memory and symptoms of ADHD
O'Donnell KJ, Glover V, Lahti J, Lahti M, Edgar RD, Räikkönen K, O'Connor TG. Maternal prenatal anxiety and child COMT genotype predict working memory and symptoms of ADHD. PLOS ONE 2017, 12: e0177506. PMID: 28614354, PMCID: PMC5470664, DOI: 10.1371/journal.pone.0177506.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAnxietyAttention Deficit Disorder with HyperactivityCatechol O-MethyltransferaseChildFemaleGene-Environment InteractionGenotypeHumansLongitudinal StudiesMaleMemory, Short-TermMothersPolymorphism, Single NucleotidePregnancyPrenatal Exposure Delayed EffectsProspective StudiesSelf ReportConceptsMaternal prenatal anxietySymptoms of ADHDPrenatal anxietyChildren's symptomsSelf-report measuresInter-individual differencesRs4680 genotypeIndividual differencesHyperactivity symptomsChildren's responsesADHDDevelopmental outcomesCOMT genotypeAnxietyAge 8 yearsMemoryVal/Val genotypeVal/ALSPAC cohortChild neurodevelopmentYears of ageFunctional genetic variationVal genotypeCOMTGene-environment interactionsDynamic interaction between fetal adversity and a genetic score reflecting dopamine function on developmental outcomes at 36 months
Bischoff AR, Pokhvisneva I, Léger É, Gaudreau H, Steiner M, Kennedy JL, O’Donnell K, Diorio J, Meaney MJ, Silveira PP, . Dynamic interaction between fetal adversity and a genetic score reflecting dopamine function on developmental outcomes at 36 months. PLOS ONE 2017, 12: e0177344. PMID: 28505190, PMCID: PMC5432105, DOI: 10.1371/journal.pone.0177344.Peer-Reviewed Original Research