2025
Linking prolonged childhood and adolescent loneliness to schizophrenia spectrum disorders: results from EU-GEI study.
Andreu-Bernabeu Á, González-Peñas J, Mora A, Bernardo M, Mezquida G, Amoretti S, Bobes J, Saiz P, García-Portilla M, Sanjuan J, Santos J, Jiménez-López E, Arrojo M, Carracedo A, Parellada M, Maric N, Atbaşoğlu C, Üçok A, Alptekin K, Saka M, Pries L, O'Donovan M, van Os J, Rutten B, Delespaul P, Guloksuz S, Arango C, Díaz-Caneja C. Linking prolonged childhood and adolescent loneliness to schizophrenia spectrum disorders: results from EU-GEI study. The British Journal Of Psychiatry 2025, 1-9. PMID: 40519115, DOI: 10.1192/bjp.2025.100.Peer-Reviewed Original ResearchGene-environment interactionsGenetic riskSchizophrenia spectrum disordersAdverse mental health outcomesGenetic liabilityAssociated with higher oddsPolygenic risk scoresIdentification of high-risk individualsMental health outcomesRelative excess riskHigh-risk individualsEU-GEILogistic regression modelsHealth outcomesExcess riskHigher oddsPrevention strategiesVulnerable populationsRisk scoreRegression modelsLonelinessEarly identificationLong-term effectsWorsening symptomsAssociated with psychosisBrain Age Disparities in Psychosis Across DSM Diagnoses and B-SNIP Biotypes
Promet L, Meda S, Alliey-Rodriguez N, Clementz B, Gershon E, Hill S, Ivleva E, Keedy S, Keshavan M, McDowell J, Parker D, Tamminga C, Pearlson G. Brain Age Disparities in Psychosis Across DSM Diagnoses and B-SNIP Biotypes. Schizophrenia Bulletin 2025, sbaf022. PMID: 40448350, DOI: 10.1093/schbul/sbaf022.Peer-Reviewed Original ResearchBrain age gapBipolar-Schizophrenia NetworkDSM diagnosesBrain agingPRS-SZComorbid disordersNon-psychotic first-degree relativesHealthy controlsAssociated with symptom severityPsychotic bipolar disorderSubtypes of psychosisStructural T1-weighted imagesBrain structural differencesPsychotropic medication useSchizoaffective disorderPsychosis probandsPsychotic disordersBipolar disorderPolygenic risk scoresSymptom severityFirst-degree relativesPsychosisAge gapDSMIntermediate phenotypesThe Eating Disorders Genetics Initiative 2 (EDGI2): study protocol
Berthold N, MacDermod C, Thornton L, Parker R, Morales S, Hog L, Kennedy H, Guintivano J, Sullivan P, Crowley J, Johnson J, Birgegård A, Fundín B, Frans E, Xu J, “Ngāti Pūkenga” M, Miller A, Aguilar M, Barakat S, Abdulkadir M, White J, Larsen J, Trujillo E, Winterman B, Zhang R, Lawson R, Wonderlich S, Wonderlich J, Schaefer L, Mehler P, Oakes J, Foster M, Gaudiani J, Vacuán E, Compte E, Petersen L, Yilmaz Z, Micali N, Jordan J, Kennedy M, Maguire S, Huckins L, Lu Y, Dinkler L, Martin N, Bulik C. The Eating Disorders Genetics Initiative 2 (EDGI2): study protocol. BMC Psychiatry 2025, 25: 532. PMID: 40419993, PMCID: PMC12105188, DOI: 10.1186/s12888-025-06777-5.Peer-Reviewed Original ResearchConceptsPolygenic risk scoresAvoidant/restrictive food intake disorderCalculate polygenic risk scoresNational Patient RegisterPsychiatric Genomics ConsortiumEating disordersLongstanding illnessEating Disorders Working GroupUnited StatesPatient RegisterCase-controlNew ZealandCase identificationGenetic architectureEvaluate clinical outcomesFood intake disorderRisk scoreClinically relevant phenotypesStudy protocolQuestionnaire batteryFunctional biologySymptom levelsAncestral backgroundMetabolic traitsGenomics ConsortiumPolygenic risks for depression and neural responses to reward and punishment in young adults
Chen Y, Li H, Luo X, Li G, Ide J, Li C. Polygenic risks for depression and neural responses to reward and punishment in young adults. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2025 PMID: 40412620, DOI: 10.1016/j.bpsc.2025.05.008.Peer-Reviewed Original ResearchPolygenic risk scoresPunishment processingNeural responsesAchenbach Adult Self-ReportInfluence of genetic riskCortical activityAdult Self-ReportYoung adultsGenetic riskRisk of depressionGambling TaskAberrant rewardDrinking severityHuman Connectome ProjectDepression severityPublished routinesBrain responsesPolygenic riskDepression scoresSelf-reportDepressionConnectome ProjectRewardBrain imagingPunishmentBody fluid biomarkers and psychosis risk in The Accelerating Medicines Partnership® Schizophrenia Program: design considerations
Perkins D, Jeffries C, Clark S, Upthegrove R, Wannan C, Wray N, Li Q, Do K, Walker E, Paul Amminger G, Anticevic A, Cotter D, Ellman L, Mongan D, Phassouliotis C, Barbee J, Roth S, Billah T, Corcoran C, Calkins M, Cerrato F, Khadimallah I, Klauser P, Winter-van Rossum I, Nunez A, Bleggi R, Martin A, Bouix S, Pasternak O, Shah J, Toben C, Wolf D, Kahn R, Kane J, McGorry P, Bearden C, Nelson B, Shenton M, Woods S. Body fluid biomarkers and psychosis risk in The Accelerating Medicines Partnership® Schizophrenia Program: design considerations. Schizophrenia 2025, 11: 78. PMID: 40399418, PMCID: PMC12095529, DOI: 10.1038/s41537-025-00610-4.Peer-Reviewed Original ResearchClinical outcomesPsychosis riskChronic systemic inflammationLevels of biomarkersResults of bloodTwo-month follow-upSystemic inflammationSaliva levelsSalivary cortisol levelsFollow-upCollection of bloodBody fluid biomarkersCHR criteriaSchizophrenia ProgramPolygenic risk scoresRisk scoreMental disordersBlood proteomeSchizophreniaPreanalytical factorsBiomarkersBloodPolygenic scoresSaliva samplesCortisol levelsThe effects of alcohol use severity and polygenic risk on gray matter volumes in young adults
Chen Y, Li H, Luo X, Li G, Ide J, Li C. The effects of alcohol use severity and polygenic risk on gray matter volumes in young adults. Frontiers In Psychiatry 2025, 16: 1560053. PMID: 40433172, PMCID: PMC12106418, DOI: 10.3389/fpsyt.2025.1560053.Peer-Reviewed Original ResearchGray matter volumeAlcohol use severityPolygenic risk scoresAlcohol dependenceMatter volumeAlcohol misuseGenetic riskRegional gray matter volumeVoxel-based morphometry analysisStudies of alcohol dependencePosterior orbitofrontal cortexEffects of alcohol exposureSemi-Structured AssessmentGenetics of AlcoholismRisk of alcohol misuseAlcohol use behaviorsChronic alcohol consumptionHuman Connectome Project dataOrbitofrontal cortexSalience circuitsDrinking severityNeurotypical adultsRight insulaLingual gyriMorphometry analysisThree-year lifestyle changes, genetic risk, and risk of frailty among older adults: A national community-based cohort study
Zhong W, Wang X, Song W, Chen H, Xie J, Yan H, Wang J, Lv Y, Li Z, Shi X, Mao C. Three-year lifestyle changes, genetic risk, and risk of frailty among older adults: A national community-based cohort study. Clinical Nutrition 2025, 50: 29-37. PMID: 40367593, DOI: 10.1016/j.clnu.2025.04.033.Peer-Reviewed Original ResearchConceptsRisk of frailtyGenetic riskHealthy lifestyleUnhealthy lifestyleOlder adultsFrailty riskLate-lifeLifestyle changesChinese Longitudinal Healthy Longevity SurveyCommunity-based cohort studyHazard ratioPolygenic risk scoresGenetic risk groupsModerate-to-moderatelyCox proportional hazards regression modelsProportional hazards regression modelsLifestyle scoreHazards regression modelsLongevity SurveyHigh frailty riskPrevent frailtyLifestyle factorsFrailty indexCohort studyLifestyle combinationThe association between cannabis use and suicidal intensity in psychiatric inpatients
Oladunjoye A, Swann A, Kosten T, Patriquin M, Bigdeli T, Barr P, Wilkinson A, Harding M, Nielsen D, Graham D. The association between cannabis use and suicidal intensity in psychiatric inpatients. American Journal On Addictions 2025 PMID: 40349103, DOI: 10.1111/ajad.70047.Peer-Reviewed Original ResearchSuicidal ideation intensityCannabis usePsychiatric inpatientsPsychological flexibilityColumbia-Suicide Severity Rating ScaleAssociated with cannabis useSuicidal intensityMale psychiatric inpatientsSubstance Involvement Screening TestSeverity Rating ScaleModel of moderationEmotion regulationPsychiatric comorbidityPolygenic risk scoresPath analysis modelSuicidal ideationSuicide attemptsRating ScaleSex-specific patternsPotential mediatorsSuicideInpatientsAssociated with greater riskCannabisAdolescentsOptimism moderates the relationship between inflammatory polygenic risk and major depressive disorder in U.S. Military veterans
Fischer I, Overstreet C, Cabrera-Mendoza B, Qiu D, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Optimism moderates the relationship between inflammatory polygenic risk and major depressive disorder in U.S. Military veterans. The World Journal Of Biological Psychiatry 2025, 26: 189-198. PMID: 40343713, DOI: 10.1080/15622975.2025.2498352.Peer-Reviewed Original ResearchConceptsMajor depressive disorderU.S. military veteransPolygenic risk scoresDepressive disorderMilitary veteransMajor depressive disorder riskPsychosocial moderatorsMDD screeningLow optimismPolygenic riskHigher optimismNationally representative sampleTrauma burdenPredisposition to inflammationStandard deviation increaseUK BiobankGenetic riskPathway-based analysisVeteransIncreased oddsRepresentative sampleRisk scoreMedical conditionsInflammatory biomarkersChronic inflammationSex-specific genetic effects on susceptibility to idiopathic pulmonary fibrosis
Leavy O, Goemans A, Hernandez-Beeftink T, Stockwell A, Allen R, Guillen-Guio B, Adegunsoye A, Booth H, Fahy W, Fingerlin T, Virk H, Hall I, Hart S, Hill M, Hirani N, Kaminski N, Ma S, McAnulty R, Sheng X, Millar A, Molina-Molina M, Navaratnam V, Neighbors M, Parfrey H, Saini G, Sayers I, Strek M, Tobin M, Whyte M, Zhang Y, Maher T, Molyneaux P, Oldham J, Yaspan B, Flores C, Martinez F, Reynolds C, Schwartz D, Noth I, Jenkins R, Wain L. Sex-specific genetic effects on susceptibility to idiopathic pulmonary fibrosis. ERJ Open Research 2025, 00200-2025. DOI: 10.1183/23120541.00200-2025.Peer-Reviewed Original ResearchPolygenic risk scoresIdiopathic pulmonary fibrosis riskGenetic association signalsIdiopathic pulmonary fibrosis susceptibilitySNP-based polygenic risk scoresAssociation signalsSex-specific genetic effectsGenetic risk predictionEvaluate genetic risksSex-specific associationsStudy meta-analysisEuropean genetic ancestryCase-control studyIdiopathic pulmonary fibrosisChronic lung conditionsGenetic riskAutosomal variantsSusceptibility to idiopathic pulmonary fibrosisRisk scoreGenetic ancestryDiagnostic biasAssociation resultsClinical prediction modelGenetic variantsMeta-analysis507. Polygenic Risk Scores Among Cognitive Subtypes of Psychosis Probands and Their Unaffected Relatives: A BSNIP Study
Charpentier J, Meda S, Dykins M, Hill S, Clementz B, McDowell J, Keedy S, Ivleva E, Tamminga C, Keshavan M, Pearlson G. 507. Polygenic Risk Scores Among Cognitive Subtypes of Psychosis Probands and Their Unaffected Relatives: A BSNIP Study. Biological Psychiatry 2025, 97: s306. DOI: 10.1016/j.biopsych.2025.02.746.Peer-Reviewed Original ResearchA genetically informed brain atlas for enhancing brain imaging genomics
Bao J, Wen J, Chang C, Mu S, Chen J, Shivakumar M, Cui Y, Erus G, Yang Z, Yang S, Wen Z, Zhao Y, Kim D, Duong-Tran D, Saykin A, Zhao B, Davatzikos C, Long Q, Shen L. A genetically informed brain atlas for enhancing brain imaging genomics. Nature Communications 2025, 16: 3524. PMID: 40229250, PMCID: PMC11997130, DOI: 10.1038/s41467-025-57636-6.Peer-Reviewed Original ResearchConceptsBrain imaging genomicsImaging genomicsComplex traits/diseasesSNP heritabilityFunctional annotationGenetic architecturePolygenic risk scoresGenomic investigationsGenetic ancestryDiscovery powerBrain atlasesHuman brain structureGenetic determinantsNeuroanatomical heterogeneityGenomeNeuroanatomical variationImaging endophenotypesBrain structuresMolecular levelBrain voxelsHeritabilityPhenotypic correlationsGiant regionGeneticsBrain conditionsLow Stability and Specificity of Polygenic Risk Scores for Major Psychiatric Disorders Limit their Clinical Utility
Mollon J, Schultz L, Knowles E, Jacquemont S, Glahn D, Almasy L. Low Stability and Specificity of Polygenic Risk Scores for Major Psychiatric Disorders Limit their Clinical Utility. Biological Psychiatry 2025 PMID: 40113122, DOI: 10.1016/j.biopsych.2025.03.006.Peer-Reviewed Original ResearchAlcohol use disorderPolygenic risk scoresSchizophrenia polygenic risk scoresPercentage of individualsHigh riskDepressive disorderLack of clinical utilityUse disorderValidity of polygenic risk scoresSchizophreniaClinical utilityMDDRisk scoreEffect sizeSNP effect sizesWhite British individualsDisordersHigh-risk individualsUK BiobankType 2 diabetesBritish individualsPRS-CSIndividualsT2DPsychiatryPolygenic score integrating neurodegenerative and vascular risk informs dementia risk stratification
D'Aoust T, Clocchiatti‐Tuozzo S, Rivier C, Mishra A, Hachiya T, Grenier‐Boley B, Soumaré A, Duperron M, Le Grand Q, Bouteloup V, Proust‐Lima C, Samieri C, Neuffer J, Sargurupremraj M, Chêne G, Helmer C, Thibault M, Amouyel P, Lambert J, Kamatani Y, Jacqmin‐Gadda H, Tregouët D, Inouye M, Dufouil C, Falcone G, Debette S. Polygenic score integrating neurodegenerative and vascular risk informs dementia risk stratification. Alzheimer's & Dementia 2025, 21: e70014. PMID: 40042447, PMCID: PMC11881617, DOI: 10.1002/alz.70014.Peer-Reviewed Original ResearchConceptsOlder community-dwelling peopleCommunity-dwelling peopleDementia risk stratificationVascular contribution to dementiaAssociated with dementia riskGenetic riskDementia clinical trialsApo E4Polygenic risk scoresGenetic risk groupsHigh-risk individualsDementia riskImprove risk predictionEast Asian ancestryAD-PRSPopulation-basedPolygenic scoresRisk stratificationMemory-clinic patientsPrevention programsClinical risk factorsDementiaClinical participantsRisk scoreAlzheimer's diseaseAssociation of social relationships and genetic risk with frailty
Song W, Zhong W, Yan H, Li Z, Gao J, Wang X, Chen P, You F, Li C, Chen H, Xie J, Lv Y, Shi X, Mao C. Association of social relationships and genetic risk with frailty. American Journal Of Geriatric Psychiatry 2025 PMID: 40155233, DOI: 10.1016/j.jagp.2025.02.015.Peer-Reviewed Original ResearchPolygenic risk scoresFrailty riskGenetic riskMendelian randomizationOlder adultsChinese Longitudinal Healthy Longevity SurveyTwo-sample Mendelian randomizationAssociations of social relationshipsSocial relationshipsEffects of social relationshipsSocial activitiesCox proportional hazards modelsIncreased frailty riskLongevity SurveyHigh frailty riskProportional hazards modelUnfavorable relationshipSocial supportTwo-time pointsRisk scoreFrailtyHazards modelGenetic susceptibilityAdditive interactionSingle-nucleotideIndependent and joint effects of genomic and exposomic loads for schizophrenia on psychotic experiences in adolescents of European ancestry
Di Vincenzo M, Prachason T, Sampogna G, Arias-Magnasco A, Lin B, Pries L, van Os J, Rutten B, Barzilay R, Fiorillo A, Guloksuz S. Independent and joint effects of genomic and exposomic loads for schizophrenia on psychotic experiences in adolescents of European ancestry. Schizophrenia 2025, 11: 26. PMID: 39984505, PMCID: PMC11845623, DOI: 10.1038/s41537-025-00569-2.Peer-Reviewed Original ResearchRisk due to interactionDistressing psychotic experiencesExcess risk due to interactionPsychotic experiencesEuropean ancestryMultilevel logistic regression modelsPolygenic risk scoresAdditive interactionStrength of associationLogistic regression modelsEarly adolescenceJoint associationsExposome scoreIncreasing strength of associationSecondary outcomesRisk scorePrimary outcomeRegression modelsStudy dataAdolescent brainSchizophreniaAdolescentsFollow-upJoint effectsOutcomesExposome-Wide Gene-By-Environment Interaction Study of Psychotic Experiences in the UK Biobank
Lin B, Pries L, Arias-Magnasco A, Klingenberg B, Linden D, Blokland G, van der Meer D, Luykx J, Rutten B, Guloksuz S. Exposome-Wide Gene-By-Environment Interaction Study of Psychotic Experiences in the UK Biobank. Biological Psychiatry Global Open Science 2025, 5: 100460. PMID: 40206033, PMCID: PMC11981733, DOI: 10.1016/j.bpsgos.2025.100460.Peer-Reviewed Original ResearchGene-by-environment interactionsPRS-SCZUK BiobankExposome-wide association studyPsychotic experiencesPolygenic risk scoresAssociated with psychotic experiencesMental distressRisk scoreAssociation studiesSleep problemsBiobankAdditive interactionPsychosis riskAgnostic analysisCorrelation testXWASGenetic vulnerabilityDistressParticipantsScoresCorrelation analysisExposureStudyRiskObservational and Genetic Analyses of Traumatic Experiences and Endometriosis
Koller D, Løkhammer S, Goroshchuk O, Denner V, Stiltner B, Mitjans M, He J, Taylor H, Lawn R, Koenen K, Polimanti R. Observational and Genetic Analyses of Traumatic Experiences and Endometriosis. JAMA Psychiatry 2025, 82: 386-394. PMID: 39908042, PMCID: PMC11800128, DOI: 10.1001/jamapsychiatry.2024.4694.Peer-Reviewed Original ResearchPolygenic risk scoresLatent class analysisAssociated with increased oddsTraumatic experiencesImpact of childhoodIndividual-level dataCase-control studyStressful eventsGenetic predispositionTrauma-related outcomesUnaffected womenMain OutcomesFinnGen cohortRisk scoreAssociation of endometriosisPosttraumatic stress disorderTrauma eventsMeta-analysisSexual traumaAssociated with endometriosisContact traumaPotential associationStress disorderPsychological traumaPhenotypic associationsPolygenic Susceptibility to Diabetes and Poor Glycemic Control in Stroke Survivors
Demarais Z, Conlon C, Rivier C, Clocchiatti-Tuozzo S, Renedo D, Torres-Lopez V, Sheth K, Meeker D, Zhao H, Ohno-Machado L, Acosta J, Huo S, Falcone G. Polygenic Susceptibility to Diabetes and Poor Glycemic Control in Stroke Survivors. Neurology 2025, 104: e210276. PMID: 39889253, DOI: 10.1212/wnl.0000000000210276.Peer-Reviewed Original ResearchConceptsStroke survivorsWorse glycemic controlPoor glycemic controlStroke patientsAssociated with worse glycemic controlGlycemic controlPolygenic risk scoresClinical management of stroke patientsAssociated with poor glycemic controlManagement of stroke patientsCross-sectional designGenetic association studiesUncontrolled diabetesSusceptibility to T2DMUK BiobankType 2 diabetes mellitusAdverse vascular outcomesRisk scoreAssociation studiesHemoglobin A1cSurvivorsVascular outcomesSusceptibility to diabetesStrokeDiabetesThe Moderating Role of Genetic and Environmental Risk Factors for Schizophrenia on the Relationship between Autistic Traits and Psychosis Expression in the General Population
Dogan M, Prachason T, Lin B, Pries L, Arias-Magnasco A, Bortoletto R, Menne-Lothmann C, Decoster J, van Winkel R, Collip D, Delespaul P, De Hert M, Derom C, Thiery E, Jacobs N, van Os J, Rutten B, Brondino N, Colizzi M, Luykx J, Fusar-Poli L, Guloksuz S. The Moderating Role of Genetic and Environmental Risk Factors for Schizophrenia on the Relationship between Autistic Traits and Psychosis Expression in the General Population. Schizophrenia Bulletin Open 2025, 6: sgaf005. PMID: 40123716, PMCID: PMC11926675, DOI: 10.1093/schizbullopen/sgaf005.Peer-Reviewed Original ResearchPsychotic experiencesNegative life eventsAutistic traitsLife eventsCommunity Assessment of Psychic ExperiencesAssociated with psychotic experiencesAutism Spectrum QuotientModerating rolePsychosis expressionInteraction effectsPolygenic risk scoresRisk factorsEmotional neglectPsychic ExperiencesPhysical neglectModeration analysisCT subtypesAutism spectrumBonferroni correctionEmotional abuseGenetic overlapMultilevel linear regression modelsTrauma screeningSexual abusePhysical abuse
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