2024
The association between aberrant salience and psychotic experiences in general population twins, and genetic vulnerability as a modifier
Drukker M, Todor T, Bongaarts J, Broggi E, Kelkar M, Wigglesworth T, Verhiel K, van Leeuwen K, Koster M, Derom C, Thiery E, De Hert M, Menne-Lothmann C, Decoster J, Collip D, van Winkel R, Jacobs N, Guloksuz S, Rutten B, van Os J. The association between aberrant salience and psychotic experiences in general population twins, and genetic vulnerability as a modifier. BMC Psychiatry 2024, 24: 736. PMID: 39462331, PMCID: PMC11515186, DOI: 10.1186/s12888-024-06176-2.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultDiseases in TwinsFemaleGenetic Predisposition to DiseaseHumansMaleMiddle AgedPsychotic DisordersTwinsYoung AdultConceptsAberrant salienceGeneral population twinsPsychotic experiencesGenetic vulnerabilityGeneral population samplePsychotic symptomsAssociated with psychotic experiencesUltra-high-risk patientsPositive symptom scalesSubclinical psychotic symptomsWhite noise taskEpisode psychosis patientsAssociated with psychosisPopulation samplePsychosis spectrumPsychosis patientsSymptom ScaleNoise taskSaliencePsychosisSevere endVulnerabilitySymptomsTaskAssociation
2022
Age- and sex-specific associations between risk scores for schizophrenia and self-reported health in the general population
Paquin V, Pries L, ten Have M, Bak M, Gunther N, de Graaf R, van Dorsselaer S, Lin B, van Eijk K, Kenis G, Richards A, O’Donovan M, Luykx J, Rutten B, van Os J, Shah J, Guloksuz S. Age- and sex-specific associations between risk scores for schizophrenia and self-reported health in the general population. Social Psychiatry And Psychiatric Epidemiology 2022, 58: 43-52. PMID: 35913550, PMCID: PMC9845157, DOI: 10.1007/s00127-022-02346-3.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedCohort StudiesFemaleGenetic Predisposition to DiseaseHumansMaleMiddle AgedRisk FactorsSchizophreniaSelf ReportYoung AdultConceptsSex-specific associationsSelf-reported healthPRS-SCZES-SCZPhysical healthGeneral populationNetherlands Mental Health SurveyIncidence Study-2Mental Health SurveyHealth SurveyRisk scoreAge 65Common genetic variantsHealth correlatesAge 18Poor healthOlder individualsMental healthPolygenic riskLinear mixed modelsAgeSexExposome scoreHealthAssociationPolygenic risk scores for predicting outcomes and treatment response in psychiatry: hope or hype?
Fusar-Poli L, Rutten B, van Os J, Aguglia E, Guloksuz S. Polygenic risk scores for predicting outcomes and treatment response in psychiatry: hope or hype? International Review Of Psychiatry 2022, 34: 663-675. PMID: 36786114, DOI: 10.1080/09540261.2022.2101352.Peer-Reviewed Original ResearchMeSH KeywordsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMental DisordersMultifactorial InheritancePsychiatryRisk FactorsConceptsPolygenic risk scoresTreatment responseRisk scoreMental disordersDetailed clinical characterizationPresent narrative reviewPotential clinical utilityMajor mental disordersIndividual genetic predispositionRisk stratificationPrognostic evaluationClinical characterizationWide association study datasetsClinical utilityGeneral populationGenetic predispositionNarrative reviewSingle nucleotide polymorphismsMapping genomic loci implicates genes and synaptic biology in schizophrenia
Trubetskoy V, Pardiñas A, Qi T, Panagiotaropoulou G, Awasthi S, Bigdeli T, Bryois J, Chen C, Dennison C, Hall L, Lam M, Watanabe K, Frei O, Ge T, Harwood J, Koopmans F, Magnusson S, Richards A, Sidorenko J, Wu Y, Zeng J, Grove J, Kim M, Li Z, Voloudakis G, Zhang W, Adams M, Agartz I, Atkinson E, Agerbo E, Al Eissa M, Albus M, Alexander M, Alizadeh B, Alptekin K, Als T, Amin F, Arolt V, Arrojo M, Athanasiu L, Azevedo M, Bacanu S, Bass N, Begemann M, Belliveau R, Bene J, Benyamin B, Bergen S, Blasi G, Bobes J, Bonassi S, Braun A, Bressan R, Bromet E, Bruggeman R, Buckley P, Buckner R, Bybjerg-Grauholm J, Cahn W, Cairns M, Calkins M, Carr V, Castle D, Catts S, Chambert K, Chan R, Chaumette B, Cheng W, Cheung E, Chong S, Cohen D, Consoli A, Cordeiro Q, Costas J, Curtis C, Davidson M, Davis K, de Haan L, Degenhardt F, DeLisi L, Demontis D, Dickerson F, Dikeos D, Dinan T, Djurovic S, Duan J, Ducci G, Dudbridge F, Eriksson J, Fañanás L, Faraone S, Fiorentino A, Forstner A, Frank J, Freimer N, Fromer M, Frustaci A, Gadelha A, Genovese G, Gershon E, Giannitelli M, Giegling I, Giusti-Rodríguez P, Godard S, Goldstein J, González Peñas J, González-Pinto A, Gopal S, Gratten J, Green M, Greenwood T, Guillin O, Gülöksüz S, Gur R, Gur R, Gutiérrez B, Hahn E, Hakonarson H, Haroutunian V, Hartmann A, Harvey C, Hayward C, Henskens F, Herms S, Hoffmann P, Howrigan D, Ikeda M, Iyegbe C, Joa I, Julià A, Kähler A, Kam-Thong T, Kamatani Y, Karachanak-Yankova S, Kebir O, Keller M, Kelly B, Khrunin A, Kim S, Klovins J, Kondratiev N, Konte B, Kraft J, Kubo M, Kučinskas V, Kučinskiene Z, Kusumawardhani A, Kuzelova-Ptackova H, Landi S, Lazzeroni L, Lee P, Legge S, Lehrer D, Lencer R, Lerer B, Li M, Lieberman J, Light G, Limborska S, Liu C, Lönnqvist J, Loughland C, Lubinski J, Luykx J, Lynham A, Macek M, Mackinnon A, Magnusson P, Maher B, Maier W, Malaspina D, Mallet J, Marder S, Marsal S, Martin A, Martorell L, Mattheisen M, McCarley R, McDonald C, McGrath J, Medeiros H, Meier S, Melegh B, Melle I, Mesholam-Gately R, Metspalu A, Michie P, Milani L, Milanova V, Mitjans M, Molden E, Molina E, Molto M, Mondelli V, Moreno C, Morley C, Muntané G, Murphy K, Myin-Germeys I, Nenadić I, Nestadt G, Nikitina-Zake L, Noto C, Nuechterlein K, O’Brien N, O’Neill F, Oh S, Olincy A, Ota V, Pantelis C, Papadimitriou G, Parellada M, Paunio T, Pellegrino R, Periyasamy S, Perkins D, Pfuhlmann B, Pietiläinen O, Pimm J, Porteous D, Powell J, Quattrone D, Quested D, Radant A, Rampino A, Rapaport M, Rautanen A, Reichenberg A, Roe C, Roffman J, Roth J, Rothermundt M, Rutten B, Saker-Delye S, Salomaa V, Sanjuan J, Santoro M, Savitz A, Schall U, Scott R, Seidman L, Sharp S, Shi J, Siever L, Sigurdsson E, Sim K, Skarabis N, Slominsky P, So H, Sobell J, Söderman E, Stain H, Steen N, Steixner-Kumar A, Stögmann E, Stone W, Straub R, Streit F, Strengman E, Stroup T, Subramaniam M, Sugar C, Suvisaari J, Svrakic D, Swerdlow N, Szatkiewicz J, Ta T, Takahashi A, Terao C, Thibaut F, Toncheva D, Tooney P, Torretta S, Tosato S, Tura G, Turetsky B, Üçok A, Vaaler A, van Amelsvoort T, van Winkel R, Veijola J, Waddington J, Walter H, Waterreus A, Webb B, Weiser M, Williams N, Witt S, Wormley B, Wu J, Xu Z, Yolken R, Zai C, Zhou W, Zhu F, Zimprich F, Atbaşoğlu E, Ayub M, Benner C, Bertolino A, Black D, Bray N, Breen G, Buccola N, Byerley W, Chen W, Cloninger C, Crespo-Facorro B, Donohoe G, Freedman R, Galletly C, Gandal M, Gennarelli M, Hougaard D, Hwu H, Jablensky A, McCarroll S, Moran J, Mors O, Mortensen P, Müller-Myhsok B, Neil A, Nordentoft M, Pato M, Petryshen T, Pirinen M, Pulver A, Schulze T, Silverman J, Smoller J, Stahl E, Tsuang D, Vilella E, Wang S, Xu S, Adolfsson R, Arango C, Baune B, Belangero S, Børglum A, Braff D, Bramon E, Buxbaum J, Campion D, Cervilla J, Cichon S, Collier D, Corvin A, Curtis D, Forti M, Domenici E, Ehrenreich H, Escott-Price V, Esko T, Fanous A, Gareeva A, Gawlik M, Gejman P, Gill M, Glatt S, Golimbet V, Hong K, Hultman C, Hyman S, Iwata N, Jönsson E, Kahn R, Kennedy J, Khusnutdinova E, Kirov G, Knowles J, Krebs M, Laurent-Levinson C, Lee J, Lencz T, Levinson D, Li Q, Liu J, Malhotra A, Malhotra D, McIntosh A, McQuillin A, Menezes P, Morgan V, Morris D, Mowry B, Murray R, Nimgaonkar V, Nöthen M, Ophoff R, Paciga S, Palotie A, Pato C, Qin S, Rietschel M, Riley B, Rivera M, Rujescu D, Saka M, Sanders A, Schwab S, Serretti A, Sham P, Shi Y, St Clair D, Stefánsson H, Stefansson K, Tsuang M, van Os J, Vawter M, Weinberger D, Werge T, Wildenauer D, Yu X, Yue W, Holmans P, Pocklington A, Roussos P, Vassos E, Verhage M, Visscher P, Yang J, Posthuma D, Andreassen O, Kendler K, Owen M, Wray N, Daly M, Huang H, Neale B, Sullivan P, Ripke S, Walters J, O’Donovan M. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature 2022, 604: 502-508. PMID: 35396580, PMCID: PMC9392466, DOI: 10.1038/s41586-022-04434-5.Peer-Reviewed Original ResearchMeSH KeywordsAllelesGenetic Predisposition to DiseaseGenome-Wide Association StudyGenomicsHumansPolymorphism, Single NucleotideSchizophreniaConceptsGenomic lociTwo-stage genome-wide association studyVariant associationsDistinct genomic lociGenome-wide association studiesTranscription factor Sp4Functional genomics dataCommon variant associationsRare variant associationsCommon risk allelesSynaptic biologyGenomic dataBiological processesAssociation studiesGenesCell typesNeurodevelopmental disordersRegion variationLociFundamental processesNeuronal functionSuch variantsRisk allelesMechanistic studiesVariants
2020
Association of Recent Stressful Life Events With Mental and Physical Health in the Context of Genomic and Exposomic Liability for Schizophrenia
Pries L, van Os J, Have M, de Graaf R, van Dorsselaer S, Bak M, Lin B, van Eijk K, Kenis G, Richards A, O’Donovan M, Luykx J, Rutten B, Guloksuz S. Association of Recent Stressful Life Events With Mental and Physical Health in the Context of Genomic and Exposomic Liability for Schizophrenia. JAMA Psychiatry 2020, 77: 1296-1304. PMID: 32805017, PMCID: PMC7711318, DOI: 10.1001/jamapsychiatry.2020.2304.Peer-Reviewed Original ResearchConceptsRecent stressful life eventsStressful life eventsAssociations of SLEsPoor physical healthMental health outcomesHealth outcomesPhysical healthGeneral populationPopulation-based prospective cohort studyPRS-SCZNetherlands Mental Health SurveyES-SCZMental healthProspective cohort studyIncidence Study-2Modifiable environmental factorsAdulthood stressful life eventsMental Health SurveyDutch general populationPoor mental healthPopulation-based health outcomesLife eventsCohort studyMean ageHealth SurveyExamining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum
Pries L, Dal Ferro G, van Os J, Delespaul P, Kenis G, Lin B, Luykx J, Richards A, Akdede B, Binbay T, Altınyazar V, Yalınçetin B, Gümüş-Akay G, Cihan B, Soygür H, Ulaş H, Cankurtaran E, Kaymak S, Mihaljevic M, Petrovic S, Mirjanic T, Bernardo M, Mezquida G, Amoretti S, Bobes J, Saiz P, García-Portilla M, Sanjuan J, Aguilar E, Santos J, Jiménez-López E, Arrojo M, Carracedo A, López G, González-Peñas J, Parellada M, Maric N, Atbaşoğlu C, Ucok A, Alptekin K, Saka M, Alizadeh B, van Amelsvoort T, Bruggeman R, Cahn W, de Haan L, Rutten B, Luykx J, van Os J, van Winkel R, Arango C, O'Donovan M, Tosato S, Rutten B, Guloksuz S. Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum. Epidemiology And Psychiatric Sciences 2020, 29: e182. PMID: 33200977, PMCID: PMC7681168, DOI: 10.1017/s2045796020000943.Peer-Reviewed Original ResearchDo Current Measures of Polygenic Risk for Mental Disorders Contribute to Population Variance in Mental Health?
Marsman A, Pries L, Have M, de Graaf R, van Dorsselaer S, Bak M, Kenis G, Lin B, Luykx J, Rutten B, Guloksuz S, van Os J. Do Current Measures of Polygenic Risk for Mental Disorders Contribute to Population Variance in Mental Health? Schizophrenia Bulletin 2020, 46: 1353-1362. PMID: 33259628, PMCID: PMC7707067, DOI: 10.1093/schbul/sbaa086.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAdverse Childhood ExperiencesAgedFamilyFemaleGenetic Predisposition to DiseaseHealth SurveysHumansLife Change EventsLongitudinal StudiesMaleMarijuana UseMiddle AgedMultifactorial InheritanceNetherlandsPsychotic DisordersSchizophreniaSocioeconomic FactorsUrban PopulationYoung AdultConceptsPolygenic risk scoresSchizophrenia polygenic risk scoresMental healthFamily historyNetherlands Mental Health SurveyPopulation-based studyPolygenic riskChildhood traumaMental Health SurveyMental health changesEnvironmental risk factorsGeneral mental healthPopulation mental healthGeneral population sampleSomatic painRisk factorsHealth SurveyRisk scorePRS-SZBipolar disorderEpidemiological settingsMental disordersHealth changesAttributable variationPain
2019
Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene–environment interaction. The EUGEI study
van Os J, Pries L, Delespaul P, Kenis G, Luykx J, Lin B, Richards A, Akdede B, Binbay T, Altınyazar V, Yalınçetin B, Gümüş-Akay G, Cihan B, Soygür H, Ulaş H, Cankurtaran E, Kaymak S, Mihaljevic M, Petrovic S, Mirjanic T, Bernardo M, Cabrera B, Bobes J, Saiz P, García-Portilla M, Sanjuan J, Aguilar E, Santos J, Jiménez-López E, Arrojo M, Carracedo A, López G, González-Peñas J, Parellada M, Maric N, Atbaşoğlu C, Ucok A, Alptekin K, Saka M, Arango C, O'Donovan M, Rutten B, Guloksuz S. Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene–environment interaction. The EUGEI study. Psychological Medicine 2019, 50: 1884-1897. PMID: 31414981, DOI: 10.1017/s003329171900196x.Peer-Reviewed Original ResearchConceptsPsychotic disordersPolygenic riskSchizophrenia polygenic riskGene-environment interactionsGenetic riskRelatives of patientsFirst-degree relativesPsychosis phenotypeAverage genetic riskIntermediate phenotypesHealthy siblingsCognitive intermediate phenotypesControl groupAnalysis of associationAverage riskPatientsEvidence for interaction between genetic liability and childhood trauma in the development of psychotic symptoms
Pinckaers F, Rotee I, Nwosu C, Krolinski P, Smeets A, Gülöksüz S, de Jong L, Vaessen T, Damen T, Uittenboogaard A, Schäfer A, Menne-Lothmann C, Decoster J, van Winkel R, Collip D, Delespaul P, De Hert M, Derom C, Thiery E, Jacobs N, Wichers M, Rutten B, van Os J, Drukker M. Evidence for interaction between genetic liability and childhood trauma in the development of psychotic symptoms. Social Psychiatry And Psychiatric Epidemiology 2019, 54: 1045-1054. PMID: 31209522, DOI: 10.1007/s00127-019-01711-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultChildChild AbuseEmotionsFemaleGenetic Predisposition to DiseaseHumansMalePsychotic DisordersRisk FactorsSurveys and QuestionnairesSymptom AssessmentConceptsChildhood traumaGenetic liabilityImpact of CTSymptom Checklist-90 scoresMixed-effects linear regression analysisSubthreshold psychotic experiencesChildhood Trauma Questionnaire-Short FormExpression of psychosisGeneral population twinsQuestionnaire-Short FormPsychosis expressionMultilevel mixed-effects linear regression analysesRisk factorsPsychotic symptomsSymptom subscalesLinear regression analysisSubthreshold expressionTotal scoreStatistical significancePsychic Experience (CAPE) questionnaireRegression analysisToward incorporating genetic risk scores into symptom networks of psychosis
Isvoranu A, Guloksuz S, Epskamp S, van Os J, Borsboom D, Investigators. Toward incorporating genetic risk scores into symptom networks of psychosis. Psychological Medicine 2019, 50: 636-643. PMID: 30867074, PMCID: PMC7093319, DOI: 10.1017/s003329171900045x.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultDepressionFamilyFemaleGenetic Predisposition to DiseaseHumansLongitudinal StudiesMaleMiddle AgedModels, BiologicalMultifactorial InheritancePsychotic DisordersRisk FactorsSchizophreniaYoung Adult
2018
Higher schizotypy predicts better metabolic profile in unaffected siblings of patients with schizophrenia
Atbasoglu E, Gumus-Akay G, Guloksuz S, Saka M, Ucok A, Alptekin K, Gullu S, van Os J. Higher schizotypy predicts better metabolic profile in unaffected siblings of patients with schizophrenia. Psychopharmacology 2018, 235: 1029-1039. PMID: 29306964, DOI: 10.1007/s00213-017-4818-z.Peer-Reviewed Original ResearchConceptsInsulin resistanceDopaminergic activityMetabolic profileHomeostatic model assessmentHDL-C levelsBetter metabolic profilesFavorable metabolic profilePancreatic insulin secretionUnaffected siblingsBeads taskResultsInsulin resistanceTertile groupRegression modelsCentral actionInsulin secretionGeneral populationGenetic predispositionGlucose metabolismModel assessmentSZ patientsRegulatory roleDirect actionSignificant predictorsHigher likelihoodLongitudinal study
2017
DNA Methylation in Schizophrenia
Pries L, Gülöksüz S, Kenis G. DNA Methylation in Schizophrenia. Advances In Experimental Medicine And Biology 2017, 978: 211-236. PMID: 28523549, DOI: 10.1007/978-3-319-53889-1_12.Peer-Reviewed Original ResearchConceptsAberrant DNA modificationsGenome-wide approachesDNA methylation changesCandidate gene studiesHigh heritability estimatesGenetic susceptibility lociHeritable psychiatric conditionEpigenetic mechanismsDNA methylationEpigenetic processesMethylation changesDNA modificationsComplex phenotypesGene studiesSusceptibility lociHeritability estimatesRelevant environmental risk factors
2014
Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations
van Os J, Rutten B, Myin-Germeys I, Delespaul P, Viechtbauer W, van Zelst C, Bruggeman R, Reininghaus U, Morgan C, Murray R, Di Forti M, McGuire P, Valmaggia L, Kempton M, Gayer-Anderson C, Hubbard K, Beards S, Stilo S, Onyejiaka A, Bourque F, Modinos G, Tognin S, Calem M, O'Donovan M, Owen M, Holmans P, Williams N, Craddock N, Richards A, Humphreys I, Meyer-Lindenberg A, Leweke F, Tost H, Akdeniz C, Rohleder C, Bumb J, Schwarz E, Alptekin K, Üçok A, Saka M, Atbaşoğlu E, Gülöksüz S, Gumus-Akay G, Cihan B, Karadağ H, Soygür H, Cankurtaran E, Ulusoy S, Akdede B, Binbay T, Ayer A, Noyan H, Karadayı G, Akturan E, Ulaş H, Arango C, Parellada M, Bernardo M, Sanjuán J, Bobes J, Arrojo M, Santos J, Cuadrado P, Rodríguez Solano J, Carracedo A, García Bernardo E, Roldán L, López G, Cabrera B, Cruz S, Díaz Mesa E, Pouso M, Jiménez E, Sánchez T, Rapado M, González E, Martínez C, Sánchez E, Olmeda M, de Haan L, Velthorst E, van der Gaag M, Selten J, van Dam D, van der Ven E, van der Meer F, Messchaert E, Kraan T, Burger N, Leboyer M, Szoke A, Schürhoff F, Llorca P, Jamain S, Tortelli A, Frijda F, Vilain J, Galliot A, Baudin G, Ferchiou A, Richard J, Bulzacka E, Charpeaud T, Tronche A, De Hert M, van Winkel R, Decoster J, Derom C, Thiery E, Stefanis N, Sachs G, Aschauer H, Lasser I, Winklbaur B, Schlögelhofer M, Riecher-Rössler A, Borgwardt S, Walter A, Harrisberger F, Smieskova R, Rapp C, Ittig S, Soguel-dit-Piquard F, Studerus E, Klosterkötter J, Ruhrmann S, Paruch J, Julkowski D, Hilboll D, Sham P, Cherny S, Chen E, Campbell D, Li M, Romeo-Casabona C, Emaldi Cirión A, Urruela Mora A, Jones P, Kirkbride J, Cannon M, Rujescu D, Tarricone I, Berardi D, Bonora E, Seri M, Marcacci T, Chiri L, Chierzi F, Storbini V, Braca M, Minenna M, Donegani I, Fioritti A, La Barbera D, La Cascia C, Mulè A, Sideli L, Sartorio R, Ferraro L, Tripoli G, Seminerio F, Marinaro A, McGorry P, Nelson B, Amminger G, Pantelis C, Menezes P, Del-Ben C, Gallo Tenan S, Shuhama R, Ruggeri M, Tosato S, Lasalvia A, Bonetto C, Ira E, Nordentoft M, Krebs M, Barrantes-Vidal N, Cristóbal P, Kwapil T, Brietzke E, Bressan R, Gadelha A, Maric N, Andric S, Mihaljevic M, Mirjanic T. Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations. Schizophrenia Bulletin 2014, 40: 729-736. PMID: 24860087, PMCID: PMC4059449, DOI: 10.1093/schbul/sbu069.Peer-Reviewed Original ResearchGene-Environment InteractionGenetic Predisposition to DiseaseHumansSchizophreniaSchizophrenic PsychologySocial Environment