6533b855fe1ef96bd12b09f1

RESEARCH PRODUCT

Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway

Javier González-peñasBerna Binnur AkdedeEstela Jiménez-lópezSilvia AmorettiSinan GuloksuzSinan GuloksuzPilar A. SaizBurçin CihanSanja Andric PetrovicMiguel BernardoAlexander RichardsMeram Can SakaGüvem Gümüş-akayJose Luis SantosSemra Ulusoy KaymakTolga BinbayJurjen J. LuykxJurjen J. LuykxHalis UlaşJulio SanjuánGisela MezquidaBerna YalınçetinManuel ArrojoPhilippe DelespaulNadja P. MaricJulio BobesAlp ÜçOkMarina MihaljevicGonzalo LópezEduardo J. AguilarMaarten BakEylem Sahin CankurtaranTijana MirjanicBochao D. LinMichael Conlon O'donovanCem AtbaşoğluKöksal AlptekinKöksal AlptekinSaskia Van DorsselaerVesile AltınyazarLotta-katrin PriesGunter KenisAngel CarracedoRon De GraafMargreet Ten HaveMaría Paz García-portillaJim Van OsJim Van OsJim Van OsMara ParelladaBart P. F. RuttenCelso ArangoHaldun Soygür

subject

RiskMultifactorial InheritancePsychosisHallucinationsAffective pathwayCLINICAL PSYCHOSISNEGATIVE SYMPTOMSDelusions03 medical and health sciences0302 clinical medicineMENTAL-HEALTH SURVEYchildhood adversityAffective dysregulationHumansMedicinegeneticspsychosisGenetic riskApplied Psychology1ST EPISODE PSYCHOSISGENERAL-POPULATIONbusiness.industryPSYCHIATRIC-DISORDERSSHORT-FORMAbsolute risk reductionNETWORK APPROACHIdeationmedicine.diseaseCHILDHOOD TRAUMA030227 psychiatryPsychiatry and Mental healthPsychotic DisordersSchizophreniaSchizophreniaSCHIZOPHRENIA SPECTRUM DISORDERSPolygenic risk scorebusinessenvironment030217 neurology & neurosurgerySchizophrenia spectrumClinical psychology

description

AbstractBackgroundThere is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation.MethodsWe analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls.ResultsThe impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: −0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465).ConclusionsThe results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

yearjournalcountryeditionlanguage
2022-07-01Psychological Medicine
https://doi.org/10.1017/s0033291720003748