000132230 001__ 132230 000132230 005__ 20240301161207.0 000132230 0247_ $$2doi$$a10.1192/j.eurpsy.2023.2480 000132230 0248_ $$2sideral$$a137475 000132230 037__ $$aART-2024-137475 000132230 041__ $$aeng 000132230 100__ $$aClougher, Derek 000132230 245__ $$aThe role of cognitive reserve and clinical symptoms in the association between genetic liability for educational attainment and functioning in first-episode psychosis: a mediation analysis 000132230 260__ $$c2024 000132230 5060_ $$aAccess copy available to the general public$$fUnrestricted 000132230 5203_ $$aBackground: Polygenic risk scores for educational attainment (PRSEA), cognitive reserve (CR), and clinical symptoms are associated with psychosocial functioning in first-episode psychosis (FEP). Nevertheless, the mechanisms underlying their complex interaction is yet to be explored. This study aimed to assess the mediating role of CR and clinical symptoms, both negative (NS) and positive (PS), on the interrelationship between PRSEA and functionality, one year after a FEP. Methods: A total of 162 FEP patients underwent clinical, functional, and genetic assessments. Using genome-wide association study (GWAS) summary results, PRSEA were constructed for each individual. Two mediation models were explored. The parallel mediation model explored the relationship of PRSEA with functionality through CR and clinical symptoms, NS, and PS. The serial mediation model tested a causal chain of the three mediators: CR, NS and PS. Mediation analysis was performed using the PROCESS function V.4.1 in SPSS V.22. Results: A serial mediation model revealed a causal chain for PRSEA > CR > NS > Functionality (β=-0.35, 95%CI [-0.85, -0.04], p<0.05). The model fit the data satisfactorily (CFI=1.00; RMSEA=0.00; SRMR=7.2x10-7). Conversely, in a parallel mediation, none of the three mediators significantly mediated the relationship between PRSEA and functionality and the model poorly fit the data (CFI=0.30; RMSEA=0.25; SRMR=0.11). Conclusions: Both CR and NS mediate the relationship between PRSEA and functionality at oneyear follow-up, using serial mediation analysis. This may be relevant for prevention and personalized early intervention to reduce illness impact and improve functional outcomes in FEP patients. 000132230 536__ $$9info:eu-repo/grantAgreement/EC/H2020/754550/EU/Biomedicine international training research programme for excellent clinician-scientists/BITRECS$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 754550-BITRECS$$9info:eu-repo/grantAgreement/ES/ISCIII/CD20-00177$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI16-00789$$9info:eu-repo/grantAgreement/ES/ISCIII/FI22/00185$$9info:eu-repo/grantAgreement/ES/ISCIII/MV22/00002$$9info:eu-repo/grantAgreement/ES/MICINN/PI15-00283$$9info:eu-repo/grantAgreement/ES/MICINN/PI18-00805$$9info:eu-repo/grantAgreement/ES/MICIU-ISCIII-FEDER/PI18-01055$$9info:eu-repo/grantAgreement/ES/MICIU-ISCIII-FEDER/PI21-00713$$9info:eu-repo/grantAgreement/ES/MICIU/PI21/00787$$9info:eu-repo/grantAgreement/ES/MINECO/PI08-0208$$9info:eu-repo/grantAgreement/ES/MINECO/PI11-00325$$9info:eu-repo/grantAgreement/ES/MINECO/PI14-00612 000132230 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/ 000132230 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion 000132230 700__ $$aG Segura, Àlex 000132230 700__ $$aForte, María Florencia 000132230 700__ $$aMezquida, Gisela 000132230 700__ $$aCuesta, Manuel J. 000132230 700__ $$aVieta, Eduard 000132230 700__ $$aAmoretti, Silvia 000132230 700__ $$0(orcid)0000-0002-9098-655X$$aLobo, Antonio$$uUniversidad de Zaragoza 000132230 700__ $$aGonzález-Pinto, Ana 000132230 700__ $$aM. Díaz-Caneja, Covadonga 000132230 700__ $$aRoldán, Alexandra 000132230 700__ $$aFico, Giovanna 000132230 700__ $$ade la Serna, Elena 000132230 700__ $$aBergé, Daniel 000132230 700__ $$aGassó, Patricia 000132230 700__ $$aRodriguez, Natalia 000132230 700__ $$aVerdolini, Norma 000132230 700__ $$aTortorella, Alfonso 000132230 700__ $$aMenculini, Giulia 000132230 700__ $$aRibasés, Marta 000132230 700__ $$aBernardo, Miguel 000132230 700__ $$aMas, Sergi 000132230 700__ $$a 000132230 7102_ $$11007$$2745$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Psiquiatría 000132230 773__ $$g(2024), 1-31$$pEur. psychiatr.$$tEUROPEAN PSYCHIATRY$$x0924-9338 000132230 8564_ $$s1208193$$uhttps://zaguan.unizar.es/record/132230/files/texto_completo.pdf$$yPostprint 000132230 8564_ $$s1495078$$uhttps://zaguan.unizar.es/record/132230/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint 000132230 909CO $$ooai:zaguan.unizar.es:132230$$particulos$$pdriver 000132230 951__ $$a2024-03-01-14:52:46 000132230 980__ $$aARTICLE