The 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

Clougher, Derek ; G Segura, Àlex ; Forte, María Florencia ; Mezquida, Gisela ; Cuesta, Manuel J. ; Vieta, Eduard ; Amoretti, Silvia ; Lobo, Antonio (Universidad de Zaragoza) ; González-Pinto, Ana ; M. Díaz-Caneja, Covadonga ; Roldán, Alexandra ; Fico, Giovanna ; de la Serna, Elena ; Bergé, Daniel ; Gassó, Patricia ; Rodriguez, Natalia ; Verdolini, Norma ; Tortorella, Alfonso ; Menculini, Giulia ; Ribasés, Marta ; Bernardo, Miguel ; Mas, Sergi ;

Resumen: Background: 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.

Idioma: Inglés

DOI: 10.1192/j.eurpsy.2023.2480

Año: 2024

Publicado en: EUROPEAN PSYCHIATRY (2024), 1-31
ISSN: 0924-9338

Financiación: info:eu-repo/grantAgreement/EC/H2020/754550/EU/Biomedicine international training research programme for excellent clinician-scientists/BITRECS
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/CD20-00177
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI16-00789
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FI22/00185
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/MV22/00002
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PI15-00283
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PI18-00805
Financiación: info:eu-repo/grantAgreement/ES/MICIU-ISCIII-FEDER/PI18-01055
Financiación: info:eu-repo/grantAgreement/ES/MICIU-ISCIII-FEDER/PI21-00713
Financiación: info:eu-repo/grantAgreement/ES/MICIU/PI21/00787
Financiación: info:eu-repo/grantAgreement/ES/MINECO/PI08-0208
Financiación: info:eu-repo/grantAgreement/ES/MINECO/PI11-00325
Financiación: info:eu-repo/grantAgreement/ES/MINECO/PI14-00612

Tipo y forma: Article (PostPrint)

Área (Departamento): Area Psiquiatría (Dpto. Medicina, Psiqu. y Derm.)