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Background: Studies have shown associations between polygenic risk scores for educational attainment (PRS EA ), cognitive reserve (CR), cognition, negative symptoms (NS), and psychosocial functioning in first-episode psychosis (FEP). However, their specific interactions remain unclear. This study aimed to investigate the mediating roles of CR, cognition, and NS in the relationship between PRS EA and psychosocial functioning one year after a FEP. Additionally, we sought to explore the impact of two NS subtypes on this relationship: diminished Expression (EXP-NS) and Motivation and Pleasure (MAP-NS)., Methods: A total of 138 FEP participants, predominantly male (70%), with a mean age of 24.77 years (SD = 5.29), underwent genetic, clinical, and cognitive assessments two months after study enrollment. Functioning evaluation followed at one-year follow-up. To investigate the mediating role of CR, cognition, and NS in the relationship between PRS EA and functioning, a serial mediation model was employed. Two further mediation models were tested to explore the differential impact of EXP-NS and MAP-NS. Mediation analysis was performed using the PROCESS macro version 4.1 within SPSS version 26., Results: The serial mediation model revealed a causal chain for PRS EA  > CR > cognition > NS > Functioning (β = -3.08, 95%CI [-5.73, -0.43], p = 0.023). When differentiating by type of NS, only EXP-NS were significantly associated in the casual chain (β = -0.17, 95% CI [-0.39, -0.01], p < 0.05)., Conclusions: CR, cognition and NS -specifically EXP-NS- mediate the association between PRS EA and psychosocial functioning at one-year follow-up in FEP patients. These results highlight the potential for personalized interventions based on genetic predisposition., (© 2024 The Author(s). Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)