Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Mar:92:52-61.
doi: 10.1016/j.euroneuro.2024.12.002. Epub 2024 Dec 24.

Interrelationships between polygenic risk scores, cognition, symptoms, and functioning in first-episode psychosis: A network analysis approach

Gustavo J Gil-Berrozpe  1 , Alex G Segura  2 , Ana M Sánchez-Torres  3 , Silvia Amoretti  4 , Eloi Giné-Servén  5 , Eduard Vieta  6 , Gisela Mezquida  7 , Antonio Lobo  8 , Ana Gonzalez-Pinto  9 , Alvaro Andreu-Bernabeu  10 , Alexandra Roldán  11 , Maria Florencia Forte  6 , Josefina Castro  12 , Daniel Bergé  13 , Natalia Rodríguez  14 , Alejandro Ballesteros  15 , Sergi Mas  16 , Manuel J Cuesta  17 , Miquel Bernardo  18 ; PEPs group
Affiliations

Interrelationships between polygenic risk scores, cognition, symptoms, and functioning in first-episode psychosis: A network analysis approach

Gustavo J Gil-Berrozpe et al. Eur Neuropsychopharmacol. 2025 Mar.

Abstract

Psychopathological manifestations and cognitive impairments are core features of psychotic disorders. Polygenic risk scores (PRS) offer insights into the relationships between genetic vulnerability, symptomatology, and cognitive impairments. This study used a network analysis to explore the connections between PRS, cognition, psychopathology, and overall functional outcomes in individuals experiencing a first episode of psychosis (FEP). The study sample comprised 132 patients with FEP. Genetic data were used to construct PRS for mental disorders and cognitive traits via PRS-continuous shrinkage. We conducted comprehensive clinical and neuropsychological assessments at 2 months post-diagnosis and again at a 2-year follow-up. A network analysis was performed to generate two distinct networks and their centrality indices, encompassing 19 variables across domains such as symptoms, cognition, functioning, and PRS. Variables were grouped within related domains, and stronger relationships were observed within domains than between them. PRS for schizophrenia showed weak negative associations with attention, working memory, and verbal memory, while PRS for cognitive performance showed weak positive associations with attention. Negative symptoms were negatively associated with functioning and verbal memory at both the 2-month and 2-year assessments, as well as with social cognition at 2 years. Poor functioning was moderately related to greater severity of Positive and Negative Syndrome Scale dimensions. This study identified pathways linking PRS, cognition, symptoms, and functioning, suggesting that genetic risk may serve as a marker of vulnerability and disorder progression. The findings also highlight the importance of considering genetic predispositions alongside clinical and cognitive factors to better understand the heterogeneity of psychotic disorders.

Keywords: Cognition; Network analysis; Polygenic risk scores; Psychopathology; Psychosis.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, AbbVie, Adamed, Alcediag, Angelini, Biogen, Beckley-Psytech, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, HMNC, Idorsia, Johnson & Johnson, Lundbeck, Luye Pharma, Medincell, Merck, Newron, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, Teva, and Viatris, outside the submitted work. Dr. R. Rodriguez-Jimenez has been a consultant for, spoken in activities of, or received grants from: Instituto de Salud Carlos III, Fondo de Investigación Sanitaria (FIS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid Regional Government (S2010/ BMD-2422 AGES; S2017/BMD-3740), JanssenCilag, Lundbeck, Otsuka, Pfizer, Ferrer, Juste, Takeda, Exeltis, Casen-Recordati, Angelini, Rovi. De-la-Camara C. received financial support to attend scientific meetings from Janssen, Almirall, Lilly, Lundbeck, Rovi, Esteve, Novartis, Astrazeneca, Pfizer and Casen Recordati. Ruiz-Lazaro PM received financial support to attend scientific meetings from Takeda, and Rovi. SA has been a consultant to and/or has received honoraria/grants from Otsuka-Lundbeck, with no financial or other relationship relevant to the subject of this article. MB has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Menarini, Rovi and Takeda. I. Baeza has received honoraria o support to attend conferences from Angelini and Lundbeck, with no financial or other relationship relevant to the subject of this article. Dr. Roldán has served as advisor or speaker for the companies Otsuka, Angelini and Casen Recordati (unrelated to the present work). FDS has received grants from the Spanish Foundation of Psychiatry and Mental Health and the European Psychiatric Association. MPGP has been a consultant to and/or has received honoraria/grants from Alter, Angelini, Alianza Otsuka-Lundbeck, Cassen-Recordati, Idorsia, Instituto de Salud Carlos III, Janssen-Cilag,Lundbeck, Otsuka, and Pfizer.

LinkOut - more resources