The study, which is part of the doctoral thesis of the first author, Irene Martinez-Serrano, was led by the IDIBAPS research groups Multimodal neuroimaging in high risk and early psychosis and Child and adolescent psychiatry and psychology, with Gisela Sugranyes and Josefina Castro-Fornieles as senior authors.
Psychotic disorders are highly heritable and polygenic diseases, meaning they depend on the combined effect of many genetic variants, each making a small contribution. To study this complexity, the research team used so-called polygenic risk scores, a tool that integrates the effect of multiple genetic variants into a single numerical indicator of genetic vulnerability.
For this work, biological samples from 414 children and adolescents aged between 8 and 18 years treated at the Hospital Clínic de Barcelona were analysed. The cohort included young people with first-episode psychosis, young people with a first-degree family history of schizophrenia or bipolar disorder, and a comparison group without these characteristics. Polygenic risk scores associated with eight psychiatric and cognitive traits were calculated from each participant’s DNA.
The results showed that both young people with psychosis and those with a family history had a higher genetic load related to bipolar disorder and ADHD compared to the control group. Moreover, the young people with psychosis showed a lower genetic predisposition associated with better cognitive performance and educational attainment.
“These results indicate that some characteristics we often observe in these young people, such as ADHD symptoms or certain cognitive and learning difficulties, are not independent phenomena, but partially share the same genetic basis as psychotic disorders,” explains Gisela Sugranyes, IDIBAPS researcher, a member of the CIBERSAM network, and senior co-author of the study.
The polygenic risk scores are still a research tool and do not have a direct clinical application. However, the long-term follow-up of these children and adolescents, combined with neuroimaging data and other international cohorts, could contribute to the future development of early biomarkers and more personalized mental health detection and intervention strategies.
Josefina Castro-Fornieles, IDIBAPS researcher and senior co-author of the study, adds: “The results of the project highlight the importance of characterizing the heterogeneity of these populations to deepen our understanding of the biological architecture of psychotic disorders. These results are a first step towards a more precise classification of patients and at-risk individuals, and towards precision prevention and intervention strategies, which will need to be developed in future studies.”
This project was made possible by funding from La Marató de 3Cat (codes 202234-30, 202222-10, and 202232-30-31), the Carlos III Health Institute / Ministry of Science, Innovation and Universities (codes PI20/00344, PI24/00407, PI20/00661, PI24/00196, PI20/00654, PI24/01052, PI25/00984, PI1800976, PI2100330, FORT23/00002_SUGR_G6, PI24/00279), European Regional Development Fund (FEDER) (co-financing of the previous projects), the European Commission (grant number 101057529), the Alicia Koplowitz Foundation, the Pons Bartran and Maria and Núria Cunillera legacies (code FCRB_CU1_2024), and the INVESTIGO-AGAUR Programme (Next Generation, Generalitat de Catalunya).
Study of reference
Martínez-Serrano, I., Segura, A.G., Ortuño, M. et al. Polygenic profiles in youth with early-onset psychosis and offspring of schizophrenia or bipolar disorder patients. Eur Child Adolesc Psychiatry (2026). https://doi.org/10.1007/s00787-026-03123-2
