Polygenic profiles in youth with early-onset psychosis and offspring of schizophrenia or bipolar disorder patients.

Authors

Irene Martínez-Serrano, Alex G Segura, María Ortuño, Adriana Fortea, Roger Borràs, Patricia Camprodon-Boadas, Elena De la Serna, Dolores Moreno, Clemente García-Rizo, Carla Torrent, Inmaculada Baeza, Natalia Rodriguez, Sergi Mas, Josefina Castro-Fornieles, Gisela Sugranyes

Published in

European child & adolescent psychiatry. Aug 10, 2026. Epub Aug 10, 2026.

Abstract

The role of genetic factors shaping liability for psychosis remains unclear. Youth with first-episode, early-onset psychosis and youth at increased familial risk for psychosis show higher rates of co-occurring psychiatric diagnoses and cognitive difficulties than the general population. This study assessed polygenic scores (PGS) for psychiatric diagnoses, cognition and educational attainment in 414 youth: N = 69 cases with non-affective, early-onset psychosis (schizophrenia, schizophreniform and schizoaffective disorders), N = 62 cases with affective, early-onset psychoses (bipolar or depressive disorders with psychotic symptoms), N = 52 offspring of patients with schizophrenia, N = 94 offspring of patients with bipolar disorder, and N = 117 healthy controls. After quality control, PGS were calculated using the PRS-CS tool. Differences in PGS were examined by fitting binary logistic models. Sensitivity analyses ruled out effects of potential confounders. PGS for schizophrenia and bipolar disorder were higher in youth with non-affective, early-onset psychoses and offspring of patients with schizophrenia, and higher PGS scores for attention deficit hyperactivity disorder (ADHD) were found in youth with non-affective, early-onset psychoses and offspring of patients with bipolar disorder, relative to controls. PGS for cognition and educational attainment were lower in youth with non-affective, early-onset psychoses, compared with youth with affective, early-onset psychoses, offspring of bipolar disorder patients, and controls (all P_FDR<0.05). Conclusion: These findings indicate shared and distinct genetic liability profiles influenced by patient and parental diagnoses. In addition to liability for schizophrenia and bipolar disorder, polygenic profiles for ADHD, cognition, and educational attainment may determine the genetic architecture of psychosis.

PMID:
42573752
Bibliographic data and abstract were imported from PubMed on 10 Aug 2026.

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