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

AI Summary

Schizophrenia and bipolar disorder PGS were elevated in youth with non-affective early-onset psychoses and in offspring of schizophrenia patients versus controls.
ADHD polygenic scores were higher in youth with non-affective early-onset psychoses and in offspring of bipolar disorder patients compared with controls.
Polygenic scores for cognition and educational attainment were lower in youth with non-affective early-onset psychoses than in affective cases, offspring of bipolar patients, and controls.

AI Summary

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.

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 PFDR<0.05).

Basic summary

Eur Child Adolesc Psychiatry. 2026 Aug 10. doi: 10.1007/s00787-026-03123-2. Online ahead of print.

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 | DOI:10.1007/s00787-026-03123-2

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