Work

Risk Indicator Aggregation and Cluster Stability Across Developmental Domains from Early to Middle Childhood in Children at Familial High-Risk of Schizophrenia or Bipolar Disorder and Population-Based Controls

Year: 2026

Type: article

Abstract: BACKGROUND AND HYPOTHESES: Children of parents with schizophrenia or bipolar disorder are at increased risk of developing a mental disorder, including psychosis. While domain-specific developmental risk indicators have been identified, studies examining the accumulated risk distribution are lacking. Hypothesizing heterogeneity, we aimed to identify clusters with differential risk indicator load across known risk domains, and to examine cluster stability across early to middle childhood in children at familial high-risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP). STUDY DESIGN: A total of 441 children at FHR-SZ or FHR-BP and population-based controls were examined across multiple domains including neurocognition, social behavior, motor function, emotion regulation, language, and psychopathology at ages 7 and 11. Data from age 7 were clustered using k-means clustering and data from age 11 were clustered using the same cluster centers. STUDY RESULTS: Four clusters were identified and named Best outcome profile, Intermediate outcome profile, Selectively affected profile, and Broadly affected profile. The clusters showed marked heterogeneity regarding child performance and functioning across domains, and associations with family and caregiver functioning were shown across groups. From age 7 to 11, 60% stayed in the same cluster. CONCLUSIONS: Our findings of partially stable clusters with differential risk profiles for later onset of psychotic disorders evidence the need to consider risk heterogeneity in preventive interventions targeting offspring at FHR-SZ or FHR-BP, since some children have profiles with serious impairments across multiple domains while others have profiles with few or no impairments and therefore may be more resilient.

Source: Schizophrenia Bulletin

DOI: 10.1093/schbul/sbag141