Schizophrenia Polygenic Risk During Typical Development Reflects Multiscale Cortical Organization.

Area of Science:

• Neuroscience
• Genetics
• Developmental Psychology

Background:

• Schizophrenia is increasingly understood as a neurodevelopmental disorder.
• Polygenic risk scores for schizophrenia (PRS-SCZ) can identify abnormal cortical development in children and adolescents.

Purpose of the Study:

• To investigate the association between PRS-SCZ and cortical morphometry in typically developing youth.
• To explore how genetic risk for schizophrenia impacts cortical development across different age groups and brain regions.

Main Methods:

• Assessed PRS-SCZ and cortical thickness in 390 typically developing children and adolescents (3-21 years) using whole-genome genotyping and MRI.
• Integrated findings with age-matched transcriptomics, cytoarchitectural, and network data.
• Compared results with large-scale meta-analyses of schizophrenia and psychiatric disorders from the ENIGMA consortium.

Main Results:

• Higher PRS-SCZ correlated with increased cortical thickness, particularly in association areas and the ventral attention network.
• This pattern of increased thickness in youth contrasted with cortical thinning observed in adult schizophrenia and mood disorders.
• A developmental trajectory was suggested, with early childhood cortical thickening shifting towards thinning in late adolescence.

Conclusions:

• Combining imaging genetics with multiscale mapping provides insights into early-life effects of schizophrenia genetic risk on the cortex.
• Findings highlight the potential of PRS-SCZ to identify neurodevelopmental alterations preceding clinical manifestation of schizophrenia.