RT Journal Article
SR Electronic
T1 Schizophrenia polygenic risk during typical development reflects multiscale cortical organization
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.13.448243
DO 10.1101/2021.06.13.448243
A1 Matthias Kirschner
A1 Casey Paquola
A1 Budhachandra S. Khundrakpam
A1 Uku Vainik
A1 Neha Bhutani
A1 Benazir Hodzic-Santor
A1 Foivos Georgiadis
A1 Noor B. Al-Sharif
A1 Bratislav Misic
A1 Boris Bernhardt
A1 Alan C. Evans
A1 Alain Dagher
YR 2022
UL http://biorxiv.org/content/early/2022/01/02/2021.06.13.448243.abstract
AB Schizophrenia is widely recognized as a neurodevelopmental disorder. Abnormal cortical development may by revealed using polygenic risk scoring for schizophrenia (PRS-SCZ). We assessed PRS-SCZ and cortical morphometry in typically developing children (3–21 years) using whole genome genotyping and T1-weighted MRI (n=390) from the Pediatric Imaging, Neurocognition and Genetics (PING) cohort. We contextualise the findings using (i) age-matched transcriptomics, (ii) histologically-defined cytoarchitectural types and functionally-defined networks, (iii) case-control differences of schizophrenia and other major psychiatric disorders. Higher PRS-SCZ was associated with greater cortical thickness, which was most prominent in areas with heightened gene expression of dendrites and synapses. PRS-SCZ related increases in vertex-wise cortical thickness were especially focused in the ventral attention network, while koniocortical type cortex (i.e. primary sensory areas) was relatively conserved from PRS-SCZ related differences. The large-scale pattern of cortical thickness increases related to PRS-SCZ mirrored the pattern of cortical thinning in schizophrenia and mood-related psychiatric disorders. Age group models illustrate a possible trajectory from PRS-SCZ associated cortical thickness increases in early childhood towards thinning in late adolescence, which resembles the adult brain phenotype of schizophrenia. Collectively, combining imaging-genetics with multi-scale mapping, our work provides novel insight into how genetic risk for schizophrenia impacts the cortex early in life.Competing Interest StatementThe authors have declared no competing interest.