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@ARTICLE{Kirschner:911339,
author = {Kirschner, Matthias and Paquola, Casey and Khundrakpam,
Budhachandra S. and Vainik, Uku and Bhutani, Neha and
Benazir-Hodzic-Santor and Al-Sharif, Noor B. and Misic,
Bratislav and Bernhardt, Boris and Evans, Alan C. and
Dagher, Alain},
title = {{S}chizophrenia polygenic risk during typical development
reflects multiscale cortical organization},
journal = {Biological psychiatry: global open science},
volume = {3},
number = {4},
address = {Amsterdam},
publisher = {Elsevier},
reportid = {FZJ-2022-04631},
pages = {1083-1093},
year = {2023},
abstract = {Schizophrenia is widely recognized as a neurodevelopmental
disorder, but determining neurodevelopmental features of
schizophrenia requires a departure from classic case-control
designs. Polygenic risk scoring for schizophrenia (PRS-SCZ)
enables investigation of the influence of genetic risk for
schizophrenia on cortical anatomy during neurodevelopment
and prior to disease onset. PRS-SCZ and cortical morphometry
were assessed in typically developing children (3 – 21
years) using T1-weighted MRI and whole genome genotyping
(n=390) from the Pediatric Imaging, Neurocognition and
Genetics (PING) cohort. Then, we sought to contextualise the
findings using (i) age-matched transcriptomics, (ii)
gradients of cortical differentiation and (iii) case-control
differences of major psychiatric disorders. Higher PRS-SCZ
was associated with greater cortical thickness in typically
developing children, while surface area and cortical volume
showed only subtle associations. Greater cortical thickness
was most prominent in areas with heightened gene expression
for dendrites and synapses. The pattern of PRS-SCZ
associations with cortical thickness reflected functional
specialisation in the cortex and was spatially related to
cortical abnormalities of patient populations of
schizophrenia, bipolar disorder, and major depression.
Finally, age interaction models indicated PRS-SCZ effects on
cortical thickness were most pronounced between ages 3 and
6, suggesting an influence of PRS-SCZ on cortical maturation
early in life. Integrating imaging-genetics with multi-scale
mapping of cortical organization, our work contributes to an
emerging understanding of how risk for schizophrenia and
related disorders manifest in early life.},
cin = {INM-1 / INM-7},
ddc = {610},
cid = {I:(DE-Juel1)INM-1-20090406 / I:(DE-Juel1)INM-7-20090406},
pnm = {5254 - Neuroscientific Data Analytics and AI (POF4-525) /
HIBALL - Helmholtz International BigBrain Analytics and
Learning Laboratory (HIBALL) (InterLabs-0015)},
pid = {G:(DE-HGF)POF4-5254 / G:(DE-HGF)InterLabs-0015},
typ = {PUB:(DE-HGF)16},
pubmed = {37881579},
UT = {WOS:001098291000001},
doi = {10.1016/j.bpsgos.2022.08.003},
url = {https://juser.fz-juelich.de/record/911339},
}