Abstract
Background
Morphology of the human cerebral cortex differs across psychiatric disorders, with
neurobiology and developmental origins mostly undetermined. Deviations in the tangential
growth of the cerebral cortex during pre/perinatal periods may be reflected in individual
variations in cortical surface area later in life.
Methods
Interregional profiles of group differences in surface area between cases and controls
were generated using T1-weighted magnetic resonance imaging from 27,359 individuals
including those with attention-deficit/hyperactivity disorder, autism spectrum disorder,
bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology
(through the Child Behavior Checklist). Similarity of interregional profiles of group
differences in surface area and prenatal cell-specific gene expression was assessed.
Results
Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity
disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal
association cortices. The same interregional profiles were also associated with interregional
profiles of (prenatal) gene expression specific to proliferative cells, namely radial
glia and intermediate progenitor cells (greater expression, larger difference), as
well as differentiated cells, namely excitatory neurons and endothelial and mural
cells (greater expression, smaller difference). Finally, these cell types were implicated
in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia
were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia,
and starvation. Genes coexpressed with endothelial and mural genes were enriched with
genes associated with maternal hypertension and preterm birth.
Conclusions
Our findings support a neurodevelopmental model of vulnerability to mental illness
whereby prenatal risk factors acting through cell-specific processes lead to deviations
from typical brain development during pregnancy.
Keywords
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Article Info
Publication History
Published online: March 03, 2022
Accepted:
February 23,
2022
Received in revised form:
February 2,
2022
Received:
October 19,
2021
Identification
Copyright
© 2022 Society of Biological Psychiatry.
