Schizophrenia Polygenic Risk During Typical Development Reflects Multiscale Cortical Organization

作者：Matthias Kirschner, Casey Paquola, Budhachandra Khundrakpam, Uku Vainik, Neha Bhutani, Benazir Hodzic-Santor, Foivos Georgiadis, Noor Al‐Sharif, Bratislav Mišić, Boris C. Bernhardt, Alan C. Evans, Alain Dagher · 发表于：Biological Psychiatry Global Open Science · 年份：2022 · DOI：10.1016/j.bpsgos.2022.08.003 · 被引用次数：12 · 研究领域：Genetic Associations and Epidemiology、Functional Brain Connectivity Studies、Schizophrenia research and treatment

Background: Schizophrenia is widely recognized as a neurodevelopmental disorder. Abnormal cortical development in otherwise typically developing children and adolescents may be revealed using polygenic risk scores for schizophrenia (PRS-SCZ). Methods: = 390) from the PING (Pediatric Imaging, Neurocognition, and Genetics) cohort. We contextualized the findings using 1) age-matched transcriptomics, 2) histologically defined cytoarchitectural types and functionally defined networks, and 3) case-control differences of schizophrenia and other major psychiatric disorders derived from meta-analytic data of 6 ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) working groups, including a total of 12,876 patients and 15,670 control participants. Results: 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 vertexwise cortical thickness were mainly distributed in association cortical areas, particularly the ventral attention network, while relatively sparing koniocortical type cortex (i.e., primary sensory areas). 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 derived from the ENIGMA consortium. Age group models illustrate a possible trajectory from PRS-SCZ-associated cortical thickness increases in early childhood towar...