Cell-type-specific genes associated with cortical structural abnormalities in pediatric bipolar disorder

Abstract

Background Pediatric bipolar disorder (PBD) has been proven to be related to abnormal brain structural connectivity, but how the abnormalities in PBD correlate with gene expression is debated. Objective This study aims at identification of cell-type-specific gene modules based on cortical structural differences in PBD. Methods Morphometric similarity networks (MSN) were computed as a marker of interareal cortical connectivity based on MRI data from 102 participants (59 patients and 43 controls). Partial least squares (PLS) regression was used to calculate MSN differences related to transcriptomic data in AHBA. The biological processes and cortical cell types associated with this gene expression profile were determined by gene enrichment tools. Results MSN analysis results demonstrated differences of cortical structure between individuals diagnosed with PBD and healthy control participants. MSN differences were spatially correlated with the PBD-related weighted genes. The weighted genes were enriched for “trans-synaptic signaling” and “regulation of ion transport”, and showed significant specific expression in excitatory and inhibitory neurons. Conclusions This study identified the genes that contributed to structural network aberrations in PBD. It was found that transcriptional changes of excitatory and inhibitory neurons might be associated with abnormal brain structural connectivity in PBD.