Cortical thickness differences are associated with cellular component morphogenesis of astrocytes and excitatory neurons in nonsuicidal self-injuring youth

Nonsuicidal self-injury (NSSI) generally occurs in youth and probably progresses to suicide. An examination of cortical thickness differences (Delta CT) between NSSI individuals and controls is crucial to investigate potential neurobiological correlates. Notably, Delta CT are influenced by specific genetic factors, and a large proportion of cortical thinning is associated with the expression of genes that overlap in astrocytes and pyramidal cells. However, in NSSI youth, the mechanisms underlying the relations between the genetic and cell type-specific transcriptional signatures to Delta CT are unclear. Here, we studied the genetic association of Delta CT in NSSI youth by performing a partial least-squares regression (PLSR) analysis of gene expression data and 3D-T1 brain images of 45 NSSI youth and 75 controls. We extracted the top-10 Gene Ontology terms for the enrichment results of upregulated PLS component 1 genes related to Delta CT to conduct the cell-type classification and enrichment analysis. Enrichment of cell type-specific genes shows that cellular component morphogenesis of astrocytes and excitatory neurons accounts for the observed NSSI-specific Delta CT. We validated the main results in independent datasets to verify the robustness and specificity. We concluded that the brain Delta CT is associated with cellular component morphogenesis of astrocytes and excitatory neurons in NSSI youth.