Negative regulators of the bone morphogenetic protein (BMP) pathway were upregulated in SCZ GPCs, including BAMBI, FST, and GREM1, whose overexpression retained SCZ GPCs at the progenitor stage.
Scores from the Scales for the Assessment of Positive and Negative Symptoms (SAPS & SANS) from 125 COS patients were assessed for fit with previously established symptom dimensions from AOS literature using confirmatory factor analysis (CFA).
This study documents that the 15q13.3 deletion and duplication exhibit pathogenicity for COS, with both copy number variants (CNVs) sharing a disrupted CHRNA7 gene.
Among the genes found disrupted in our study, SEZ6, RYR2, GPR153, GTF2IRD1, TTBK1 and ITGA6 have been previously linked to neuronal function or to psychiatric disorders, and thus may be considered as COS candidate genes.
Loss-of-function mutations in UPF3B result in variable clinical presentations including intellectual disability (ID, syndromic and non-syndromic), autism, childhood onset schizophrenia and attention deficit hyperactivity disorder.
By contrast, in healthy children, possession of the risk allele was associated with different trajectories in gray matter only and was confined to frontotemporal regions, reflecting epistatic or other illness-specific effects mediating NRG1 influence on brain development in COS.