Noticeably, similar changes were not seen in PRODH mutant mice [134]. In our analysis, this gene, which encodes a key enzyme involved in proline catabolism, was instead found to have the largest number of connections to other DEGs, as well as to non-DEGs, in brain regions of the late adolescent period to early adulthood (Table 3). Function analysis of the co-expressed network in these late stage brain regions indicated that a subset of 22q11.2 genes may affect SZ brain development and act by disrupting mitochondrial function, particularly during activity-dependent synaptogenesis, which requires substantial metabolic support [135] (Fig. 7). This finding is consistent with a blood-based WGCNA analysis in 22q11DS patients in which a module of genes enriched for protein folding and metabolic process was identified to be associated with psychosis phenotype [57]. Interestingly, the network structure of this module could be re-established only in the adolescent stage of the BrainSpan data (WGCNA module preservation score > 2). Within the 22q11.2 region, there are six genes that are known to affect mitochondrial function: PRODH, MRPL40, SLC25A1, TXNRD2, T10, and ZDHHC8. Together
