22q11.2 haploinsufficiency seems to have a robust and persistent impact on MAPK signaling pathway. As mentioned earlier, ERK/MAPK signaling was also found to be significantly disrupted in a transcriptomic study of peripheral blood mononuclear cells (PBMC's) from SZ patients with 22q11.2 deletion [69]. Knockout of DGCR8, which maps to the 22q11.2 deleted region, was reported to down-regulate ERK/MAPK and PI3K/AKT signaling in muscle [19]. Moreover, reduced expression of ERK2 was reported in children with a 1 Mb micro-deletion in 22q11.2 [121]. Finally, abnormal activity of the MAPK signaling pathway was observed in postmortem SZ brain without 22q11.2 deletion [122, 123]. Taken together, these findings suggest that altered expression of MAPK signaling could be a common pathway in the pathogenesis of SZ.
