The 22q11.2 deletion is the strongest known genetic risk factor for
schizophrenia. Research has implicated
microRNA-mediated dysregulation in
22q11.2 deletion syndrome (
22q11.2DS)
schizophrenia-risk. Primary candidate genes are DGCR8 (
DiGeorge syndrome critical region gene 8), which encodes a component of the microprocessor complex essential for
microRNA biogenesis, and MIR185, which encodes
microRNA 185. Mouse models of
22q11.2DS have demonstrated alterations in brain
microRNA biogenesis, and that DGCR8 haploinsufficiency may contribute to these alterations, e.g., via down-regulation of a specific
microRNA subset. miR-185 was the top-scoring down-regulated
microRNA in both the prefrontal cortex and the hippocampus, brain areas which are the key foci of
schizophrenia research. This reduction in miR-185 expression contributed to dendritic and spine development deficits in hippocampal neurons. In addition, miR-185 has two validated targets (RhoA, Cdc42), both of which have been associated with altered expression levels in
schizophrenia. These combined data support the involvement of miR-185 and its down-stream pathways in
schizophrenia. This review summarizes evidence implicating
microRNA-mediated dysregulation in
schizophrenia in both 22q11.2DS-related and idiopathic cases.