Substantial evidence has implicated the involvement of AKT signaling in major mental and mood disorders (Beaulieu et al., 2009). Both AKT1 and its upstream activator NRG1 have been identified as susceptibility genes for schizophrenia (Emamian et al., 2004; Mei and Xiong, 2008; Stefansson et al., 2002; Tosato et al., 2005). Interestingly, a number of studies have suggested hyperactivation of NRG signaling in schizophrenia patients, including increased expression of type IV NRG1 in the hippocampus resulted from a mutation in the promoter region (Law et al., 2006) and up-regulation of specific ErbB4 splice isoforms that activate PI3K (Law et al., 2007). At the functional level, NRG1 signaling through ErbB4 receptors promotes neuronal maturation and dendritic growth (Mei and Xiong, 2008). The similarities in neuronal phenotypes among genetic manipulations of multiple AKT signaling components and DISC1 further support the notion that they work in the same pathway in regulating neuronal development. While it remains an intriguing hypothesis that defects in adult hippocampal neurogenesis may contribute to psychiatric disorders (Ming and Song, 2009), the signaling mechanism identified here provides an important framework to
