Fifth, our study may provide new insight into the relationship between developmental stress and schizophrenia. Both genetic predisposition and environmental factors, as well as interactions and correlations between them, are thought to contribute to the etiology of psychiatric disorders (Caspi and Moffitt, 2006; Tsuang et al., 2004). We present an example of how a genetic risk factor and an environmental stimulus, each relatively innocuous by itself, can have profound effects on neuronal development when combined. These results may provide one mechanistic explanation for how genetic risk alone can remain causally insufficient for disease manifestation, even in the Scottish family with the chromosomal translocation that disrupted DISC1 (Millar et al., 2000). Analogous gene-environment interactions on risk for schizophrenia have recently been reported in the context of obstetric complications (Nicodemus et al., 2008). Importantly, interaction between DISC1 and depolarizing GABA signaling operates both during normal adult neurogenesis and early postnatal neurogenesis after stress and converge on the downstream mTOR pathway. Our results suggest that adult hippocampal neurogenesis may be more sensitive to dysfunction of susceptibility genes for mental disorders and support the possibility that defects in adult neurogenesis may contribute to the adult onset manifestations of schizophrenia (Ming and Song, 2009).
