Fourth, our study links two important susceptibility factors for schizophrenia, DISC1 and GABA signaling, within a common pathway that regulates neuronal development. These results therefore support the emerging theme that many risk genes converge to regulate common neurotransmitter systems and signaling pathways (Balu and Coyle, 2011). Previous studies have implicated GABA and GABAARs in risk for schizophrenia and emphasized the inhibitory GABAergic action in the pathophysiology of schizophrenia (Lewis et al., 2005; Perry et al., 1979). Our results specifically point to a critical role for depolarizing GABA action, involving two Cl− transporters NKCC1 and KCC2, in DISC1-dependent regulation of neuronal development. The NKCC1 (SLC12A2) locus has been linked to schizophrenia in a meta-analysis (Lewis et al., 2003) and resides within the chromosome 5 region that has been implicated repeatedly in schizophrenia (Almasy et al., 2008). A genome-wide association study also identified NKCC1 as a potential susceptibility gene for schizophrenia (Potkin et al., 2009). Furthermore, NKCC1 expression in the dorsolateral prefrontal cortex of some schizophrenia patients was over seven times higher (Dean et al., 2007) and the ratio of NKCC1/KCC2 is
