DISC1 has been extensively studied in schizophrenia and mood disorder patients (Millar et al., 2000). It is very interesting that some loci associated with SD in this population are also implicated in schizophrenia. Schizophrenia is associated with increased rates of substance dependence, perhaps due to many traits associated with schizophrenia including impulsive decision making, disturbances in reward-related processes, and the propensity to self-medicate dysphoria (Krystal et al., 2006). NMDA receptor function has been implicated in both disorders (Harrison and Weinberger, 2005; Liechti and Markou, 2008). However, schizophrenia appears to be associated with decreased NMDA receptor function, while alcohol dependence, for example, is associated with enhanced NMDA receptor function (Krystal et al., 1995; Krystal et al., 2003a; Krystal et al., 2003c). Characterizing the impact of each variant on NMDA receptor function in vivo will be an important step in putting the current findings in a neurobiological context.
