Secondly, data on currently approved as well emerging therapies suggest that individual patient factors determine sensitivity to medications targeting different peptide systems [for review, see (Heilig et al., 2011). Functional genetic variation as well as environmental exposures (including drug exposure) is able to influence the functional activity of individual mediator systems. As an example, it was recently found that a functional NPSR polymorphism is associated with panic anxiety and autonomic reactivity to stress (Domschke et al., 2011), as well as increased basolateral amygdala activation during emotional processing (Dannlowski et al., 2011). These data strongly suggest that if NPSR antagonists turn out to have a therapeutic potential in addictive disorders, their efficacy will likely vary with patient genetics at this locus. Association of variation at the TacR1 locus that encodes the NK1R with alcoholism suggests a similar possibility, although in that case, the functional consequences have not yet been established. Furthermore, if the history of drug exposure influences CRF2R signalling in a way that modulates stress reactivity, as suggested by animal data (Vuong et al., 2010), then drug exposure history may also need to be taken in account to define optimally responsive patient populations.
