MSX1 encodes Msh homeobox 1, a regulator of early central nervous system and craniofacial development that is also expressed in the adult brain (Fig. 1 and Table 3). Indeed, MSX1 is expressed at higher levels in the adult hippocampus than in the fetal hippocampus (Ramos et al., 2004). In a genome-wide DNA methylation study examining hippocampal expression of GABA-related genes, MSX1 contained the greatest number of differentially methylated positions associated with schizophrenia and bipolar disorder (Ruzicka et al., 2015). In addition, MSX1 is differentially expressed in the striatum of rats that display a conditioned place preference for psychostimulants (Dela Pena et al., 2013). Functionally, MSX1 is essential for maintaining the neurogenic potential of midbrain dopaminergic neurons through regulation of β-catenin signaling (Joksimovic and Awatramani, 2014). The cross-talk between MSX1 and β-catenin signaling may mediate stress-related phenotypes because intact β-catenin signaling is required for stress-resilience (Dias et al., 2014). Taken together, it can be speculated that genetic variation in MSX1 may lead to altered gene expression of the transcript in the hippocampus and/or striatum associated with compulsive drug and alcohol consumption;
