GRM5 and major depressive disorder: Functional inhibition of mGlu5 represents a promising treatment approach for multiple disorders including depression, anxiety, substance use disorder and comorbid sleep disruptions, yet mitigating the risk of adverse effects remains a concern for clinical development (McGeehan and Olive, 2003; Busse et al., 2004; Dölen et al., 2007; Morin et al., 2010; Lindemann et al., 2015; Gould et al., 2018).