We and others have previously demonstrated roles for ERβ signaling in enhancing memory processes (Boulware et al., 2013; Hanson et al., 2018; Jacome et al., 2010; Kim and Frick, 2017; Pereira et al., 2014; Walf et al., 2006), reducing anxiety-and depression-like behaviors (Li et al., 2014; Lund et al., 2005; Oyola et al., 2012; Rocha et al., 2005; Walf et al., 2004, 2008; Walf and Frye, 2005a, 2005b), and reducing vasomotor symptoms (Opas et al., 2006; Zhao et al., 2011) in OVX rodents. Here, ESR2 is linked to depressive disorder.