Our results show that administration of ATRA induced anxiety- and depression-like behavior in young mice, accompanied by a decreased expression of the synaptic gene DLG2 and an increased expression of SynDIG1. DLG2 mRNA levels were correlated with anxiety-like behavior and positively correlated with RARγ. SynDIG1 mRNA levels was correlated with depression-like behavior and negatively correlated with RARγ. Our study findings reveal possible novel links between retinoid signaling and depression. Here, DLG2 is linked to major depressive disorder.