Males displayed specific deficits in neurotrophic support (<i>Bdnf</i> and BDNF) and glucocorticoid signaling (<i>Nr3c1</i>), whereas females exhibited impairments in social bonding pathways (<i>Oxtr</i>) and postsynaptic scaffolding proteins (PSD-95 and SHANK3).<h4>Discussion</h4>Vicarious trauma is sufficient to drive depression-like pathology through distinct molecular trajectories in males and females. Here, DLG4 is linked to major depressive disorder.