Based on the immune hyperactivity hypothesis of depression (Felger and Miller, 2014; Haroon et al., 2012; Miller et al., 2009; Raison and Miller, 2013), several clinical trials have demonstrated efficacy of COX-2 inhibition as an augmentation strategy to selective-serotonin reuptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD) (Akhondzadeh and Jafari, 2010; Akhondzadeh et al., 2009; Muller et al., 2006). The gene discussed is PTGS2; the disease is major depressive disorder.