Signaling pathways active in MDD include activation of ATR in response to replication stress, NRIF signals cell death from the nucleus, fas signaling pathway, p53-Independent G1/S DNA damage checkpoint and Nicotinamide salvaging, and EGF signaling pathway etc. We noticed that many MDD signatures involves several immunity process, such as T cell receptor signaling pathway and JNK signaling in the CD4+ TCR pathway, IL2-mediated signaling events, IL1 signaling and IL6-mediated signaling events and Calcium signaling in the CD4+ TCR pathway and TCR signaling in CD4+ T cells. This evidence concerns the gene CD4 and major depressive disorder.