The aim of the present study is to explore whether relevant proinflammatory cytokines such as TNF-α, and IL-1β, and chemokines such as CXCL12, CCL2, CCL11, and CX3CL1 could be potential biomarkers for the detection of co-occurrence of MDD in patients with CUD and/or AUD, and to distinguish primary MDD from substance-induced MDD. Here, CXCL12 is linked to major depressive disorder.