Systems Genomics Support for Immune and Inflammation Hypothesis of Depression

ABSTRACT: BACKGROUND: Immune system plays an important role in brain development and function. With the discovery of increased circulating inflammatory cytokine levels in depression over two decades ago, evidence implicating immune system alterations in the disease has increasingly accumulated. OBJECTIVE: To assess the underlying etiology and pathophysiology, a brief overview of the hypothesis free genomic, transcriptomic and proteomic studies in depression is presented here in order to specifically examine if the immune and inflammation hypothesis of depression is supported. RESULTS: It is observed that genes identified in genome-wide association studies, and genes showing differential expression in transcriptomic studies in human depression do separately overrepresent processes related to both development as well as functioning of the immune system, and inflammatory response. These processes are also enriched in differentially expressed genes reported in animal models of antidepressant treatment. It is further noted that some of the genes identified in genome sequencing and proteomic analyses in human depression, and transcriptomic studies in chronic social defeat stress, an established animal model of depression, relate to immune and inflammatory pathways. CONCLUSION: In conclusion, integrative genomics evidence supports the immune and inflammation hypothesis of depression.