Systemic integrative characterization of neuroimmunological dysregulation in patients with Major Depressive Disorder

Mental disorders, impacting 700 million globally, are a leading global health challenge. The 2019 COVID-19 pandemic (COVID-19) intensified these concerns. Notably, depression not only adds to this burden but also increases susceptibility to immune-related diseases like cancer, autoimmunity, and infectious diseases, revealing underexplored neuroimmune relationships. An integrative analysis was conducted among patients with Major Depressive Disorder (MDD) (70 controls and 69 MDD) and patients with COVID-19 (65 controls, 85 COVID-19 non-depression, and 33 COVID-19 depression). A systematic search was performed on gene expression datasets deposited in the Gene Expression Omnibus and published articles to characterize potential neuroimmune interactions between COVID-19 and MDD of greatest relevance according to the investigated groups, their interaction networks, and correlations. The meta-analysis identified distinct patterns in up-regulated (2202 DEGs) and down-regulated DEGs (differentially expressed genes) (10183 DEGs) with specific filter criteria (0<log2FoldChange<0 and p-value<0.05). Functional enrichment analysis highlighted an increase in immune pathways in up-regulated DEGs, suggesting an exacerbated immune response, while down-regulated DEGs highlighted pathways of the nervous system, indicating negative modulation. The complex interaction between the nervous and immune systems, evidenced by pathway clustering, underscores the potential direct impact of the immune response on neuronal function. The observed neuroimmune dysregulation suggests a link between MDD manifestations and the effects of COVID-19 on the nervous system. Therefore, this study will contribute to expanding the current understanding of the pathophysiological factors related to neuroimmune dysregulation in MDD, potentially the intersection between psychiatric disorders and other diseases such as viral infections.