Do viral-associated pathways underlie the immune activation during the acute phase of severe major depression?

BackgroundMajor depressive disorder (MDD) and its most severe phenotype, major dysmood disorder (MDMD), are distinguished by the activation of the immune-inflammatory response system, T cell activation, and a relative T regulatory cell suppression. Nevertheless, these immune data were not used to characterize the features of the immune protein-protein interaction (PPI) network of MDMD. ObjectivesTo identify the networks nodes and bottlenecks as well as the biological processes that are overrepresented in the PPI network, we conducted PPI network, annotation, and enrichment analyses. ResultsThe PPI network analysis has identified the following backbone genes: tumor necrosis factor- (TNF), interleukin (IL)6, CXCL12, CXCL10, CCL5, cluster of differentiation (CD)4, CD8A, human leukocyte antigen (HLA)-DR, and FOXP3. A "cellular and defense response", an "immune response system response", and "a viral process that involves viral protein interaction with cytokines and cytokine receptors" were all highly associated with the network. The chemokine network and TNF and nuclear factor-{kappa}B (NFKB) pathways are additional biological pathways that are enriched in the PPI network. Molecular complex detection extracted one component from the data, including viral protein interaction with cytokine and cytokine receptors and "regulated by RELA" (an NFKB subunit). ConclusionsViral processes may underlie the activation of T cells and the cytokine and chemokine networks that are associated with MDMD. Future research on the pathogenesis of MDMD and MDD should examine whether and which viral infections are associated with the onset of these conditions, or whether viral reactivation is associated with the recurrence of illness.