Cellular immune phenotype of major depressive disorder – findings from the EMBARC study

Major depressive disorder (MDD) is associated with immune dysfunction. This study aimed to characterize the cellular immunophenotypes that may underpin immune dysregulation in MDD. Peripheral blood mononuclear cell (PBMC) samples at baseline from participants with MDD from the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study were included. A panel of 33 antibodies was analyzed using mass cytometry to compare the immune cell abundance and marker expression profiles between participants with mild and moderate/severe depression. Mass cytometry data were investigated using (1) Uniform Manifold Approximation and Projection for Dimension Reduction (UMAP), (2) FlowSOM (self-organizing maps) for clustering, and (3) Significance Analysis of Microarrays (SAM) for statistical analyzes. FlowSOM identified 8 clusters of distinct cell types. The abundance of cytotoxic T, NK, NK T, and Naïve B cells was significantly lower in participants with moderate/severe depression compared to mild depression. NKT cells had significantly lower CD56 and CD16 expression in patients with moderate/severe depression compared to patients with mild depression. Our observations provide evidence for alterations in B, NKT, and NK cell abundance and their cell surface markers in moderate/severe depression. Further investigations into immune cell dysfunction in moderate/severe depression are necessary.